Perbandingan Granisetron 0,01 mg/KgBb dengan Ondansetron 0,08 Mg/Kg.Bb Untuk Mencegah Mual Muntah Pascaoperasi Dini Mastektomi Radikal Modifikasi

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Budi Fitriyana

2013-04-01

Full Text Available Postoperative nausea and vomiting not only cause discomfort to the patient, but also lead to electrolyte imbalance, regurgitation and aspiration, bleeding and loss of surgical sutures. Patients who experience postoperative nausea and vomiting will require further attention and treatment which of course increases the cost of medical services. Women who underwent mastectomy with accompanying decision underarm lymph nodes have a high risk of postoperative nausea and vomiting. Many anti-vomiting are given including antihistamines, butyrophenon, and dopamine receptor antagonists have been reported to have undesirable side effects including excessive sedation, hypotension, dry mouth, dysphoria, hallucinations and extrapyramidal effects. 5 HT3 receptor antagonists provide a major advancement for treatment of postoperative nausea and vomiting due to fewer side effects when compared with anti-vomiting medications before. This study will compare the two drugs 5 HT3 receptor antagonist granisetron with ondansetron in preventing postoperative nausea and vomiting modified radical mastectomy early. Conducted research on 58 patients ASA I and II modified radical mastectomy is performed under general anesthesia. Sampling was carried out using double-blind randomized controlled trial. Samples were divided into two groups by block randomization. Group G is given granisetron 0.01 gr / kg.bb and group O is given ondansetron 0.08 mg / kg.bb. Drug treatment is administered intravenously 30 minutes before the surgery ended on a complete evaluation of blood pressure, heart rate, oxygen saturation and length of surgery. Postoperative nausea and vomiting shortly after surgery assessed every hour until 6 hours after surgery (early postoperative nausea and vomiting to 4 scale (0-3. Data were analyzed by t-test, Chi-square test, Mann-Whitney test and Fisher's Exact test on Windows SPSS ver.16 The results suggest there is a tendency complaints of postoperative nausea and

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

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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.

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

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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...

The effects of acute multiple intraperitoneal injections of the GABAB receptor agonist baclofen on food intake in rats.

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Patel, Sunit M; Ebenezer, Ivor S

2008-12-28

This study was undertaken to examine the effects of acute repeated administration of the GABA(B) receptor agonist baclofen on food intake in rats. In Experiment 1, the effects of repeated intraperitoneal (i.p.) injections of the GABA(B) receptor agonist baclofen (1 and 2 mg/kg) at 2 h intervals were investigated on food intake in non-deprived male Wistar rats. Both doses of baclofen significantly increased food intake after the 1st injection (PGABA(B) receptor agonists on food intake and energy homeostasis.

Postoperative impairment of motor function at train-of-four ratio ≥0.9 cannot be improved by sugammadex (1 mg kg-1).

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Baumüller, E; Schaller, S J; Chiquito Lama, Y; Frick, C G; Bauhofer, T; Eikermann, M; Fink, H; Blobner, M

2015-05-01

A train-of-four ratio (TOFR) ≥0.9 measured by quantitative neuromuscular monitoring is accepted as an indication of sufficient neuromuscular recovery for extubation, even though many postsynaptic acetylcholine receptors may still be inhibited. We investigated whether antagonism with sugammadex after spontaneous recovery to TOFR≥0.9 further improves muscle function or subjective well-being. Following recovery to TOFR≥0.9 and emergence from anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip strength were measured before and after surgery (before and after test drug administration). At discharge from the postanaesthesia care unit, well-being was assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR-40). Patients' fine motor function [6 (sd 4) vs 15 (3) pegs (30 s)(-1), Psugammadex or placebo, motor function was significantly improved in both groups but did not reach the preoperative level. There was no difference between groups at any time. Global well-being was unaffected (QoR-40: placebo, 174 vs 185; sugammadex, 175 vs 186, P>0.05). Antagonizing rocuronium at TOF≥0.9 with sugammadex 1.0 mg kg(-) (1) did not improve patients' motor function or well-being when compared with placebo. Our data support the view that TOFR≥0.9 measured by electromyography signifies sufficient recovery of neuromuscular function. The trial is registered at ClinicalTrials.gov (NCT01101139). © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats measured under different feeding conditions.

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Ebenezer, Ivor S; Patel, Sunit M

2011-02-25

The effects of intraperitoneal (i.p.) administration of the GABA(B) receptor agonist baclofen were assessed in rats under different feeding conditions. In Experiment 1, it was observed that baclofen (1-4 mg/kg) significantly (at least, P<0.05) increased cumulative food intake in non-deprived rats during the 120 min measurement period during the early light phase of the light-dark cycle. By contrast, during the early dark phase of the light-dark cycle in non-deprived rats, the 1mg/kg doses of baclofen significantly increased cumulative feeding at 30, 60 and 120 min (at least P<0.05), the 2mg/kg dose significantly increased feeding at 30 and 60 min (at least P<0.05) and the 4 mg/kg dose had no effects on feeding. In Experiment 2, baclofen (1-4 mg/kg) was found to produce no significant effects on food intake in rats that were food-deprived for 22 h. In Experiment 3, the effects of baclofen were investigated on food intake in 16 h food-deprived rats that had received an oral preload for 2h prior to drug administration. Baclofen (1-4 mg/kg) significantly increased cumulative food consumption (at least, P<0.05) only during the first 30 min after administration in these animals. The results of this study indicate that the effects of baclofen on food intake may be related to the state of hunger or satiety of the animals and the time during the light-dark cycle when the drug is administered. Copyright © 2010 Elsevier B.V. All rights reserved.

Final report of AFRIMETS.M.M-S6: supplementary comparison of 100 mg, 100 g 500 g, 1 kg and 5 kg stainless steel mass standards

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Mautjana, R. T.; Molefe, P. T.; Mayindu, N. F.; Armah, M. N.; Ramasawmy, V.; Albasini, G. L.; Matali, S.; Richmond, H.; Rusimbi, V.; Kiwanuka, J.; Mutale, D. M.; Mutsimba, F.

2018-01-01

This report summarizes the results of AFRIMETS.M.M-S6 mass standards comparison conducted between eleven participating laboratories/countries. Two sets of five weights with nominal values 100 mg, 100 g, 500 g, 1 kg and 5 kg were used as the traveling standards. These nominal values were decided from the needs of participating laboratories submitted to the pilot laboratory through a questionnaire and agreed upon by all participants. The traveling standards were hand carried between laboratories starting from February 2014 and were received from the last participants in October 2014. The programme was coordinated by National Metrology Institute of South Africa (NMISA), who provided the travelling standards and reference values for the comparison. The corrections to the BIPM as-maintained mass unit [5] have insignificant influence on the results of this comparison. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men.

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Andrews, J; Honeybourne, D; Ashby, J; Jevons, G; Fraise, A; Fry, P; Warrington, S; Hawser, S; Wise, R

2007-09-01

A validated microbiological assay was used to measure concentrations of iclaprim (AR-100) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF) after a single 1.6 mg/kg intravenous 60 min iv infusion of iclaprim. Male volunteers were randomly allocated to three nominal sampling time intervals 1-2 h (Group A), 3-4 h (Group B) and 5.5-7.0 h (Group C) after the start of the drug infusion. Mean iclaprim concentrations in plasma, BM, AM and ELF, respectively, were for Group A 0.59 mg/L (SD 0.18), 0.51 mg/kg (SD 0.17), 24.51 mg/L (SD 21.22) and 12.61 mg/L (SD 7.33); Group B 0.24 mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38 mg/L (SD 5.17); and Group C 0.14 mg/L (SD 0.05), no detectable level in BM, 5.28 mg/L (SD 2.30) and 2.66 mg/L (SD 2.08). Iclaprim concentrations in ELF and AM exceeded the MIC(90) for penicillin-susceptible Streptococcus pneumoniae (MIC90 0.06 mg/L), penicillin-intermediate S. pneumoniae (MIC90 2 mg/L), penicillin-resistant S. pneumoniae (MIC90 4 mg/L) for 7, 7 and 4 h, respectively, and Chlamydia pneumoniae (MIC90 0.5 mg/L) for 7 h. Mean iclaprim concentrations in ELF exceeded the MIC90 for Haemophilus influenzae (MIC90 4 mg/L) and Moraxella catarrhalis (MIC90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC90 was exceeded for up to 7 h. Furthermore, the MIC90 for methicillin-resistant Staphylococcus aureus of 0.12 mg/L was exceeded at all sites for up to 7 h. These data suggest that iclaprim reaches lung concentrations that should be effective in the treatment of community-acquired pneumonia.

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

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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.

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

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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.

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

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Bains, Rasneer S; Ebenezer, Ivor S

2013-01-05

It has been previously reported that the GABA(B) receptor agonist baclofen decreases food intake after oral administration and fat intake after intraperitoneal administration. The aim of the study was to investigate the effects of baclofen (1-4 mg/ kg) administered orally (Experiment 1) on food intake in non-deprived rats (n=6) and intraperitoneally (Experiment 2) on fat intake in non-deprived rats (n=8) that were naïve to baclofen (1st set of trials) and in the same group of rats after they were sub-chronically exposed to baclofen (2nd set of trials). The results from Experiment 1 show that baclofen had no effects on food intake during the 1st set of trials, but the 2 and 4 mg/kg doses significantly increased food consumption during the 2nd set of trials. Baclofen produced sedation during the 1st set of trials, but tolerance occurred to this effect and was not apparent during the 2nd set of trials. These observations suggest that the motor effects may have competed with the hyperphagic effects of baclofen during the 1st set of trials. The data from Experiment 2 show that baclofen had no effects on fat intake during either the 1st or 2nd set of trials. The results of the study thus indicate that orally administrated baclofen increases food intake and intraperitoneal administration has no effect on fat intake in non-deprived rats under the conditions used in this study. These findings may have important implications for research on the use of baclofen in studies concerned with ingestive behaviours. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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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.

[A case report of the combination therapy with S-1 plus CDDP intraperitoneal chemotherapy for CY positive cancer patient].

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Ishii, Yasushi; Iwasaki, Yoshiki; Ohashi, Manabu; Iwanaga, Tomohiro; Ohinata, Ryouki; Takahashi, Keiichi; Matsumoto, Hiroshi; Yamaguchi, Tatsurou; Nakano, Daisuke

2011-11-01

A male patient in his 50s underwent distal gastrectomy for gastric cancer. In operation, there was no peritoneal dissemination. But peritoneal lavage cytology revealed positive peritoneal dissemination. Thus, we set an intraperitoneal infuser port to this patient. On specimen, a type-3 tumor was located in the gastric lesser of antrum to angle. Microscopic examination of specimens revealed a signet ring cell carcinoma and poorly differentiated adenocarcinoma under serosa, and positive of lymph node metastasis. The diagnosis was pT4N2M1P0CY1H0, Stage IV( Japanese classification of gastric carcinoma The 14 Edition). CDDP was administered through the infuser port (on day 7, a first dose of 60 mg/m2 and 30 mg/m2 for second) combined with oral administration of S-1 (100 mg/body) for two weeks, with one week of drug withdrawal. This chemotherapy was repeated for 11 courses. After that, peritoneal lavage cytology became negative. S-1 oral administration was continued for four years, and this patient has been well for five years and six months after the surgery. Therefore, it is suggested that intraperitoneal chemotherapy with cisplatin is an effective treatment for microscopical peritoneal dissemination.

Intravenous rocuronium 0.3 mg/kg improves the conditions for tracheal intubation in cats: a randomized, placebo-controlled trial.

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Sakai, Daniel M; Zornow, Kailee Anne; Campoy, Luis; Cable, Christina; Appel, Leslie D; Putnam, Holly J; Martin-Flores, Manuel

2018-01-01

Objectives We evaluated the use of rocuronium 0.3 mg/kg intravenously (IV) to facilitate tracheal intubation in cats anesthetized for elective ovariohysterectomy. Methods Thirty female cats were randomly allocated to receive rocuronium 0.3 mg/kg IV or an equal volume of normal saline, following induction of anesthesia with ketamine and midazolam. Thirty seconds after induction, a single investigator, unaware of treatment allocation, attempted tracheal intubation. The number of attempts and the time to complete intubation were measured. Intubating conditions were assessed as acceptable or unacceptable based on a composite score consisting of five different components. Duration of apnea after induction was measured and cases of hemoglobin desaturation (SpO 2 rocuronium 12 s [range 8-75 s]; saline 60 s [range 9-120 s]) and with fewer attempts (rocuronium 1 [range 1-2]; saline 2 [range 1-3], both P = 0.006) in cats receiving rocuronium. Unacceptable intubating conditions on the first attempt occurred in 3/15 cats with rocuronium and in 10/15 with saline ( P = 0.01). Apnea lasted 4 ± 1.6 mins with rocuronium and 2.3 ± 0.5 mins with saline ( P = 0.0007). No cases of desaturation were observed. Conclusions and relevance Rocuronium 0.3 mg/kg IV improves intubating conditions compared with saline and reduces the time and number of attempts to intubate with only a short period of apnea in cats.

On the effects of the Fusarium toxin deoxynivalenol (DON) administered per os or intraperitoneal infusion to sows during days 63 to 70 of gestation.

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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

Effects of intraperitoneal and intranasal application of Lentinan on cellular response in rats.

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Markova, Nadya; Kussovski, Vesselin; Radoucheva, Tatyana; Dilova, Krasimira; Georgieva, Neli

2002-11-01

Lentinan (Ajinomoto, Japan) was administrated intraperitoneally (i.p.) and intranasally (i.n.) at different doses (1, 5 and 10 mg/kg) to rats. Effectiveness of Lentinan treatment was evaluated by comparative testing of cell activation (establishing the number, glycolytic and acid phosphatase activity, H2O2 production and killing ability against Salmonella enteritidis and Staphylococcus aureus) at two different compartments--peritoneal and broncho-alveolar cavities. The results indicated that Lentinan induced high-grade activation of peritoneal cells (PCs) and especially of broncho-alveolar cells (BACs) with markedly enhanced effector function (killing ability against S. aureus). Generally, Lentinan, known usually with its parenteral routes of application, can be successful to stimulate the host cell response in the respiratory tract by intranasal route of administration.

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

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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

Intraperitoneal pre-insufflation of 0.125% bupivaciane with tramadol for postoperative pain relief following laparoscopic cholecystectomy

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Aslam Jamal

2016-01-01

Full Text Available Background and Aims: Laparoscopic cholecystectomy is associated with a fairly high incidence of postoperative discomfort which is more of visceral origin than somatic. Studies have concluded that the instillation of local anesthetic with opioid around gall bladder bed provides more effective analgesia than either local anesthetic or opioid alone. Material and Methods: The study included 90 American Society of Anesthesiologists I-II patients of age 16-65 years scheduled for laparoscopic cholecystectomy under general anesthesia. The patients received the study drugs at the initiation of insufflation of CO 2 in the intraperitoneal space by the operating surgeon under laparoscopic camera guidance over the gallbladder bed. Patients in Group T received tramadol 2 mg/kg in 30 ml normal saline, in Group B received bupivacaine 30 ml of 0.125% and in Group BT received tramadol 2 mg/kg in 30 ml of 0.125% bupivacaine intraperitoneally. Postoperative pain assessment was done at different time intervals in the first 24 h using Visual Analog Scale of 0-10 (0 = No pain, 10 = Worst pain imagined. Time to first dose of rescue analgesic and total analgesics required in the first 24 h postoperatively were also recorded. The incidence of side effects during the postoperative period was recorded. Results: Reduction in postoperative pain was elicited, at 4 and 8 h postoperatively when Group BT (bupivacaine-tramadol group was compared with Group T (tramadol group or Group B (bupivacaine group (P < 0.01. There was a significantly lower requirement of analgesics during first 24 h postoperatively in Group BT compared to Group B or T but no significant difference in the intake of analgesics was noted between Groups B Group T. Time to first dose of rescue analgesic was also significantly prolonged in Group BT compared to Group B or T. The incidence of nausea and vomiting was comparable in all the study groups. Conclusions: Intraperitoneal application of bupivacaine with

Conscious Sedation Efficacy of 0.3 and 0.5 mg/kg Oral Midazolam for Three to Six Year-Old Uncooperative Children Undergoing Dental Treatment: A Clinical Trial

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Masoud Fallahinejad Ghajari

2016-10-01

Full Text Available Objectives: Midazolam with variable dosages has been used to induce sedation in pediatric dentistry. The aim of this study was to compare the efficacy of two dosages of oral midazolam for conscious sedation of children undergoing dental treatment.Materials and Methods: In this randomized crossover double blind clinical trial, 20 healthy children (ASA I aged three to six years with negative or definitely negative Frankl behavioral rating scale were evaluated. Half of the children received 0.5mg/kg oral midazolam plus 1mg/kg hydroxyzine (A orally in the first session and 0.3mg/kg oral midazolam plus 1mg/kg hydroxyzine (B in the next session. The other half received the drugs on a reverse order. Sedation degree by Houpt sedation rating scale, heart rate and level of SpO2 were assessed at the beginning and after 15 and 30 minutes. The data were analyzed using SPSS 19 and Wilcoxon Signed Rank and McNemar’s tests.Results: The results showed that although administration of 0.5mg/kg oral midazolam was slightly superior to 0.3mg/kg oral midazolam in terms of sedation efficacy, the differences were not significant (P>0.05. The difference in treatment success was not significant either (P>0.05. Heart rate, oxygen saturation (SpO2 and respiratory rate were within the normal range and did not show a significant change (P>0.05.Conclusions: The overall success rate of the two drug combinations namely 0.5mg/kg oral midazolam plus hydroxyzine and 0.3mg/kg oral midazolam plus hydroxyzine was not significantly different for management of pediatric patients.Keywords: Conscious Sedation; Pediatric Dentistry; Midazolam; Hydroxyzine

Efek Toksisitas Ekstrak Daun Sirih Merah Terhadap Gambaran Mikroskopis Ginjal Tikus Putih Diabetik yang Diinduksi Aloksan

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Ni Made Rina Yulinta

2013-08-01

Full Text Available Penelitian ini bertujuan untuk mengetahui efek toksik dari ekstrak daun sirih merah terhadap gambaran mikroskopis ginjal tikus putih diabetes mellitus yang diinduksi aloksan. Sebanyak 20 ekor tikus putih jantan galur Sprague-dawley umur ± 3 bulan digunakan dalam penelitian ini. Seluruh sampel tersebut dibagi secara acak menjadi lima kelompok perlakuan yaitu: (P0 tikus sehat yang hanya diberikan aquades; (P1 tikus yang diberikan aloksan 120 mg/kg bb/intraperitoneal; (P2 tikus yang diberikan aloksan 120 mg/kg bb/intraperitoneal dan ekstrak daun sirih merah 50 mg/kg bb/peroral; (P3 tikus yang diberikan aloksan 120 mg/kg bb/intraperitoneal dan ekstrak daun sirih merah 100mg/kg bb/peroral; (P4 tikus yang diberikan aloksan 120mg/kg bb/intraperitoneal dan suspensi glibenklamid 1 mg/kgbb/peroral. Perlakuan diberikan selama 30 hari. Pada hari ke-31 semua tikus dieuthanasi dan dinekropsi untuk melihat gambaran mikroskopis ginjal. Hasil penelitian menunjukkan bahwa pemberian ekstrak daun sirih merah (Piper crocatum dosis 50 mg/kg bb dan 100 mg/kg bb tidak menunjukkan perubahan patologi terhadap gambaran mikroskopis ginjal. Hal ini menunjukkan ekstrak daun sirih merah dosis 50 mg/kgbb dan dosis 100 mg/kgbb tidak toksik terhadap jaringan ginjal tikus putih diabetes mellitus.

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

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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.

Parenteral magnesium load testing with 28Mg in weanling and young adult rats

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Caddell, J.L.; Calhoun, N.R.; Howard, M.P.; Patterson, K.Y.; Smith, J.C. Jr.

1981-01-01

A sound diagnostic test for Mg deficiency is needed. This is a report of the parenteral Mg load test conducted in weanling and young adult rats fed a purified basal diet containing 3 mg magnesium/100 g with 150 mg of added magnesium/100 g (control) or 0 added magnesium (deficient). Weanlings were studied at about 1 week of dietary treatment and young adults at 2 weeks. The protocol included: a) a 6-hour preload urinary collection; b) an intraperitoneal load of 15 mg of magnesium/kg (weanlings) or 12 mg/kg (young adults) with 2 microCi 28Mg given simultaneously with each load; c) a 6-hour postload urinary collection; d) chemical analysis of selected tissues and urine for Mg; and e) 28Mg counting 6 and 24 hours postload. Controls all excreted large amounts of Mg pre- and postload, retaining less than 26% of nonradioactive loads. They had high urinary 28Mg counts. In Mg-deficient animals, the concentration of Mg in bone more than halved. These animals avidly conserved Mg and retained over 85% of nonradioactive Mg loads. Their 28Mg activity in vital organs was 3--6 times greater than in controls. We concluded that the parenteral Mg load test reliably identifies severe Mg deficiency

Intraperitoneal instillation of ropivacaine plus dexmedetomidine for pain relief after laparoscopic hysterectomy: A comparison with ropivacaine alone

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Sunil Chiruvella

2016-01-01

Full Text Available Background and Aims: Intraperitoneal (IP instillation of local anesthetics has been shown to minimize postoperative pain after laparoscopic surgeries. We compared the antinociceptive effects of IP dexmedetomidine combined with ropivacaine with that of IP ropivacaine alone in the patients undergoing laparoscopic hysterectomy. Materials and Methods: At the end of laparoscopic hysterectomy, in a double-blind, randomized manner, one of the following injections was given intraperitoneally. The patients were allocated into the following two groups: The patients in ropivacaine group (R group (N = 30 were given 30 mL of 0.2% ropivacaine plus 2 mL of normal saline; the patients in ropivacaine plus dexmedetomidine group (RD group (N = 30 were given 30 mL of 0.2% ropivacaine combined with 1 μg/kg dexmedetomidine (diluted in 2 mL normal saline through trocars. All the patients were given diclofenac sodium when they had pain [visual analogue scale (VAS 3]. Results: VAS score at different time intervals, overall VAS in 24 h was significantly lower (1.86 ± 0.46 vs 4.7 ± 0.94, time to first request of analgesia (min was longest (126 ± 24 vs 59 ± 13 and total analgesic consumption (mg was lowest (95 ± 15 vs 175 ± 75 in RD group than in R group. Conclusion: The antinociceptive effects of the intraperitoneal instillation of ropivacaine in combination with dexmedetomidine is superior to ropivacaine alone.

Single Low Dose Primaquine (0.25 mg/kg Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

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Germana Bancone

.7% were greater than in G6PD normal subjects (0.3%, -0.8 and -1.7% but were clinically insignificant. Fractional drops in haemoglobin concentration larger than 25% following single dose primaquine were observed in 1.8% of the population but were asymptomatic.The single low dose (0.25mg/kg of primaquine is clinically well tolerated and can be used safely without prior G6PD testing in populations with high prevalence of G6PD deficiency. The present evidence supports a broader use of low dose primaquine without G6PD testing for the treatment and elimination of falciparum malaria.ClinicalTrials.gov NCT01872702.

The preventive effect of Rofecoxib in postoperative intraperitoneal adhesions.

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Aldemir, M; Oztürk, H; Erten, C; Büyükbayram, H

2004-02-01

Previous studies showed that nonsteroidal anti-inflammatory (NSAI) drugs suppressed prostaglandin synthesis and were able to prevent adhesion formation following surgical trauma to the peritoneum. The selective suppression inflammatory cascade may prevent adhesion formation. Therefore, we planned this study to experimentally evaluate the effects of Rofecoxib, the selective cyclo-oxygenase-2 inhibitor, in postoperative intraperitoneal adhesions in an animal model. Male Sprague-Dawley rats were divided into three groups of 10. All rats underwent midline laparotomy under ketamine anaesthesia (25 mg/kg im). In group 1 (n = 10), the sham operation group (SG); abdominal walls were closed without any process after 2 minutes. In Group 2 (n = 10), the control group (CG); standard serosal damage was constituted and the abdominal wall was closed. In group 3 (n = 10), the COX-2 group (COXG), after serosal damage, the abdominal wall was closed. A 12 mg/kg/day dose of was given orally to the rats during one week. On the 7th postoperative day, all rats were sacrificed and intra-abdominal adhesions were evaluated both macroscopically and microscopically. Macroscopically, no serious adhesion formations were seen in the SG. Multiple adhesion formations of the CG were significantly more than those of the SG (p < 0.0001). It was determined that adhesions of the COXG diminished (p < 0.0001) when macromorphological adhesion scale results of the COXG were compared with those of the CG. The adhesion scores of the CG were compared microscopically with those of the COXG and granulation tissue formation and fibrosis in the COXG were found to be significantly less than those of the CG (respectively p = 0.002, p < 0.0001). We were of the opinion that Rofecoxib, the selective cyclo-oxygenase inhibitor, was effective in the prevention of postoperative peritoneal adhesions.

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

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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

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.

Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

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Darmani, N A

2001-01-01

We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1

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

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

1994-11-11

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

Preemptive analgesic effects of midazolam and diclofenac in rat model

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Antigona Hasani

2011-05-01

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

[EVALUATION OF THE CYTOGENETIC AND MUTAGEN-MODIFYING ACTIVITY OF CAFFEINE IN MOUSE BONE MARROW CELLS].

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Durnev, A D; Kulakova, A V; Zhanataev, A K; Oganesiants, L A

2015-01-01

The cytogenetic and mutagen-modifying activity of caffeine was studied with the method of chromosomal aberrations in bone marrow cells of mice hybrids F1 CBAxC57BL/6. Caffeine per se was administered intragastrically or intraperitoneally, and in combination with mutagens--intragastrically. Mutagens injected intraperitoneally. Caffeine at doses of 10 and 100 mg/kg (single dose) and 10 mg/kg (five days) in parenteral administration and oral introduction failed to possess cytogenetic activity. In combination with mutagens caffeine (1, 10 and 100 mg/kg) had no effect on the cytogenetic activity of dioxydine (200 mg/kg/intraperitoneally) for a single coadministration, five-day pre or five-day coadministration. In combination with other mutagens under the same processing conditions caffeine at doses of 10 and 100 mg/kg significantly increased cytogenetic effects of cyclophosphamide (20 mg/kg) in the pretreatment of the animals and at the dose of 100 mg/kg significantly attenuated the cytogenetic effect of cisplatin (5 mg/kg) in single and repeated co-administration. Thus we have shown the absence of caffeine cytogenetic activity in vivo and showed the multidirectional effect of caffeine in doses far exceeding its daily consumption, to the manifestation ofcytogenetic effects of certain chemical mutagens in some modes of processing animals.

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

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

2015-11-15

The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase I studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m(2); IP PTX [without intravenous (IV) PTX], 80 mg/m(2); and IP PTX (with IV PTX), 20 mg/m(2). Phase II studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase III study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase II studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

Lack of micronucleus induction activity of ethyl tertiary-butyl ether in the bone marrow of F344 rats by sub-chronic drinking-water treatment, inhalation exposure, or acute intraperitoneal injection.

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Noguchi, Tadashi; Kamigaito, Tomoyuki; Katagiri, Taku; Kondou, Hitomi; Yamazaki, Kazunori; Aiso, Shigetoshi; Nishizawa, Tomoshi; Nagano, Kasuke; Fukushima, Shoji

2013-01-01

Ethyl tertiary-butyl ether (ETBE) is an oxygenated gasoline additive synthesized from ethanol and isobutene that is used to reduce CO2 emissions. To support the Kyoto Protocol, the production of ETBE has undergone a marked increase. Previous reports have indicated that exposure to ETBE or methyl tertiary-butyl ether resulted in liver and kidney tumors in rats and/or mice. These reports raise concern about the effects of human exposure being brought about by the increased use of ETBE. The present study was conducted to evaluate the genotoxicity of ETBE using micronucleus induction of polychromatic erythrocytes in the bone marrow of male and female rats treated with ETBE in the drinking-water at concentrations of 0, 1,600, 4,000 or 10,000 ppm or exposed to ETBE vapor at 0, 500, 1,500 or 5,000 ppm for 13 weeks. There were no significant increases in micronucleus induction in either the drinking water-administered or inhalation-administered groups at any concentration of ETBE; although, in both groups red blood cells and hemoglobin concentration were slightly reduced in the peripheral blood in rats administered the highest concentration of ETBE. In addition, two consecutive daily intraperitoneal injections of ETBE at doses of 0, 250, 500 or 1,000 mg/kg did not increase the frequency of micronucleated bone marrow cells in either sex; all rats receiving intraperitoneal injections of ETBE at a dose of 2,000 mg/kg died after treatment day 1. These data suggest that ETBE is not genotoxic in vivo.

In vitro and in vivo activities of antibiotic PM181104

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Mahajan, G.B.; Thomas, B.; Parab, R.; Patel, Z.E.; Kuldharan, S.; Yemparala, V.; Mishra, P.D.; Ranadive, P.; DeSouza, L.; Pari, K.; Sivaramkrishnan, H.

assigned into 7 different treatment groups (6 mice per group) and infected intra-peritoneally with 0.1mL of MRSA strain E710 culture containing 108 -109 cfu of bacteria. PM181104 prepared in formulation was administered at 1.25, 2.5, 5 and 10mg/kg intra-venous... and 10mg/kg intra-venous (i.v.) dose immediately post infection to 3 different groups. One group received formulation excipients (vehicle control) by i.v. route and one group received 25mg/kg standard antibiotic linezolid by intra-peritoneal (i...

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

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Ardeshir, Rashid Alijani; Zolgharnein, Hossein; Movahedinia, Abdolali; Salamat, Negin; Zabihi, Ebrahim

2017-01-01

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...

Effects of intraperitoneal administration of the GABAB receptor positive allosteric modulator 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) on food intake in non-deprived rats.

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Ebenezer, Ivor S

2012-09-05

γ-Aminobutyric acid-(B) (GABA(B)) receptor positive allosteric modulators (PAMs) act on an allosteric site on the GABA(B) receptor to potentiate the effects of GABA and GABA(B) receptor agonists. It has previously been demonstrated that the GABA(B) receptor agonist baclofen increases food intake in non-deprived rats. The aim of this study was to investigate whether the GABA(B) receptor PAM 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) would (i) increase food intake, and (ii) potentiate the hyperphagic effects of baclofen in rats. In Experiment 1, the effects of intraperitoneal (i.p.) administration of CGP7930 (1, 6 and 12 mg/kg) was investigated on food intake in non-deprived male Wistar rats. The 12 mg/kg dose of CGP7930 significantly increased cumulative food intake 30, 60 and 120 min (PGABA and GABA(B) receptor agonists by allosteric modulation of the GABA(B) receptor. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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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

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

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João Batista Santos Garcia

2007-08-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: O efeito analgésico de infusões intraperitoneais de anestésicos locais após colecistectomia videolaparoscópica é controverso e os resultados descritos vão de alívio considerável à pequena redução da dor. O objetivo deste estudo foi avaliar a eficácia da administração intraperitoneal da mistura com excesso enantiomérico de 50% de bupivacaína (S75-R25 para o alívio da dor no pós-operatório de colecistectomia videolaparoscópica. MÉTODO: Estudo aleatório, placebo-controlado e duplamente encoberto com 40 pacientes submetidos à colecistectomia videolaparoscópica divididos em dois grupos: GI (n = 20 que recebeu 80 mL de solução de bupivacaína S75-R25 a 0,125% intraperitoneal no fim da operação; GII (n = 20 que recebeu 80 mL de solução fisiológica a 0,9%. Ambos os grupos receberam 40 mg de tenoxicam e 30 mg.kg-1 de dipirona, por via venosa, pouco antes do fim da operação. A analgesia no pós-operatório (PO foi feita com tramadol. Foram avaliados os escores de dor em repouso, ao sentar e à manobra de Valsalva, segundo a escala numérica ao despertar e 2, 4, 8, 12 e 24 horas no PO; a presença de dor no ombro; o tempo para a primeira solicitação do analgésico; e o seu consumo cumulativo. RESULTADOS: Houve diferença estatística significativa entre os escores de dor às 12 horas no PO com o paciente em repouso (GI JUSTIFICATIVA Y OBJETIVOS: El efecto analgésico de infusiones intraperitoneales de anestésicos locales después colecistectomía videolaparoscópica es controvertido y los resultados descritos van desde el alivio considerable a la pequeña reducción del dolor. El objetivo de este estudio fue evaluar la eficacia de la administración intraperitoneal de la mezcla con exceso enantiomérico de 50% de bupivacaína (S75-R25 para el alivio del dolor en el postoperatorio de colecistectomía videolaparoscópica. MÉTODO: Estudio aleatorio, placebo-controlado y doblemente encubierto con

DL- and PO-phosphatidylcholines as a promising learning and memory enhancer

OpenAIRE

Nagata, Tetsu; Yaguchi, Takahiro; Nishizaki, Tomoyuki

2011-01-01

Abstract In the water maze test, oral administration with 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho)(5 mg/kg) alone or DLPhtCho (5 mg/kg) plus 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho)(5 mg/kg) significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine, with more efficient effect than (POPhtCho)(5 mg/kg) alone, arachidonic acid (AA)(5 mg/kg) alone, docosahexaenoic acid (DHA)(5 mg/kg) alone, or 1-palmitoyl-2-lino...

Eradication of colon cancer cells before tumour formation in the peritoneal cavity of mice treated with intraperitoneal Re-186 radioimmunotherapy

International Nuclear Information System (INIS)

Kinuya, S.; Hiramatsu, T.; Michigishi, T.

2006-01-01

A treatment adjuvant to surgical resection of the primary lesion has been proven to be beneficial in improving the prognosis of patients with high risks of peritoneal dissemination of colon cancer. This study was performed to determine the comparative efficacy of intraperitoneal radioimmunotherapy (RIT) using Re-186 or I-131 labeled murine antibodies in the extermination of cancer cells. A murine anti-colorectal IgG1, A7 monoclonal antibody, was radio-labeled either with I-131 (by the chloramine-T method) or Re-186 (by the MAG3 pre-chelated method). A total number of 16 mice were subjected to RIT with Re-186 A7 (N=8) or I-131 A7 (N=8) at equitoxic doses in Balb/c bu/nu mice 10 min after intraperitoneal injection of LS180 human colon cancer cells. A third group of mice were subjected to chemotherapy with 5-fluorouracil at 30 mg/kg for 4 consecutive days following the intraperitoneal injection of the same LS180 human colon cancer cells. There were 19 mice in the control group who were not subjected to any form of therapy. The results revealed that the mean survival of mice in the control (N-19), I-131 A7 RIT (N=8) and Chemotherapy (N=6) groups were 33.8 ± 1.0, 80.1 ± 2.5 and 49.3 ± 5.3 days respectively. The eight mice who were subjected to Re-186 A7 RIT showed much better survival compared to the other groups. Two of the eight mice from this group died at 105 and 111 days following Re-186 A7 RIT. Other six mice were sacrificed at 172 days, and autopsy revealed no macroscopic peritoneal tumor growth. Based on this pilot study we concluded that individual tumor cells in the peritoneal cavity would be effectively exterminated by intraperitoneal RIT with Re-186 A7. (author)

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...

Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

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Mohammad Reza Zarrindast

2009-04-01

Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

Cafeína (150 mg/kg y aprendizaje espacial (retención y adquisición en ratones

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María del Pilar Santacruz

2003-01-01

Full Text Available En este trabajo se evaluó el papel que juega la cafeína (150mg/kg en el aprendizaje espacial (adquisición y retención en ratones mediante las mediciones de la latencia de salida, velocidad, aciertos, regresos, errores y excretas en un laberinto de 3 x 3 metros. Los sujetos fueron moldeados para una ruta en el laberinto y luego se aleatorizaron 20 machos y 20 hembras para la administración de cafeína (s.c. y solución salina durante ocho días consecutivos; luego se observó la retención de este aprendizaje y se moldeó otra ruta para evaluar su retención 24 horas después: La cafeína incrementó la retención del aprendizaje 1, donde hubo los mayores aciertos, y en el segundo las hembras con cafeína exhibieron mayor velocidad y aciertos mientras que los machos, presentaron menores aciertos y velocidad que todos los grupos; como vemos, en el segundo caso, la cafeína fortaleció la retención del aprendizaje 2 en las hembras y la debilitó en los machos. Se concluye que la cafeína (150mg/kg influyó positivamente en la retención del aprendizaje espacial, mas no en la adquisición. Este artículo está asociado a la línea de investigación en Cafeína y Cognición de la Universidad de la Sabana.

Isopiestic Investigation of the Osmotic and Activity Coefficients of {yMgCl2 + (1 - y)MgSO4}(aq) and the Osmotic Coefficients of Na2SO4.MgSO4(aq) at 298.15 K

Energy Technology Data Exchange (ETDEWEB)

Miladinovic, J; Ninkovic, R; Todorovic, M; Rard, J A

2007-06-06

Isopiestic vapor pressure measurements were made for {l_brace}yMgCl{sub 2} + (1-y)MgSO{sub 4}{r_brace}(aq) solutions with MgCl{sub 2} ionic strength fractions of y = 0, 0.1997, 0.3989, 0.5992, 0.8008, and (1) at the temperature 298.15 K, using KCl(aq) as the reference standard. These measurements for the mixtures cover the ionic strength range I = 0.9794 to 9.4318 mol {center_dot} kg{sup -1}. In addition, isopiestic measurements were made with NaCl(aq) as reference standard for mixtures of {l_brace}xNa{sub 2}SO{sub 4} + (1-x)MgSO{sub 4}{r_brace}(aq) with the molality fraction x = 0.50000 that correspond to solutions of the evaporite mineral bloedite (astrakanite), Na{sub 2}Mg(SO{sub 4}){sub 2} {center_dot} 4H{sub 2}O(cr). The total molalities, m{sub T} = m(Na{sub 2}SO{sub 4}) + m(MgSO{sub 4}), range from m{sub T} = 1.4479 to 4.4312 mol {center_dot} kg{sup -1} (I = 5.0677 to 15.509 mol {center_dot} kg{sup -1}), where the uppermost concentration is the highest oversaturation molality that could be achieved by isothermal evaporation of the solvent at 298.15 K. The parameters of an extended ion-interaction (Pitzer) model for MgCl2(aq) at 298.15 K, which were required for an analysis of the {l_brace}yMgCl{sub 2} + (1-y)MgSO{sub 4}{r_brace}(aq) mixture results, were evaluated up to I = 12.025 mol {center_dot} kg{sup -1} from published isopiestic data together with the six new osmotic coefficients obtained in this study. Osmotic coefficients of {l_brace}yMgCl{sub 2} + (1-y)MgSO{sub 4}{r_brace}(aq) solutions from the present study, along with critically-assessed values from previous studies, were used to evaluate the mixing parameters of the extended ion-interaction model.

Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose–response curves in mice

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Raghda A.M. Salama

2016-07-01

Full Text Available Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose–response curves. This study aims at identifying the equivalent intraperitoneal (i.p. doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose–response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.. The dose–response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents, the area under the ‘change in mechanical threshold’-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations.

Five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin B (Ambisome for visceral leishmaniasis in Bihar, India.

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Sakib Burza

Full Text Available BACKGROUND: Visceral Leishmaniasis (VL; also known as Kala-azar is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF and the Rajendra Memorial Research Institute (RMRI implemented a VL treatment project in Bihar, India-an area highly endemic for Leishmania donovani-using this regimen as first-line treatment. METHODS AND PRINCIPAL FINDINGS: Intravenous Ambisome 20 mg/kg was administered in four doses of 5 mg/kg over 4-10 days, depending on the severity of disease. Initial clinical cure at discharge was defined as improved symptoms, cessation of fever, and recession of spleen enlargement. This observational retrospective cohort study describes 8749 patients with laboratory-confirmed primary VL treated over a 5-year period: 1396 at primary healthcare centers, 7189 at hospital, and 164 at treatment camps. Initial clinical cure was achieved in 99.3% of patients (8692/8749; 0.3% of patients (26/8749 defaulted from treatment and 0.4% (31/8749 died. Overall, 1.8% of patients (161/8749 were co-infected with HIV and 0.6% (51/8749 with tuberculosis. Treatment was discontinued because of severe allergic reactions in 0.1% of patients (7/8749. Overall, 27 patients (0.3% were readmitted with post Kala-azar dermal leishmaniasis (PKDL. Risk factors for late presentation included female sex, age >15 years and being from a scheduled caste. In 2012, a long-term efficacy survey in the same area of Bihar determined relapse rates of VL after 5 years' intervention with Ambisome. Of 984 immunocompetent patients discharged between September 2010 and December 2011, 827 (84.0% were traced in order to determine their long-term outcomes. Of these, 20 patients (2.4% had relapsed or received further treatment for VL. Of those completing 6

CHAPTER 1

African Journals Online (AJOL)

Dr Olaleye

2009-11-12

Nov 12, 2009 ... 10mg/kg b/w. Ketamine was administered intraperitoneally as anesthesia before the surgeries. On the thirty-fifth day post-surgery all the animals were sacrificed and their small intestines were harvested. 10cm length of jejunum and ileum respectively were used to make everted sacs for the in vitro study.

Intraperitoneal Injection of Ethanol for the Euthanasia of Laboratory Mice (Mus musculus) and Rats (Rattus norvegicus).

Science.gov (United States)

Allen-Worthington, Krystal H; Brice, Angela K; Marx, James O; Hankenson, F Claire

2015-11-01

Compassion, professional ethics, and public sensitivity require that animals are euthanized humanely and appropriately under both planned and emergent situations. According to the 2013 AVMA Guidelines for the Euthanasia of Animals, intraperitoneal injection of ethanol is "acceptable with conditions" for use in mice. Because only limited information regarding this technique is available, we sought to evaluate ethanol by using ECG and high-definition video recording. Mice (n = 85) and rats (n = 16) were treated with intraperitoneal ethanol (70% or 100%), a positive-control agent (pentobarbital-phenytoin combination [Pe/Ph]), or a negative-control agent (saline solution). After injection, animals were assessed for behavioral and physiologic responses. Pain-assessment techniques in mice demonstrated that intraperitoneal injection of ethanol was not more painful than was intraperitoneal Pe/Ph. Median time to loss of consciousness for all mice that received ethanol or Pe/Ph was 45 s. Median time to respiratory arrest was 2.75, 2.25, and 2.63 min, and time (mean ± SE) to cardiac arrest was 6.04 ± 1.3, 2.96 ± 0.6, and 4.03 ± 0.5 min for 70% ethanol, 100% ethanol, and Pe/Ph, respectively. No mouse that received ethanol or Pe/Ph regained consciousness. Although successful in mice, intraperitoneal ethanol at the doses tested (9.2 to 20.1 g/kg) was unsuitable for euthanasia of rats (age, 7 to 8 wk) because of the volume needed and prolonged time to respiratory effects. For mice, intraperitoneal injection of 70% or 100% ethanol induced rapid and irreversible loss of consciousness, followed by death, and should be considered as "acceptable with conditions."

Effect of long-term intraperitoneal zinc administration on liver glycogen levels in diabetic rats subjected to acute forced swimming.

Science.gov (United States)

Bicer, Mursel; Gunay, Mehmet; Akil, Mustafa; Avunduk, Mustafa Cihat; Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

2011-03-01

This study aims to examine the effect of zinc administration on liver glycogen levels of rats in which diabetes was induced with streptozotocin and which were subjected to acute swimming exercise. The study was conducted on 80 adult Sprague-Dawley male rats, which were equally allocated to eight groups: group 1, general control; group 2, zinc-administrated control; group 3, zinc-administrated diabetic control; group 4, swimming control; group 5, zinc-administrated swimming; group 6, zinc-administrated diabetic swimming; group 7, diabetic swimming; group 8, diabetic control group. In order to induce diabetes, animals were injected with 40 mg/kg intraperitoneal (ip) streptozotocin. The injections were repeated in the same dose after 24 h. Animals which had blood glucose at or above 300 mg/dl 6 days after the last injections were accepted as diabetic. Zinc was administrated ip for 4 weeks as 6 mg/kg/day per rat. Hepatic tissue samples taken from the animals at the end of the study were fixed in 95% ethyl alcohol. Cross sections of 5 µm thickness, taken by the help of a microtome from the tissue samples buried in paraffin, were placed on a microscope slide and stained with periodic acid-Schiff and evaluated by light microscope. All microscopic images were transferred to a PC and assessed with the help of Clemex PE3.5 image analysis software. The lowest liver glycogen levels in the study were obtained in groups 3, 4, 6, 7, and 8. Liver glycogen levels in group 5 were higher than groups 3, 4, 6, 7, and 8, but lower than groups 1 and 2 (p swimming exercise were restored by zinc administration and that diabetes induced in rats prevented the protective effect of zinc.

Is early detection of anastomotic leakage possible by intraperitoneal microdialysis and intraperitoneal cytokines after anterior resection of the rectum for cancer?

Science.gov (United States)

Matthiessen, Peter; Strand, Ida; Jansson, Kjell; Törnquist, Cathrine; Andersson, Magnus; Rutegård, Jörgen; Norgren, Lars

2007-11-01

This prospective study assessed methods of detecting intraperitoneal ischemia and inflammatory response in patients with and without postoperative complications after anterior resection of the rectum. In 23 patients operated on with anterior resection of the rectum for rectal carcinoma, intraperitoneal lactate, pyruvate, and glucose levels were monitored postoperatively for six days by using microdialysis with catheters applied in two locations: intraperitoneally near the anastomosis, and in the central abdominal cavity. A reference catheter was placed subcutaneously in the pectoral region. Cytokines, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha, were measured in intraperitoneal fluid by means of a pelvic drain for two postoperative days. The intraperitoneal lactate/pyruvate ratio near the anastomosis was higher on postoperative Day 5 (P = 0.029) and Day 6 (P = 0.009) in patients with clinical anastomotic leakage (n = 7) compared with patients without leakage (n = 16). The intraperitoneal levels of IL-6 (P = 0.002; P = 0.012, respectively) and IL-10 (P = 0.002; P = 0.041, respectively) were higher on postoperative Days 1 and 2 in the leakage group, and TNF-alpha was higher in the leakage group on Day 1 (P = 0.011). In-hospital clinical anastomotic leakage was diagnosed on median Day 6, and leakage after hospital discharge on median Day 20. The intraperitoneal lactate/pyruvate ratio and cytokines, IL-6, IL-10, and TNF-alpha, were increased in patients who developed symptomatic anastomotic leakage before clinical symptoms were evident.

INTRAPERITONEAL DEXTROSE ADMINISTRATION AS AN ALTERNATIVE EMERGENCY TREATMENT FOR HYPOGLYCEMIC YEARLING CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

Science.gov (United States)

Fravel, Vanessa A; Van Bonn, William; Gulland, Frances; Rios, Carlos; Fahlman, Andreas; Graham, James L; Havel, Peter J

2016-03-01

The Marine Mammal Center (TMMC) cares for malnourished California sea lion (CSL) (Zalophus californianus) pups and yearlings every year. Hypoglycemia is a common consequence of malnutrition in young CSLs. Administering dextrose during a hypoglycemic crisis is vital to recovery. Traditional veterinary approaches to treat hypoglycemia pose therapeutic challenges in otariids, as vascular access and catheter maintenance can be difficult. The current approach to a hypoglycemic episode at TMMC is to administer dextrose intravenously (i.v.) by medically trained personnel. Intraperitoneal (i.p.) dextrose administration is an attractive alternative to i.v. administration because volunteer staff with basic training can administer treatment instead of waiting for trained staff to treat. This study compares the effects of i.v., i.p., and no dextrose administration on serum glucose and insulin in clinically healthy, euglycemic CSL yearlings. Three groups of animals, consisting of five sea lions each, were treated with 500 mg/kg dextrose using one of the following routes: i.v., i.p., or no dextrose (control). A jugular catheter was placed, and blood samples were collected at times 0, 5, 15, 30, 60, 120, 180, and 240 min after dextrose administration. I.v. dextrose administration resulted in an increase of serum glucose concentrations from a baseline level of approximately 150 mg/dl to a peak of approximately 350 mg/dl. The resulting hyperglycemia persisted for approximately 2 hr and was associated with an attenuated plasma insulin response compared with most terrestrial mammals. Intraperitoneal dextrose administration resulted in increases of serum glucose to approximately 200 mg/dl, which gradually declined to baseline by 2 hr after dextrose administration. These data suggest that the initial treatment of a hypoglycemic crisis in young malnourished CSLs can be accomplished with i.p. dextrose, thus enabling minimally trained volunteer staff to respond immediately to a crisis

A comparison of intraperitoneal bupivacaine-tramadol with bupivacaine-magnesium sulphate for pain relief after laparoscopic cholecystectomy: A prospective, randomised study

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Anurag Yadava

2016-01-01

Full Text Available Background and Aims: In laparoscopic surgeries, intraperitoneal instillation of local anaesthetics and opioids is gaining popularity, for better pain relief. This study compared the quality and duration of post-operative analgesia using intraperitoneal tramadol plus bupivacaine (TB or magnesium plus bupivacaine (MB. Methods: In this study, 186 patients undergoing laparoscopic cholecystectomy were randomly divided into two groups: group TB received intraperitoneal tramadol with bupivacaine and group MB received intraperitoneal magnesium sulphate (MgSO 4 with bupivacaine. The visual analogue scale (VAS to assess pain, haemodynamic variables and side effects were noted and compared at different time points. The primary outcome was to compare the analgesic efficacy and duration of pain relief. The secondary outcomes included comparison of haemodynamic parameters and side effects among the two groups. The data analysis was carried out with unpaired Student′s t-test and Chi-square test using software SPSS 20.0 version. Results: The mean of VAS pain score after 1, 2, 4, 6 and 24 h of surgery was more in TB group compared to MB group, and the difference was statistically significant (P < 0.05. The total rescue analgesia consumption in 24 h after surgery was 2.4 g (mean of paracetamol in TB group and 1.4 g (mean of paracetamol in MB group which was statistically significant (P < 0.05. There were no statistically significant differences in the secondary outcomes. Conclusion: Intraperitoneal instillation of bupivacaine-MgSO 4 renders patients relatively pain-free in first 24 h after surgery, with longer duration of pain-free period and less consumption of rescue analgesic as compared to bupivacaine-tramadol combination.

Characteristics of the Emotional and Behavioral Reactions of Rats under Chronic Stress Immobilization During Treatment with 5-R-thio-tetrazol [1,5-c] quinazoline Derivatives

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О. Y. Tozyuk

2013-10-01

Full Text Available Hypokinesia can reduce physical performance and impair human health, which is evident by significant morphofunctional changes in the body. To correct these abnormalities and prevent their occurrence actoprotectors are used in hospitals. In previous studies [Stepanyuk G.I, 2012] we found that 5-R-thio-tetrazol [1,5-c] quinasoline derivatives quite clearly improved physical performance of rats according to swimming test. In terms of actoprotective activity compound-leader КВ-28 (sodium 2-( tetrazol [1,5-с] quinazolin -5- ylthioacetate for certain predominated over reference compound bemityl. WORK OBJECTIVE. To describe the influence of course administration of sodium 2-( tetrazol [1,5-с] quinazolin -5- ylthio acetate in comparison with bemityl on the behavioral reactions of rats under 18-day hypokinesia. RESEARCH MATERIALS AND METHODS. Chronic stress immobilization was modeled by keeping rats in small wooden cases for 16 hours / day for 18 days. Animals were divided into 4 groups of 6 animals in each: I - intact animals, II - rats stressed with hypokinesia without correction (control, III and IV - hypokinetic rats who one-time within 18 days take daily intraperitoneally КВ -28 (1,7 mg/kg and bemityl (32 mg/kg at doses equal to their ED50 according to swimming test. Orientative-searching and emotional activity were assessed by neuroethological "open field" test [Buresh, 1991] on the 4th, 12th and 18th day of experiment, that accordingly characterize the stage of anxiety, resistance and exhaustion of general adaptation syndrome [Stefanov, 2001]. To analyze the behavior the following neurophysiological indices were used: horizontal motor activity (number of the crossed squares, vertical activity (number of racks, number of examined holes and autonomic balance: number of washings (grooming and defecation acts (number of boluses and urinations. Duration of observation was 3 min. RESULTS AND THEIR DISCUSSION. In the course of the experiment a

The effects of an intraperitoneal single low dose of ketamine in attenuating the postoperative skin/muscle incision and retraction-induced pain related to the inhibition of N-methyl-D-aspartate receptors in the spinal cord.

Science.gov (United States)

Shen, Yu; Xu, Li; Liu, Ming; Lei, Yishan; Gu, Xiaoping; Ma, Zhengliang

2016-03-11

Chronic postoperative pain (CPOP) is a common clinical problem which might be related to central sensitization. It has been widely accepted that NMDA (N-methyl-D-aspartate) receptors are among the triggers of central sensitization. Ketamine is a non-competitive NMDA receptor antagonist that is widely used in alleviating postoperative pain, but its effect on CPOP has been rarely reported. In the present study, the skin/muscle incision and retraction (SMIR) model was used to investigate the role of NMDARs in chronic postoperative pain and the effect of an intraperitoneal single low dose ketamine (10mg/kg) of attenuating SMIR-induced CPOP. We assessed pain behaviours after a SMIR operation by paw withdrawal threshold (PWMT) and paw withdrawal latency (PWMTL). Western blotting were performed to examine the role of NMDARs in SMIR-induced CPOP and the effect of ketamine on the expression and phosphorylation of NMDARs. The SMIR operation induced long-lasting mechanical hyperalgesia, and the up-regulation of phosphorylated NMDARs and total NMDARs at the spinal level. A single intraperitoneal administration of low dose ketamine (10mg/kg) during surgery alleviated pain behaviors and inhibited the up-regulation of phosphorylated NMDARs and total NMDARs. Our datas suggested that NMDARs play important roles in SMIR-induced CPOP. A single intraperitoneal low dose of ketamine could attenuate SMIR-induced CPOP, which might be associated with the inhibition of NMDARs. Our finding might provide a new, simple method of addressing CPOP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Studies On The Effect of Selenium And Vitamin (E) on Irradiated Male rats

International Nuclear Information System (INIS)

Mohamed, A.A.

2004-01-01

The aim of the present work is to investigate the protective role of intraperitoneally administered selenium and/or vitamin E on γ- radiation induced injury in adult male albino rats. Male albino rats(120-140 gm), were divided into the following groups:1- Control group: consisted of 10 rats. 2- Irradiated group: consisted of 10 rats exposed to whole body gamma irradiation at a dose level of 6 (Gy). 3- Injected -irradiated group: consisted of 90 rats intraperitoneally administered with selenium (Na 2 SeO 3 ) at a dose level of 0.2 mg/Kg body weight or with vitamin E (di-αtocopheryl acetate) at a dose level of 10 mg/kg body weight or with combined dose of selenium and vitamin E (0.2 mg/Kg body weight + 10 mg/Kg body weight)

Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine.

Science.gov (United States)

Payandemehr, Borna; Rahimian, Reza; Bahremand, Arash; Ebrahimi, Ali; Saadat, Seyedehpariya; Moghaddas, Peiman; Fadakar, Kaveh; Derakhshanian, Hoda; Dehpour, Ahmad Reza

2013-06-13

The anticonvulsant effects of agmatine, an endogenous polyamine and a metabolite of l-arginine, have been shown in various experimental seizure models. Agmatine also potentiates the anti-seizure activity of morphine. The present study aimed to investigate a possible involvement of nitric oxide (NO) pathway in the protection by agmatine and morphine co-administration against pentylenetetrazole (PTZ) -induced seizure in male mice. To this end, the thresholds for the clonic seizures induced by the intravenous administration of PTZ, a GABA antagonist, were assessed. Intraperitoneal administration of morphine at lower dose (1mg/kg) increased the seizure threshold. Also intraperitoneal administration of agmatine (5 and 10mg/kg) increased the seizure threshold significantly. Combination of subeffective doses of morphine and agmatine led to potent anticonvulsant effects. Non-effective doses of morphine (0.1 and 0.5mg/kg) were able to induce anticonvulsant effects in mice pretreated with agmatine (3mg/kg). Concomitant administration of either the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (1, 5mg/kg, i.p.) or the selective NOS inhibitor 7-NI (15, 30mg/kg, i.p.), with an ineffective combination of morphine (0.1mg/kg) plus agmatine (1mg/kg) produced significant anticonvulsant impacts. Moreover, the NO precursor, l-arginine (30, 60mg/kg, i.p.), inhibited the anticonvulsant action of agmatine (3mg/kg) plus morphine (0.5mg/kg) co-administration. Our results indicate that pretreatment of animals with agmatine enhances the anticonvulsant effects of morphine via a mechanism which may involve the NO pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation.

Science.gov (United States)

Pastor, Raúl; Sanchis-Segura, Carles; Aragon, Carlos M G

2004-12-01

Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission. Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values. The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol. This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are

Intraperitoneal Dexamethasone As A New Method for Relieving Postoperative Shoulder Pain after Gynecologic Laparoscopy

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Zahra Asgari

2012-01-01

Full Text Available Background: In this study, we tried to show the efficacy of Intraperitoneal dexamethasoneon relieving shoulder pain after gynecologic laparoscopy.Materials and Methods: In this double-blind randomized clinical trial, 63 patients who werecandidates for gynecologic laparoscopy were included. At the end of the procedure patientsrandomly received 16 mg dexamethasone (n=31 or placebo (n=32 intraperitoneally. Visualanalogue scale (VAS was used for clinical evaluation of pain severity during 24 hours afterlaparoscopy . A physician, who was not aware whether patients were treated with drug or placebo,evaluated the patients.Results: The severity of pain in the dexamethasone group within 0, 2, 4, 8, 12, 24 hoursafter procedure was significantly less than in the placebo group (p<0.001. The averageconsumption of opioids as analgesic/ sedative in the placebo group was more than thedexamethasone group (p=0.025.Conclusion: Findings of this study show that the prescription of 16 mg of dexamethasone(single dose in the peritoneal cavity may significantly reduce the severity of painafter Laparoscopy in comparison with placebo and may decrease the need for narcoticsas pain relief (Registration Number: IRCT201105306640N1.

High pressure does not counterbalance the advantages of open techniques over closed techniques during heated intraperitoneal chemotherapy with oxaliplatin.

Science.gov (United States)

Facy, Olivier; Combier, Christophe; Poussier, Matthieu; Magnin, Guy; Ladoire, Sylvain; Ghiringhelli, François; Chauffert, B; Rat, Patrick; Ortega-Deballon, Pablo

2015-01-01

Heated intraperitoneal chemotherapy (HIPEC) treats residual microscopic disease after cytoreductive surgery. In experimental models, the open HIPEC technique has shown a higher and more homogenous concentration of platinum in the peritoneum than achieved using the closed technique. A 25-cm H2O pressure enhances the penetration of oxaliplatin. Because pressure is easier to set up with the closed technique, high pressure may counterbalance the drawbacks of this technique versus open HIPEC, and a higher pressure may induce a higher penetration. Because higher concentration does not mean deeper penetration, a study of tissues beneath the peritoneum is required. Finally, achieving a deeper penetration (and a higher concentration) raises the question of the passage of drugs through the surgical glove and the surgeon's safety. Four groups of pigs underwent HIPEC with oxaliplatin (150 mg/L) for 30 minutes in open isobaric pressure and pressure at 25 cm H2O, and closed pressure at 25 and 40 cm H2O. Systemic absorption and peritoneal mapping of the concentration of platinum were analyzed, as well as in the retroperitoneal tissue and the surgical gloves. Blood concentrations were higher in open groups. In the parietal surfaces, the concentrations were not different between the isobaric and the closed groups (47.08, 56.39, and 48.57 mg/kg, respectively), but were higher in the open high-pressure group (85.93 mg/kg). In the visceral surfaces, they were lower in the closed groups (3.2 and 3.05 mg/kg) than in the open groups (7.03 and 9.56 mg/kg). Platinum concentrations were similar in the deep retroperitoneal tissue when compared between isobaric and high-pressure procedures. No platin was detected in the internal aspect of the gloves. The use of high pressure during HIPEC does not counterbalance the drawbacks of closed techniques. The tissue concentration of oxaliplatin achieved with the open techniques is higher, even if high pressure is applied during a closed technique

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)

A Simple Model for Inducing Optimal Increase of SDF-1 with Aminoglycoside Ototoxicity

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Hyun Mi Ju

2017-01-01

Full Text Available Objectives. As a homing factor of stem cell, stromal derived factor-1 (SDF-1 is important for the regenerative research in ototoxicity. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. We developed a mouse model with maximal increase in SDF-1 levels in the inner ear, according to the “one-shot” doses of kanamycin and furosemide. Methods. C57BL/6 mice had kanamycin (420, 550, and 600 mg/kg dissolved in PBS, followed by an intraperitoneal injection of furosemide (130 mg/kg. The injuries of inner ear were measured with hearing thresholds, histology, and outer hair cell counts at 0, 3, 5, 7, 10, and 14 days before the sacrifice. The levels of SDF-1 in the inner ear were tested by real-time RT-PCR and immunohistochemistry. Results. There were a significant reduction in hearing thresholds and a maximal increase of SDF-1 levels in the furosemide 130 mg/kg + kanamycin 550 mg/kg group, but severe hearing deterioration over time was observed in the furosemide 130 mg/kg + kanamycin 600 mg/kg group and four mice were dead. SDF-1 was detected mostly in the stria vascularis and organ of Corti showing the highest increase in expression. Conclusion. We observed optimal induction of the stem cell homing factor in the newly generated aminoglycoside-induced ototoxicity mouse model using a “one-shot” protocol. This study regarding high SDF-1 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.

Efficacy and safety of intravenous alteplase at 0.6 mg/kg more than 3 h after acute middle cerebral artery occlusion in patients selected using perfusion-diffusion mismatch

International Nuclear Information System (INIS)

Nakashima, Kazuya; Ohnishi, Hideyuki; Taomoto, Katsushi; Kuga, Yoshihiro; Kodama, Yuuji; Kubota, Hisashi; Tominaga, Takashi; Hayashi, Masato; Miyata, Shiro

2011-01-01

Thrombolytic treatment with alteplase at 0.6 mg/kg is approved for use within 3 h of stroke onset in Japan. Thus, only a small percentage of patients can benefit. A meta-analysis and more recent studies suggest a benefit to patients beyond 3 h with alteplase at 0.9 mg/kg or desmoteplase. We assessed the efficacy and safety of intravenous alteplase at 0.6 mg/kg more than 3 h after stroke onset in patients with acute MCA occlusion who were selected using perfusion-diffusion mismatch. Patients with MCA occlusion eligible for intravenous alteplase within 3 h were selected using MRI (diffusion-weighted (DW), fluid-attenuated inversion recovery (FLAIR), T2*, T2)/MR angiography (MRA) and beyond 3 h using evidence of perfusion-diffusion mismatch. Recanalization was evaluated using MRA within 24 h after treatment. Baseline characteristics, recanalization rates, early and late good clinical outcomes (National Institute of Health Stroke Scale (NIHSS) scores of 0 to 1 or 8-points or greater improvement at 24 h and mRS scores of 0 or 1 on the 90th day), symptomatic intracranial hemorrhage (within 72 h) and mortality (at the 90th day) were evaluated for both groups. Also for both groups, the relationships between recanalization and early and late good clinical outcomes were evaluated. 63 patients with MCA occlusion were treated using intravenous alteplase within 3 h (n=53) and beyond 3 h (n=10). No statistically significant differences were found between the two groups for recanalization rates (52.8 vs. 70.0%), early and late good clinical outcomes (early: 41.5 vs. 60.0%, late: 37.7 vs. 50.0%), symptomatic intracranial hemorrhage (0 vs. 0%), or mortality (1.9 vs. 0%). Our data suggest that intravenous alteplase at 0.6 mg/kg beyond 3 h after MCA occlusion for patients selected using perfusion-diffusion mismatch has the same efficacy and safety as treatment within 3 h. However, a larger sample size is needed to evaluate the relationship between recanalization and clinical outcomes

ADRIAMYCIN-LOADED ALBUMIN-HEPARIN CONJUGATE MICROSPHERES FOR INTRAPERITONEAL CHEMOTHERAPY

NARCIS (Netherlands)

CREMERS, HFM; SEYMOUR, LW; LAM, K; LOS, G; KWON, G; BAE, YH; KIM, SW; FEIJEN, J

1994-01-01

Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of

Twiny pro: 5.1 kg of propane dressed in apple green; Twiny pro: 5.1 kg de propane en habillage vert pomme

Energy Technology Data Exchange (ETDEWEB)

Anon.

1998-05-01

Designed for professional and outdoors uses, Twini Pro - the new Primagaz 5.1 kg propane cylinder - is a complement to the Twiny butane 6 kg cylinder was launched during the first week of March in some 2,500 outlets, before 5,000 and 7,000 points later

Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

OpenAIRE

Shaker, Mohamed E.; Zalata, Khaled R.; Mehal, Wajahat Z.; Shiha, Gamal E.; Ibrahim, Tarek M.

2011-01-01

Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. Male Wistar rats received intraperitoneal injections of CCl4 twice weekly for 8 weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20 mg/kg), nilotinib (10 and 20 mg/kg) and silymarin (100 mg/kg) durin...

Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline.

Science.gov (United States)

Porter, M H; Hrupka, B J; Altreuther, G; Arnold, M; Langhans, W

2000-12-01

Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.

Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats.

Science.gov (United States)

Zhao, Long-shan; Yin, Ran; Wei, Bin-bin; Li, Qing; Jiang, Zhen-yuan; Chen, Xiao-hui; Bi, Kai-shun

2012-11-01

To compare the pharmacokinetic parameters of cefuroxime lysine, a new second-generation of cephalosporin antibiotics, after intravenous (IV), intraperitoneal (IP), or intramuscular (IM) administration. Twelve male and 12 virgin female Sprague-Dawley rats, weighing from 200 to 250 g, were divided into three groups (n=4 for each gender in each group). The rats were administered a single dose (67.5 mg/kg) of cefuroxime lysine via IV bolus or IP or IM injection. Blood samples were collected and analyzed with a validated UFLC-MS/MS method. The concentration-time data were then calculated by compartmental and non-compartmental pharmacokinetic methods using DAS software. After IV, IP or IM administration, the plasma cefuroxime lysine disposition was best described by a tri-compartmental, bi-compartmental or mono-compartmental open model, respectively, with first-order elimination. The plasma concentration profiles were similar through the 3 administration routes. The distribution process was rapid after IV administration [t(1/2(d)), 0.10 ± 0.11 h vs 1.36 ± 0.65 and 1.25 ± 1.01 h]. The AUMC(0-∞) is markedly larger, and mean residence time (MRT) is greatly longer after IP administration than that in IV, or IM routes (AUMC(0-∞): 55.33 ± 20.34 vs 16.84 ± 4.85 and 36.17 ± 13.24 mg·h(2)/L; MRT: 0.93 ± 0.10 h vs 0.37 ± 0.07 h and 0.65 ± 0.05 h). The C(max) after IM injection was significantly higher than that in IP injection (73.51 ± 12.46 vs 49.09 ± 7.06 mg/L). The AUC(0-∞) in male rats were significantly higher than that in female rats after IM administration (66.38 ± 16.5 vs 44.23 ± 6.37 mg·h/L). There was no significantly sex-related difference in other pharmacokinetic parameters of cefuroxime lysine between male and female rats. Cefuroxime lysine shows quick absorption after IV injection, a long retension after IP injection, and a high C(max) after IM injection. After IM administration the AUC(0-∞) in male rats was significantly larger than that in

Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration

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Binh T. T. Pham

2018-01-01

Full Text Available Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent.

Dose of rocuronium for rapid tracheal intubation following remifentanil 2 μg kg-1 and propofol 2 mg kg-1.

Science.gov (United States)

Oh, Ah-Young; Cho, Suk-Ju; Seo, Kwang-Suk; Ryu, Jung-Hee; Han, Sung-Hee; Hwang, Jung-Won

2013-09-01

Full relaxation is not mandatory for successful tracheal intubation. We tried to find the dose of rocuronium that gave acceptable intubation conditions in a rapid sequence intubation with remifentanil and propofol. A dose-finding study of rocuronium using a modified Dixon's up-and-down method. A single tertiary care teaching hospital. Patients undergoing elective surgery under general anaesthesia. After premedication with midazolam and glycopyrrolate, anaesthesia was induced using remifentanil 2 μg kg and propofol 2 mg kg, and a predetermined dose of rocuronium was administered. The dose of rocuronium was determined by a modified Dixon's up-and-down method starting from 0.8 mg kg with an interval of 0.1 or 0.05 mg kg. Intubation was performed 60 s after the start of the rocuronium injection. Intubation conditions were graded as excellent, good or poor. Excellent or good were regarded as clinically acceptable. A dose of rocuronium needed for acceptable intubation condition in 50% of patients (ED50) during rapid tracheal intubation after induction of anaesthesia with remifentanil and propofol. Twenty-eight patients were enrolled to obtain six crossovers. The ED50 of rocuronium was 0.20 mg kg (95% confidence interval, CI 0.17 to 0.23 mg kg) by a modified Dixon's up-and-down method. After induction of anaesthesia with remifentanil 2 μg kg and propofol 2 mg kg, the ED50 of rocuronium for acceptable intubation condition was 0.20 mg kg (95% CI, 0.17 to 0.23 mg kg) for rapid sequence intubation. Thus, we recommend that the intubation dose should be 0.8 mg kg. Clinical trial registration KCT0000094.

[Comparison of 1 mg/body and 3 mg/body of intravenous granisetron for the prevention of chemotherapy-induced nausea and vomiting and adverse events in hematological malignancy patients].

Science.gov (United States)

Motohashi, Shinya; Hori, Katsuhito; Ono, Takaaki; Ohnishi, Kazunori; Kawakami, Junichi

2012-01-01

Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network. In contrast, the approved dose in Japan is 0.04 mg/kg (3 mg/body). Randomized controlled trials (RCTs) which compared 1 mg/body with 3 mg/body of intravenous granisetron for CINV had been reported in Japan. In these RCTs, however, hematological malignancy patients were excluded. We performed observational retrospective study to compare 1 mg/body with 3 mg/body of intravenous granisetron for the prevention of CINV and adverse events in hematological malignancy patients. Number of the patients and chemotherapy courses were 15 and 30 in the 1 mg/body group, and 15 and 27 in the 3 mg/body group, respectively. No nausea rates in the 1 and 3 mg/body group were 83% and 89% of courses, respectively. No vomiting rates in the 1 and 3 mg/body group were 97% and 100% of courses, respectively. The incidences of constipation in the 1 and 3 mg/body group were 34% and 45% of courses, respectively. Anaphylaxis and headache did not occur in both groups. Our findings suggested that 1 mg/body of intravenous granisetron can prevent from CINV in hematological malignancy patients, as well as 3 mg/body.

Chemical and biological studies of Lobelia flaccida (C. Presl) A.DC ...

African Journals Online (AJOL)

Chemical and biological studies of Lobelia flaccida (C. Presl) A.DC leaf: a medicinal plant used by traditional healers in Eastern Cape, South Africa. ... (85 mg/kg, intraperitoneally)-induced convulsion model in mice, normal saline and diazepam (1 mg/kg, i.p.) served as negative and positive control groups respectively.

Study of sedative preanaesthetic and anxiolytic effects of herbal extract of Tilia platyphyllos scop in comparison with diazepam in the rat

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A Rezaie

2011-05-01

Full Text Available Tilia platyphyllos scop belongs to the Tiliaceae family and mainly grows in northern parts of the country. It has various pharmacological effects including anxiolytic, antibacterial, anticonvulsant, spasmolytic, tranquilization and sedation, hypnotic and muscular relaxation. In order to study sedative, preanaesthetic and anxiolytic effects herbal extract of Tiliaplatyphyllos scop in comparison with diazepam in different groups of female Wistar rats with the same age and weight, doses of 150 mg/kg, 300 mg/kg and  450 mg/kg of herbal extract, 1.2 mg/kg of diazepam and equal volumes of dimethyl sulfoxide as a placebo were injected to rats intraperitoneally 30 minutes prior to evaluation of sedative and preanaesthetic effects (induced sleep duration following 40 mg/kg administration intraperitoneally and anxiolytic effects (using elevated plus maze and Rotarod test. Statistical results obtained represent a significant increase in sleep time induced with ketamine and also a significant increase in time spent by rats in open arms of maze with high and low doses of Tiliaplatyphyllos scop herbal extract (p

Pharmacokinetics of Intraperitoneal Cefalothin and Cefazolin in Patients Being Treated for Peritoneal Dialysis-Associated Peritonitis.

Science.gov (United States)

Roberts, Darren M; Ranganathan, Dwarakanathan; Wallis, Steven C; Varghese, Julie M; Kark, Adrian; Lipman, Jeffrey; Roberts, Jason A

2016-01-01

♦ The standard treatment of peritoneal dialysis (PD)-associated peritonitis (PD-peritonitis) is intraperitoneal (IP) administration of antibiotics. Only limited data on the pharmacokinetics and appropriateness of contemporary dose recommendations of IP cefalothin and cefazolin exist. The aim of this study was to describe the pharmacokinetics of IP cefalothin and cefazolin in patients treated for PD-peritonitis. ♦ As per international guidelines, IP cefalothin or cefazolin 15 mg/kg once daily was dosed with gentamicin in a 6-hour dwell to patients with PD-peritonitis during routine care. Serial plasma and PD effluent samples were collected over the first 24 hours of therapy. Antibiotic concentrations were quantified using a validated chromatographic method with pharmacokinetic analysis performed using a non-compartmental approach. ♦ Nineteen patients were included (cefalothin n = 8, cefazolin n = 11). The median bioavailability for both antibiotics exceeded 92%, but other pharmacokinetic parameters varied markedly between antibiotics. Both antibiotics achieved high PD effluent concentrations throughout the antibiotic dwell. Cefazolin had a smaller volume of distribution compared with cefalothin (14 vs 40 L, p = 0.003). The median trough total plasma antibiotic concentration for cefazolin and cefalothin during the dwell differed (plasma 56 vs 13 mg/L, p Peritoneal Dialysis.

DL- and PO-phosphatidylcholines as a promising learning and memory enhancer

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Nishizaki Tomoyuki

2011-01-01

Full Text Available Abstract In the water maze test, oral administration with 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho(5 mg/kg alone or DLPhtCho (5 mg/kg plus 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho(5 mg/kg significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine, with more efficient effect than (POPhtCho(5 mg/kg alone, arachidonic acid (AA(5 mg/kg alone, docosahexaenoic acid (DHA(5 mg/kg alone, or 1-palmitoyl-2-linoleil-sn-glycero-3-phosphoserine (PLPhtSer(5 mg/kg alone. POPhtCho (5 mg/kg alone or DLPhtCho (5 mg/kg plus POPhtCho (5 mg/kg also significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine, but otherwise no significant effect was obtained with DLPhtCho (5 mg/kg alone, AA (5 mg/kg alone, DHA (5 mg/kg alone, or PLPhtSer (5 mg/kg alone. Oral co-administration with DLPhtCho (5 mg/kg and POPhtCho (5 mg/kg significantly shortened the acquisition latency for rats untreated with scopolamine as compared with the latency for administration with polyethylene glycol (PEG, DLPhtCho alone at doses of 5 and 10 mg/kg, or POPhtCho alone at doses of 5 and 10 mg/kg, while no efficient effect on the retention latency was obtained. To assess the effect of DLPhtCho and POPhtCho on cognitive functions for humans, Mini Mental State Examination (MMSE test was performed in subjects with cognitive disorders (the average MMSE score, 15. Oral co-intake with DLPhtCho (50 mg and POPhtCho (45 mg once after breakfast everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 5 months after intake, and the increase in the score was significantly greater than that for oral intake with DLPhtCho (100 mg/day alone or POPhtCho (90 mg/kg alone. Taken together, the results of the present study show that co-intake with DLPhtCho and POPhtCho could enhance learning and memory ability and improve cognitive disorders for both the

DL- and PO-phosphatidylcholines as a promising learning and memory enhancer.

Science.gov (United States)

Nagata, Tetsu; Yaguchi, Takahiro; Nishizaki, Tomoyuki

2011-01-28

In the water maze test, oral administration with 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho)(5 mg/kg) alone or DLPhtCho (5 mg/kg) plus 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho)(5 mg/kg) significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine, with more efficient effect than (POPhtCho)(5 mg/kg) alone, arachidonic acid (AA)(5 mg/kg) alone, docosahexaenoic acid (DHA)(5 mg/kg) alone, or 1-palmitoyl-2-linoleil-sn-glycero-3-phosphoserine (PLPhtSer)(5 mg/kg) alone. POPhtCho (5 mg/kg) alone or DLPhtCho (5 mg/kg) plus POPhtCho (5 mg/kg) also significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine, but otherwise no significant effect was obtained with DLPhtCho (5 mg/kg) alone, AA (5 mg/kg) alone, DHA (5 mg/kg) alone, or PLPhtSer (5 mg/kg) alone. Oral co-administration with DLPhtCho (5 mg/kg) and POPhtCho (5 mg/kg) significantly shortened the acquisition latency for rats untreated with scopolamine as compared with the latency for administration with polyethylene glycol (PEG), DLPhtCho alone at doses of 5 and 10 mg/kg, or POPhtCho alone at doses of 5 and 10 mg/kg, while no efficient effect on the retention latency was obtained. To assess the effect of DLPhtCho and POPhtCho on cognitive functions for humans, Mini Mental State Examination (MMSE) test was performed in subjects with cognitive disorders (the average MMSE score, 15). Oral co-intake with DLPhtCho (50 mg) and POPhtCho (45 mg) once after breakfast everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 5 months after intake, and the increase in the score was significantly greater than that for oral intake with DLPhtCho (100 mg/day) alone or POPhtCho (90 mg/kg) alone. Taken together, the results of the present study show that co-intake with DLPhtCho and POPhtCho could enhance learning and memory ability and improve cognitive disorders for both the

Warning against co-administration of 3,4-methylenedioxymethamphetamine (MDMA) with methamphetamine from the perspective of pharmacokinetic and pharmacodynamic evaluations in rat brain.

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Yuki, Fuchigami; Rie, Ikeda; Miki, Kuzushima; Mitsuhiro, Wada; Naotaka, Kuroda; Kenichiro, Nakashima

2013-04-11

3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine often cause serious adverse effects (e.g., rhabdomyolysis, and cardiac disease) following hyperthermia triggered by release of brain monoamines such as dopamine and serotonin. Therefore, evaluation of brain monoamine concentrations is useful to predict these drugs' risks in human. This study aimed to evaluate risks of co-administration of MDMA and methamphetamine, both of which are abused frequently in Japan, based on drug distribution and monoamine level in the rat brain. Rats were allocated to three groups: (1) sole MDMA administration (12 or 25 mg/kg, intraperitoneally), (2) sole methamphetamine administration (10 mg/kg, intraperitoneally) and (3) co-administration of MDMA (12 mg/kg, intraperitoneally) and methamphetamine (10 mg/kg, intraperitoneally). We monitored pharmacokinetic and pharmacodynamic variables for drugs and monoamines in the rat brain. Area under the curve for concentration vs. time until 600 min from drug administration (AUC₀₋₆₀₀) increased from 348.0 to 689.8 μgmin/L for MDMA and from 29.9 to 243.4 μMmin for dopamine in response to co-administration of methamphetamine and MDMA compared to sole MDMA (12 mg/kg) administration. After sole methamphetamine or that with MDMA administration, AUC₀₋₆₀₀ of methamphetamine were 401.8 and 671.1 μgmin/L, and AUC₀₋₆₀₀ of dopamine were 159.9 and 243.4 μMmin. In conclusion, the brain had greater exposure to MDMA, methamphetamine and dopamine after co-administration of MDMA and methamphetamine than when these two drugs were given alone. This suggests co-administration of MDMA with methamphetamine confers greater risk than sole administration, and that adverse events of MDMA ingestion may increase when methamphetamine is co-administered. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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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.

Extraperitoneal vs. intraperitoneal route for permanent colostomy: a meta-analysis of 1,071 patients.

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Lian, Lei; Wu, Xian-Rui; He, Xiao-Sheng; Zou, Yi-Feng; Wu, Xiao-Jian; Lan, Ping; Wang, Jian-Ping

2012-01-01

Parastomal hernia is a common complication after colostomy construction. Whether an extraperitoneal route for colostomy creation can reduce the risk of parastomal hernia remains controversial. A meta-analysis was performed to evaluate the value of extraperitoneal route in the prevention of parastomal hernia and other postoperative complications related to colostomy. A literature search of Medline, Embase, Ovid, and Cochrane databases from the years 1966 to 2010 was performed. Studies comparing extraperitoneal colostomy with intraperitoneal colostomy were identified. Extraperitoneal colostomy was performed to prevent colostomy-related complications. Data on the following outcomes were sought: incidence of postoperative colostomy complications including parastomal hernia, prolapse, and bowel obstruction. Seven retrospective studies with a combined total of 1,071 patients (250 extraperitoneal colostomy and 821 intraperitoneal colostomy) were identified. There was a significantly lower rate of parastomal hernia (odds ratio, 0.41; 95% confidence interval, 0.23-0.73, p = 0.002) in the extraperitoneal colostomy group. However, the occurrences of bowel obstruction and prolapse were not significantly different between the two groups. A limitation of the study lies on the meta-analysis of observational studies. Extraperitoneal colostomy is associated with a lower rate of postoperative parastomal hernia as compared to intraperitoneal colostomy. Prospective randomized controlled trial is warranted to further determine the role of extraperitoneal route in the prevention of parastomal hernia.

Concentrations of tylvalosin and 3-O-acetyltylosin attained in the synovial fluid of swine after administration by oral gavage at 50 and 5 mg/kg.

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Canning, P; Bates, J; Hammen, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Karriker, L

2016-12-01

The objectives of this study were to determine the concentration of tylvalosin (TVN) and its metabolite, 3-O-acetyltylosin (3AT) in the synovial fluid of growing pigs when administered as a single bolus by oral gavage at target doses of 50 mg/kg (Trial 1) and 5 mg/kg (Trial 2). TVN is a water soluble macrolide antimicrobial used in swine production. The stability of the drug in synovial fluid samples stored at -70 °C up to 28 days was also evaluated in Trial 2. In Trial 1, eight pigs were randomly assigned to one of eight time points for euthanasia and synovial fluid collection: 0, 1, 2, 3, 4, 6, 9, 12 h postgavage. For Trial 2, 24 pigs were randomly allocated to one terminal collection time point at 0, 2, 4, 6, 8 or 10 h postgavage. Synovial fluid was analyzed to determine TVN and 3AT concentrations. TVN and 3AT were detected in Trial 1 at all time points, except 0 h. At 2 h postgavage for trial 2, the mean concentrations peaked at 31.17 ng/mL (95% CI: 18.62-52.16) for TVN and at 58.82 ng/mL (95% CI: 35.14-98.46) for 3AT. Storage duration did not impact TVN or 3AT concentrations (P-value 0.9732). © 2016 John Wiley & Sons Ltd.

A prospective randomised controlled study for evaluation of high-volume low-concentration intraperitoneal bupivacaine for post-laparoscopic cholecystectomy analgesia

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Shruti Jain

2018-01-01

Full Text Available Background and Aims: Low-volume high-concentration bupivacaine irrigation of the peritoneal cavity has been reported to be ineffective for short-term analgesia after laparoscopic cholecystectomy (LC. This study was conducted to evaluate the effectiveness of intraperitoneal instillation of high-volume low-concentration bupivacaine for post-operative analgesia in LC. Methods: Sixty patients undergoing LC were included in this prospective, double-blind, randomised study. Patients were divided into two (n = 30 groups. In Group S, intraperitoneal irrigation was done with 500 ml of normal saline. In Group B, 20 ml of 0.5% (100 mg bupivacaine was added to 480 ml of normal saline for intraperitoneal irrigation during and after surgery. Post-operative pain was assessed by numeric pain rating scale (NRS at fixed time intervals. Duration of analgesia (DOA, total rescue analgesic requirement (intravenous tramadol, presence of shoulder pain, nausea and vomiting were recorded for the initial 24 h post-operatively. Results: Mean DOA in Group S was 0.06 ± 0.172 h (3.6 ± 10.32 min and that in Group B was 19.35 ± 8.64 h (P = 0.000. Cumulative requirement of rescue analgesic in 24 h in Group S was 123.33 ± 43.01 mg and that in Group B was 23.33 ± 43.01 mg (P = 0.000. There was no significant difference in incidence of shoulder pain, nausea and vomiting between the groups. Conclusion: High-volume low-concentration of intraperitoneal bupivacaine significantly increases post-operative DOA and reduces opioid requirement after LC.

Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression.

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Eraky, Salma M; El-Mesery, Mohamed; El-Karef, Amro; Eissa, Laila A; El-Gayar, Amal M

2018-05-01

Lysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis. Hepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson's trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry. Silymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression. Silymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Random comparison study of the clinical response to 153Sm-EDTMP 1.0 mCi/kg and 1.5 mCi/kg

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Pan, Z.; Zhu, S.

2001-01-01

Sixty-seven patient with painful bone metastases were randomized to two groups. Group 1 (n=34) received 1.0 mCi/kg of 153 Sm-EDTMP and group II (n=33) received 1.5 mCi/kg. All of them met inclusion criteria and there was no significantly difference between the basic conditions of two groups. After receiving 153 Sm-EDTMP intravenously, all patients were kept in close follow-up weekly with blood counting, physician visiting and collecting patient's self-filling-in diary including pain score, Karnofsky performance scale and analgesic consumption. The follow-up duration was six weeks. The final overall condition assessed by physician were graded into no change (including worse), slight relief, significant relief and complete relief. Only significant relief and complete relief were considered as effectiveness for pain relief. Haematological toxicity grade was evaluated based on the nadir of WBC ad PLT counts. The results indicated that the higher dosage group had a higher effectiveness rate (75.76%) compared to the lower dosage group (67.65%), but without statistic significance (x 2 =0.5365, 0.25 153 Sm-EDTMP could be used for those patients with better haematological function and 1.0 mCi/kg used for those patients with poorer haematological function. (author)

Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis.

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Satoi, Sohei; Fujii, Tsutomu; Yanagimoto, Hiroaki; Motoi, Fuyuhiko; Kurata, Masanao; Takahara, Naminatsu; Yamada, Suguru; Yamamoto, Tomohisa; Mizuma, Masamichi; Honda, Goro; Isayama, Hiroyuki; Unno, Michiaki; Kodera, Yasuhiro; Ishigami, Hironori; Kon, Masanori

2017-02-01

To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.

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

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Daniela F. Gusmão

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

40 KG Sample of Fish-Clay from Stevns Klint, Denmark

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Gwozdz, R.; Hansen, H. J.; Rasmussen, K. L.

1992-07-01

In March 1986 a 50-m-long exposure of the cliff at Stevns Klint fell down and exposed about 40 square meters of Fish Clay. Due to this extraordinary event we were able to pick by hand about 50 kg black KT boundary layer material. After drying, the material was homogenized using a wooden pestle and an agate mortar. The powdered material was sieved through 200 mesh nylon gauze. The fraction larger than 200 mesh was collected and powdered again in an agate mortar. After four repetitions the amount of material with grain size less than 200 mesh was about 40 kg. The fraction larger than 200 mesh was reduced to about 7 kg. The 40-kg powder was mixed in a rotating polyethylene drum for three weeks. The material was analyzed by instrumental neutron activation analysis, atomic absorption and X-ray fluorescence analysis for about 40 elements. INAA was made on 20 aliquots with weight about 300 mg, 20 aliquots with weight about 80 mg, and 30 with weights between 10 and 20 mg. The preliminary results show that our KT boundary sample (1) is very homogeneous, (2) is very close in composition to other K-T boundary clays analyzed by us or described in the literature, and (3) has an Ir concentration of 32 +- 2 ng/g. We hope that our Fish Clay sample (termed by us "Mesozoic Midnight") after analysis in other laboratories and by other analytical methods may qualify as reference material in analytical work on boundary clay material.

Intraperitoneal pressure in peritoneal dialysis

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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

The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus.

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Yang, Fan; Li, Bing; Dong, Xiaoming; Cui, Wenpeng; Luo, Ping

2017-07-01

Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3β phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN. Copyright © 2017 Elsevier GmbH. All rights reserved.

Analgesic and anti-inflammatory activities of hydro-alcoholic extract of Lavandula officinalis in mice: possible involvement of the cyclooxygenase type 1 and 2 enzymes

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Yasaman Husseini

Full Text Available Abstract Lavandula officinalis Chaix, Lamiaceae, extracts can inhibit inflammation and also pain induced by formalin in mice. This study evaluated the effects of L. officinalis hydro-alcoholic extract on pain induced by formalin and also cyclooxygenase (COX type 1 and 2 activity in mice. To evaluate probable analgesic and anti-inflammatory effects of the extract, flowers were prepared by maceration and extraction in alcohol and their analgesic effects were studied in male mice, using formalin and hot plate tests. The effect of intraperitoneal hydro-alcoholic extracts of L. officinalis (100, 200, 250, 300, 400 and 800 mg/kg, subcutaneous morphine (10 mg/kg, dexamethasone (10 mg/kg; i.p. and indomethacin (10 mg/kg; i.p. on formalin induced pain were studied. Our results indicated that administration of the extract (100, 200, 250, 300, 400 and 800 mg/kg; i.p. has inhibitory effects on inflammation induced by formalin injection into the animals hind paw. Moreover, this inhibitory effect was equal to the effects of morphine, dexamethasone and indomethacin. The extract in100, 200 and 300 mg/kg; significantly reduced heat-induced pain. The extract also reduced COX activity in dose dependent manner, where the inhibitory effect on COX1 activity was 33% and on COX2 activity was 45%. Here for the first time we show that L. officinialis extract can modulate pain and inflammation induced by formalin by inhibition of COX enzymes.

Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory.

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Shen, Fang; Li, Yi-Jing; Shou, Xiao-Jing; Cui, Cai-Lian

2012-09-01

Evidence suggests that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP dependent protein kinase (PKG) signaling pathway plays a key role in memory processing, but the actual participation of this signaling cascade in the hippocampal CA1 during morphine-induced reward memory remains unknown. In this study, we investigated the role of the NO/sGC/PKG signaling pathway in the CA1 on morphine-induced reward memory using a conditioned place preference (CPP) paradigm. We found that rats receiving an intraperitoneal (i.p.) injection of 4mg/kg morphine exhibited CPP, whereas rats treated with only 0.2mg/kg morphine failed to produce CPP. Intra-CA1 injection of the neuronal NO synthase (nNOS) inhibitor 7-NI, the sGC inhibitor ODQ or the PKG inhibitor Rp-8-Br-PET-cGMPS had no effect on the acquisition of CPP by 4mg/kg morphine. Intra-CA1 injection of 7-NI blocked the consolidation of CPP induced by 4mg/kg morphine, and this amnesic effect of 7-NI was mimicked by ODQ and Rp-8-Br-PET-cGMPS. Intra-CA1 injection of the NOS substrate L-arg or the sGC activator YC-1 with an ineffective dose of morphine (0.2mg/kg, i.p.) elicited CPP. This response induced by L-arg or YC-1 was reversed by pre-microinjection of Rp-8-Br-PET-cGMPS in the CA1. These results indicated that the activation of the NO/sGC/PKG signaling pathway in the CA1 is necessary for the consolidation of morphine-related reward memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing's syndrome in obese patients.

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Sahin, Mustafa; Kebapcilar, Levent; Taslipinar, Abdullah; Azal, Omer; Ozgurtas, Taner; Corakci, Ahmet; Akgul, Emin Ozgur; Taslipinar, Mine Yavuz; Yazici, Mahmut; Kutlu, Mustafa

2009-01-01

Obesity is currently a major public health problem and one of the potential underlying causes of obesity in a minority of patients is Cushing's syndrome (CS). Traditionally, the gold standard screening test for CS is 1 mg dexamethasone overnight suppression test. However, it is known that obese subjects have high false positive results with this test. We have therefore compared the 1 mg and 2 mg overnight dexamethasone suppression tests in obese subjects. Patients whose serum cortisol after ODST was >50 nM underwent and a low-dose dexamethasone suppression test (LDDST); 24-hour urine cortisol was collected for basal urinary free cortisol (UFC). For positive results after overnight 1-mg dexamethasone suppression test we also performed the overnight 2-mg dexamethasone suppression test. We prospectively evaluated 100 patients (22 men and 78 women, ranging in age from 17 to 73 years with a body mass index (BMI) >30 kg/m2 who had been referred to our hospital-affiliated endocrine clinic because of simple obesity. Suppression of serum cortisol to suppression. Thyroid function tests, lipid profiles, homocysteine, antithyroglobulin, anti-thyroid peroxidase antibody levels, vitamin B12, folate levels, insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg postdexamethasone (postdex) suppression cortisol levels were measured. We found an 8% false-positive rate in 1 mg overnight test and 2% in 2 mg overnight test (p=0.001). There was no correlation between the cortisol levels after ODST and other parameters. Our results indicate that the 2 mg overnight dexamethasone suppression test (ODST) is more convenient and accurate than 1-mg ODST as a screening test for excluding CS in subjects with simple obesity.

Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats.

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Chikakiyo, Motoya; Shimada, Mitsuo; Nakao, Toshihiro; Higashijima, Jun; Yoshikawa, Kozo; Nishioka, Masanori; Iwata, Takashi; Kurita, Nobuhiro

2012-01-01

The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. Interleukin (IL)-1β, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1β and IFN-γ expression was improved significantly by DKT (P DKT (P DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.

EFEK INFUSA AKAR TEMPUYUNG (SONCHUS ARVENSIS TERHADAP PENURUNAN KADAR ASAM URAT PADA TIKUS PUTIH (RATTUS NORVEGICUS

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Kurnia Retnowati

2014-08-01

Full Text Available Tempuyung (Sonchus arvensis consisted of fiavonoid were effect as obstruct xantine oksidase enzyme, antioxidant captur superoxsidase radical. The fiavonoid total in leave of tempuyung is 0,1044%, in its root have 0,5% fiavonoid and the more is apigenin-7-O-glikosida (3,4,5. This research aim to know effect of infusa root of tempuyung (Sonchus arvensis to lower the uric acid level at blood serum and infusa root of Tempuyung (Sonchus arvensis to lower the uric acid level at mouse blood serum compared to allopurinol.This research is laboratory experimental method. The object were 25 Wistar male mice 2-3 months old, 150-200 gr divided into 5 groups. Negative Control group given potassium oxonate by intraperitoneal, Positive Control group given potassium oxonate by intraperitoneal, added by allopurinol 18mg/kgBB, Infusa Concentrated Group 1 given potassium oxonate by intraperitoneal added by infusa root of tempuyung 1,25g/kgBB, Infusa Concentrated Group 2 given potassium oxonate by intraperitoneal added by infusa root of tempuyung 2,5g/kgBB, Infusa Concentrated Group 3 given potassium oxonate by intraperitoneal added by infuse root of tempuyung 5g/kgBB. Executed until one day, where measurement of uric acid of mouse blood serum done before and after treatment. Measurement of uric acid level is done by using spectrophotometer. Obtained to be data to be analysed with Kolgomorov-Smirnov test, One-Way ANOVA and continued with LSD (Least Significant Difference test with 95% confidence interval (CI. Result of statistical test of research shoe that infusa root of Tempuyung (Sonchus arvensis dose 1,25g/kgBB, 2,5g/ kgBB, 5g/kgBB have effect to lower the uric acid level at mouse blood serum. Infusa root of Tempuyung (Sonchus arvensis concentrated 5g/kgBB proportional wih dose allopurinol 18mg/kgBB to lower the uric acid level at mouse blood serum. Keyword: Infusa, root of Tempuyung (Sonchus arvensis, uric acid

Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis

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le Roux, Carel; Aroda, Vanita; Hemmingsson, Joanna; Cancino, Ana Paula; Christensen, Rune; Pi-Sunyer, Xavier

2018-01-01

Objective To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Results Significantly greater weight loss (0–56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. Conclusion This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m². PMID:29145215

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

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Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

2016-06-01

To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

Toxicological characteristics and primary radiobiological screening of Cystizid-M

International Nuclear Information System (INIS)

Minkova, M.; Pantev, T.; Georgieva, R.

1987-01-01

The toxic and radioprotective properties of the potential radioprotector of the mollecular combination Cystisid-M (cysteamine-adenosin-5'-monophosphate - CAM) were investigated. The experiments were carried out on male mice C 57 BI irradiated with 137 Cs source. The intraperitoneal administration of 1000 mg/kg b.w. and 500 mg/kg b.w., injected 15 min prior to the irradiation with 8,5 Gr (LD 90/30 ) was performed, and orally 3000 mg/kg b.w. and 1500 mg/kg b.w. was introduced into the stomach 45 min prior to the irradiation with 8,2 Gr (LD 83/30 ). The radioprotective effect of CAM was recorded according to: individual survival curves up to the 30th day; the biometrical coefficients 'ALPHA' (the individual survival expectancy in the population); and S 30 (the group survival expectancy). At the intraperitoneal administration of the protector the values of LD 50 = 1390 mg/kg b.w. and MPD (maximum permissible dose) = 1200 mg/kg b.w. were found. At the oral administration these doses were LD 50/3 = 4630 mg/kg b.w. and MPD = 3500 mg/kg b.w. It was established that CAM injected intraperitoneally in a dose of 1000 mg/kg b.w. ensured 75% survival of the protected mice against 10% of the control ones, increased the mean survival of the deceased and reduced the percentage of the animals died during the height of the bone marrow syndrome. The twofold lower dose exetted a considerably slighter effect. At oral administration the protector did not significantly modify the survival of the animals. The data obtained revealed the perspectiveness of the tested protective agent radiobiological investigations are required

WAY 267,464, a non-peptide oxytocin receptor agonist, impairs social recognition memory in rats through a vasopressin 1A receptor antagonist action.

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Hicks, Callum; Ramos, Linnet; Reekie, Tristan A; Narlawar, Rajeshwar; Kassiou, Michael; McGregor, Iain S

2015-08-01

Recent in vitro studies suggest that the oxytocin receptor (OTR) agonist WAY 267,464 has vasopressin 1A receptor (V1AR) antagonist effects. This might limit its therapeutic potential due to the positive involvement of the V1AR in social behavior. The objective of this study was to assess functional V1AR antagonist-like effects of WAY 267,464 in vivo using a test of social recognition memory. Adult experimental rats were tested for their recognition of a juvenile conspecific rat that they had briefly met 30 or 120 min previously. The modulatory effects of vasopressin (AVP), the selective V1AR antagonist SR49059, and WAY 267,464 were examined together with those of the selective OTR antagonist Compound 25 (C25). Drugs were administered immediately after the first meeting. Control rats showed recognition of juveniles at a 30 min, but not a 120 min retention interval. AVP (0.005, but not 0.001 mg/kg intraperitoneal (i.p.)) improved memory such that recognition was evident after 120 min. This was prevented by pretreatment with SR49059 (1 mg/kg) and WAY 267,464 (10, 30, and 100 mg/kg). Given alone, SR49059 (1 mg/kg) and WAY 267,464 (30 and 100 mg/kg) impaired memory at a 30 min retention interval. The impairment with WAY 267,464 was not prevented by C25 (5 mg/kg), suggesting V1AR rather than OTR mediation of the effect. Given alone, C25 also impaired memory. These results highlight a tonic role for endogenous AVP (and oxytocin) in social recognition memory and indicate that WAY 267,464 functions in vivo as a V1AR antagonist to prevent the memory-enhancing effects of AVP.

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

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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.

The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent activation of the HPA axis.

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Zaretsky, Dmitry V; Zaretskaia, Maria V; Sarkar, Sumit; Rusyniak, Daniel E; DiMicco, Joseph A

2017-07-13

The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper, we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH 1 antagonist CP-154,526 (CP) (10 and 20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus. Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma ACTH (from 105±13 to 278±51pg/ml after 20mg/kg). This effect was accompanied by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the paraventricular nucleus of the hypothalamus. When the drug was administered i.p., CP-induced activation of the HPA appears to mask the inhibitory effect of CP on stress-induced ACTH secretion, an effect which was readily apparent when the drug was given i.a. Intraperitoneal administration of CP also increased the baseline MAP which may account for previous reports that treatment with this drug attenuated the increases associated with stress. CP given by either route had no effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies in which CP 154,526 is given, the route of delivery must be given careful consideration. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Effects of a diuretic and its combination with chelating agent on the removal of depleted uranium in rats

International Nuclear Information System (INIS)

Ikeda, Mizuyo; Fukuda, Satoshi; Nakamura, Mariko; Yoshida, Hiroki; Yan Xueming; Xie Yuyuan

2008-01-01

We examined the effects of a diuretic, isotonic saline, and chelating agent, catechol-3, 6-bis (methyleimiodiacetic acid) (CBMIDA), on the excretion and prevention of renal damage of depleted uranium (DU). Male Wistar rats (8 weeks old) divided into seven groups were preinjected intraperitoneally with 4 mg/kg DU and then the six groups were injected intraperitoneally with a diuretic, a diuretic plus isotonic saline, 480 mg/kg or 720 mg/kg CBMIDA alone, or 480 mg/kg or 720 mg/kg CBMIDA plus a diuretic and saline for three days, and the one group was as the control (no treatment). The rats were killed 6 days after DU injection. The results indicated that the diuretic alone and the diuretic with isotonic saline were not effective in removing uranium from the body and protecting the renal function, and also did not help to increase significantly the effects of CBMIDA. (author)

Synthesis and Anti-hyperlipidemic Activity of 3H-benzo [4, 5] thieno [2, 3-d] [1, 2, 3] triazin-4-ones: Possible Mechanism of Altered Lipid Metabolism

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Gollapalle L. Viswanatha

2012-09-01

Full Text Available Objectives: The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 (3-(methyl-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one, CP-2 (3-(ethyl- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno[2,3-d][1,2,3] triazin-4-one and CP-6 (3-(2-chloro phenyl-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one against dexamethasone and Triton WR-1339-induced hyper-lipidemia in rats.Methods: Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone (10 mg/kg, subcutaneous [s.c.] and Triton WR-1339 (200 mg/kg, intraperitoneal [i.p] induced hyperlipidemia in rats.Results: Administration of single dose of Triton WR-1339 (200 mg/kg i.p and dexamethasone (10 mg/kg s.c. for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compare to normal control. Pretreatment with Atorvastatin (10 mg/kg, p.o., CP-1 (25 & 50 mg/kg, CP-2 (25 & 50 mg/kg and CP-6 (25 & 50mg/kg showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2.Conclusion: These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia.

[Combination Chemotherapy Including Intraperitoneal(IP)Administration of Paclitaxel(PTX)followed by PTX, CDDP and S-1Triplet Chemotherapy for CY1P0 Gastric Cancer].

Science.gov (United States)

Shinkai, Masayuki; Imano, Motohiro; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Kimura, Yutaka; Imamoto, Haruhiko; Furukawa, Hiroshi; Yasuda, Takushi

2017-11-01

We evaluate the feasibility and efficacy of combination chemotherapy including single intraperitoneal( IP)administration of paclitaxel(PTX), followed by triplet chemotherapy(PTX, cisplatin[CDDP]and S-1: PCS)for CY1P0 gastric cancer. First of all, we performed staging laparoscopy and confirmed CY1P0, and secondary, administrated PTX intraperitoneally. Thirdly, patients received PCS chemotherapy for 2 courses. After antitumor effect had been confirmed, we performed second look laparoscopy. In the case of CY0P0, we performed gastrectomy with D2 lymph nodes dissection. Total 4 patients were enrolled. Grade 3 leukopenia and neutropenia were observed in one patient while intraperitoneal and systemic-chemotherapy. One patients showed PR and 3 patients showed SD. All patients underwent second look laparoscopy. CY0P0 was observed in all patients and gastrectomy with D2 dissection was performed for all patients. Postoperative complications were observed in 2 patients. Two patients were still alive without recurrence, while the remaining 2 had died of liver metastasis and #16 LN metastasis. Combination chemotherapy including single IP PTX followed by PCS systemic-chemotherapy for CY1P0 gastric cancer is feasible and efficient.

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

Comparative antioxidant and hypoglycaemic effects of aqueous ...

African Journals Online (AJOL)

Diabetes was induced intraperitoneally using 50 mg/kg streptozotocin, while diabetic rats were treated in 12 h cycles for four weeks with 100 mg/kg of the extract and glibenclamide (2.5 mg/kg). Nondiabetic control rats received distilled water. The levels of fasting blood sugar (FBS), thiobarbituric acid reactive substance ...

Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis.

Science.gov (United States)

le Roux, Carel; Aroda, Vanita; Hemmingsson, Joanna; Cancino, Ana Paula; Christensen, Rune; Pi-Sunyer, Xavier

2017-01-01

To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Significantly greater weight loss (0-56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m². © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Effects of IMOD and Angipars on Mouse D-Galactose-Induced Model of Aging

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Samane Ghanbari

2012-10-01

Full Text Available The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model of. Aging was induced by D-galactose (500 mg/kgadministered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day]intraperitoneally for 4 weeks; IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks, Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks; and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α, interlukine-1β (IL-β, interlukine-6 (IL-6, NF-kappaB (NF-κb, total antioxidant power (TAP, lipid peroxides (LPO and male sex hormones i.e.testosterone and dehydroepiandrosterone-sulfate (DHEA-S were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones that were declined in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

Effect of intra-peritoneal fludarabine on rat spinal cord tolerance to fractionated irradiation

Energy Technology Data Exchange (ETDEWEB)

Gregoire, V; Ruifrok, A C.C.; Price, R E; Brock, W A; Hittelman, W N; Plunkett, W K; Ang, K K

1995-07-01

The effect of fludarabine (9-{beta}-d-arabinosyl-2-fluoroadenine-5'-monophosphate), an adenine nucleoside analogue, on the tolerance of the spinal cord to fractionated irradiation was studied in a rat model. Anesthesized female Fisher 344 rats received irradiation to 2 cm of the cervical spine with a telecobalt unit (dose rate 1.14 Gy/min). Radiation was administered in two, four or eight fractions spread over a 48-h period with or without fludarabine. Animals assigned to combined therapy received two daily intraperitoneal injections of fludarabine (150 mg/kg) given 3 h prior to the first daily radiation fraction. It was found that fludarabine reduced the iso-effect dose required to induce leg paresis at 9 months after irradiation for all fractionation schedules. Dose modification factors of 1.23, 1.29 and greater than 1.27 were obtained for two, four and eight fractions, respectively. Fitting the data with the direct analysis method of Thames et al. with an incomplete repair model [18] showed that the potentiating effect of fludarabine may be mediated through reduction in the number of 'tissue-rescuing units' (lnK). Alpha and {beta} values were slightly but not significantly decreased, whereas the ({alpha}({beta})) ratio was unchanged. These features suggest that fludarabine did not significantly inhibit cellular repair processes but rather reduced the spinal cord tolerance by a fixed additive toxic effect on the same target cells. In rodent models, the combination of fludarabine and fractionated radiation has previously been found to yield a therapeutic gain, i.e., the drug enhanced tumor response to a greater extent than it reduced normal tissue tolerance. However, given our results, caution should be exercised in extrapolating these findings to the clinic. Normal tissue reactions will have to be monitored rigorously in phase I clinical studies.

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

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Gisele Ferreira Amaral

Full Text Available ABSTRACT Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP and the serum levels of interleukin 1 beta (IL-1β and tumor necrosis factor alpha (TNF-α after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days- (1 amitriptyline (Amt-10 mg/kg/day, by gavage; (2 gabapentin (Gb-60 mg/kg/day, by gavage; (3 methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]; (4 morphine (Mo-10 mg/kg/day, IP; or (5 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc. The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1β decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo.

Design, synthesis and biological evaluation of new hybrid anticonvulsants derived from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives.

Science.gov (United States)

Kamiński, Krzysztof; Rapacz, Anna; Łuszczki, Jarogniew J; Latacz, Gniewomir; Obniska, Jolanta; Kieć-Kononowicz, Katarzyna; Filipek, Barbara

2015-05-15

The purpose of this study was to synthesize the library of 33 new N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamides, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamides, and 2-(2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. The coupling reaction of the 2-(2,5-dioxopyrrolidin-1-yl)propanoic acid, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid, or 2-(2,5-dioxopyrrolidin-1-yl)butanoic acid with the appropriately substituted benzylamines in the presence of the coupling reagent, N,N-carbonyldiimidazole (CDI) generated the final compounds 4-36. Spectral data acquired via (1)H NMR, (13)C NMR, and LC-MS confirmed the chemical structures of the newly prepared compounds. The initial anticonvulsant screening was performed in mice intraperitoneally (ip), using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The rotarod test determined the acute neurological toxicity (NT). The results of preliminary pharmacological screening revealed that 25 compounds showed protection in half or more of the animals tested in the MES and/or scPTZ seizure models at the fixed dose of 100mg/kg. The broad spectra of activity across the preclinical seizure models displayed compounds 4, 7, 8, 13, 15-18, 24, and 26. The quantitative pharmacological studies in mice demonstrated the highest protection for compounds 4 (ED50 MES=67.65 mg/kg, ED50scPTZ=42.83 mg/kg); 8 (ED50 MES=54.90 mg/kg, ED50scPTZ=50.29 mg/kg); and 20 (ED50scPTZ=47.39 mg/kg). These compounds were distinctly more potent and provided better safety profiles in the rotarod test compared to valproic acid or ethosuximide, which were used as model AEDs. Compound 8 underwent only a slight metabolic change by the human liver microsomes (HLMs), and also did not affect the activity of human cytochrome P450 isoform

[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.

Azilsartan reduced TNF-α and IL-1β levels, increased IL-10 levels and upregulated VEGF, FGF, KGF, and TGF-α in an oral mucositis model.

Directory of Open Access Journals (Sweden)

Aurigena Antunes de Araújo

Full Text Available Oral mucositis (OM is a common complication of treatments for head and neck cancer, particularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT, an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU-induced oral mucositis (OM in Syrian hamsters. OM was induced by the intraperitoneal administration of 5-FU on experimental days 1 (60 mg/Kg and 2 (40 mg/Kg. Animals were pretreated with oral AZT (1, 5, or 10 mg/kg or vehicle 30 min before 5-FU injection and daily until day 10. Experimental treatment protocols were approved by the Animal Ethics Committee Use/CEUA (Number 28/2012 of the UFRN. Macroscopic analysis and cheek pouch samples were removed for histopathologic analysis. Myeloperoxidase (MPO, Malonyldialdehyde (MDA, interleukin-1 beta (IL-1β, interleukin-10 (IL-10, and tumour necrosis factor-alpha (TNF-α were analysed by Enzyme Linked Immuno Sorbent Assay (ELISA. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, keratinocyte growth factor (KGF, and transforming growth factor (TGF-α were measured by immunohistochemistry. Analysis of variance followed by Bonferroni's test was used to calculate the means of intergroup differences (p ≤ 0.05. Treatment with 1 mg/kg AZT reduced levels MPO (p<0.01, MDA (p<0.5 and histological inflammatory cell infiltration, and increased the presence of granulation tissue. AZT treatment at 1 mg/kg reduced the TNF-α (p<0.05 and IL-1β (p<0.05 levels, increased the cheek pouch levels of IL-10 (p<0.01, and upregulated VEGF, FGF, KGF, and TGF-α. Administration of AZT at higher doses (5 and 10 mg/kg did not significantly reverse the OM. AZT at a dose of 1 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.

Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation

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Bélin Poletto Mezzomo

2015-12-01

Full Text Available In addition to their applicability as biopesticides, Bacillus thuringiensis (Bt Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crystals genetically modified to express Cry1Ac individually, administered orally (p.o. or with a single intraperitoneal (i.p. injection 24 h before euthanasia, to simulate the routes of mucosal and parenteral immunizations in Swiss mice. Blood samples were used to perform hemogram, and bone marrow was used for the micronucleus test. Cry1Ac presented cytotoxic effects on erythroid lineage in both routes, being more severe in the i.p. route, which also showed genotoxic effects. The greater severity noted in this route, mainly at 6.75 mg/kg, as well as the intermediate effects at 13.5 mg/kg, and the very low hematotoxicity at 27 mg/kg, suggested a possible inverse agonism. The higher immunogenicity for the p.o. route, particularly at 27 mg/kg, suggested that at this dose, Cry 1Ac could potentially be used as a mucosal adjuvant (but not in parenteral immunizations, due to the genotoxic effects observed. This potential should be investigated further, including making an evaluation of the proposed inverse agonism and carrying out cytokine profiling.

Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice

DEFF Research Database (Denmark)

Ordóñez-Gutiérrez, Lara; Re, Francesca; Bereczki, Erika

2015-01-01

, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid...... Aβ may be therapeutically relevant in AD. FROM THE CLINICAL EDITOR: Intraperitoneal injection of small unilamellar vesicles containing phosphatidic acid or cardiolipin significantly reduced the amount of amyloid-beta (Aß) peptide in the plasma in a rodent model. Brain levels of Aß were also affected...

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

Effect of piroxicam, metamizol, and S-adenosylmethionine in a murine model of experimental trichomoniasis

Directory of Open Access Journals (Sweden)

Nogal-Ruiz J.J.

2005-03-01

Full Text Available Biological effects of piroxicam, metamizol, and S-adenosylmethionine (S-AMET have been tested in NMRI mice infected intraperitoneally with Trichomonas vaginalis. An intraperitoneal treatment during ten preinfection days with piroxicam (10 mg/Kg/day, or metamizol (275 mg/Kg/day, but not with S-AMET (17 mg/Kg/day induced a significant decrease of abdominal lesions and mortality, assessed by means of a pathogenicity index. The trichomonicidal activity of piroxicam, metamizol, and S-AMET was tested in vitro at the concentration of 300 μM, but found ineffective. These assays have shown the usefulness of the experimental trichomoniasis model for the study of the immunomodulating activity of synthetic drugs.

Involvement of dopamine D1/D2 receptors on harmane-induced amnesia in the step-down passive avoidance test.

Science.gov (United States)

Nasehi, Mohammad; Piri, Morteza; Nouri, Maryam; Farzin, Davood; Nayer-Nouri, Touraj; Zarrindast, Mohammad Reza

2010-05-25

Ingestion of harmane and other alkaloids derived from plant Peganum harmala has been shown to elicit profound behavioural and toxic effects in humans, including hallucinations, excitation, feelings of elation, and euphoria. These alkaloids in the high doses can cause a toxic syndrome characterized by tremors and convulsions. Harmane has also been shown to act on a variety of receptor systems in the mammalian brain, including those for serotonin, dopamine and benzodiazepines. In animals, it has been reported to affect short and long term memory. In the present study, effects of dopamine D1 and D2 receptor antagonists on the harmane (HA)-induced amnesia and exploratory behaviors were examined in mice. One-trial step-down and hole-board paradigms were used for the assessment of memory retention and exploratory behaviors in adult male NMRI mice respectively. Intraperitoneal (i.p.) administration of HA (5 and 10 mg/kg) immediately after training decreased memory consolidation, while had no effect on anxiety-like behavior. Memory retrieval was not altered by 15- or 30 min pre-testing administration of the D1 (SCH23390, 0.025, 0.05 and 0.1 mg/kg) or D2 (sulpiride 12.5, 25 and 50 mg/kg) receptor antagonists, respectively. In contrast, SCH23390 (0.05 and 0.1 mg/kg) or sulpiride (25 and 50 mg/kg) pre-test administration fully reversed HA-induced impairment of memory consolidation. Finally, neither D1 nor D2 receptor blockade affected exploratory behaviors in the hole-board paradigm. Altogether, these findings strongly suggest an involvement of D1 and D2 receptors modulation in the HA-induced impairment of memory consolidation. Copyright 2010 Elsevier B.V. All rights reserved.

Does curcumin or pindolol potentiate fluoxetine′s antidepressant effect by a pharmacokinetic or pharmacodynamic interaction?

OpenAIRE

H.A.S. Murad; M. I. Suliaman; H. Abdallah; May Abdulsattar

2014-01-01

This study was designed to study potentiation of fluoxetine′s antidepressant effect by curcumin or pindolol. Twenty eight groups of mice (n=8) were used in three sets of experiments. In the first set, 9 groups were subjected to the forced swimming test after being treated intraperitoneally with three vehicles, fluoxetine (5 and 20 mg/kg), curcumin (20 mg/kg), pindolol (32 mg/kg), curcumin+fluoxetine (5 mg/kg) and pindolol+fluoxetine (5 mg/kg). One hour after the test, serum and brain fluoxeti...

Radioprotection by caffeine pre-treatment and post-treatment in the bone marrow chromosomes of mice given whole-body γ-irradiation

International Nuclear Information System (INIS)

Farooqi, Z.; Kesavan, P.C.

1992-01-01

The effect of caffeine given as pre- and post-treatment in mice exposed to whole-body γ-irradiation (1.5 Gy 60 Co γ-rays) was studied. The pre-treatment was either acute or chronic. The acute dose (5 mg/kg and 15 mg/kg body weight) was in the form of an injection given intraperitoneally, 30 min before irradiation. The chronic administration was in the form of caffeine solution (4.208x10 -3 M and 7.72x10 -4 M) contained in drinking water for 5 weeks prior to radiation exposure. The acute pre-treatment with caffeine reduced the radiation-induced frequency of chromosomal aberrations discernibly, whereas chronic pre-treatment afforded a much more significant degree of radioprotection. The caffeine post-treatment (5 mg/kg and 15 mg/kg body weight) was given in the form of an intraperitoneal injection to the mice immediately following whole-body γ-irradiation. It is noted that both post-treatment concentrations of caffeine also significantly reduced the frequency of chromosomal aberrations induced by γ-rays. These data are briefly discussed in terms of possible mechanistic considerations. (author). 33 refs.; 3 tabs

Radioprotection by caffeine pre-treatment and post-treatment in the bone marrow chromosomes of mice given whole-body [gamma]-irradiation

Energy Technology Data Exchange (ETDEWEB)

Farooqi, Z.; Kesavan, P.C. (Jawaharlal Nehru Univ., New Delhi (India). School of Life Sciences)

1992-10-01

The effect of caffeine given as pre- and post-treatment in mice exposed to whole-body [gamma]-irradiation (1.5 Gy [sup 60]Co [gamma]-rays) was studied. The pre-treatment was either acute or chronic. The acute dose (5 mg/kg and 15 mg/kg body weight) was in the form of an injection given intraperitoneally, 30 min before irradiation. The chronic administration was in the form of caffeine solution (4.208x10[sup -3] M and 7.72x10[sup -4] M) contained in drinking water for 5 weeks prior to radiation exposure. The acute pre-treatment with caffeine reduced the radiation-induced frequency of chromosomal aberrations discernibly, whereas chronic pre-treatment afforded a much more significant degree of radioprotection. The caffeine post-treatment (5 mg/kg and 15 mg/kg body weight) was given in the form of an intraperitoneal injection to the mice immediately following whole-body [gamma]-irradiation. It is noted that both post-treatment concentrations of caffeine also significantly reduced the frequency of chromosomal aberrations induced by [gamma]-rays. These data are briefly discussed in terms of possible mechanistic considerations. (author). 33 refs.; 3 tabs.

Manganese-Disrupted Interaction of Dopamine D1 and NMDAR in the Striatum to Injury Learning and Memory Ability of Mice.

Science.gov (United States)

Song, Qifan; Deng, Yu; Yang, Xinxin; Bai, Ying; Xu, Bin; Liu, Wei; Zheng, Wenxue; Wang, Can; Zhang, Meng; Xu, Zhaofa

2016-12-01

Manganese (Mn) is widely regarded as a neurotoxic heavy metal that causes learning and memory deficits. Recently, it has been proved that the striatum is related to memory and learning ability. However, no previous study focused on the effect of Mn-induced learning and memory deficits on the striatum. This study aims to investigate the probable interaction of dopamine D1 receptor (DR1) and N-methyl-D-aspartate receptor (NMDAR), two cognition-related receptors in the striatum during Mn exposure. Mice are randomly divided into four groups, including control group, 12.5 mg/kg MnCl 2 group, 25 mg/kg MnCl 2 group, and 50 mg/kg MnCl 2 group. The mice receive intraperitoneal injections of 0, 12.5, 25, and 50 mg/kg MnCl 2 once daily for 2 weeks. Then, learning and memory ability, pathological changes, expression, and interaction of DR1 and NMDAR are determined. It has been found that Mn disrupted spatial learning and memory ability of mice by Morris water maze test and the passive avoidance test. Pathological and ultrastructure were injured. Mn decreased the immunohistochemical activities, protein levels, and messenger RNA (mRNA) expression of DR1, NR1, and NR2A. Mn exposure inhibited interaction between DR1 and NMDAR in striatum by double immunofluorescent staining and co-immunoprecipitation. In conclusion, our study illustrated that Mn caused learning and memory dysfunction via injury of striatum and inhibition of interaction between DR1 and NMDAR in striatum.

Effects of harmane and other β-carbolines on apomorphine-induced licking behavior in rat.

Science.gov (United States)

Farzin, Davood; Haghparast, Abbas; Motaman, Shirine; Baryar, Faegheh; Mansouri, Nazanin

2011-04-01

Harmane, harmine and norharmane are β-carboline compounds which have been referred to as inverse agonists of benzodiazepine receptors. The effect of these compounds on apomorphine-induced licking behavior was studied in rats. Subcutaneous (s.c.) injection of apomorphine (0.5 mg/kg) induced licking. The licking behavior was counted with a hand counter and recorded for a period of 75 min by direct observation. Intraperitoneal (i.p.) injections of harmane (1.25-5 mg/kg), harmine (2.5-10 mg/kg) and norharmane (1.25-5 mg/kg) significantly reduced the licking behavior. In rats pretreated with reserpine (5 mg/kg, i.p., 18 h before the test), the effects of harmane (4 mg/kg, i.p.), harmine (7.8 mg/kg, i.p.) and norharmane (2.5 mg/kg, i.p.) were unchanged. When flumazenil (2 mg/kg, i.p.) was administered 20 min before apomorphine, it was able to antagonize the effects of harmane, harmine and norharmane. It was concluded that the β-carbolines harmane, harmine and norharmane reduce the licking behavior via an inverse agonistic mechanism located in the benzodiazepine receptors. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of hydroalcoholic extract of Lavandula officinalis on nicotine-induced convulsion in mice.

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Arzi, A; Ahamehe, M; Sarahroodi, S

2011-06-01

Epilepsy an important CNS (central nervous system) problem that about 1% of world's population suffer of it. The aim of study was to evaluate of anticonvulsant effect of hydroalcoholic extract of Lavandula officinalis. In this study, anticonvulsant activity of the hydroalcoholic extract of Lavandula officinalis (L. officinalis) was studied against chemoconvulsant-induced seizures in male mice. Lavandula officinalis (100, 200, 400, 600 and 800 mg kg(-1)), diazepam (0.15 mg kg(-1)) and normal saline (10 mL kg(-1)) were injected intraperitoneally, respectively in different groups of mice, 30 min before nicotine (5 mg kg(-) i.p.). The onset time intensity and duration of convulsions and the percentage of death were recorded. Also the time-response (0, 15, 30, 45, 60 min before nicotine injection) for most effective dose of plant extract (600 mg kg(-1)) was investigated. The results showed that hydroalcoholic extract of Lavandula officinalis had anticonvulsant effect. The most effective dose of plant extract was 600 mg kg(-1). In time-response study for the most effective dose of extract (600 mg kg(-1)), the onset, duration and intensity of convulsion significantly (p Lavandula.

Biliary excretion of ouabain in isolated perfused rat liver after treatment with microsomal enzyme inducers

International Nuclear Information System (INIS)

Nevasaari, K.; Alakare, B.; Kaerki, N.T.

1976-01-01

The effect of pretreatment with spironolactone, phenobarbital and 3,4-benzpyrene on biliary excretion of ouabain was studied in isolated perfused rat liver system after a single dose of 3 H-ouabain. Spironolactone pretreatment (100 mg/kg intraperitoneally for 4 days) changed the time course of the excretion, thus accelerating the transport of ouabain into the bile. Phenobarbital pretreatment (75 mg/kg intraperitoneally for 4 days) enhanced bile flow and increased biliary excretion of ouabain only after 15 min. At longer time periods the increase in bile flow diluted the bile level of ouabain there being no difference in the amounts excreted into the bile between the treated and untreated groups. 3,4-benzpyrene pretreatment (20 mg/kg intraperitoneally for 4 days) was without efffect on biliary excretion of ouabain. The results suggest that spironolactone differs from phenobarbital in its enhancing effect on biliary excretion of ouabain, possibly through a specific effect on an unknown hepatic transport mechanism. (author)

Study on analgesic and anti-inflammatory properties of Cordia myxa fruit hydro-alcoholic extract.

Science.gov (United States)

Ranjbar, Mohammadmehdi; Varzi, Hossein Najafzadeh; Sabbagh, Atefeh; Bolooki, Adeleh; Sazmand, Alireza

2013-12-15

Cordia myxa is a plant which is used in tropical regions of the world. Analgesic and anti-inflammatory effect of fruit of this medicinal plant was investigated in mice. Hydro-alcoholic extract of it was prepared by maceration method. Formalin test was conducted in six groups of mice (6 animals in each group) and acetic acid test in another six groups (6 mice). Groups one to six in each test were administered normal saline, oral indomethacin, intraperitoneal tramadol, 100 mg kg(-1) oral extract, 200 mg kg(-1) oral extract and 100 mg kg(-1) intraperitoneal extract, respectively. The duration of foot lickings were calculated in formalin- administered (1st) group within min 0 to 5 (acute phase) and 15 to 25 (chronic phase). Acetic acid-induced writhings were counted within 10 min in the 2nd group. The results showed that hydro-alcoholic extract of Cordia myxa fruit was considerably effective in formalin test. Also, analgesic and anti-inflammatory properties of this plant's fruit in both acute and chronic phase are somewhat similar to these properties in the study on animal model of experimental colitis.

The Combination of Antidepressant Duloxetine with Piracetam in Mice does not Produce Enhancement of Nootropic Activity

OpenAIRE

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu; Sarkar, Amrita; Patel, Sonam; Savai, Jay

2014-01-01

There is a strong association between depression and memory impairment. The present study aims to assess the nootropic activity of duloxetine and piracetam combination. Male Swiss Albino mice were divided randomly into 4 groups. Treatment of normal saline (10 ml/kg), duloxetine (10 mg/kg), piracetam (100 mg/kg), and duloxetine (5 mg/kg) plus piracetam (50 mg/kg) were given through intra-peritoneal route to group I-IV, respectively. Transfer latency in elevated plus maze (EPM) and time spent i...

Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine.

Science.gov (United States)

Zhang, Jun; Goering, Peter L; Espandiari, Parvaneh; Shaw, Martin; Bonventre, Joseph V; Vaidya, Vishal S; Brown, Ronald P; Keenan, Joe; Kilty, Cormac G; Sadrieh, Nakissa; Hanig, Joseph P

2009-08-01

The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosine in kidneys of gentamicin sulfate (Gen)- and cisplatin (Cis)-treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Gen for six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, mainly in the S1/S2 segments but less so in the S3 segment, and RPA-1 was increased in the epithelial cells of collecting ducts (CD) in the cortex. Spatial expression of iNOS or nitrotyrosine with Kim-1 or RPA-1 was detected. In Cis-treated rats, Kim-1 was expressed only in the S3 segment cells, and RPA-1 and RPA-2 were increased in the epithelial cells of medullary CD or medullary loop of Henle (LH), respectively. Spatial expression of iNOS or nitrotyrosine with RPA-1 or RPA-2 was also identified. These findings suggest that peroxynitrite formation may be involved in the pathogenesis of Gen and Cis nephrotoxicity and that Kim-1, RPA-1, and RPA-2 have the potential to serve as site-specific biomarkers for Gen or Cis AKI.

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 <5 ng/mL was 49 days after administration. The unusual 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.

Mg,Ca-ATPase activity under irradiation

International Nuclear Information System (INIS)

Ladutin, V.V.; Orlova, V.V.; Lob, P.A.; Gerasiminko, I.V.; Mack, E.I.

2003-01-01

Full text: The influence of different doses irradiation at the Mg,Ca-ATPase activity at the rat brain has been investigated. The analyses were made at the apparatus of LKB and Carl-Ceis-Jena firm with help of reagents of Sigma and Boehringer firm. Rats decapitated after 1, 3, 6, 24 and 48 h after action of irradiation. Dose 0.206 C/kg. Erythrocytes. 1 and 3h after irradiation influence- decrease of Mg,Ca-ATPase activity to 86-87% relatively control level, 24 and 48 h - increase of activity to the control level. Dose 0.312 C/kg. Large hemispheres. 1h - decrease of ATPase activity to 90% relatively control, 3h - increase to control level, 24h - fall to 86%, after 48h small increase to 93% relatively control. Dose 9.287 C/kg. Large hemispheres. 1h - sharp fall of Mg, Ca-ATPase activity to 67 % relatively control, increase of activity to 96% after 3h and sharp fall of activity to 64% 6h after action of irradiation. Dose 9.287 C/kg. Cerebellum. 1h - sharp decrease of ATPase activity to 80%. After 3h -sharp increase to 160% relatively control level and sharp fall of ATPase activity to 47% relatively control after 6h. The mechanism of radiation pathology of active ion transport has been discussed

Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

Directory of Open Access Journals (Sweden)

Cui G

2013-12-01

Full Text Available Guiyun Cui,1,* Xinxin Yang,1,* Xiaoying Wang,2,* Zunsheng Zhang,1 Xuanye Yue,1 Hongjuan Shi,1 Xia Shen11Department of Neurology, 2Department of Ultrasound, the Affiliated Hospital of Xuzhou Medical College, Jiangsu, People’s Republic of China *These authors contributed equally to this workBackground: Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID. The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum and output (globus pallidus, substantia nigra regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved.Methods: A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally and benserazide (12.5 mg/kg, intraperitoneally for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg on the expression of Arc and proenkephalin was also evaluated.Results: Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg significantly improved stepping of the lesioned forepaw. Real

In Vivo Protection against Strychnine Toxicity in Mice by the Glycine Receptor Agonist Ivermectin

Directory of Open Access Journals (Sweden)

Ahmed Maher

2014-01-01

Full Text Available The inhibitory glycine receptor, a ligand-gated ion channel that mediates fast synaptic inhibition in mammalian spinal cord and brainstem, is potently and selectively inhibited by the alkaloid strychnine. The anthelminthic and anticonvulsant ivermectin is a strychnine-independent agonist of spinal glycine receptors. Here we show that ivermectin is an effective antidote of strychnine toxicity in vivo and determine time course and extent of ivermectin protection. Mice received doses of 1 mg/kg and 5 mg/kg ivermectin orally or intraperitoneally, followed by an intraperitoneal strychnine challenge (2 mg/kg. Ivermectin, through both routes of application, protected mice against strychnine toxicity. Maximum protection was observed 14 hours after ivermectin administration. Combining intraperitoneal and oral dosage of ivermectin further improved protection, resulting in survival rates of up to 80% of animals and a significant delay of strychnine effects in up to 100% of tested animals. Strychnine action developed within minutes, much faster than ivermectin, which acted on a time scale of hours. The data agree with a two-compartment distribution of ivermectin, with fat deposits acting as storage compartment. The data demonstrate that toxic effects of strychnine in mice can be prevented if a basal level of glycinergic signalling is maintained through receptor activation by ivermectin.

Sedative and anticonvulsant properties of Passiflora edulis dried ...

African Journals Online (AJOL)

-D-aspartate- induced turning behavior in mice. The ED50 for the protection against seizures -induced by strychnine was 320 mg/kg intraperitoneally (i.p.). For N-methyl-D-aspartate -induced turning behavior, the ED50 was 300 mg/kg i.p. ...

A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy

Science.gov (United States)

Grabenstatter, Heidi L.; Dudek, F. Edward

2010-01-01

Purpose Animal models with spontaneous epileptic seizures may be useful in the discovery of new antiepileptic drugs (AEDs). The purpose of the present study was to evaluate the efficacy of carisbamate on spontaneous motor seizures in rats with kainate-induced epilepsy. Methods Repeated, low-dose (5 mg/kg), intraperitoneal injections of kainate were administered every hour until each male Sprague-Dawley rat had experienced convulsive status epilepticus for at least 3 h. Five 1-month trials (n= 8–10 rats) assessed the effects of 0.3, 1, 3, 10 and 30 mg/kg carisbamate on spontaneous seizures. Each trial involved six AED-versus-vehicle tests comprised of carisbamate or 10% solutol-HS-15 treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Results Carisbamate significantly reduced motor seizure frequency at doses of 10 and 30 mg/kg, and caused complete seizure cessation during the 6-h post-drug epoch in 7 of 8 animals at 30 mg/kg. The effects of carisbamate (0.3–30 mg/kg) on spontaneous motor seizures appeared dose dependent. Conclusions These data support the hypothesis that a repeated-measures, cross-over protocol in animal models with spontaneous seizures is an effective method for testing AEDs. Carisbamate reduced the frequency of spontaneous motor seizures in a dose-dependent manner, and was more effective than topiramate at reducing seizures in rats with kainate-induced epilepsy. PMID:18494790

Antidiabetic Activity Test of Ethanolic Seri Leave’s (Muntingia Calabura L.) Extract in Male Rats Induced by Alloxan

OpenAIRE

Herlina Herlina; Annisa Amriani; Indah Solihah; Rizky Sintya

2018-01-01

Antidiabetic activity test of ethanol extract of seri leave (Muntingia calabura L.) rats induced by alloxan has been done. Male wistar albino rats are used as animal models which divided into 6 groups, normal group (aquadest), negative control group (Na CMC 0,5%), positive control group (glibenclamide 0,43 mg/200 gBB), and 1, 2, and 3 treatment groups (ethanol extract of seri leave 65, 130, dan 260 mg/kgBB). Rats blood glucose level after induced intraperitoneally by alloxan 130 mg/kgBB can b...

Beneficial metabolic effects of CB1R anti-sense oligonucleotide treatment in diet-induced obese AKR/J mice.

Directory of Open Access Journals (Sweden)

Yuting Tang

Full Text Available An increasing amount of evidence supports pleiotropic metabolic roles of the cannibinoid-1 receptor (CB1R in peripheral tissues such as adipose, liver, skeletal muscle and pancreas. To further understand the metabolic consequences of specific blockade of CB1R function in peripheral tissues, we performed a 10-week-study with an anti-sense oligonucleotide directed against the CB1R in diet-induced obese (DIO AKR/J mice. DIO AKR/J mice were treated with CB1R ASO Isis-414930 (6.25, 12.5 and 25 mg/kg/week or control ASO Isis-141923 (25 mg/kg/week via intraperitoneal injection for 10 weeks. At the end of the treatment, CB1R mRNA from the 25 mg/kg/week CB1R ASO group in the epididymal fat and kidney was decreased by 81% and 63%, respectively. Body weight gain was decreased in a dose-dependent fashion, significantly different in the 25 mg/kg/week CB1R ASO group (46.1±1.0 g vs veh, 51.2±0.9 g, p<0.05. Body fat mass was reduced in parallel with attenuated body weight gain. CB1R ASO treatment led to decreased fed glucose level (at week 8, 25 mg/kg/week group, 145±4 mg/dL vs veh, 195±10 mg/dL, p<0.05. Moreover, CB1R ASO treatment dose-dependently improved glucose excursion during an oral glucose tolerance test, whereas control ASO exerted no effect. Liver steatosis was also decreased upon CB1R ASO treatment. At the end of the study, plasma insulin and leptin levels were significantly reduced by 25 mg/kg/week CB1R ASO treatment. SREBP1 mRNA expression was decreased in both epididymal fat and liver. G6PC and fatty acid translocase/CD36 mRNA levels were also reduced in the liver. In summary, CB1R ASO treatment in DIO AKR/J mice led to improved insulin sensitivity and glucose homeostasis. The beneficial effects of CB1R ASO treatment strongly support the notion that selective inhibition of the peripheral CB1R, without blockade of central CB1R, may serve as an effective approach for treating type II diabetes, obesity and the metabolic syndrome.

Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice

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Zhao Meng

2012-07-01

Full Text Available Abstract Background Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1 in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results A single intraperitoneal administration of oxaliplatin (1–10 mg/kg induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg, also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg, or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg in a dose-dependent manner, while capsaicin (TRPV1 agonist-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG neurons with oxaliplatin (30–300 μM for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons

Protective effect of gallic acid against cisplatin-induced ototoxicity in rats.

Science.gov (United States)

Kilic, Korhan; Sakat, Muhammed Sedat; Akdemir, Fazile Nur Ekinci; Yildirim, Serkan; Saglam, Yavuz Selim; Askin, Seda

2018-04-07

Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days. Cisplatin+Gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days and a single intraperitoneal dose of 15mg/kg cisplatin at 3rd day. A control group received 1mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. In Cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the Cisplatin+Gallic acid group, this biochemical, histopathological and functional changes were reversed. In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic

Anticonvulsant effect of the ethanol extract of Caesalpiniapulcherrima (L. Sw., Fabaceae, leaves

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Dinesh Kumar

2010-08-01

Full Text Available In this study, ethanol extract of Caesalpinia pulcherrima (L. Sw., Fabaceae, leaves (CPEE was investigated for anticonvulsant effect against maximal electroshock (MES and pentylenetetrazole (PTZ induced seizures in rats and mice at dose levels 200 and 400 mg/kg, i.p. respectively. Diazepam (3 mg/kg, i.p. was used as a standard anticonvulsant drug for comparison. CPEE was found to be safe up to the dose of 4000 mg/kg in mice, when administered intraperitoneally. The extract at 400 mg/kg dose produced significant (p<0.01 anticonvulsant effect w.r.t. control against PTZ-induced clonic seizures. In MES-induced seizure model, there were no significant alterations in the onset as well as duration of hind limb extension seizures as compared to control at a dose of 200 mg/kg when administered intraperitoneally. However, the extract (CPEE, 400 mg/kg i.p. significantly (p<0.01 delayed the onset as well as decreased the duration of hind limb extension seizures (HLES as compared to control. However, the extract, CPEE, percentage protection of the animals was increased at higher dose (200 mg/kg in both the models. The results of the study suggest that ethanol extract of Caesalpinia pulcherrima (L. Sw. leaves possess anticonvulsant effect.

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

DEFF Research Database (Denmark)

Wogensen, L; Helqvist, S; Pociot, F

1990-01-01

Previous studies have demonstrated a stimulatory effect of interleukin-1 beta (IL-1 beta) on insulin and glucagon release from the perfused rat pancreas, accompanied by selective lysis of 20% of beta-cells as assessed by electronmicroscopy. However, we have not observed an inhibitory action of IL-1...... beta on insulin release from the perfused pancreas as shown for isolated islets. To test whether periodical exposure of the endocrine pancreas to circulating IL-1 beta in vivo affects insulin release from the intact perfused pancreas, rats were treated with daily intraperitoneal injections of 4...

Effect of breastfeeding piperine on the learning of offspring mice: interaction with caffeine and diazepam.

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Moghadamnia, Ali Akbar; Zangoori, Vahid; Zargar-Nattaj, Seyed Sadegh; Tayebi, Pooya; Moghadamnia, Yasaman; Jorsaraei, Seyed Gholam Ali

2010-01-01

Piperine, the main alkaloid of black pepper (Piper nigrum), has been suggested to display several pharmacological properties, including pain relief, anticonvulsant, antidepressant-like, antianxiety, sedative, and anti-inflammatory effects. This study was designed to investigate the effect of piperine on learning in mice and the interaction of the effect with caffeine and diazepam. Piperine (100 mg/kg intraperitoneally) was injected into the mouse mothers or nursing dams during breastfeeding for 25 days at five-day intervals. After feeding the newborn mice, their learning was evaluated using a step-through passive avoidance task. Mouse learning was assessed 1 hr and 24 hr and 1 week after a training session. Piperine increased learning in the first (1 hr: 243.33 s vs 55.17 s, P = 0.002) and third assessments (1 week: 226 s vs 97 s, P effect of a low dose of caffeine (25 mg/kg intraperitoneally after a shock of 2 s duration) in a first assessment (295.17 s vs 149.17 s, P = 0.026) compared to a higher dose of caffeine. Piperine reversed diazepam (1 mg/kg intraperitoneally) suppression of learning 24 hours after training by a 4 s shock (298 s vs 135.67 s, P = 0.03). According to the results, piperine alone significantly increased learning 1 hour and 1 week after training assessments, and learning can be improved in the short term when followed by piperine administration. It was also shown that piperine can potentiate the effect of a low dose of caffeine and can reverse the effect of diazepam.

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

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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

Toxicological evaluation of essential oil from the leaves of Croton tetradenius (Euphorbiaceae) on Aedes aegypti and Mus musculus.

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Carvalho, Karine da Silva; E Silva, Sandra Lúcia da Cunha; de Souza, Ivone Antonia; Gualberto, Simone Andrade; da Cruz, Rômulo Carlos Dantas; Dos Santos, Frances Regiane; de Carvalho, Mário Geraldo

2016-09-01

For control of Aedes aegypti, the main vector of dengue, botanical insecticides can be a viable alternative. Herein, we evaluated the chemical composition and insecticidal activity of the essential oils of the leaves of Croton tetradenius on Ae. aegypti larvae and adults. We also evaluated the acute toxicity in Mus musculus. The essential oil chemical analysis was performed using chromatography coupled with mass spectrometry and flame ionization detection. Female mice were used for assessing toxicity according to the Organization for Economic Cooperation and Development's Test Guideline 423/2001. Doses administered to mice orally and intraperitoneally were 5, 50, 300, and 2000 mg kg(-1). There was a greater toxic effect on larvae (LC50 = 0.152 mg mL(-1) and LC90 = 0.297 mg mL(-1)) and on adults (LC50 = 1.842 mg mL(-1) and LC90 = 3.156 mg mL(-1)) of Ae. aegypti after 24 h of exposure, when compared to other periods of exposure. Chemical analysis revealed 26 components, with camphor (25.49 %) as the major component. The acute toxicity via the intraperitoneal route identified an LD50 = 200 mg kg(-1) and by the oral route an LD50 = 500 mg kg(-1). Thus, the essential oil of C. tetradenius presents insecticidal potential for Ae. aegypti and has high safety threshold at the concentrations evaluated in this study.

Effects of hydrogen-rich saline on endotoxin-induced uveitis

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Wei-ming Yan

2017-01-01

Full Text Available The therapeutic effects of hydrogen-rich saline (HRS have been reported for a wide range of diseases mainly via selectively reducing the amount of reactive oxygen species. Oxidative stress plays an important role in the pathogenesis of uveitis and endotoxin-induced uveitis (EIU. In this study, we investigated whether HRS can mitigate EIU in rats. Sprague-Dawley rats were randomly divided into Norm group, Model group, HRS group, dexamethasone (DEX group, and rats in the latter three groups were injected with equal amount of lipopolysaccharide (LPS to induce EIU of different severities (by 1 mg/kg of LPS, or 1/8 mg/kg of LPS. Rats in HRS group were injected with HRS intraperitoneally at three different modes to purse an ameliorating effect of EIU (10 mL/kg of HRS immediately after injection of 1 mg/kg of LPS, 20 mL/kg of HRS once a day for 1 week before injection of 1 mg/kg of LPS and at 0, 0.5, 1, 2, 6, 8, 12 hours after LPS administration, or 20 mL/kg of HRS once a day for 1 week before injection of 1/8 mg/kg of LPS, and at 0, 0.5, 1, 2, 6, 8, 12, 24 hours and once a day for 3 weeks after LPS administration. Rats of DEX group were injected with 1 mL/kg of DEX solution intraperitoneally immediately after LPS administration. Rats in Norm and Model groups did not receive any treatment. All rats were examined under slit lamp microscope and graded according to the clinical signs of uveitis. Electroretinogram, quantitative analysis of protein in aqueous humor (AqH and histological examination of iris and ciliary body were also carried out. Our results showed that HRS did not obviously ameliorate the signs of uveitis under slit lamp examination and the inflammatory cells infiltration around iris and cilliary body of EIU induced by 1 mg/kg or 1/8 mg/kg of LPS (P > 0.05, while DEX significantly reduced the inflammation reflected by the above two indicators (P 0.05, while DEX had an obvious therapeutic effect (P < 0.05. However, HRS exerted an inhibition

Effect of the methanolic extracts of different parts of Ferula assa-foetida on naloxone-induced withdrawal behavior in morphine-dependent mice

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Mahnaz Khanavi

2017-08-01

Full Text Available Objective: Ferula assa-foetida, a native species in Iran, is used for treatment of several diseases particularly for neurological disorders in Iranian Traditional Medicine. The aim of this study is to investigate the effect of methanolic roots, fruits, and aerial parts extracts of Ferula assa-foetida on withdrawal syndrome in morphine-dependent mice. Materials and Methods: Aerial parts, roots, and fruits of the plant were separately extracted with 80% MeOH. For induction of dependence, morphine (50, 50 and 75 mg/kg was injected subcutaneously three times daily (10 am, 1 pm and 4 pm for three days and a last dose of morphine (50 mg/kg was administrated on the fourth day. Withdrawal syndrome was induced by injection of naloxone (5 mg/kg, intraperitoneal 2 hr after the final dose of morphine. Different doses of the extracts were administered i.p. 60 minutes before naloxone injection and withdrawal sign was recorded 2 minutes after naloxone injection for a period of 60 minutes.   Results: Pre-treatment of animals with different doses (2.5, 5, 10, 20 mg/kg of methanolic extract of the aerial parts of F. assa-foetida caused a significant decrease in naloxone-induced behavior. Intraperitoneal administration of different doses (10, 15, 20, 25 mg/kg of methanolic extract of the fruit significantly reduced the naloxone-induced withdrawal behavior (p

5-HT7 receptor activation: procognitive and antiamnesic effects.

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Meneses, A; Perez-Garcia, G; Liy-Salmeron, G; Ponce-López, T; Lacivita, E; Leopoldo, M

2015-02-01

The serotonin (5-hydroxytryptamine (5-HT)) 5-HT7 receptor is localized in brain areas mediating memory; however, the role of this receptor on memory remains little explored. First, demonstrating the associative nature of Pavlovian/instrumental autoshaping (P/I-A) task, rats were exposed (three sessions) to CS-US (Pavlovian autoshaping), truly random control, free operant, and presentations of US or CS, and they were compared with rats trained-tested for one session to the P/I-A procedure. Also, effects of the 5-HT7 receptor agonist LP-211 administered intraperitoneally after training was determined on short- (1.5 h) and long-term memory 24 and 48 h) and on scopolamine-induced memory impairment and cAMP production. Autoshaping and its behavioral controls were studied. Other animals were subjected to an autoshaping training session and immediately afterwards were given (intraperitoneal) vehicle or LP-211 (0.1-10 mg/kg) and/or scopolamine (0.2 mg/kg) and tested for short-term memory (STM) and long-term memory (LTM); their brains were extracted for the cAMP ELISA immunoassay. P/I-A group produced the higher %CR. LP-211 did not affect STM; nonetheless, at 0.5 and 1.0 mg/kg, it improved LTM. The 5-HT7 receptor antagonist SB-269970 (SB; 10.0 mg/kg) alone had no effect; nevertheless, the LP-211 (1.0 mg/kg) LTM facilitation was reversed by SB. The scopolamine (0.2 mg/kg) induced-decrement in CR was accompanied by significant increased cAMP production. The scopolamine-induced decrement in CR and increments in cAMP were significantly attenuated by LP-211. Autoshaping is a reliable associative learning task whose consolidation is facilitated by the 5-HT7 receptor agonist LP-211.

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

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

2012-10-15

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

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

International Nuclear Information System (INIS)

Langer, R.D.; Lorke, D.E.; Neidl van Gorkom, K.F.; Petroianu, G.; Azimullah, S.; Nurulain, S.M.; Singh, S.; Fuchsjäger, M.

2012-01-01

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

Intercellular Adhesion Molecule-1 Levels in Experimental Brain Injury and the Effects of Alpha-tocopherol

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Nilgun Senol

2014-06-01

Full Text Available Aim: The mechanisms, responsible for the secondary injuries occuring after acute injury of the brain are; release of nitrous oxide which is an inflammatory mediator, abnormal formation of free oxygen radicals and excessive stimulation of excitatory aminoacids. In this study, it is aimed to investigate changes in intercellular adhesion molecule levels in the brain, that occur subsequent to blunt head trauma, and after administration of an antioxidant agent, vitamin E. Material and Method: In this study, rats were divided into 4 groups. In group A; rats had only skin incision, group B; rats were traumatized after the skin incision, group C; isotonic (30mg/kg was given intraperitoneally after 30 minutes of the trauma, group D; alpha-tocopherol (30mg/kg was given intraperitoneally, after 30 minutes of the trauma. All the rats in these groups were sacrified after 24 hours. Biparietal and bifrontal lobs were taken about 3x5x1mm tickness and intercellular adhesion molecule-1 levels were studied by enzyme-linked immunosorbent assay kit. Results: As the result of the statistical analysis, it is detected that although there is an increase in intercellular adhesion molecule levels in brain parenchyma after trauma, it is statistically unsignificant. However, as the traumatized group and the group given alpha-tocopherol after trauma was compared, a statistically significant decrease in intercellular adhesion molecule-1 levels in the alpha-tocopherol given group was seen. Discussion: Alpha-tocopherol, an antioxidant agent, causes decrease in intercellular adhesion molecule levels, by decreasing inflammation.

Effect and mechanism of Qishen Yiqi Pills on adriamycin- induced cardiomyopathy in mice.

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Tong, Jia-Yi; Xu, Yan-Juan; Bian, Ye-Ping; Shen, Xiang-Bo; Yan, Lei; Zhu, Xin-Yi

2013-09-01

To study the effect and probable mechanism of Qishen Yiqi Pills on adriamycin (ADR)-induced cardiomyopathy in mice. Sixty-four mice were randomly divided into (1) the ADR group: saline (1 mL/100 g) administered every day by intragavage, ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks; (2) the ADR + Qishen Yiqi Pills I group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the beginning of the third week Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (3) the ADR + Qishen Yiqi Pills II group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the same time Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (4) the control group: saline (1 mL/100 g) administered every day by intragavage, saline (1 mL·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks. Six weeks later, cardiac function, myocardial pathology, and expression of Bcl-2 and Bax were evaluated. 1. The left ventricular diastolic diameter and the left ventricular systolic diameter were significantly increased (P Pills I group and the ADR + Qishen Yiqi Pills II group improved. 2. Myocardial morphologic observation showed that the myocardial fibers were disordered, there was cell edema, and gap widening in the ADR group. The degree of myocardial cell injury was reduced in the ADR + Qishen Yiqi Pills I group and ADR + Qishen Yiqi Pills II group compared with the ADR group. 3. The expression of Bax in the ADR group was significantly up-regulated, and the expression of Bcl-2 was significantly downregulated in the ADR group compared with the ADR + Qishen Yiqi Pills I group, the ADR + Qishen Yiqi Pills II group, and the control group (P Pills can effectively improve the cardiac function of ADR-induced cardiomyopathy, and the

Effects of FK506 on Hippocampal CA1 Cells Following Transient Global Ischemia/Reperfusion in Wistar Rat

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Zahra-Nadia Sharifi

2012-01-01

Full Text Available Transient global cerebral ischemia causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In experimental group 1, FK506 (6 mg/kg was given as a single dose exactly at the time of reperfusion. In the second group, FK506 was administered at the beginning of reperfusion, followed by its administration intraperitoneally (IP 6, 24, 48, and 72 hours after reperfusion. FK506 failed to show neurotrophic effects on CA1 region when applied as a single dose of 6 mg/kg. The cell number and size of the CA1 pyramidal cells were increased, also the number of cell death decreased in this region when FK506 was administrated 48 h after reperfusion. This work supports the possible use of FK506 in treatment of ischemic brain damage.

Peripheral administration of oxytocin increases social affiliation in the naked mole-rat (Heterocephalus glaber).

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Mooney, Skyler J; Douglas, Natasha R; Holmes, Melissa M

2014-04-01

The neuropeptide oxytocin regulates a wide variety of social behaviors across diverse species. However, the types of behaviors that are influenced by this hormone are constrained by the species in question and the social organization that a particular species exhibits. Therefore, the present experiments investigated behaviors regulated by oxytocin in a eusocial mammalian species by using the naked mole-rat (Heterocephalus glaber). In Experiment 1, adult non-breeding mole-rats were given intraperitoneal injections of either oxytocin (1mg/kg or 10mg/kg) or saline on alternate days. Animals were then returned to their colony and behavior was recorded for minutes 15-30 post-injection. Both doses of oxytocin increased huddling behavior during this time period. In Experiment 2, animals received intraperitoneal injections of either oxytocin (1mg/kg), an oxytocin-receptor antagonist (0.1mg/kg), a cocktail of oxytocin and the antagonist, or saline across 4 testing days in a counterbalanced design. Animals were placed in either a 2-chamber arena with a familiar conspecific or in a small chamber with 1week old pups from their home colony and behaviors were recorded for minutes 15-30 post-injection. Oxytocin increased investigation of, and time spent in close proximity to, a familiar conspecific; these effects were blocked by the oxytocin antagonist. No effects were seen on pup-directed behavior. These data suggest that oxytocin is capable of modulating affiliative-like behavior in this eusocial species. Copyright © 2014 Elsevier Inc. All rights reserved.

Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice.

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Javadi-Paydar, Mehrak; Zakeri, Marjan; Norouzi, Abbas; Rastegar, Hossein; Mirazi, Naser; Dehpour, Ahmad Reza

2012-01-06

Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.

Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

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Chao He

2018-01-01

Full Text Available Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF- 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO- 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp. before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg, after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

Liu et al.,Afr J Tradit Complement Altern Med. (2013) 10(5):310-312 ...

African Journals Online (AJOL)

AJTCAM

ml of Silybum marianum extract (high-, medium-, and low-doses) per day. ... being fasted for 12 h, were intraperitoneally injected with 10% chloral hydrate (40 mg/kg) to .... lipopolysaccharide-induced sepsis and inhibition of interleukin-1β and ...

Twenty-six-week oral carcinogenicity study of 3-monochloropropane-1,2-diol in CB6F1-rasH2 transgenic mice.

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Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun Ju; Son, Hwa-Young; Moon, Kyoung-Sik

2017-01-01

The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 rasH2-Tg (rasH2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female rasH2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N-methyl-N-nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most rasH2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using rasH2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.

The Korean herbal formulation Yukmijihwangtang stimulates longitudinal bone growth in animal models.

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Cho, Sung-Min; Lee, Sun Haeng; Lee, Donghun; Lee, Ji Hong; Chang, Gyu Tae; Kim, Hocheol; Lee, Jin Yong

2017-05-02

Yukmijihwangtang (YJT) is a traditional Korean medicine that has been used to treat kidney-yin deficiency symptoms such as dizziness and tinnitus. In addition, because it is also thought to nourish kidney-yin, it has been used to treat short stature from congenital deficiency. This study evaluated the effects of YJT on longitudinal bone growth in rats. Female adolescent rats were randomly assigned to groups that received distilled water (per os [p.o.] twice a day; control), recombinant human growth hormone (rhGH; 20 μg/kg, subcutaneous [s.c.] once a day), or two different doses of YJT (100 or 300 mg/kg, p.o. twice a day). In each group, treatment was maintained for 4 days. Rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU; 50 mg/kg) to label proliferating chondrocytes on days 2 - 4. Tetracycline hydrochloride (20 mg/kg) was injected intraperitoneally to form fluorescent bands on the growth plates on day 3 for measuring the longitudinal bone growth rate. Expression of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate was identified using immunohistochemistry. There was a significant increase in the rate of bone growth in the 300 mg/kg YJT group (523.8 ± 23.7 μm/day; P growth plate in the 300 mg/kg YJT and rhGH groups. YJT increased the longitudinal bone growth rate by stimulating chondrocyte proliferation with increasing increments of local IGF-1 and BMP-2 expression. Based on these findings, YJT may be a therapeutic candidate for the treatment of growth retardation during adolescence.

Acute and subacute toxicity of 10B-paraboronophenylalanine

International Nuclear Information System (INIS)

Taniyama, K.; Fujiwara, H.; Kuno, T.; Saito, N.; Shuntoh, H.; Sakaue, M.; Tanaka, C.

1989-01-01

The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug

Radiographic, Hematologic and Biochemical Alterations in Peritoneal Fluid after Intraperitoneal Injection of Barium Sulfate and Gastrografin in Rabbit

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Sardar Jafari-Shoorijeh

2012-07-01

Full Text Available Background: Evaluation of contrast-induced changes in the peritoneal area may reveal the effects of their permeation followed by gastrointestinal perforation. This study aims to compare the radiographic changes and hematological and biochemical parameters of peritoneal fluid and blood after intraperitoneal injection of barium sulfate and gastrografin to the rabbit.Materials and Methods: In this clinical trial, 15 healthy male rabbits were randomly divided into 3 groups. Respectively to each group 10 ml/kg barium sulfate 30%, 10 ml/kg gastrografin, and 10 ml/kg saline was intraperitoneally injected. Before injection and 24 hours after injection, blood samples and peritoneal fluid were collected to measure glucose, total protein, WBC count and pH. Lateral and dorsal-ventral radiography was provided 20 min and 24 hours after contrast injection.Results: After injection of barium sulfate, serum glucose decreased, cell count and blood neutrophil percentage increased, glucose and the percentage of peritoneal fluid lymphocytes decreased (p<0.05. The amount of total protein, cell count and peritoneal fluid neutrophil percentage increased (p<0.05. Gastrografin injection only increased peritoneal fluid total protein (p=0.04. Other blood factors and peritoneal fluid showed no significant changes. In radiographies, barium sulfate remained in abdominal area and rapid absorption of gastrografin was observed.Conclusion: The use of gastrografin has fewer side effects than barium sulfate and is recommended in patients suspected with gastrointestinal perforation.

Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 7-monohydroxyethylrutoside in mice.

NARCIS (Netherlands)

Hassan, MA Abou El; Kedde, MA; Zwiers, UT; Tourn, E; Haenen, GR; Vijgh, van der W.J.F.

2003-01-01

PURPOSE: The pharmacokinetics and bioavailability of monoHER, a promising protector against doxorubicin-induced cardiotoxicity, were determined after different routes of administration. METHODS: Mice were treated with 500 mg.kg(-1) monoHER intraperitoneally (i.p.), subcutaneously (s.c.) or

The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

Science.gov (United States)

Nasehi, Mohammad; Hasanvand, Simin; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2018-05-16

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25 µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25 µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4 µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625 µg/mouse) or sulpiride (0.1 µg/mouse) increased pre-training harmane (4 and 8 mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625 µg/mouse) reversed amnesia induced by an effective dose of harmane (12 mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625 µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.

Performance of Mg-14Li-1Al-0.1Ce as anode for Mg-air battery

Energy Technology Data Exchange (ETDEWEB)

Ma, Yibin; Li, Deyu [School of Chemical Engineering and Technology, Harbin Institute of Technology, West Street No. 92, Harbin 150001 (China); Li, Ning [School of Chemical Engineering and Technology, Harbin Institute of Technology, West Street No. 92, Harbin 150001 (China); Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, Harbin Engineering University, Harbin 150001 (China); Zhang, Milin; Huang, Xiaomei [Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, Harbin Engineering University, Harbin 150001 (China)

2011-02-15

In this research, a new Mg-air battery based on Mg-14Li-1Al-0.1Ce was prepared and the battery performance was investigated by constant current discharge test. The corrosion behavior of Mg, AZ31 and Mg-Li-Al-Ce were studied by self-corrosion rate measurement and potentiodynamic polarization measurement. The characteristics of Mg-Li-Al-Ce after discharge were investigated by electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results show that Mg-Li-Al-Ce is more active than Mg and AZ31. The self-corrosion rate is found to be in the order: Mg-Li-Al-Ce < Mg < AZ31. It has been observed that the Mg-air battery based on Mg-Li-Al-Ce offers higher operating voltage, anodic efficiency and capacity than those with Mg and AZ31. SEM and EIS results show that the discharge product of Mg-Li-Al-Ce is loosely adhered to the alloy surface, and thus Mg-Li-Al-Ce could keep high discharge activity during discharge. (author)

Effect of ethyl-, methyl- and hydroxyethyl-nitrosourea on the mouse testis

Energy Technology Data Exchange (ETDEWEB)

Oakberg, E.F.; Crosthwait, C.D.

1983-01-01

Hybrid male 101 x C3HF/sub 1/ mice were given intraperitoneal injections of methyl-, ethyl- and hydroxyethyl-nitrosourea and killed 3-16 days later. All compounds were similar in that all differentiating spermatogonia from type A/sub 1/ to early type B were killed by 50 mg/kg and higher doses of ENU and by 75 mg/kg MNU. Cells exposed to leptotene to 100 and 250 mg/kg ENU and 455 mg/kg HENU showed a delayed response with degeneration in pachytene 5 days later. Labeling prior to exposure to ENU indicated that the effect of stage of the mitotic cycle on sensitivity to cell killing is less marked than for radiation. This may be the explanation for the s-shaped mutation induction curve obtained with ENU in contrast to the humped dose-response curve observed for radiation.

JB-9322, a new selective histamine H2-receptor antagonist with potent gastric mucosal protective properties.

Science.gov (United States)

Palacios, B; Montero, M J; Sevilla, M A; Román, L S

1995-05-01

1. JB-9322 is a selective histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. 2. The affinity of JB-9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1 intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB-9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB-9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by ethanol. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1. By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition, the protective effect of JB-9322 was independent of prostaglandin synthesis. 6. These results indicate that JB-9322 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.

Opioid receptor mediated anticonvulsant effect of pentazocine.

Science.gov (United States)

Khanna, N; Khosla, R; Kohli, J

1998-01-01

Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting thereby that its anticonvulsant action is probably mediated by Sigma opiate binding sites. Its anticonvulsant effect was potentiated by both the anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid agonist, on the other hand, failed to protect the animals against maximal electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

The effects of benzodiazepine (triazolam), cyclopyrrolone (zopiclone) and imidazopyridine (zolpidem) hypnotics on the frequency of hippocampal theta activity and sleep structure in rats.

Science.gov (United States)

Yoshimoto, M; Higuchi, H; Kamata, M; Yoshida, K; Shimizu, T; Hishikawa, Y

1999-01-01

In order to investigate the relative efficacy and safety of zopiclone and zolpidem, we compared the effects of higher doses of zopiclone and zolpidem on the frequency of hippocampal theta activity and sleep structure with that of triazolam. Rats were divided into triazolam treatment group (1 mg/kg, 5 mg/kg), zopiclone treatment group (20 mg/kg, 100 mg/kg) and zolpidem treatment group (20 mg/kg, 100 mg/kg). Rats were injected intraperitoneally with these drugs or their vehicle. Polygraphic sleep recording and visual frequency analysis of the hippocampal EEG activity in REM sleep were carried out for 6 h after each injection. Zolpidem, unlike triazolam and zopiclone, had a much milder reducing-effect on the frequency of hippocampal theta activity and suppressing-effect on REM sleep. These results suggest that zolpidem may prove to be a safer hypnotic drug which has fewer or milder side effects than are benzodiazepine and cyclopyrrolone hypnotics.

New observations about the antineoplasic properties of the non-oily residue from the Ricinus communis seed, cultivated in Pernambuco, Brazil and its association with Co sup(60) ionizing irradiation

International Nuclear Information System (INIS)

Souza, I.A. de; Santana, C.F. de; Martins, D.G.; Santos, E.R. dos; Lins, L.J.P.

1991-01-01

Based on results obtained by other authors on Ricinus communis, we are investigating the antineoplasic action of the non-oily residue from ketonic extract of the seed pulp of one of the R. communis varieties cultivated in the Stat of Pernambuco. Hipocratic tests yielded a DL sub(50) of 3mg/kg. The antineoplasic tests on Yoshida sarcoma with a dosage of 0.1 mg/kg/day by intraperitoneal injection detected a 50,5% inhibition of the tumour growth. When Ricinus communis was used in alternating days in the same dosage, the inhibition recorded was 40.16%. With an oral application of 10 mg/kg/day we recorded an inhibition of 58.5%. When it was associated with Co sup(60), an inhibition of 72.45% was observed. Radiations of Co sup(60) applied alone in the same dosage (12.0 Gy) yielded an inhibition of 63.02%. Based on these results we conclude that our variety of Ricinus communis has an antineoplasic action when used orally of intraperitoneally. (author)

Is Chronic Curcumin Supplementation Neuroprotective Against Ischemia for Antioxidant Activity, Neurological Deficit, or Neuronal Apoptosis in an Experimental Stroke Model?

Science.gov (United States)

Altinay, Serdar; Cabalar, Murat; Isler, Cihan; Yildirim, Funda; Celik, Duygu S; Zengi, Oguzhan; Tas, Abdurrahim; Gulcubuk, Ahmet

2017-01-01

To investigate the neuroprotective effect of chronic curcumin supplementation on the rat forebrain prior to ischemia and reperfusion. Forebrain ischemia was induced by bilateral common carotid artery occlusion for 1/2 hour, followed by reperfusion for 72 hours. Older rats were divided into five groups: Group I received 300 mg/kg oral curcumin for 21 days before ischemia and 300 mg/kg intraperitoneal curcumin after ischemia; Group II received 300 mg/kg intraperitoneal curcumin after ischemia; Group III received 300 mg/kg oral curcumin for 21 days before ischemia; Group IV had only ischemia; Group V was the sham-operated group. The forebrain was rapidly dissected for biochemical parameter assessment and histopathological examination. In forebrain tissue, enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase were significantly higher in Group I than Groups II or III (p curcumin-treated groups compared with the ischemic group. We also found a marked reduction in apoptotic index after 72 hours in the groups receiving curcumin. Significantly more TUNEL-positive cells were observed in the ischemic group compared to those treated with curcumin. We demonstrated the neuroprotective effect of chronic curcumin supplement on biochemical parameters, neurological scores and apoptosis following ischemia and reperfusion injury in rats.

Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome 1.

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Sedman, Tuuli; Rünkorg, Kertu; Krass, Maarja; Luuk, Hendrik; Plaas, Mario; Vasar, Eero; Volke, Vallo

2016-01-01

Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg) was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes.

Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome 1

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Tuuli Sedman

2016-01-01

Full Text Available Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes.

Minocycline inhibits alkali burn-induced corneal neovascularization in mice.

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Ou Xiao

Full Text Available The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV. A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS or minocycline twice a day (60 mg/kg or 30 mg/kg for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs. The mRNA expression levels of vascular endothelial growth factor (VEGF and its receptors (VEGFRs, basic fibroblast growth factor (bFGF, matrix metalloproteinases (MMPs, interleukin-1α, 1β, 6 (IL-1α, IL-1β, IL-6 were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1β and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1β, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1β, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d. can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs.

Turmeric (Curcuma longa) attenuates food allergy symptoms by regulating type 1/type 2 helper T cells (Th1/Th2) balance in a mouse model of food allergy.

Science.gov (United States)

Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Choi, Dae Woon; Kwon, Da-Ae; Bae, Min-Jung; Sung, Ki-Seung; Shon, Dong-Hwa

2015-12-04

Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies. Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA. Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice. Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antioxidant and Hypoglycaemic Effects of Ardisia Compressa (HBEK ...

African Journals Online (AJOL)

Purpose: To evaluate the possible hypoglycaemic, hypolipidemic, and antioxidant activities of Ardisia compressa (AC) on a rat model of type 2 diabetes. Methods: Diabetes was induced in female Wistar rats by intraperitoneal (i.p.) administration of streptozotocin (65 mg/kg) and nicotinamide (120 mg/kg). The diabetic ...

The Protective Role of Carbon Monoxide (CO Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO

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Katarzyna Magierowska

2016-03-01

Full Text Available Carbon monoxide (CO produced by heme oxygenase (HO-1 and HO-2 or released from the CO-donor, tricarbonyldichlororuthenium (II dimer (CORM-2 causes vasodilation, with unknown efficacy against stress-induced gastric lesions. We studied whether pretreatment with CORM-2 (0.1–10 mg/kg oral gavage (i.g., RuCl3 (1 mg/kg i.g., zinc protoporphyrin IX (ZnPP (10 mg/kg intraperitoneally (i.p., hemin (1–10 mg/kg i.g. and CORM-2 (1 mg/kg i.g. combined with NG-nitro-l-arginine (l-NNA, 20 mg/kg i.p., 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 mg/kg i.p., indomethacin (5 mg/kg i.p., SC-560 (5 mg/kg i.g., and celecoxib (10 mg/kg i.g. affects gastric lesions following 3.5 h of water immersion and restraint stress (WRS. Gastric blood flow (GBF, the number of gastric lesions and gastric CO and nitric oxide (NO contents, blood carboxyhemoglobin (COHb level and the gastric expression of HO-1, HO-2, hypoxia inducible factor 1α (HIF-1α, tumor necrosis factor α (TNF-α, cyclooxygenase (COX-2 and inducible NO synthase (iNOS were determined. CORM-2 (1 mg/kg i.g. and hemin (10 mg/kg i.g. significantly decreased WRS lesions while increasing GBF, however, RuCl3 was ineffective. The impact of CORM-2 was reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM-2 decreased NO and increased HO-1 expression and CO and COHb content, downregulated HIF-1α, as well as WRS-elevated COX-2 and iNOS mRNAs. Gastroprotection by CORM-2 and HO depends upon CO’s hyperemic and anti-inflammatory properties, but is independent of NO.

Intraperitoneal administration of high doses of polyethylene glycol (PEG) causes hepatic subcapsular necrosis and low-grade peritonitis with a rise in hepatic biomarkers

International Nuclear Information System (INIS)

Pellegrini, Giovanni; Starkey Lewis, Phil J.; Palmer, Luke; Hetzel, Udo; Goldring, Christopher E.; Park, B. Kevin; Kipar, Anja; Williams, Dominic P.

2013-01-01

Polyethylene glycols (PEGs) are commonly employed as excipients in preclinical studies and in vitro experiments to dissolve poorly hydrosoluble drugs. Their use is generally considered safe in both animals and humans; however, limited data is available concerning the safety of PEGs when administered parenterally. The results of our investigation demonstrate that PEG-400 can have an irritant effect on serosal surfaces and causes subcapsular hepatocellular necrosis in mice when administered intraperitoneally at a high dose (4 mL/kg). Accordingly, levels of serum biomarkers of liver injury need to be carefully interpreted in studies where PEG is administered intraperitoneally and always in association with the results of the histological assessment

Involvement of nitrergic system of CA1in harmane induced learning and memory deficits.

Science.gov (United States)

Nasehi, Mohammad; Piri, Morteza; Abdollahian, Mojgan; Zarrindast, Mohammad Reza

2013-01-17

Harmane (HA) is a β-carboline alkaloid derived from the Peganum harmala plant which induces memory impairment. On the other hand some of the investigations showed that β-carboline alkaloids inhibit NO production. Thus, the aim of the present study was to investigate the role of nitrergic system of the dorsal hippocampus (CA1) in HA-induced amnesia in male adult mice. One-trial step-down passive avoidance and hole-board apparatuses were used for the assessment of memory retrieval and exploratory behaviors respectively. The data indicated that pre-training intraperitoneal (i.p.) administration of HA (12 and 16 mg/kg) decreased memory acquisition. Sole pre-training or pre-testing administration of L-NAME, a nitric oxide synthesis inhibitor (5, 10 and 15 μg/mice, intra-CA1) did not alter memory retrieval. On the other hand, pre-training (10 and 15 μg/mice, intra-CA1) and pre-testing (5, 10 μg/mice, intra-CA1) injections of L-NAME restored HA-induced amnesia (16 mg/kg, i.p.). Furthermore, neither sole pre-training nor pre-testing administration of l-arginine, a NO precursor (3, 6 and 9 μg/mice, intra-CA1), altered memory retrieval. In addition, pre-testing (6 and 9 μg/mice, intra-CA1), but not pre-training, injection of l-arginine increased HA-induced amnesia (16 mg/kg, i.p.). These results suggest that the nitrergic system of CA1 is involved in HA-induced amnesia. Copyright © 2012 Elsevier Inc. All rights reserved.

[Intraoperative chemotherapy with intraperitoneal activated carbon particles adsorbing mitomycin C against peritoneal dissemination of gastric cancer].

Science.gov (United States)

Iwamoto, A; Takahashi, T; Sasabe, T; Itoh, M; Kondoh, S; Seiki, K; Yoneyama, C; Shimotsuma, M; Hagiwara, A; Yamaguchi, T

1989-08-01

A new form of dosage (MMC-CH) was composed of activated carbon particles adsorbing mitomycin C. Intraperitoneal administration of MMC-CH was tested clinically for prophylactic and therapeutic effects on peritoneal carcinomatosis of gastric cancer. The criteria of MMC-CH's administration were equal or less than 70 years old, more than 40 kg in body weight, no disfunction of liver and kidney, no particular findings in electrocardiography, S2 or S3 in the grade of serosal invasion, P0, P1, P2 or P3 in the grade of peritoneal dissemination, according to the General Rules for the Gastric Cancer Study in Surgery and Pathology by the Japanese Research Society for Gastric Cancer. MMC-CH was given to 44 patients undergoing gastrectomy for gastric cancer in our department from 1985 to 1988. The 44 patients were composed of 12 patients with P0 findings (P0 patients), 8 patients with P1 findings (P1 patients), 12 patients with P2 findings (P2 patients), and 12 patients with P3 findings (P3 patients). MMC-CH at 50 mg/person in terms of mitomycin C was administered intraperitoneally before the operation wound was closed. Fifty-seven patients in our department from 1983 to 1987 for whom the same criteria were applicable and did not receive MMC-CH therapy, served as the control group. The 57 patients were composed of 23 P0 patients, 21 P1 patients, 10 P2 patients, and 3 P3 patients. There was statistically with chi 2 test no significant difference of age, sex, depth of infiltration macroscopically and microscopically defined progression of lymph-nodal metastases between the MMC-CH group and the control group. Survival rate was calculated with Kaplan-Meier's method in the overall patients in each of the MMC-CH group or the control group. The overall survival rate in the MMC-CH group was statistically significantly (p less than 0.01-0.05) higher from day 460 to day 552 and from day 736 to day 800 than that in the control group. Next, the patients were classified into two subgroups

Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1

Directory of Open Access Journals (Sweden)

Laura Foucault-Fruchard

2018-01-01

Full Text Available Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days. Western blot assay results showed that the expression of heme oxygenase-1 (HO-1, the key component of the cholinergic anti-inflammatory pathway, in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water, and that the increase in HO-1 expression was independent of change in α7nAChR expression. These findings suggest that HO-1 expression is unrelated to α7nAChR density and the increase in HO-1 expression likely contributes to α7nAChR activation-related neuroprotective effect in early-stage Huntington's disease.

Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry

DEFF Research Database (Denmark)

Kiss, A; Bundzikova, J; Pirnik, Z

2010-01-01

rats were injected intraperitoneally with haloperidol (1 mg/kg), clozapine (30 mg/kg), olanzapine (30 mg/kg), risperidone (2mg/kg), and vehicle (5% chremophor) and were sacrificed 60 min later by a fixative. Fos, Fos/OXY, and Fos/AVP labelings were visualized by immunohistochemistry in the SON, 5...... accessory (ACS) cell groups, and 4 distinct PVN subdivisions using a computerized light microscope. Most apparent activation of single Fos, Fos/OXY, and Fos/AVP cells was induced by clozapine and olanzapine; effects of risperidone and haloperidol were substantially lower; no colocalizations were revealed...... of risperidone and haloperidol. Variabilities in Fos distribution in the PVN, SON, and ACS induced by antipsychotics may be helpful to understand more precisely the extent of their extra-forebrain actions with possible presumption of their functional impact and side effect consequences....

Estudo toxicológico pré-clínico (agudo do extrato do Syzygium aromaticum (L em roedores

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Rômulo O. H. Valente

Full Text Available O objetivo desta pesquisa foi estimar a toxicidade aguda do extrato do cravo-da-índia (Syzygium aromaticum Linné em roedores. O extrato hidro-alcoólico a 80% foi concentrado em evaporador rotativo obtendo-se uma mistura final de extrato pilular. Camundongos albinos (Mus musculus fêmeas, divididos em 13 lotes de seis animais foram observados por 24 horas a partir da administração do extrato diluído em solução fisiológica a 0,9% nas dosagens de 137,5; 180; 187,5; 250; 375; 437,5; 500 e 1.000 mg/kg para via intraperitoneal e 1.000; 2.400; 2.880; 4.000 e 5.000 mg/kg para via oral. O cálculo proporcional foi realizado a fim de se obter a mesma dose para todos os animais de cada grupo. As punções foram por via intraperitoneal sendo respeitados intervalos de cinco minutos entre as administrações individuais. Nos ensaios de toxicidade por via oral a solução foi introduzida no trato digestório dos animais através de cânula metálica acoplada a seringa (gavagem. Os animais apresentaram alguns sinais de toxicidade, porém não letais até a dose de 5.000 mg/kg. A DL50 para via intraperitoneal foi calculada pelo método de Karber e Behrens (1964, sendo estabelecida em 255 mg/kg (muito tóxico, grau 4. Conclui-se que sob condições agudas de exposição, o extrato do cravo-da-índia é um agente tóxico, devendo ser considerado como tal, dependendo da dose administrada ou absorvida, tempo e freqüência de exposição e vias de administração.

Involvement of the cholinergic system of CA1 on harmane-induced amnesia in the step-down passive avoidance test.

Science.gov (United States)

Nasehi, Mohammad; Sharifi, Shahrbano; Zarrindast, Mohammad Reza

2012-08-01

β-carboline alkaloids such as harmane (HA) are naturally present in the human food chain. They are derived from the plant Peganum harmala and have many cognitive effects. In the present study, effects of the nicotinic system of the dorsal hippocampus (CA1) on HA-induced amnesia and exploratory behaviors were examined. One-trial step-down and hole-board paradigms were used to assess memory retention and exploratory behaviors in adult male mice. Pre-training (15 mg/kg) but not pre-testing intraperitoneal (i.p.) administration of HA decreased memory formation but did not alter exploratory behaviors. Moreover, pre-testing administration of nicotine (0.5 µg/mouse, intra-CA1) decreased memory retrieval, but induced anxiogenic-like behaviors. On the other hand, pre-test intra-CA1 injection of ineffective doses of nicotine (0.1 and 0.25 µg/mouse) fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which did not alter exploratory behaviors. Furthermore, pre-testing administration of mecamylamine (0.5, 1 and 2 µg/mouse, intra-CA1) did not alter memory retrieval but fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which had no effect on exploratory behaviors. In conclusion, the present findings suggest the involvement of the nicotinic cholinergic system in the HA-induced impairment of memory formation.

Health-Related Quality of Life, Treatment Satisfaction, and Costs Associated With Intraperitoneal Versus Subcutaneous Insulin Administration in Type 1 Diabetes

NARCIS (Netherlands)

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

OBJECTIVE - To investigate the effects of continuous intraperitoneal insulin infusion (CIPII) compared with subcutaneous insulin on health-related quality of life (HRQOL) and treatment satisfaction, and to perform a cost analysis in type 1 diabetes. RESEARCH DESIGN AND METHODS - We used an

NPY intraperitoneal injections produce antidepressant-like effects and downregulate BDNF in the rat hypothalamus.

Science.gov (United States)

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

2012-06-01

Several studies have documented an involvement of Neuropeptide Y (NPY) in stress-related disorders. Stress-related disorders are also characterized by changes in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), neurotrophins implicated in the survival and function of neurons. Thus the aim of this study was to investigate whether an NPY intraperitoneal treatment has antidepressant-like effects in rats subjected to a classical stress paradigm, the Forced Swim Test (FST), in association with changes in local brain neurotrophin production. Rats were intraperitoneally injected with either NPY (60 μg/kg) or a vehicle for three consecutive days between two FST sessions and then tested for time spent (or delay onset) in immobile posture. Moreover, we measured by enzyme-linked immunosorbent assay (ELISA) neurotrophin levels in the hypothalamus and corticosterone levels in plasma. The data showed that NPY induced a significant delay in the onset and a significant reduction in the duration of the immobility posture in FST. We also found that NPY decreased BDNF levels in the hypothalamus and corticosterone levels in plasma. Immobility posture in FST can be reduced by antidepressant drugs. Thus, our data show an antidepressant-like effect of NPY associated with changes in BDNF levels in the hypothalamus and reduced activity of hypothalamic-pituitary-adrenal (HPA) axis. These findings, while confirming the involvement of the NPY system in stress-related disorders, suggest that a less invasive route of administration, such as an intraperitoneal injection, may be instrumental in coping with stressful events in animal models and perhaps in humans. © 2012 Blackwell Publishing Ltd.

In vivo postirradiation protection by a vitamin E analog, alpha-TMG.

Science.gov (United States)

Satyamitra, Merriline; Uma Devi, P; Murase, Hironobu; Kagiya, V T

2003-12-01

The water-soluble vitamin E derivative alpha-TMG is an excellent radical scavenger. A dose of 600 mg/kg TMG significantly reduced radiation clastogenicity in mouse bone marrow when administered after irradiation. The present study was aimed at investigating the radioprotective effect of postirradiation treatment with alpha-TMG against a range of whole-body lethal (8.5-12 Gy) and sublethal (1-5 Gy) doses of radiation in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from micronuclei and chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 600 mg/kg TMG within 10 min of lethal irradiation increased survival, giving a dose modification factor (DMF) of 1.09. TMG at doses of 400 mg/kg and 600 mg/kg significantly reduced the percentage of aberrant metaphases, the different types of aberrations, and the number of micronucleated erythrocytes. DMFs of 1.22 and 1.48 for percentage aberrant metaphases and 1.6 and 1.98 for micronuclei were obtained for 400 mg/kg and 600 mg/kg TMG, respectively. No drug toxicity was observed at these doses. The effectiveness of TMG when administered postirradiation suggests its possible utility for protection against unplanned radiation exposures.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40mg Sb v/kg/dia, de 12/12h, por 30 dias na forma cutaneo-mucosa de leishmaniose

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Raimunda N.R. Sampaio

1997-12-01

Full Text Available Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40mg/kg/day of pentavalent antimony (SbV, in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxics effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40mg Sb/kg/day was less tolerated on account of its renal toxics

Opioid system contribution to the antidepressant-like action of m-trifluoromethyl-diphenyl diselenide in mice: A compound devoid of tolerance and withdrawal syndrome.

Science.gov (United States)

Rosa, Suzan G; Pesarico, Ana P; Tagliapietra, Carolina F; da Luz, Sônia Ca; Nogueira, Cristina W

2017-09-01

Animal and clinical researches indicate that the opioid system exerts a crucial role in the etiology of mood disorders and is a target for intervention in depression treatment. This study investigated the contribution of the opioid system to the antidepressant-like action of acute or repeated m-trifluoromethyl-diphenyl diselenide administration to Swiss mice. m-Trifluoromethyl-diphenyl diselenide (50 mg/kg, intragastric) produced an antidepressant-like action in the forced swimming test from 30 min to 24 h after treatment. This effect was blocked by the µ and δ-opioid receptor antagonists, naloxonazine (10 mg/kg, intraperitoneally) and naltrindole (3 mg/kg, intraperitoneally), and it was potentiated by a κ-opioid receptor antagonist, norbinaltrophimine (1 mg/kg, subcutaneously ). Combined treatment with subeffective doses of m-trifluoromethyl-diphenyl diselenide (10 mg/kg, intragastric) and morphine (1 mg/kg, subcutaneously) resulted in a synergistic antidepressant-like effect. The opioid system contribution to the m-trifluoromethyl-diphenyl diselenide antidepressant-like action was also demonstrated in the modified tail suspension test, decreasing mouse immobility and swinging time and increasing curling time, results similar to those observed using morphine, a positive control. Treatment with m-trifluoromethyl-diphenyl diselenide induced neither tolerance to the antidepressant-like action nor physical signs of withdrawal, which could be associated with the fact that m-trifluoromethyl-diphenyl diselenide did not change the mouse cortical and hippocampal glutamate uptake and release. m-Trifluoromethyl-diphenyl diselenide treatments altered neither locomotor nor toxicological parameters in mice. These findings demonstrate that m-trifluoromethyl-diphenyl diselenide elicited an antidepressant-like action by direct or indirect μ and δ-opioid receptor activation and the κ-opioid receptor blockade, without inducing tolerance, physical signs of withdrawal and

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

Science.gov (United States)

Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

2012-05-01

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

Hypo glycemic and Hypolipidaemic Effect of cinnamon Extract in Diabetic and irradiated Rats

International Nuclear Information System (INIS)

Mohamed, E.T.

2013-01-01

This study was made to investigate the antidiabetic and hypolipidemic potential of cinnamon against radiation and/or streptozotocin (STZ) induced diabetes in rats. In the experiment, a total of 36 rats were used and the rats were divided into six groups each of six rats: group 1, normal untreated rats; group 2, animals received only cinnamon (200 mg/kg/day) for 30 consecutive days; group 3, animals exposed to 4 Gy whole body gamma radiation as a single shot dose; group 4, animals were injected intraperitoneally with a freshly prepared solution of streptozotocin (45 mg/kg) in 0.1 M citrate buffer, ph 4.5; group 5, rats were injected intraperitoneally with a freshly prepared solution of streptozotocin (45 mg/kg), followed by irradiation at a dose level of 4 Gy; and group 6, rats were given orally cinnamon (200 mg/kg/day) for 30 days then injected intraperitoneally with a freshly prepared solution of streptozotocin followed by irradiation at a dose level of 4 Gy. Blood samples were collected from all groups for the determination of serum fasting blood sugar (FBG), glycidate hemoglobin (HbA1c), plasma insulin, serum C-peptide, serum total cholesterol (TC), Serum triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C). In diabetic and irradiated groups there was a highly significant increase in the percentage of (HbA1c) and concentration of FBG, TC, TG, LDL-C and a significant decrease in the level of HDL-C, plasma insulin and C-peptide compared to those of control group. Treatment of the diabetic irradiated rats with cinnamon caused a significant decrease in the percentage of HbA1c and concentration of FBG, TC, TG, LDL-C and significant increase in the level of HDL-C, plasma insulin and C-peptide compared to the diabetic irradiated rats. On the basis of these results, one could conclude that cinnamon exhibit hypo glycemic and hypolipidaemic properties and could be considered a promising agent for diabetes

Monoglycerides and fatty acids from Ibervillea sonorae root: isolation and hypoglycemic activity.

Science.gov (United States)

Hernández-Galicia, Erica; Calzada, Fernando; Roman-Ramos, Rubén; Alarcón-Aguilar, Francisco J

2007-03-01

Eleven monoglycerides (MG), 1-monopalmitin (1), glyceryl 1-monomargarate (2), 1-monostearin (3), glyceryl 1-monononadecylate ( 4), glyceryl 1-monoarachidate (5), glyceryl 1-monobehenate (6), glyceryl 1-monotricosanoate (7), glyceryl 1-monotetracosanoate (8), glyceryl 1-monopentacosanoate (9), glyceryl 1-monohexacosanoate (10) and glyceryl 1-monooctacosanoate (11), together with five fatty acids (FA), lauric acid (12), myristic acid (13), pentadecanoic acid (14), palmitic acid (15) and stearic acid (16) were isolated of the root of IBERVILLEA SONORAE Greene (Cucurbitaceae). Their structures were determined by spectroscopic and chemical methods as well as GC-MS analysis. The hypoglycemic activity of the dichloromethane (DCM) extract, of fractions (F1-F10 and SF1-SF5), of monoglycerides (MG) and of fatty acids (FA) mixtures obtained of the root from I. SONORAE was evaluated in normoglycemic and alloxan-induced diabetic mice. The results showed that by intraperitoneal administration the DCM extract (300 mg/kg), F9 (300 mg/kg) and SF1 (150 mg/kg) significantly reduced glucose levels in both models. For fraction SF1, the hypoglycemic activity was more pronounced than that of tolbutamide (150 mg/kg) used as control. However, neither MG (75 mg/kg) nor FA (75 mg/kg) mixtures isolated from SF1 exhibited a significant hypoglycemic effect. However, when MG and FA were combined in equal proportions (75 mg: 75 mg/kg), their effect was comparable to that of SF1. The observed activity for the DCM extract, F9, SF1 and the MG-FA mixture provides additional support for the popular use of this plant in the treatment of diabetes mellitus in Mexican traditional medicine.

Pharmacodynamics of Imipenem in Combination with beta-Lactamase Inhibitor MK7655 in a Murine Thigh Model

NARCIS (Netherlands)

Mavridou, E.; Melchers, M.J.B.; Mil, A.C. van; Mangin, E.; Motyl, M.R.; Mouton, J.W.

2015-01-01

MK7655 is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases. Pharmacokinetics (PK) of imipenem-cilastatin (IMP/C) and MK7655 were determined for intraperitoneal doses of 4 mg/kg to 128 mg/kg of body weight. MIC and pharmacodynamics (PD) studies of MK7655 were performed

Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain. A possible new animal model of autism

DEFF Research Database (Denmark)

Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

2014-01-01

The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20mg/kg or 100mg/kg) continuously during the last 9-12 day...

Withaferin-A displays enhanced anxiolytic efficacy without tolerance ...

African Journals Online (AJOL)

Withaferin-A dose-dependently (10 tob40 mg/kg) displayed anxiolytic activity, as measured by an increase in open arm exploration time in the elevated plus-maze (EPM), following intraperitoneal (i.p.) administration in rats. Acute administration of withaferin-A at 40.0 mg/kg significantly (P<0.05) increased open arm ...

Corrigendum to “Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain" [Neurosci.Lett. 580 (2014) 12–16] A possible new animal model of autism

DEFF Research Database (Denmark)

Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

2015-01-01

The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20 mg/kg or 100 mg/kg) continuously during the last 9–12 d...

Evaluation of anticonvulsant effects of methanolic extract of Olax ...

African Journals Online (AJOL)

Anticonvulsant activity of MEOS was evaluated in chicks using maximal electroshock test, and in mice using pentylenetetrazole and strychnine-induced seizure models at doses of 100, 200 and 400 mg/kg. The intraperitoneal median lethal dose of MEOS was estimated to be 3800 mg/kg body weight in mice. MEOS at doses ...

[Effect of the proteolytic enzyme papain on the body organs and systems of experimental animals].

Science.gov (United States)

Udod, V M; Storozhuk, V T; Trofimenko, S P; Shabash, E G; Markelov, S I

1983-01-01

When administered intravenously and intraarterially papaine (2.5 and 10 mg/kg) produces no toxic effects on respiration, arterial pressure, brain and intracranial circulation. Intrapleural, intraperitoneal and interstitial administration of papaine solutions in doses under 4.5 mg/kg produces no local or general changes on the part of experimental animals' organism.

The effects of thiamin on lead metabolism: organ distribution of lead 203.

OpenAIRE

Kim, J S; Hamilton, D L; Blakley, B R; Rousseaux, C G

1992-01-01

The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi lead 203. They were treated with either thiamin (25 or 50 mg/kg body weight), calcium ethylenediaminetetraacetic acid (CaEDTA) (50 mg/kg body weight), or combinations of thiamin and CaEDTA. The whole body retention and the organ distribution of lead 203 varied depending upon the route of lead a...

Effect of pomegranate peel alone and in combination with rosiglitazone on hyperglycemia and dyslipidemia in type 2 diabetes mellitus

International Nuclear Information System (INIS)

Shujaat, A.; Hussain, M.M.

2016-01-01

To evaluate the effect of pomegranate peel extract with or without rosiglitazone on plasma glucose and lipid profile in insulin resistant diabetic rats. Study Design: Randomized controlled trial. Place and Duration of Study: Department of Physiology, Army Medical College, Rawalpindi, in collaboration with National Institute of Health (N.I.H), Islamabad from 1st January 2011 to 28th May 2011. Material and Methods: Type 2 diabetes mellitus was induced in sixty healthy rats. The diabetic rats were divided into four groups, namely diabetic control group which received intraperitoneal injection of normal saline daily, pomegranate group which was treated similar to control group and also received pomegranate peel extract (200mg/kg body weight) orally once daily, rosiglitazone group which received intraperitoneal injection of rosiglitazone (5mg/kg body weight) daily and the combined group received both pomegranate extract (100 mg/kg body weight, orally) and intraperitoneal injection of rosiglitazone (2.5 mg/kg body weight) daily for 28 days. After four weeks of treatment, terminal intracardiac sampling was done to measure plasma glucose and lipid profile. Results: The plasma glucose and mean serum levels of cholesterol, triglyceride, low density lipoproteins and very low density lipoproteins was significantly reduced (p<0.001) in pomegranate, rosiglitazone and combined groups respectively as compared to the diabetic control. The mean serum levels of high density lipoproteins were significantly (p<0.001) elevated in above mentioned groups as compared to the diabetic control. Conclusion: Pomegranate peel extract is hypoglycemic and hypolipidemic agent in low doses when used alone or in combination with rosiglitazone in type 2 diabetic rats. (author)

Purified deoxynivalenol or feed restriction reduces mortality in rainbow trout, Oncorhynchus mykiss (Walbaum), with experimental bacterial coldwater disease but biologically relevant concentrations of deoxynivalenol do not impair the growth of Flavobacterium psychrophilum.

Science.gov (United States)

Ryerse, I A; Hooft, J M; Bureau, D P; Hayes, M A; Lumsden, J S

2015-09-01

Diets containing deoxynivalenol (DON) were fed to rainbow trout Oncorhynchus mykiss (Walbaum) for 4 weeks followed by experimental infection (intraperitoneal) with Flavobacterium psychrophilum (4.1 × 10(6) colony-forming units [CFU] mL(-1) ). Mortality of rainbow trout fed either 6.4 mg kg(-1) DON or trout pair-fed the control diet was significantly reduced (P trout fed the control diet to apparent satiation (trout were fed one of three experimental diets; a control diet, a diet produced with corn naturally contaminated with DON (3.3 mg kg(-1) DON) or a diet containing purified DON (3.8 mg kg(-1) ); however, these fish were not experimentally infected. The presence of DON resulted in significant reduction (P trout fed diets containing purified DON (3.8 mg kg(-1) ) was significantly higher (P < 0.05) at 35 day post-exposure compared with controls. The antimicrobial activity of DON was examined by subjecting F. psychrophilum in vitro to serial dilutions of the chemical. Complete inhibition occurred at a concentration of 75 mg L(-1) DON, but no effect was observed below this concentration (0-30 mg L(-1) ). © 2014 John Wiley & Sons Ltd.

Pharmacokinetics and normal organ dosimetry following intraperitoneal rhenium-186-labeled monoclonal antibody

International Nuclear Information System (INIS)

Breitz, H.B.; Durham, J.S.; Fisher, D.R.

1995-01-01

Pharmacokinetics, biodistribution and radiation dose estimates following intraperitoneal administration of a 186 Re-labeled murine antibody, NR-LU-10, were assessed in 27 patients with advanced ovarian cancer. Quantitative gamma camera imaging and gamma counting of serum and intraperitoneal fluid radioactivity were used to obtain data for dosimetry estimation. The MIRD intraperitoneal model was used to estimate dose to normal organs from radioactivity within the peritoneal cavity. The absorbed dose to normal peritoneum was estimated in two ways: from the gamma camera activity and peritoneal fluid samples. Serum activity peaked at 44 hr and depended on the concentration of radioactivity in the peritoneal fluid. Mean cumulative urinary excretion of 186 Re was 50% by 140 hr. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean ± s.d.) were whole body 0.7 ± 0.3; marrow 0.4 ±0.1; liver 1.9 ±0.9; lungs 1.3 ± 0.7; kidneys 0.2 ± 0.2; intestine 0.2 ±0.2. Peritoneal surface dose estimates varied depending on the volume of fluid infused and the method of dose determination. Using gamma camera data, the peritoneal dose ranged for 7 to 36 rad/mCi. Using peritoneal fluid sample data, the dose ranged from 2 to 25 rad/mCi. Significant myelosuppression was observed at marrow doses above 100 rad. Noninvasive methods of dose estimation for intraperitoneal administration of radioimmunoconjugates provide reasonable estimates when compared with previously described methods. 31 refs., 6 figs., 2 tabs

Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock

Energy Technology Data Exchange (ETDEWEB)

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhang, Hailin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Wang, Xiumei; Wang, Yu; He, Zehong; Yao, Huan

2016-08-15

LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10 mg/kg) or DEX (5 mg/kg) at 1 and 12 h before injecting LPS (30 mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72 h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway. - Highlights: • Cavidine significantly reduced mortality in mice during 72 h after LPS injection. • Cavidine attenuated histopathological changes in lung, liver and kidney. • Cavidine decreased the level of early inflammatory cytokine TNF-α, IL-6 in LPS- stimulated mice. • Cavidine inhibited late inflammatory cytokine HMGB1 through MAPK pathway.

7-NI and ODQ Disturbs Memory in the Elevated Plus Maze, Morris Water Maze, and Radial Arm Maze Tests in Mice.

Science.gov (United States)

Mutlu, Oguz; Akar, Furuzan; Celikyurt, Ipek Komsuoglu; Tanyeri, Pelin; Ulak, Guner; Erden, Faruk

2015-01-01

Nitric oxide (NO) is an atypical neurotransmitter that causes changes in cognition. Nitric oxide synthase (NOS) and guanylate cyclase (GC) inhibitors have been shown to exert some effects on cognition in previous studies; however, the findings have been controversial. This study was aimed at understanding the effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on spatial memory in modified elevated plus maze (mEPM), Morris water maze (MWM), and radial arm maze (RAM) tests. Male Balb-c mice were treated via intraperitoneal injections with 7-NI (15 mg/kg), ODQ (3, 10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline. ODQ (3 mg/kg) and 7-NI (15 mg/kg) significantly increased the second-day latency in the mEPM test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly increased the escape latency in second, third, and fourth sessions, decreased the time spent in the escape platform's quadrant, and increased the mean distance to the platform in the probe trial of the MWM test. ODQ (3, 10 mg/kg) and 7-NI (15 mg/kg) significantly increased the number of errors, whereas only 7-NI increased the latency in the RAM test. The administration of L-arginine (100 mg/kg) prior to 7-NI inverted the effects of 7-NI, which supports the role of NO on cognition. Our study shows that the NO/cGMP/GS pathway can regulate spatial memory in mice.

Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

Science.gov (United States)

Schneider, M; Paulin, A; Dron, F; Woehrlé, F

2014-12-01

The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Caffeine enhances and accelerates the expression of sensitization induced by coca paste indicating its relevance as a main adulterant.

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Prieto, José P; Galvalisi, Martín; López-Hill, Ximena; Meikle, María N; Abin-Carriquiry, Juan A; Scorza, Cecilia

2015-08-01

Caffeine is an active adulterant found in several drugs of abuse including coca paste (CP). We had previously demonstrated that caffeine potentiated the acute stimulant effect induced by CP seized samples. The role of caffeine in the expression of sensitization elicited by a CP seized sample (CP1) was here evaluated. CP1 (equivalent dose of 10 mg/kg of cocaine), cocaine (pure, 10 mg/kg), a combination of cocaine 10 mg/kg plus caffeine 2.5 mg/kg (CP1-surrogate) and saline (control) were intraperitoneally injected in male rats under two different sensitization schedules. Ambulatory locomotion was recorded in 58 animals. After five daily CP1 injections and 5 days of withdrawal, CP1-challenged animals displayed a more robust sensitization than cocaine-treated animals. When a 3 injections-regime of CP1-surrogate or cocaine was assayed, only CP1-surrogate was able to elicit sensitization. Caffeine enhances and accelerates the CP1-induced sensitization. Results may shed light on the fast and high dependence observed in CP users. © American Academy of Addiction Psychiatry.

Toxicity studies of Cordia salicifolia extract Estudo da toxidade do extrato de Cordia salicifolia

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Roberto Kenji Nakamura Cuman

2005-03-01

Full Text Available Este estudo foi realizado para determinar a toxicidade aguda do extrato total de Cordia salicifolia (DL50 após administração oral e intraperitoneal em camundongos, assim como os efeitos do extrato sobre alguns parâmetros bioquímicos no plasma de ratos após um tratamento prolongado (90 dias. A DL50 do extrato administrado por v.o. foi maior que 2000 mg/Kg, enquanto a DL50 por via i.p. foi aproximadamente 920 mg/Kg. A administração oral diária do extrato nas doses de 20, 100, 200 e 400 mg/kg por um período de 90 dias não causou modificações no ganho de peso corporal, no peso dos órgãos, nos parâmetros hematológicos e bioquímicos dos animais. Estes resultados indicam que a administração do extrato por um período mais prolongado não provocou efeitos de toxicidade nos animaisThis study was carried out to determine the acute toxicity of the whole Cordia salicifolia extract (LD50 after oral and intraperitoneal administration in mice, and its effect on certain biochemical parameters in the plasma of rats after 90 days of administration. The oral LD50 value of the extract was higher than 2000 mg/kg while the LD50 by intraperitoneal injections was about 920 mg/kg. A daily oral administration of extracts at 20, 100, 200 and 400 mg/kg doses for 90 days did not cause significant changes in the body weight gain, organs weight or biochemical assays and hematology in the animals. The results showed that the administration of the extract for a prolonged period did not produce toxic effects in the animals

Attenuation of cisplatin-induced nephrotoxicity in rats using ...

African Journals Online (AJOL)

The rats received a single dose injection of 10 mg/kg cisplatin. Other groups of rats received zerumbone (100 and 200 mg/kg), corn oil or the vehicle, dimethyl sulfoxide (DMSO) intraperitoneally for 4 days prior to cisplatin-injections. All animals were decapitated 16 h after cisplatin injection. Trunk blood was collected and ...

Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus.

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Rege N

1989-10-01

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

Protective effects of udenafil citrate, piracetam and dexmedetomidine treatment on testicular torsion/detorsion-induced ischaemia/reperfusion injury in rats.

Science.gov (United States)

Tuglu, D; Yuvanc, E; Ozan, T; Bal, F; Yilmaz, E; Atasoy, P; Kisa, U; Batislam, E

2016-08-01

The aim of this study was to investigate the antioxidant properties of udenafil citrate (1.4 mg kg(-1) -2.8 mg kg(-1) ), dexmedetomidine 25 μg kg(-1) and piracetam 200 mg kg(-1) administered on ipsilateral/contralateral testes after ischaemia in a rat model of testicular torsion/detorsion (T/D) and define its protective effect histologically. Fifty-six Wistar albino rats were included and randomly assigned into 6 groups. No intervention was performed in control group (Group 1, n = 8) and in torsion/detorsion group, (Group 2, n = 8). Udenafil 1.4 mg kg(-1) was given to torsion/detorsion group (Group 3, n = 10), udenafil 2.8 mg kg(-1) was given to torsion/detorsion group (Group 4, n = 10), piracetam 200 mg kg(-1) was given to torsion/detorsion group (Group 5, n = 10) and dexmedetomidine 25 μg kg(-1) was given to torsion/detorsion group (Group 6, n = 10) intraperitoneally after 60 mins of testicular torsion. Biochemical and histopathological testicular injury were evaluated. When the tissue was examined by TOS values, Group 3, Group 4 and Group 5 were significantly lower than Group 2. In contrary Group 6 values were significantly higher than Group 2. The increasing doses of udenafil demonstrated antioxidant properties on the testis tissue and histopathological that protects the testicles. © 2015 Blackwell Verlag GmbH.

Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats.

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Ferreira, Ana; Rodrigues, Márcio; Marques, Alexandre; Falcão, Amílcar; Alves, Gilberto

2017-08-01

Considering the potential of flavonoids in reversing the P-glycoprotein (P-gp)-mediated multidrug resistance, this work aimed to assess the combined effects of silymarin and (-)-epigallocatechin gallate (EPG) on the pharmacokinetics of the P-gp substrates oxcarbazepine (OXC) and licarbazepine (LIC). Rats were pre-treated intraperitoneally with silymarin (25 mg/kg), EPG (25 mg/kg), silymarin/EPG (12.5/12.5 mg/kg; 6.25/18.75 mg/kg; 18.75/6.25 mg/kg) or verapamil (25 mg/kg, reference P-gp inhibitor) before the intraperitoneal administration of OXC (50 mg/kg). Pre-treatment with dual silymarin/EPG combinations originated peak plasma concentrations of OXC and LIC (pharmacologically active metabolite of OXC) similar to those achieved in the presence of verapamil (positive control). Moreover, the effects promoted by silymarin/EPG combinations on the magnitude of systemic drug exposure to OXC and LIC were also reflected in the corresponding drug levels attained in the brain (biophase). These findings evidence the synergistic effect of silymarin and EPG in enhancing the degree of systemic exposure to OXC and LIC in rats, which occurred in a comparable extent to that observed with verapamil. Hence, our findings support the combination of flavonoid-type P-gp inhibitors and P-gp substrate antiepileptic drugs as a potential therapeutic strategy for the management of pharmacoresistant epilepsy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Some effects of prenatal exposure to d-amphetamine sulfate and phenobarbital on developmental neurochemistry and on behavior.

Science.gov (United States)

Zemp, J W; Middaugh, L D

1975-01-01

Amphetamine. Prenatal intraperitoneal injection of d-amphetamine sulfate (5 mg/kg) produces decreases in the levels of catecholamines in the brain the day of birth and increases on day 30. Open-field activity from days 12 to 31 was higher for the group of animals injected with amphetamine or saline if scores were totaled across all test days. At day 75 the offspring of amphetamine-injected mothers exhibited altered open-field behavior. The effects were not observed with subcutaneous injection regardless of the dose used (2.5, 5.0, and 10.0 mg/kg). The lowest subcutaneous dose decreases neonatal viability. Phenobarbital. Prenatal intraperitoneal injection of phenobarbital (80 mg/kg) resulted in decreased litter size, increases mortality, and decreased amounts of nucleic acid and protein in the brains of surviving offspring. Behavioral deficits associated with response perseveration could be demonstrated at 60 days in the mice prenatally exposed to this dosage. Subcutaneous injections of phenobarbital to pregnant mice at 80 and 40 mg/kg, but not 20 mg/kg, doses increased neonatal mortality. Mature animals prenatally exposed to 40 mg/kg phenobarbital have altered open-field behavior and differ from control animals on a passive avoidance task. Mature offspring prenatally exposed to the 20 or 40 mg/kg dose also responded less than controls on an operant task requiring an increasing number of responses per reinforcement. These studies suggest that prenatal exposure to phenobarbital has in some way altered the animals' reactivity to stimualtion.

Ionizing radiation effects on the KG1A primitive hematopoietic cell line

International Nuclear Information System (INIS)

Clave, Emmanuel; Carosella, Edgardo D.; Gluckman, Eliane; Dubray, Bernard; Socie, Gerard

1996-01-01

Purpose: Better understanding of radiation-induced effects on the hematopoietic system is important in both the context of therapeutic intervention and accidental exposure. However, direct study of these effects on the hematopoietic stem cell pool is hampered by the small number of accessible cells. We, thus, studied radiation-induced effects on the KG1a stem cell line. Methods and Materials: We confirmed and extended the immunophenotype of KG1a with monoclonal antibodies, established a radiation survival curve, and quantified mRNAs by Northern blotting 30 min after 1, 2, and 3 Gy of ionizing radiation (IR) and followed for up to 48 h after a 3 Gy dose. Cell cycle status and apoptosis were assessed by fluorescent-activated cell sorter (FACS) analysis, cell morphology, and DNA fragmentation. Results: KG1a was found to be CD34+, CD7+, Thy1 low, CD38 low, lineage negative (neg), C-KITneg and HLA-DRneg, a phenotype consistent with a primitive hematopoietic origin. This immunophenotype was not altered by x-ray irradiation. The D 0 value was 1.75 Gy. We showed a time-dependent variation of c-jun mRNA expression with an early and transient dose-dependent induction followed by a second increase at 24 and 48 h: a biphasic dose-dependent variation of bcl-2 expression 30 min after irradiation with a reduction of mRNA level at 1 Gy, and a normalization at higher doses and stable levels of mRNA for c-fos, c-myc, G-CSF, GM-CSF, IL-6, TNF-α, TGF-β, and MIP-1α genes. Cell cycle analysis showed the absence of G1/S phase arrest, a point consistent with the absence of detection of P53 mRNA by Northern blot analysis. The dose-dependent G2/M phase arrest was not followed by significant apoptotic cell death. Conclusion: Taken together, this data indicates that radiation-induced cell death of KG1a, a cell line that has a relatively high D 0 value, does not seem to be the result of the apoptotic pathway but occurs subsequent to a G2/M phase arrest

Effect of Anapsos® in a murine model of experimental trichomoniasis

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Nogal-Ruiz J.J.

2003-12-01

Full Text Available Immunomodulator effect of Anapsos® (Polypodium leucotomos extract in NMRI (US Naval Medical Research Institute outbred mice infected by the intraperitoneal route with 107 Trichomonas vaginalis has been tested. Gross histopathologic changes in abdominal organs and mortality rate, as a consequence of the pathogenicity of the protozoa and the immune response of the host, were evaluated. Among the different treatment regimes assayed, Anapsos® at doses of 20 mg/Kg/day administered for 10 days before infection decreases the parasite pathogenicity index (PI in the treated animals when compared to those of the untreated control group. The immunosuppresor treatments with azathioprine (100 mg/Kg/day x 1, cyclophosphamide (100 mg/Kg/day x 1, and FK-506 (10 mg/Kg/day x 10 significantly decreased the PI, while an immunostimulant treatment with glycophosphopeptical (13 mg/Kg/day x 10 increased it. These assays have shown the usefulness of the murine model of experimental trichomoniasis for the study of immunomodulator activity of natural or synthetic drugs.

Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

International Nuclear Information System (INIS)

Woźny, Maciej; Lewczuk, Bogdan; Ziółkowska, Natalia; Gomułka, Piotr; Dobosz, Stefan; Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł

2016-01-01

To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg −1 ) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg −1 ) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

Investigation of Peripheral Effects of Citrus Limon Essential Oil on Somatic Pain in Male Wistar Rats: Role of Histaminergic System

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Ali Mojtahedin

2016-12-01

Full Text Available Background & Objective: One of the plants used in traditional medicine is lemon which has analgesic effect. However, little research has been performed on the analgesic effect of lemon and mechanisms of action with an emphasis on neurotransmitters systems. Therefore, the present study set to investigate the peripheral effects of lemon essential oil on somatic pain using formalin test with an emphasis on histaminergic system in male Wistar rats. Materiala & Methods: Sixty male rats weighing approximately 200-250g and aged 14-16 wk were divided into 10 groups: sham (Salin + Formalin 1% intraplantar, three treatment groups with lemon essential oil (EO (12.5, 25 and 50 mg/kg, three treatment groups with Chlorpheniramine (5, 10 and 20 mg/kg, 1 treatment group with Histamine (10 mg/kg, 1 pretreatment group with Chlorpheniramine (20 mg/kg + EO (50mg/kg, and 1 pretreatment group with Histamine (10 mg/kg + EO (50 mg/kg. Formalin test was used to assess somatic pain. Data analysis was performed using one-way ANOVA. Results:  Intraperitoneal injection of lemon essential oil reduced the pain response induced by formalin in both phases (P<0.05. Pretreatment with chlorpheniramine and lemon essential oil enhanced the analgesic response in both phases (P<0.05. Conclusion: Lemon essential oil had analgesic effects, probably caused by the histaminergic system.

Dosis letal 50 de lorazepam en ratón (Mus musculus Albino, cepa suizo-icr

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Francisco Alejandro Múnera G.

2000-10-01

Full Text Available Objective: The lethal dose 50 (LD50 of  lorazepam in albino mice (Musmusculus, swiss ICR strain, was determined as a first step in the study of the conjoint toxicity of admixtures of scopolamine and benzodiazepines ("new burundanga". Method: Sixty adult male mice were randomly assigned to five experimental groups and to a control one. The dose of lorazepam administered intraperitoneally to each group was: group 1,10 mg kg_1; group 11,20 mg kgI; group 111,40mg kgL; group IV,80mgkg'; group V,160mg kg-l.The control group received only the vehicle solution. Mortality was recorded during 15 days after injection. Necropsies were performed to all the mice dead during the assay and to the survivors. Data were processed using probit analysis and survival analysis. Results: Estimated LD50 were 90.71 mg kg- 1, with 95% confidence range of 65,02to 150,13mg kg- 1.Deaths occurred within the first six days after injection of doses higher than 80 mg kg:', mostly during the first 48 hours. Conclusions: The estimated LD50 of  lorazepam in this experiment almost doubles the reported one, this finding suggests a higher resistance of the mice strain used in this experiment The critic period for lorazepam poisoning spans the first 48 hours.

Grapefruit Derived Flavonoid Naringin Improves Ketoacidosis and Lipid Peroxidation in Type 1 Diabetes Rat Model.

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Alfred N Murunga

Full Text Available Hypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known.To investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats.Sprague-Dawley rats divided into 5 groups (n = 7 were orally treated daily with 3.0 ml/kg body weight (BW/day of distilled water (group 1 or 50 mg/kg BW of naringin (groups 2 and 4, respectively. Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW twice daily, respectively.Stretozotocin (STZ only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA, acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI, hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG compared to the STZ only-treated group.Naringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.

Isopiestic investigation of the osmotic coefficients of MgBr{sub 2}(aq) and study of bromide salts solubility in the (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) system at T = 323.15 K. Thermodynamic model of solution behaviour and (solid + liquid) equilibria in the MgBr{sub 2}(aq), and (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) systems to high concentration and temperature

Energy Technology Data Exchange (ETDEWEB)

Christov, Christomir, E-mail: christov@svr.igic.bas.b [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, ul. ' Acad. G. Bonchev' , bl. 11, 1113 Sofia (Bulgaria)

2011-03-15

The isopiestic method has been used to determine the osmotic coefficients of the binary solutions MgBr{sub 2}(aq) (from 0.4950 to 2.5197 mol {center_dot} kg{sup -1}) at the temperature T = 323.15 K. Sodium chloride solutions have been used as isopiestic reference standards. The solubility of the bromide minerals in the mixed system (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) has been investigated at T = 323.15 K by the physico-chemical analysis method. In addition to simple salts {l_brace}KBr(cr) and MgBr{sub 2} . 6H{sub 2}O(cr){r_brace}, equilibrium crystallization of the highly incongruent double salt with stoichiometric composition 1:1:6 {l_brace}bromcarnallite: KBr . MgBr{sub 2} . 6H{sub 2}O(cr){r_brace} was also established. The results obtained from the isopiestic and solubility measurements have been combined with all other experimental thermodynamic quantities available in the literature (osmotic coefficients, and solubility of the bromide mineral) to construct a chemical model that calculates solute and solvent activities and (solid + liquid) equilibria in the MgBr{sub 2}(aq) binary, and (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) mixed systems from dilute to high solution concentration within the (273.15 to 438.15) K temperature range. The solubility modelling approach based on fundamental Pitzer specific interaction equations is employed. It was found, that the standard for 2-1 type of electrolytes approach with three ({beta}{sup (0)}, {beta}{sup (1)}, and C{sup {phi}}) single electrolyte ion interaction parameters gives excellent agreement with osmotic coefficients from T = (298.15 to 373.45) K; up to saturation at 298.15 K, and up to m(MgBr{sub 2}) = 5.83 mol {center_dot} kg{sup -1} at 373.45 K, and with MgBr{sub 2} {center_dot} 6H{sub 2}O(cr) equilibrium pure water solubility data within the (273.15 to 438.15) K temperature range and up to {approx}8.5 mol {center_dot} kg{sup -1} used in parameterization. The model for the ternary system gives very good

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

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R.R. Guerra

2009-11-01

Full Text Available Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF. Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg by intraperitoneal injections of thioacetamide (200 mg/kg. Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1 and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a reduced the relative mRNA expression of the genes: Col-α1 (-53%, TIMP-1 (-31.7%, TGF-β1 (-57.7%, and MMP-2 (-41.6%, whereas Plau mRNA remained unchanged; b reduced GGT (-43.1%, ALT (-17.6%, and AST (-12.2% serum levels; c increased liver weight (11.3%, and reduced liver collagen (-37.1%, regenerative nodules size (-22.1%, and fibrous septum thickness. Progranulin protein (immunohistochemistry and mRNA (in situ hybridization were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.

The effects of chronic intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats.

Science.gov (United States)

Patel, Sunit M; Ebenezer, Ivor S

2008-09-28

This study was undertaken to examine the effects of repeated administration of the GABA(B) receptor agonist baclofen on food intake in male Wistar rats. In the 1st Experiment, the effects of daily administration of physiological saline and baclofen (2 mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non-deprived rats (n=6 in each group). Baclofen significantly (P<0.05) increased cumulative food intake each day over the treatment period during the 60 min measurement period following administration. Tolerance did not develop to the short-term hyperphagic effect of baclofen over the course of the experiment. In addition, treatment with baclofen did not alter body weight of the animals over the 27 day treatment period when compared with the saline control rats. In the 2nd Experiment, the effects of acute and chronic administration of baclofen (2 mg/kg) were investigated on 24 h food intake in rats. The rats were injected daily for 21 days with either saline (n=6) or baclofen (n=6). Food intake was measured in 30 min time bins for 24 h on treatment Days 1, 12 and 21 following injection. The results showed that while baclofen produced short-term increases in food consumption following injection on treatment Days 1, 12 and 21, the daily (24 h) food intake of the animals was not significantly different from those of control rats. Thus, these data reveal that while chronic administration of baclofen (2 mg/kg) produces short-term increases in feeding without the development of tolerance, daily (24 h) food consumption is not affected. These findings are consistent with the observation that chronic administration of baclofen (2 mg/kg) had no effect on the body weight of these animals.

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

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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

CDEX-1 1 kg point-contact germanium detector for low mass dark matter searches

International Nuclear Information System (INIS)

Kang Kejun; Yue Qian; Wu Yucheng

2013-01-01

The CDEX collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold point-contact p-type germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact P + electrode and the outside N + electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both P + and N + electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments. (authors)

Circadian Variation in the Response to Experimental Endotoxemia and Modulatory Effects of Exogenous Melatonin

DEFF Research Database (Denmark)

Alamili, Mahdi; Klein, Mads; Lykkesfeldt, Jens

2013-01-01

Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we...... investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5 mg/kg), LPS + melatonin (1 mg/kg), or LPS...

Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis.

Science.gov (United States)

Shaker, Mohamed E; Zalata, Khaled R; Mehal, Wajahat Z; Shiha, Gamal E; Ibrahim, Tarek M

2011-04-15

Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl(4)) rat model. Male Wistar rats received intraperitoneal injections of CCl(4) twice weekly for 8weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20mg/kg), nilotinib (10 and 20mg/kg) and silymarin (100mg/kg) during the last 4weeks of CCl(4)-intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20mg/kg) was the most effective treatment to counteract CCl(4)-induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10mg/kg), nilotinib (20mg/kg) and silymarin (100mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl(4)-treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl(4)-induced fibrosis was ameliorated significantly by nilotinib (20mg/kg) and imatinib (20mg/kg). Unlike nilotinib, imatinib (20mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.

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Liao, Tien You; Tzeng, Wen-Yu; Wu, Hsin-Hua; Cherng, Chianfang G; Wang, Ching-Yi; Hu, Sherry S-J; Yu, Lung

2016-04-01

Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.

A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson's disease by reducing chronic inflammation in the brain.

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Cao, Lijun; Li, Dongfang; Feng, Peng; Li, Lin; Xue, Guo-Fang; Li, Guanglai; Hölscher, Christian

2016-04-13

The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD.

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

Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test.

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Filho, Carlos B; Del Fabbro, Lucian; de Gomes, Marcelo G; Goes, André T R; Souza, Leandro C; Boeira, Silvana P; Jesse, Cristiano R

2013-01-05

The opioid system has been implicated as a contributing factor for major depression and is thought to play a role in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of hesperidin in the mouse forced swimming test. Our results demonstrate that hesperidin (0.1, 0.3 and 1 mg/kg; intraperitoneal) decreased the immobility time in the forced swimming test without affecting locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) in the forced swimming test was prevented by pretreating mice with naloxone (1 mg/kg, a nonselective opioid receptor antagonist) and 2-(3,4-dichlorophenyl)-Nmethyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl] acetamide (DIPPA (1 mg/kg), a selective κ-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, a peripherally acting opioid receptor antagonist), naltrindole (3 mg/kg, a selective δ-opioid receptor antagonist), clocinnamox (1 mg/kg, a selective μ-opioid receptor antagonist) or caffeine (3 mg/kg, a nonselective adenosine receptor antagonist). In addition, a sub-effective dose of hesperidin (0.01 mg/kg) produced a synergistic antidepressant-like effect in the forced swimming test when combined with a sub-effective dose of morphine (1 mg/kg). The antidepressant-like effect of hesperidin in the forced swimming test on mice was dependent on its interaction with the κ-opioid receptor, but not with the δ-opioid, μ-opioid or adenosinergic receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders. Published by Elsevier B.V.

Cognitive Improving Effects by Highbush Blueberry (Vaccinium crymbosum L.) Vinegar on Scopolamine-Induced Amnesia Mice Model.

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Hong, Seong Min; Soe, Kyong Hee; Lee, Taek Hwan; Kim, In Sook; Lee, Young Min; Lim, Beong Ou

2018-01-10

The present study aimed to evaluate the preventive effects of highbush blueberry (Vaccinium corymbosum L.) vinegar (BV) on cognitive functions in a scopolamine (Sco)-induced amnesia model in mice. In this study, Sco (1 mg/kg, intraperitoneal injection) was used to induce amnesia. ICR mice were orally administered donepezil (5 mg/kg), blueberry extract (120 mg/kg), and BV (120 mg/kg) for 7 days. After inducing cognitive impairment by Sco, a behavioral assessment using behavior tests (i.e., Y-maze and passive avoidance tests) was performed. The BV group showed significantly restored cognitive function in the behavioral tests. BV facilitated cholinergic activity by inhibiting acetylcholinesterase activity, and enhanced antioxidant enzyme activity. Furthermore, BV was found to be rehabilitated in the cornu ammonis 1 neurons of hippocampus. In our study, we demonstrated that the memory protection conferred by BV was linked to activation of brain-derived neurotrophic factor (BDNF)/cAMP response element binding protein (CREB)/serine-threonine kinase (AKT) signaling.

Effect of infliximab on renal injury due to methotrexate in rat.

Science.gov (United States)

Kirbas, Aynur; Cure, Medine Cumhur; Kalkan, Yildiray; Cure, Erkan; Tumkaya, Levent; Sahin, Osman Zikrullah; Yuce, Suleyman; Kizilkaya, Bayram; Pergel, Ahmet

2015-05-01

Methotrexate, an antagonist of folic acid used in the treatment of many cancers and inflammatory diseases, is associated with side effects that limit its usage. Infliximab has been reported to have a protective effect against nephrotoxicity induced by some drugs and ischemic reperfusion. We aimed to investigate whether infliximab has a protective effect against methotrexate-induced nephrotoxicity. We administered methotrexate at a dose of 20 mg/kg as a single intraperitoneal injection in 10 rats (methotrexate group). Another group of 10 rats received a single dose of infliximab, 7 mg/kg, intraperitoneally (infliximab group). The methotrexate and infliximab group received a similar single injection of infliximab 72 hours prior to methotrexate injection. After 72 hours a single dose of methotrexate, 20 mg/kg, was administered intraperitoneally. Five days after methotrexate injection, blood samples were collected and the kidney tissues were removed for biochemical and histological examination. The methotrexate group had significantly higher tissue levels of tumor necrosis factor-α (P = .008), interleukin-1β (P = .04), nitric oxide (P < .001), and adenosine deaminase (P < .001) than the methotrexate and infliximab group after the 5-day study. The methotrexate group also had significantly higher total histological scores (P < .001) and carbonic anhydrase-II activity (P < .001) when compared to the methotrexate and infliximab group. Infliximab has a strong protective effect against methotrexate-induced nephrotoxicity by suppressing cytokines release. It may decrease methotrexate-induced nephrotoxicity by regulating carbonic anhydrase-II enzyme activities and slowing down purine metabolism.

Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants.

Science.gov (United States)

Malik, Sachin; Ahuja, Priya; Sahu, Kapendra; Khan, Suroor Ahmad

2014-09-12

A series of 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-dione (7a-7d, 8a-8d, 9a-9c) have been prepared and evaluated for their anticonvulsant activities. Preliminary anticonvulsant activity was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests after intraperitoneal (ip) injection into mice, which are the most widely employed models for early identification of anticonvulsant candidate. The acute neurological toxicity (NT) was determined applying rotorod test. The quantitative evaluation after oral administration in rats showed that the most active was 3-(benzo[d]isoxazol-3-yl)-1-(4-fluorophenyl) pyrrolidine-2, 5-dione (8a) with ED50 values of 14.90 mg/kg. Similarly the most potent in scPTZ was 3-(benzo[d]isoxazol-3-yl)-1-cyclohexylpyrrolidine-2, 5-dione (7d) with ED50 values of 42.30 mg/kg. These molecules were more potent and less neurotoxic than phenytoin and ethosuximide which were used as reference antiepileptic drugs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Impacts of fullerene C60 and virgin olive oil on cadmium-induced genotoxicity in rats.

Science.gov (United States)

Aly, Fayza M; Kotb, Ahmed M; Haridy, Mohie A M; Hammad, Seddik

2018-07-15

Currently, cadmium is considered to be one of the major environmental pollutants. Environmentally, cadmium is released in various forms e.g. oxide, chloride and sulphide. The aim of the present study was to examine the genotoxic impact of fullerene nanoparticles C 60 (C 60 ) and virgin olive oil (VOO) on cadmium chloride (CdCl 2 )-induced genotoxicity in rats. To evaluate these effects on DNA damage and chromosomal frequency, 25 albino rats were randomly assigned to 5 groups (n=5 per group): Group 1 served as a control; Group 2 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg); Group 3 animals were treated with C 60 (4mg/kg, orally) every other day for 20days; Group 4 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg) and an oral dose of C 60 (4mg/kg); and Group 5 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg) and oral doses of VOO every other day for 20 consecutive days. Genotoxic and anti-genotoxic effects of C 60 and VOO were evaluated in the liver, kidney and bone marrow using molecular and cytogenetic assays. As expected, CdCl 2 and C 60 administration was associated with band number alterations in both liver and kidney; however, C 60 pretreatment recovered to approximately basal number. Surprisingly, C 60 and VOO significantly attenuated the genotoxic effects caused by CdCl 2 in livers and kidneys. In bone marrow, in addition to a reduction in the chromosomal number, several chromosomal aberrations were caused by CdCl 2 . These chromosomal alterations were also reversed by C 60 and VOO. In conclusion, molecular and cytogenetic studies showed that C 60 and VOO exhibit anti-genotoxic agents against CdCl 2 -induced genotoxicity in rats. Further studies are needed to investigate the optimal conditions for potential biomedical applications of these anti-genotoxic agents. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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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.

Characterisation and Safety of Intraperitoneal Perioperative Administration of Antibacterial Agents

DEFF Research Database (Denmark)

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

2017-01-01

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....

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

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effects of gabapentin in mouse forced swimming test.

Science.gov (United States)

Ostadhadi, Sattar; Akbarian, Reyhaneh; Norouzi-Javidan, Abbas; Nikoui, Vahid; Zolfaghari, Samira; Chamanara, Mohsen; Dehpour, Ahmad-Reza

2017-07-01

Gabapentin as an anticonvulsant drug also has beneficial effects in treatment of depression. Previously, we showed that acute administration of gabapentin produced an antidepressant-like effect in the mouse forced swimming test (FST) by a mechanism that involves the inhibition of nitric oxide (NO). Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (K ATP ), in the present study we investigated the involvement of K ATP channels in antidepressant-like effect of gabapentin. Gabapentin at different doses (5-10 mg/kg) and fluoxetine (20 mg/kg) were administrated by intraperitoneal route, 60 and 30 min, respectively, before the test. To clarify the probable involvement of K ATP channels, mice were pretreated with K ATP channel inhibitor or opener. Gabapentin at dose 10 mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20 mg/kg). Co-administration of subeffective dose (1 mg/kg) of glibenclamide (inhibitor of K ATP channels) with gabapentin (3 mg/kg) showed a synergistic antidepressant-like effect. Also, subeffective dose of cromakalim (opener of K ATP channels, 0.1 mg/kg) inhibited the antidepressant-like effect of gabapentin (10 mg/kg). None of the treatments had any impact on the locomotor movement. Our study, for the first time, revealed that antidepressant-like effect of gabapentin in mice is mediated by blocking the K ATP channels.

Toxicity Of The Essential Oil Of The Cytral Chemotype Of Lippia Alba (Mill. N. E. Brown Toxicidad del aceite esencial de Lippia alba (Mill. N. E. Brown quimiotipo citral

Directory of Open Access Journals (Sweden)

Jesús Olivero-Verbel

2010-06-01

Full Text Available The essential oil (EO of Lippia alba (Mill. N. E. Brown (Verbenaceae has been traditionally used to treat several diseases. In this study, the acute toxic effects of the citral chemotype of L. alba EO were evaluated in mice. Animals were treated via intraperitoneal receiving the L. alba essential oil at doses between 50 and 2500 mg/kg, and the control group received sesame oil (vehicle. The EO induced dose-dependent neurotoxic effects at doses greater than 1000 mg/kg, including decreased locomotion, motor skills and muscle strength, hypotonia, dyspnea, kyphosis and convulsions. The EO was lethal at a dose of 2500 mg/kg. Animals receiving 1000 mg/kg were euthanized at the end of the treatment period and their blood and livers were collected for analysis. Mice exposed to L. alba EO presented signifcantly greater plasma alanine aminotransferase (ALT activities than the control group. Liver histological changes included mild infammation, in particular, an increase in nuclear size. Compared to vehicle control group, changes in expression for selected genes were signifcant for FABP5, a fatty acid transport related gene. In summary, the intraperitoneal administration of L. alba EO (citral chemotype causes neurological damage in mice at doses equal or greater than 1500 mg/kg, whereas at 1000 mg/kg, it generates mild liver damage. Therefore, the systemic use of this EO raises concerns about its safety.El aceite esencial (AE de Lippia alba (Mill. NE Brown (Verbenaceae ha sido utilizado tradicionalmente para tratar varias enfermedades. En este estudio, los efectos tóxicos agudos del AE de Lippia alba quimiotipo citral fueron evaluados en ratones. Los animales fueron tratados por vía intraperitoneal recibiendo el AE en dosis entre 50 y 2500 mg/kg de peso, y el grupo control aceite de sésamo (vehículo. Dosis superiores a 1000 mg/kg del AE mostraron efectos neurotóxicos incluyendo disminución de la locomoción e hipotonía, disnea, cifosis y

Three-dimensional contrast-enhanced magnetic-resonance angiography of the renal arteries: Interindividual comparison of 0.2 mmol/kg gadobutrol at 1.5 T and 0.1 mmol/kg gadobenate dimeglumine at 3.0 T

International Nuclear Information System (INIS)

Attenberger, Ulrike I.; Wintersperger, Bernd J.; Sourbron, Steven P.; Reiser, Maximilian F.; Michaely, Henrik J.; Schoenberg, Stefan O.; Lodemann, Klaus-Peter

2008-01-01

The purpose was to evaluate the image quality of high-spatial resolution MRA of the renal arteries at 1.5 T after contrast-agent injection of 0.2 mmol/kg body weight (BW) in an interindividual comparison to 3.0 T after contrast-agent injection of 0.1 mmol/kg BW contrast agent (CA). After IRB approval and informed consent, 40 consecutive patients (25 men, 15 women; mean age 53.9 years) underwent MRA of the renal arteries either at a 1.5-T MR system with 0.2 mmol/kg BW gadobutrol or at a 3.0-T MR scanner with 0.1 mmol/kg BW gadobenate dimeglumine used as CA in a randomized order. A constant volume of 15 ml of these contrast agents was applied. The spatial resolution of the MRA sequences was 1.0 x 0.8 x 1.0 mm 3 at 1.5 T and 0.9 x 0.8 x 0.9 mm 3 at 3.0 T, which was achieved by using parallel imaging acceleration factors of 2 at 1.5 T and 3 at 3.0 T, respectively. Two radiologists blinded to the administered CA and the field strength assessed the image quality and the venous overlay for the aorta, the proximal and distal renal arteries independently on a four-point Likert-type scale. Phantom measurements were performed for a standardized comparison of SNR at 1.5 T and 3.0 T. There was no significant difference (p > 0.05) between the image quality at 3.0 T with 0.1 mmol/kg BW gadobenate dimeglumine compared to the exams at 1.5 T with 0.2 mmol/kg BW gadobutrol. The median scores were between 3 and 4 (good to excellent vessel visualization) for the aorta (3 at 1.5 T/4 at 3.0 T for reader 1 and 2). For the proximal renal arteries, median scores were 3 for the left and right renal artery at 1.5 T for both readers. At 3.0 T, median scores were 3 (left proximal renal artery) and 4 (right proximal renal artery) for reader 1 and 3 (left/right) for reader 2 at 3.0 T. For the distal renal arteries, median scores were between 2 and 3 at both field strengths (moderate and good) for both readers. The κ values for both field strengths were comparable and ranged between 0

Three-dimensional contrast-enhanced magnetic-resonance angiography of the renal arteries: Interindividual comparison of 0.2 mmol/kg gadobutrol at 1.5 T and 0.1 mmol/kg gadobenate dimeglumine at 3.0 T

Energy Technology Data Exchange (ETDEWEB)

Attenberger, Ulrike I.; Wintersperger, Bernd J.; Sourbron, Steven P.; Reiser, Maximilian F. [University Hospitals-Grosshadern, Ludwig-Maximilians-University Munich, Institute of Clinical Radiology, Munich (Germany); Michaely, Henrik J.; Schoenberg, Stefan O. [University Hospital Mannheim, University of Heidelberg, Institute of Clinical Radiology, Mannheim (Germany); Lodemann, Klaus-Peter [Bracco-Altana Pharma, Konstanz (Germany)

2008-06-15

The purpose was to evaluate the image quality of high-spatial resolution MRA of the renal arteries at 1.5 T after contrast-agent injection of 0.2 mmol/kg body weight (BW) in an interindividual comparison to 3.0 T after contrast-agent injection of 0.1 mmol/kg BW contrast agent (CA). After IRB approval and informed consent, 40 consecutive patients (25 men, 15 women; mean age 53.9 years) underwent MRA of the renal arteries either at a 1.5-T MR system with 0.2 mmol/kg BW gadobutrol or at a 3.0-T MR scanner with 0.1 mmol/kg BW gadobenate dimeglumine used as CA in a randomized order. A constant volume of 15 ml of these contrast agents was applied. The spatial resolution of the MRA sequences was 1.0 x 0.8 x 1.0 mm{sup 3} at 1.5 T and 0.9 x 0.8 x 0.9 mm{sup 3} at 3.0 T, which was achieved by using parallel imaging acceleration factors of 2 at 1.5 T and 3 at 3.0 T, respectively. Two radiologists blinded to the administered CA and the field strength assessed the image quality and the venous overlay for the aorta, the proximal and distal renal arteries independently on a four-point Likert-type scale. Phantom measurements were performed for a standardized comparison of SNR at 1.5 T and 3.0 T. There was no significant difference (p > 0.05) between the image quality at 3.0 T with 0.1 mmol/kg BW gadobenate dimeglumine compared to the exams at 1.5 T with 0.2 mmol/kg BW gadobutrol. The median scores were between 3 and 4 (good to excellent vessel visualization) for the aorta (3 at 1.5 T/4 at 3.0 T for reader 1 and 2). For the proximal renal arteries, median scores were 3 for the left and right renal artery at 1.5 T for both readers. At 3.0 T, median scores were 3 (left proximal renal artery) and 4 (right proximal renal artery) for reader 1 and 3 (left/right) for reader 2 at 3.0 T. For the distal renal arteries, median scores were between 2 and 3 at both field strengths (moderate and good) for both readers. The {kappa} values for both field strengths were comparable and ranged

A thioacetamide-induced hepatic encephalopathy model in C57BL/6 mice: a behavioral and neurochemical study Modelo de encefalopatia hepática induzida por tioacetamida em camundongos C57BL/6: estudo comportamental e neuroquímico

Directory of Open Access Journals (Sweden)

Aline Silva de Miranda

2010-08-01

Full Text Available OBJECTIVE: Hepatic encephalopathy (HE is a neuropsychiatric syndrome resulting from liver failure. In the present study, we aimed to standardize an animal model of HE induced by thioacetamide (TAA in C57BL/6 mice evaluating behavioral symptoms in association with liver damage and alterations in neurotransmitter release. METHOD: HE was induced by an intraperitoneal single dose of TAA (200 mg/kg, 600 mg/kg or 1,200 mg/kg. Behavioral symptoms were evaluated using the SHIRPA battery. Liver damage was confirmed by histopathological analysis. The glutamate release was measured using fluorimetric assay. RESULTS: The neuropsychiatric state, motor behavior and reflex and sensory functions were significantly altered in the group receiving 600 mg/kg of TAA. Biochemical analysis revealed an increase in the glutamate release in the cerebral cortex of HE mice. CONCLUSION: HE induced by 600mg/kg TAA injection in C57BL/6 mice seems to be a suitable model to investigate the pathogenesis and clinical disorders of HE.OBJETIVO: A encefalopatia hepática (EH é uma síndrome neuropsiquiátrica resultante da falência hepática. O objetivo do presente estudo foi estabelecer um modelo de EH induzida por tioacetamida (TAA em camundongos C57BL/6 avaliando transtornos comportamentais, falência hepática e alterações na liberação de neurotransmissores. MÉTODO: A EH foi induzida por meio de uma única dose intraperitoneal de TAA (200 mg/kg, 600 mg/kg, 1.200 mg/kg. As alterações comportamentais foram avaliadas utilizando a bateria SHIRPA. A falência hepática foi confirmada através de análises histopatológicas e a liberação de glutamato medida, por ensaio fluorimétrico. RESULTADOS: Foram encontradas alterações significativas no estado neuropsiquiátrico, comportamento motor e função reflexa e sensorial no grupo que recebeu 600 mg/kg de TAA. Análises bioquímicas revelaram aumento na liberação de glutamato no córtex cerebral dos camundongos com EH

Effects of 7-NI and ODQ on memory in the passive avoidance, novel object recognition, and social transmission of food preference tests in mice.

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Akar, Furuzan; Mutlu, Oguz; Komsuoglu Celikyurt, Ipek; Bektas, Emine; Tanyeri, Pelin; Ulak, Guner; Erden, Faruk

2014-03-19

Nitric oxide (NO) is an intercellular messenger that plays a critical role in learning and memory processes. Effects of nitric oxide synthase (NOS) inhibitors and guanylate cyclase (GC) inhibitors on cognitive function remain controversial. The aim of this study was to investigate effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on different aspects of memory in passive avoidance (PA), novel object recognition (NOR), and social transmission of food preference (STFP) tests. Male Balb-c mice were treated intraperitoneally with 7-NI (15 mg/kg), ODQ (3,10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline. ODQ (10 mg/kg) and 7-NI (15 mg/kg) significantly decreased second-day latency in PA test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly decreased the ratio index in the NOR test. 7-NI and ODQ (10 mg/kg) decreased cued/non-cued food eaten in STFP test. Amount of time spent in center zone significantly increased in ODQ (10 mg/kg) and 7-NI (15 mg/kg) groups in open field test, but there was no effect on total distance moved and speed of animals. ODQ (10 mg/kg) significantly increased number of entries into new compartments in exploratory activity apparatus, while 7-NI had no effect. Administration of L-arginine (100 mg/kg) before 7-NI reversed 7-NI-induced effects, supporting the role of NO in cognition. Our results confirm that inhibition of NO/cGMP/GS pathway might disturb emotional, visual, and olfactory memory in mice. Also, 7-NI and ODQ had anxiolytic effects in open field test, and ODQ also enhanced exploratory activity.

Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

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Perry A. Soriano

2011-01-01

Full Text Available Introduction. We examined the murine hepatectomy model of liver regeneration (LR in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP injections of a control, oxaliplatin (15 mg/kg, or irinotecan (100 mg/Kg or 250 mg/Kg solution. Hepatectomy (70% was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. -tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, =0.048 with no difference on D7 (=0.21. Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3. Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis.

Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

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Soriano, Perry A.; Liu, Nian; Castillo, Erick; Foster, Brock; Artinyan, Avo; Kim, Joseph; Huang, Wendong; Wagman, Lawrence D.

2011-01-01

Introduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15 mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solution. Hepatectomy (70%) was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D) 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. T-tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, P = 0.048) with no difference on D7 (P = 0.21). Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg) showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3). Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis. PMID:22164336

Safety Profile of Meswak Root Extract on Liver, Kidney, Sexual Hormones and Hematological Parameters of Rats

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Abeer Y. IBRAHIM

2012-02-01

Full Text Available This study was conducted to investigate the safety profile of Salvadora persica (Salvadoraceae aqueous alcoholic root extract by carrying out acute and sub-chronic toxicity assessment in order to find out any side effect of the traditionally using of these root sticks. Regarding to acute toxicity test, mice were administered the extract up to 5 g kg-1, intraperitoneally. Animals were then observed for behavioural changes; signs of toxicity, and mortality within 24 h. Surviving mice were monitored for 7 days for signs of delayed toxicity. In the sub-chronic toxicity test, rats were daily treated with the extract at a dose of 400 mg kg-1 intraperitoneally, for 30 days. At the end of the test period, hematological and biochemical parameters were determined in blood and serum samples with determination of vital organs weights. In the acute toxicity test, the extract was practically non-toxic showing no mortality and visible signs of delayed toxicity. The LD50, given intraperitoneally, was estimated to be 4 g kg-1. Administration of extract (at a dose of 400 mg Kg-1 b.wt. to male and female rats for 30 days did not produce any significant (P < 0.05 effect on hematological and most biochemical parameters also vital organs weights. The root extract showed adverse effects on sexual hormones, by increasing estrogen secretion and reducing testosterone level in male rats. At the same time, the extract reduces progesterone level in female satellite group. Overall, Meswak aqueous extract is safe concerning liver and kidney functions and hematological assessments; however, it induces reversal effect on sexual hormones levels determined in sera.

Industrial production of MgH2 and its application

International Nuclear Information System (INIS)

Uesugi, H.; Sugiyama, T.; Nii, H.; Ito, T.; Nakatsugawa, I.

2011-01-01

Research highlights: → Tablet and powder Mg were hydrogenated in a 50 kg batch furnace based on thermal equilibrium method. → Compression of Mg tablet improved the hydrogenation yield. → Hydrolysis of MgH 2 using citric acid generated hydrogen under 373 K. → A MgH 2 -hydrogen reactor utilizing hydraulic head pressure was developed. → - Abstract: A process for the industrial production of magnesium hydride (MgH 2 ) based on a thermal equilibrium method and its application to portable hydrogen sources is proposed. Mg powders and tablets compressed with mechanically ground Mg ribbons were successfully hydrogenated in a 50-kg-batch furnace. The resultant MgH 2 showed a hydrogen yield of around 96% with good reproducibility. The compression ratio of Mg tablets was found to be an important factor in the hydrogenation yield. A hydrolysis technique using citric acid as an additive was employed to generate hydrogen under 373 K. Increasing the concentration of citric acid and the temperature accelerated the hydrolysis reactivity. A hydrogen reactor utilizing hydraulic head pressure was developed. It generated hydrogen continuously for 1 h at a flow rate of 100 ml min -1 with hydrolysis of 5 g of tablet-form MgH 2 . The conversion yield was around 70%, regardless of the flow rate.

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.

7-NI and ODQ Disturbs Memory in the Elevated plus Maze, Morris Water Maze, and Radial Arm Maze Tests in Mice

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Oguz Mutlu

2015-01-01

Full Text Available Nitric oxide (NO is an atypical neurotransmitter that causes changes in cognition. Nitric oxide synthase (NOS and guanylate cyclase (GC inhibitors have been shown to exert some effects on cognition in previous studies; however, the findings have been controversial. This study was aimed at understanding the effects of an NOS inhibitor, 7-nitroindazole (7-NI, and a guanylate cyclase inhibitor, 1 H -[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, on spatial memory in modified elevated plus maze (mEPM, Morris water maze (MWM, and radial arm maze (RAM tests. Male Balb-c mice were treated via intraperitoneal injections with 7-NI (15 mg/kg, ODQ (3, 10 mg/kg, L-arginine (100 mg/kg + 7-NI (15 mg/kg, or physiological saline. ODQ (3 mg/kg and 7-NI (15 mg/kg significantly increased the second-day latency in the mEPM test. 7-NI (15 mg/kg and ODQ (10 mg/kg significantly increased the escape latency in second, third, and fourth sessions, decreased the time spent in the escape platform's quadrant, and increased the mean distance to the platform in the probe trial of the MWM test. ODQ (3, 10 mg/kg and 7-NI (15 mg/kg significantly increased the number of errors, whereas only 7-NI increased the latency in the RAM test. The administration of L-arginine (100 mg/kg prior to 7-NI inverted the effects of 7-NI, which supports the role of NO on cognition. Our study shows that the NO/cGMP/GS pathway can regulate spatial memory in mice.

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

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Gouda M El-labban

2011-01-01

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

Perbandingan Insidensi Hipotensi Saat Induksi Intravena Propofol 2 Mg/Kg Bb Pada Posisi Supine dengan Perlakuan dan Tanpa Perlakuan Elevasi Tungkai

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Beni Indra

2016-01-01

  of blood to venous reservoir, especially capacitance venule of legs. Leg elevation can provide hemodynamic stability by increases cardiac preload and recruits blood contained in the venous reservoir. This is Open Randomized Control Trial include 184 elective surgery patients with American Society of Anaesthesiologist (ASA physical status I and II. Anesthesia  was induced with propofol. Patients were randomly allocated into two groups with 92 patients in each. All the patients received Ringer’s Lactate (10 ml/kg and premedicated with fentanyl (2 mcg/kg and midazolam (0,05 mg/kg before induction of anesthesia. Group A was performed passive leg raising 45 degree 1 minute before injection of propofol until  the end of study and group B (control did not receive any maneuver. Parametric data were analyzed with t-test and categorical data was done by using Chi-square test. A p value of less than 0,05 was consider significant. Demografic characteristics (age, sex, body weight and height and  baseline haemodynamic parameters of the patients were similar in two groups (p > 0.05 except for BMI (p < 0.05 . The incidence of hypotension was significantly lower in group A (12 %, than group  B (27,2% at the first minute after propofol  injection, p value = 0.016 (p < 0,05. In the third minute, incidence of hypotension was also significantly lower in group A (15,2% than group B (23,9%, p value = 0,014 (p < 0,05. Leg elevation maneuver 45º significantly decrease incidence of hypotension after propofol induction. Keywords: Propofol, hypotension, leg elevation

In vivo radiosensitizing effect of nitroimidazole derivative KIN-804

International Nuclear Information System (INIS)

Tada, Takuhito; Nakajima, Toshifumi; Onoyama, Yasuto; Murayama, Chieko; Mori, Yomoyuki; Nagasawa, Hideko; Hori, Hitoshi; Inayama, Seiichi

1994-01-01

In vivo characteristics of 2-nitroimidazole-1-methylacetohydroxamate (KIN-804), which is a newly developed hypoxic cell radiosensitizer, are presented. The toxicity, pharmacokinetics, and radiosensitizing effect of KIN-804 were studied by in vivo experiments using C3H/He mice bearing the SCCVII tumor. Results were compared with misonidazole (MISO). LD 50 7 of KIN-804 and MISO were 3200 mg/kg and 2000 mg/kg, respectively. The peak concentration of KIN-804 in the tumor occurred 20 min after intraperitoneal injection and reached about 62% of the maximum concentration in the blood. The concentrations in brain and sciatic nerve were very low and clearance from sciatic nerve was rapid. Enhancement ratios of KIN-804 calculated using the growth delay method were 1.22, 1.50, and 1.71 at doses of 50, 100, and 200 mg/kg, respectively, compared with 1.36 for MISO at a dose of 100 mg/kg. In the TCD 50 assay, enhancement ratios at a dose of 200 mg/kg were 1.69 for KIN-804 and 1.52 for MISO, respectively. KIN-804 is a promising radiosensitizer since it shows less toxicity and higher radiosensitizing activity than MISO. 10 refs., 5 figs

Phoenixin-14 injected intracerebroventricularly but not intraperitoneally stimulates food intake in rats.

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Schalla, Martha; Prinz, Philip; Friedrich, Tiemo; Scharner, Sophie; Kobelt, Peter; Goebel-Stengel, Miriam; Rose, Matthias; Stengel, Andreas

2017-10-01

Phoenixin, a recently discovered 20-amino acid peptide was implicated in reproduction. However, the expression in food intake-regulatory nuclei such as the paraventricular nucleus, the arcuate nucleus and the nucleus of the solitary tract suggests an implication of phoenixin in food intake regulation. Therefore, we investigated the effects of phoenixin-14, the shorter form of phoenixin, on food intake following intracerebroventricular (icv) and intraperitoneal (ip) injection in ad libitum fed male Sprague-Dawley rats. Phoenixin-14 injected icv (0.2, 1.7 or 15nmol/rat) during the light phase induced a dose-dependent increase of light phase food intake reaching significance at a minimum dose of 1.7 nmol/rat (+72%, pfood intake microstructure showed an icv phoenixin-14-induced increase in meal size (+51%), meal duration (+157%), time spent in meals (+182%) and eating rate (+123%), while inter-meal intervals (-42%) and the satiety ratio (-64%) were decreased compared to vehicle (pfood intake was observed (p>0.05). The light phase icv phoenixin-14-induced increase of water intake did not reach statistical significance compared to vehicle (+136%, p>0.05). The increase of food intake following icv phoenixin-14 was not associated with a significant alteration of grooming behavior (0.4-fold, p=0.377) or locomotion (6-fold, p=0.066) compared to vehicle. When injected ip at higher doses (0.6, 5nmol/kg or 45nmol/kg body weight) during the light phase, phoenixin-14 did not affect food intake (p>0.05). In summary, phoenixin-14 exerts a centrally-mediated orexigenic effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Stevia and stevioside protect against cisplatin nephrotoxicity through inhibition of ERK1/2, STAT3, and NF-κB activation.

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Potočnjak, Iva; Broznić, Dalibor; Kindl, Marija; Kropek, Matija; Vladimir-Knežević, Sanda; Domitrović, Robert

2017-09-01

We investigated the effect of natural sweetener Stevia rebaudiana and its constituent stevioside in cisplatin (CP)-induced kidney injury. Male BALB/cN mice were orally administered 10, 20, and 50 mg/kg body weight of Stevia rebaudiana ethanol extract (SE) or stevioside 50 mg/kg, 48 h after intraperitoneal administration of CP (13 mg/kg). Two days later, CP treatment resulted in histopathological changes showing kidney injury. Increased expression of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), and heme oxygenase-1 (HO-1) in mice kidneys suggested oxidative stress. CP treatment also increased renal expression of nuclear factor-kappaB (NF-κB) p65 subunit and phosphorylated inhibitor of NF-κB (IκBα), as well as expression of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Induction of apoptosis and inhibition of the cell cycle in kidneys was evidenced by increased expression of p53, Bax, caspase-9, and p21, proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), with concomitant suppression of Bcl-2 and cyclin D1 expression. The number of apoptotic cells in kidneys was also assessed. CP administration resulted in activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3). Both SE and stevioside attenuated CP nephrotoxicity by suppressing oxidative stress, inflammation, and apoptosis through mechanism involving ERK1/2, STAT3, and NF-κB suppression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Wortmannin as Targeted Therapeutic Agent for the Treatment of ...

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(7 mg/kg) in DMSO daily intraperitoneally whereas the animals in control groups received an equal volume of DMSO for 21 days after the cancer attained palpable stage. Western blot analysis was carried out using enhanced chemiluminescence reagent while Protean IEF cell unit was used for 1-D electrophoresis. Results: ...

DJ-1-dependent protective activity of DJ-1-binding compound no. 23 against neuronal cell death in MPTP-treated mouse model of Parkinson's disease

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Kazuko Takahashi-Niki

2015-03-01

Full Text Available Parkinson's disease (PD is caused by dopaminergic cell death in the substantia nigra, leading to a reduced level of dopamine in the striatum. Oxidative stress is one of the causes of PD. Since symptomatic PD therapies are used, identification of compounds or proteins that inhibit oxidative stress-induced neuronal cell death is necessary. DJ-1 is a causative gene product of familial PD and plays a role in anti-oxidative stress reaction. We have identified various DJ-1-binding compounds, including compound-23, that restored neuronal cell death and locomotion defects observed in neurotoxin-induced PD models. In this study, wild-type and DJ-1-knockout mice were injected intraperitoneally with 1 mg/kg of compound-23 and then with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP at 1 h after injection. Five days after administration, the effects of compound-23 on MPTP-induced locomotion deficits, on dopaminergic cell death and on brain dopamine levels were analyzed by rotor rod tests, by staining cells with an anti-TH antibody and by an HPLC, respectively. The results showed that compound-23 inhibited MPTP-induced reduction of retention time on the rotor rod bar, neuronal cell death in the substantia nigra and striatum and dopamine content in wild-type mice but not in DJ-1-knockout mice, indicating a DJ-1-dependent effect of compound-23.

Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

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Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

2016-12-01

This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an alternative therapy for ovarian cancer in an octogenarian patient.

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Giger-Pabst, Urs; Solass, Wiebke; Buerkle, Bernd; Reymond, Marc-André; Tempfer, Clemens B

2015-04-01

Octogenarians with ovarian cancer limited to the abdomen may not be willing or able to undergo systemic chemotherapy. Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin is a form of intra-abdominal chemotherapy which can be applied repeatedly and potentially prevents from the systemic side-effects of chemotherapy. We present the case of an 84-year-old woman with laparoscopically and histologically confirmed ovarian cancer who refused to undergo systemic chemotherapy. She was treated with eight courses q 28-104 days of low-dose PIPAC with cisplatin at 7.5 mg/m(2) and doxorubicin at 1.5 mg/m(2) at 12 mmHg and 37 °C for 30 min. Objective tumor response was noted, defined as tumor regression on histology, and stable disease noted by peritoneal carcinomatosis index on repeated video-laparoscopy and abdominal computed tomographic scan. The treatment was well-tolerated with no Common Terminology Criteria for Adverse Events (CTCAE) CTCAE >2. With a follow-up of 15 months, the patient is alive and clinically stable. The quality of life measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 demonstrated improvement over 5-6 months (global physical score, global health score, global quality of live) without cumulative increase of gastrointestinal toxicity. Low-dose PIPAC is a new form of intraperitoneal chemotherapy which may be applied repeatedly in octogenarian patients. PIPAC may be an alternative and well-tolerated treatment for selected octogenarian patients with ovarian cancer limited to the abdomen who cannot be treated with systemic chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The effects of intraperitoneal administration of the GABA(B) receptor agonist baclofen on food intake in CFLP and C57BL/6 mice.

Science.gov (United States)

Ebenezer, Ivor S; Prabhaker, Monika

2007-08-13

The effects of the GABA(B) receptor agonist baclofen were investigated on food intake in non-deprived CFLP and C57BL/6 mice. In Experiment 1, baclofen (1-8 mg /kg) administered i.p. to CFLP mice, produced a dose-related increase in food intake. The 4 and 8 mg/kg doses produced significant increases in cumulative feeding when measure 120 min after administration (at least P GABA(B) agonist baclofen produces an increase in food consumption in two different strains of mice and extend previous observations made in rat to another rodent species.

Effects of the resin and smoke condensate of Cannabis sativa on the oestrous cycle of the rat

Energy Technology Data Exchange (ETDEWEB)

Lares, A; Ochoa, Y; Bolanos, A; Aponte, N; Montenegro, M

1981-01-01

This study is concerned with variations in the oestrous cycle of the Sprague-Dawley rat following the intraperitoneal administration of maize oil solutions of Cannabis sativa resin and smoke condensate in doses of 10 and 20 mg/kg. Oestrus was shortened with doses of both the resin and the smoke condensate, whereas dioestrus was lengthened with the 20 mg/kg smoke condensate. ALso observed was a lengthening of postoestrus following the administration of 20 mg/kg of either the resin or the smoke condensate.

Preventative and therapeutic effects of a GABA transporter 1 inhibitor administered systemically in a mouse model of paclitaxel-induced neuropathic pain

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Willias Masocha

2016-12-01

Full Text Available Background There is a dearth of drugs to manage a dose-limiting painful peripheral neuropathy induced by paclitaxel in some patients during the treatment of cancer. Gamma-aminobutyric acid transporter-1 (GAT-1 whose expression is increased in the brain and spinal cord during paclitaxel-induced neuropathic pain (PINP might be a potential therapeutic target for managing PINP. Thus, our aim was to evaluate if systemic administration of a GAT-1 inhibitor ameliorates PINP. Methods The reaction latency to thermal stimuli (hot plate test; at 55 °C and cold stimuli (cold plate test; at 4 °C of female BALB/c mice was recorded before and after intraperitoneal treatment with paclitaxel, its vehicle, and/or a selective GAT-1 inhibitor NO-711. The effects of NO-711 on motor coordination were evaluated using the rotarod test at a constant speed of 4 rpm or accelerating mode from 4 rpm to 40 rpm over 5 min. Results The coadministration of paclitaxel with NO-711 3 mg/kg prevented the development of paclitaxel-induced thermal hyperalgesia and cold allodynia at day 7 after drug treatment. NO-711 at 3 mg/kg produced antihyperalgesic activity up to 1 h and antiallodynic activity up to 2 h in mice with established paclitaxel-induced thermal hyperalgesia and cold allodynia. No motor deficits were observed with NO-711 at a dose of 3 mg/kg, whereas a higher dose 5 mg/kg caused motor impairment and reduced mean time spent on the rotarod at a constant speed of 4 rpm. However, at a rotarod accelerating mode from 4 rpm to 40 rpm over 5 min, NO-711 3 mg/kg caused motor impairment up to 1 h, but had recovered by 2 h. Conclusions These results show that systemic administration of the GAT-1 inhibitor NO-711 has preventative and therapeutic activity against paclitaxel-induced thermal hyperalgesia and cold allodynia. NO-711’s antiallodynic effects, but not antihyperalgesic effects, were independent of its motor impairment/sedation properties. Thus, low doses of GAT-1

Efecto del adyuvante vacunal AFCo1 intranasal sobre la concentración plasmática de teofilina en ratas Effect of intranasal vaccine adjuvant AFCo1 on plasma concentration of theophylline in rats

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Alexander Batista Duharte

2012-08-01

Full Text Available En este estudio se evaluó el efecto del adyuvante Finlay cocleato 1 (AFCo1, aplicado 4 veces por vía intranasal en 2 niveles de dosis (50 µg y 100 µg sobre la concentración plasmática de teofilina, administrada a las 24 horas de la última aplicación (5 mg/kg, por vía intraperitoneal en ratas Sprague-Dawley. Se empleó como control positivo de inflamación la aplicación de 2 dosis por vía subcutánea de adyuvante completo de Freund (ACF. Las ratas que recibieron AFCo1 no mostraron cambios significativos en la concentración sérica de teofilina; mientras que las tratadas con ACF desarrollaron inflamación local asociadas a signos de toxicidad a la teofilina y elevación de las cifras de inmunoglobulina G específica, de las concentraciones plasmáticas y el tiempo de vida media de teofilina en suero, en comparación con los grupos restantes. Estos resultados indican que la inmunoestimulación inducida por AFCo1 intranasal no incrementa los parámetros farmacocinéticos ni la toxicidad de la teofilina en el modelo empleado.The effect of the adjuvant Finlay cochleate1 (AFCo1, applied intranasally 4 times in 2 dose levels (50 µg and 100 µg on plasma concentration of theophylline administered 24 hours after the last application (5 mg/kg intraperitoneally in Sprague-Dawley rats was evaluated in this study. Application subcutaneously of 2 doses of Freund's complete adjuvant (FCA was used as positive control of inflammation. Rats receiving AFCo1 had no significant changes in serum theophylline concentration, while those treated with FCA developed local inflammation associated with signs of theophylline toxicity and increased specific G immunoglobulin, plasma concentrations and serum theophylline half-life as compared with the remaining groups. These results show that intranasal AFCo1-induced immunostimulation does not increase pharmacokinetic parameters and theophylline toxicity in the model used.

Timing of hypertonic glucose and thermochemotherapy with 1-(4-amino-2-methylpyrimidine-5-yl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in the BT4An rat glioma: relation to intratumoral pH reduction and circulatory changes after glucose supply

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Schem, Baard-Christian; Roszinski, Stefan; Krossnes, Baard Kronen; Mella, Olav

1995-01-01

Purpose: Intraperitoneal hypertonic glucose has previously been shown to induce hyperglycemia, hemoconcentration, and to influence systemic and tumor circulation, and, thus, enhance the effect of thermochemotherapy with 1-(4-amino-2-methylpyrimidine-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). However, the optimal timing and the precise mechanisms responsible are not known. The effect of different time intervals between glucose load and thermochemotherapy with ACNU in the treatment of BT 4 An tumors, therefore, was investigated. Changes of serum glucose (Se-glucose), hemoglobin, systemic circulation parameters, tumor pH, and tumor temperature, induced by intraperitoneal glucose and/or hyperthermia, were measured to assess their effect on tumor growth. Methods and Materials: (a): Inbred BD IX rats with BT 4 An tumors on the hind leg were treated with ACNU 7 mg/kg intravenously just before waterbath hyperthermia, and intraperitoneal hypertonic glucose (6 g/kg) at different time intervals before (240-0 min) or immediately after thermochemotherapy. (b): Intratumoral pH and temperature were measured at different intervals after intraperitoneal glucose, and during hyperthermia with or without previous glucose. (c): Hemoglobin, hematocrit, and Se-glucose were measured at different times after intraperitoneal glucose. (d): Mean arterial pressure, pulse pressure, and heart rate were measured for 120 min after intraperitoneal glucose. Results: (a): The number of tumor controls and the growth delay was greatest with glucose 45 min before thermochemotherapy, and least with a time interval of 240 min. Glucose after thermochemotherapy delayed tumor growth. (b): After intraperitoneal glucose alone, intratumoral pH decreased gradually from 6.76 to 5.86 after 240 min. Hyperthermia 120 min after glucose induced a rapid further pH drop, while hyperthermia alone had no significant influence on pH. Intratumoral temperature was

Protective Effect of Coenzyme Q10 on Methamphetamine-Induced Apoptosis in Adult Male Rats

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Fatemeh Gholipour

2017-06-01

Full Text Available Background: The negative consequence of methamphetamine abuse is due to neuropathologic changes in the brain, which reduces dopaminergic neurons and result in damage to different brain areas. Neurotoxicity induced by methamphetamine increases the oxidative stress and associated with neuronal apoptosis. The role of the antioxidant coenzyme Q10 probably produces its neuroprotective effects. Therefore, the purpose of the present study was to examine the protective effect of coenzyme Q10 on methamphetamine-induced apoptosis in adult male rats.Materials and Methods: Fifty Wistar eight-week adult rats randomly divided into 5 groups: Healthy control, methamphetamine injection (Meth, methamphetamine injection and CoQ10 5mg/kg treatment (Meth+Post CoQ10 5mg/kg, methamphetamine injection and CoQ10 10mg/kg treatment (Meth+Post CoQ10 10mg/kg, methamphetamine injection and CoQ10 20mg/kg treatment (Meth+Post CoQ10 20mg/kg. Methamphetamine with a purity of 96% with a dosage of 20 mg/kg was injected Intraperitoneal. Coenzyme Q10 for three treatment groups was injected intraperitoneally for 14 days in a dosage of 5, 10 and 20 mg/kg/day. The protein expressions of Baxand Bcl2 were evaluated by western blotting technique.Results: Bax protein expression was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.010 and so Meth+Post CoQ10 10mg/kg (p=0.004 comparing to Meth group. In addition, Bcl2 protein expression was significantly higher in Meth+Post CoQ10 5mg/kg comparing to Meth group (p=0.018. However, there were no significant differences between control and CoQ10 treatment groups. Bax/Bcl2 ratio was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.005, Meth+Post CoQ10 10mg/kg (p=0.008 and Meth+Post CoQ10 20mg/kg (p=0.044 comparing to Meth group.Conclusion: We suggest that CoQ10 reduces the methamphetamine-induced apoptosis in the striatum of the rats through the reduction of apoptotic factors and increase of anti-apoptotic pathways.

Effect of corn silk extract on acetaminophen induced renal damage in mice

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Mehboob, F.; Tahir, M.

2015-01-01

To evaluate the protective role of Corn Silk extract on Acetaminophen induced nephrotoxicity in albino mice. Study Design: Laboratory based randomized controlled trials. Place and Duration of Study: The study was carried out in experimental research laboratory University of Health Sciences and Anatomy department, Lahore. The study duration was one year from February 2012 to February 2013. Material and Methods: Twenty seven male albino mice, 6-8 weeks old weighing 30 + 5 gm, were used; these animals were randomly divided into three groups having nine mice in each group. Group A served as control and was given 16.6ml/kg normal saline intraperitoneally on first day of experiment and was sacrificed on 10th day of the experiment. Group B was treated with acetaminophen 600 mg/kg dissolved in 16.6 ml of normal saline intraperitoneally on 1st day of experiment and was sacrificed after 48 hours. Group C was given acetaminophen at a dose of 600 mg/kg intraperitoneally on first day of experiment and then corn silk extract was given by oral route at a dose of 400 mg/kg for next 8 days. The animals were sacrificed on 10th day of the experiment, the kidneys were removed; 3mm three tissue pieces were fixed in 10% formaline; processed and stained with H and E for histological study. Results: It was observed on microscopic examination that Corn silk extract reduced deleterious effects of acetaminophen on tubules of kidney as evidenced by reduction of tubular vacuolation and necrosis, absence of protein casts, vascular congestion and inflammation. Conclusion: It is concluded from current results that corn silk extract protects acetaminophen induced nephrotoxicity. (author)

The radiosensitizing effects of ornidazole in hypoxic mammalian tissue: an in vivo study

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Okkan, S.; Uzel, R.

1982-01-01

In this study the sensitizing effects of ornidazole is investigated in vivo. The selected test system is the acute killing effect of radiation within 4-6 days after abdominal irradiation ranging from 9 to 24 Gy, in groups of C 57 black mice. Ornidazole is given intraperitoneally in 500 mg/kg, 100 mg/kg, 20 mg/kg doses prior to irradiation of animals breathing air, oxygen or nitrogen. A decreae of LD 50 dose is observed from 24.39 +/- 5.66 to 16.38 +/- 1.86 and 18.04 +/- 2.48 Gy, respectively, in nitrogen breathing animals. No sensitizing effect was observed in doses of 20 mg/kg. Enhancement Ratio (ER) was found to be 1.48 +/- 0.25 and 1.35 +/- 0.27; relative sensitizing efficiency (RSE) was 40% and 29% respectively. No sensitizing effect was observed in animals irradiated in oxic conditions. These results showed that ornidazole (Ro-7-0207) has a sensitizing effect on hypoxic cells in vivo. It is worthwhile to try this drug in a clinical study

Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

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Soman, A; Honeybourne, D; Andrews, J; Jevons, G; Wise, R

1999-12-01

The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

Antidiabetic activity of medium-polar extract from the leaves of Stevia rebaudiana Bert. (Bertoni) on alloxan-induced diabetic rats

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Misra, Himanshu; Soni, Manish; Silawat, Narendra; Mehta, Darshana; Mehta, B. K.; Jain, D. C.

2011-01-01

Objective: To investigate the medicative effects of medium-polar (benzene:acetone, 1:1, v/v) extract of leaves from Stevia rebaudiana (family Asteraceae) on alloxan-induced diabetic rats. Materials and Methods: Diabetes was induced in adult albino Wistar rats by intraperitoneal (i.p.) injection of alloxan (180 mg/kg). Medium-polar extract was administered orally at daily dose of 200 and 400 mg/kg body wt. basis for 10 days. The control group received normal saline (0.9%) for the same duration. Glibenclamide was used as positive control reference drug against Stevia extract. Results: Medium-polar leaf extract of S. rebaudiana (200 and 400 mg/kg) produced a delayed but significant (P Stevia extract was found to antagonize the necrotic action of alloxan and thus had a re-vitalizing effect on β-cells of pancreas. PMID:21687353

Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy.

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Speyer, J L; Beller, U; Colombo, N; Sorich, J; Wernz, J C; Hochster, H; Green, M; Porges, R; Muggia, F M; Canetta, R

1990-08-01

From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy.

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

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Chen, Xia; Sun, Chang-Kai; Han, Guo-Zhu; Peng, Jin-Yong; Li, Ying; Liu, Yan-Xia; Lv, Yuan-Yuan; Liu, Ke-Xin; Zhou, Qin; Sun, Hui-Jun

2009-04-21

To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice. Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner. TP possess potential hepatoprotective properties and can suppress CYP450 expression.

Neuropharmacological profile and chemical analysis of fresh rhizome essential oil of Curcuma longa (turmeric) cultivated in Southwest Nigeria.

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Oyemitan, Idris A; Elusiyan, Christianah A; Onifade, Ayoola O; Akanmu, Moses A; Oyedeji, Adebola O; McDonald, Armando G

2017-01-01

Curcuma longa (turmeric) is commonly used as spice and also used to treat fever, cough and febrile convulsions in Nigeria. This study determined the chemical composition of the essential oil of C. longa and evaluated its neuropharmacological activity in mice. Essential oil of C. longa (EOCL) fresh rhizome was obtained by hydrodistillation and its chemical composition determined by GC-MS. Acute toxicity (LD 50 ) profile of the essential oil was determined orally (p.o.) and intraperitoneally (i.p.); and the EOCL (50-200 mg/kg, i.p.) was evaluated for its behavioural, anxiolytic, sedative and anticonvulsant activities using appropriate models in Albino mice (Vom Strain, Jos, Nigeria). Analysis of the oil showed the presence of 23 compounds with turmerone (35.9%) being the major component. The LD 50 values obtained for the mice were 2154 mg/kg, p.o., and 693 mg/kg, i.p. The EOCL (50-200 mg/kg, i.p.) caused significant (p longa species was turmerone; the oil was slightly toxic orally but moderately toxic intraperitoneally in mice; exhibited significant anxiolytic, sedative and anticonvulsant activities in mice.

Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy in Combination with Intravenous Chemotherapy as Postoperative Adjuvant Therapy for Advanced Gastric Cancer.

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Wu, Zhibing; Ma, Shenglin; Jing, Saisai; Deng, Qinghua; Zheng, Zhishuang; Wu, Kan; Li, Juan; Chen, Sumei; Tang, Rongjun; Li, Xiadong

2014-06-01

The aim is to evaluate the preliminary efficacy and side effects of paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) as postoperative adjuvant therapy for patients of locally advanced gastric cancer (GC) at high risk for recurrence after curative resection. Four GC patients who underwent radical gastrectomy with D2 lymphadenectomy were enrolled. All patients received paclitaxel 135 mg/m2 on day 1, 5-FU 500 mg/m2 on days 1-5, LV 200 mg/m2 on days 1-5 intravenous chemotherapy, cisplatin 75 mg/m2 on day 5, and HIPEC one month after surgery. It was repeated at 3 weeks intervals and at least two cycles administered. A total of 181 cycles of chemotherapy were administered (median, 4 cycles). The median disease free survival time of patients was 40.8 months. The median overall survival time was 48.0 months. The one-, two-, and three-year recurrence rates were 14.6%, 26.8%, and 46.3%, respectively. The main relapse patterns were remnant GC and metastases of retroperitoneal lymph nodes. The morbidity of grade 3 and 4 toxicities of myelosuppression, nausea/ vomiting were less than 10%. The side effects of grade 1 and 2 of hematologic toxicity, nausea and vomiting, abnormal function of liver, kidney or cardiac, fatigue and neurotoxicity were well tolerated. Cisplatin HIPEC combined with paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy regimen could improve the survival rate and decrease the postoperative recurrence of locally advanced GC.

Interaction between harmane, a class of β-carboline alkaloids, and the CA1 serotonergic system in modulation of memory acquisition.

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Nasehi, Mohammad; Ghadimi, Fatemeh; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2017-09-01

This study set to assess the involvement of dorsal hippocampus (CA1) serotonergic system on harmane induced memory acquisition deficit. We used one trial step-down inhibitory avoidancetask to evaluate memory retention and then, open field test to evaluate locomotor activity in adult male NMRI mice. The results showed that pre-training intra-peritoneal (i.p.) administration of harmane (12mg/kg) induced impairment of memory acquisition. Pre-training intra-CA1 administration of 5-HT1B/1D receptor agonist (CP94253; 0.5 and 5ng/mouse) and 5-HT2A/2B/2C receptor agonist (α-methyl 5-HT; 50ng/mouse) impaired memory acquisition. Furthermore, intra-CA1 administration of 5-HT1B/1D receptor antagonist (GR127935; 0.5ng/mouse) and 5-HT2 receptor antagonist (cinancerine; 5ng/mouse) improved memory acquisition. In addition, pre-training intra-CA1 injection of sub-threshold dose of CP94253 (0.05ng/mouse) and α-methyl 5-HT (5ng/mouse) potentiated impairment of memory acquisition induced by harmane (12mg/kg, i.p.). On the other hand, pre-training intra-CA1 infusion of sub-threshold dose of GR127935 (0.05ng/mouse) and cinancerine (0.5ng/mouse) with the administration of harmane (12mg/kg, i.p.) weakened impairment of memory acquisition. Moreover, all above doses of drugs did not change locomotor activity. The present findings suggest that there is an interaction between harmane and the CA1 serotonergic system in modulation of memory acquisition. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Mifepristone 5 mg versus 10 mg for emergency contraception: double-blind randomized clinical trial

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Carbonell JL

2015-01-01

Full Text Available Josep Lluis Carbonell,1 Ramon Garcia,2 Adriana Gonzalez,2 Andres Breto,2 Carlos Sanchez2 1Mediterranea Medica Clinic, Valencia, Spain; 2Eusebio Hernandez Gynecology and Obstetrics Teaching Hospital, Havana, Cuba Purpose: To estimate the efficacy and safety of 5 mg and 10 mg mifepristone for emergency contraception up to 144 hours after unprotected coitus. Methods: This double-blind randomized clinical trial was carried out at Eusebio Hernandez Hospital (Havana, Cuba. A total of 2,418 women who requested emergency contraception after unprotected coitus received either 5 mg or 10 mg mifepristone. The variables for assessing efficacy were the pregnancies that occurred and the fraction of pregnancies that were prevented. Other variables assessed were the side effects of mifepristone, vaginal bleeding, and changes in the date of the following menstruation. Results: There were 15/1,206 (1.2% and 9/1,212 (0.7% pregnancies in the 5 mg and 10 mg group, respectively (P=0.107. There were 88% and 93% prevented pregnancies in the 5 mg and 10 mg group, respectively. The side effect profiles were similar in both groups. Delayed menstruation ≥7 days was experienced by 4.9% and 11.0% of subjects in the 5 mg and 10 mg group, respectively (P=0.001. There was a significant high failure rate for women weighing >75 kg in the 5 mg group. Conclusion: It would be advisable to use the 10 mg dose of mifepristone for emergency contraception as there was a trend suggesting that the failure rate of the larger dose was lower. Keywords: mifepristone, emergency contraception

In vitro and in vivo antitrypanosomal activity of Xanthium strumarium leaves.

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Talakal, T S; Dwivedi, S K; Sharma, S R

1995-12-15

Antitrypanosomal activity of crude 50% ethanolic extract of Xanthium strumarium leaves was studied in vitro and in vivo. The extract exhibited trypanocidal activity at all four concentrations tested i.e. 5, 50, 500 and 1000 micrograms/ml, in vitro. In vivo trial revealed that the extract exerted antitrypanosomal effect at dosage of 100, 300 and 1000 mg/kg, intraperitoneally. At 100 and 300 mg/kg doses the survival period of the Trypanosoma evansi infected mice was significantly prolonged. However, the extract was found to be toxic to the animals at 1000 mg/kg dose.

Anticonvulsant activity of bioflavonoid gossypin

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Srinivasan Duraisamy

2009-06-01

Full Text Available The anticonvulsant activity of gossypin was investigated by studying the effects on seizures induced by pentelentetrazole, strychnine and maximal electroshock convulsive methods in mice. Gossypin (10 and 20 mg/kg significantly reduced the duration of convulsion in tonic seizure induced by pentelenetetrazole (95 mg/kg, intraperitoneally. Gossypin (20 mg/kg p.o significantly reduced the tonic extensor convulsion induced by strychnine and maximum electroshock-induced convulsions. The data obtained suggest that gossypin have anticonvulsant property and may probably be affecting both GABA aminergic and glycine inhibitory mechanism.

Anticonvulsant activity of bioflavonoid gossypin

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Duraisami Rasilingam

2009-03-01

Full Text Available The anticonvulsant activity of gossypin was investigated by studying the effects on seizures induced by pentelentetrazole, strychnine and maximal electroshock convulsive methods in mice. Gossypin (10 and 20 mg/kg significantly reduced the duration of convulsion in tonic seizure induced by pentelenetetrazole (95 mg/kg, intraperitoneally. Gossypin (20 mg/kg p.o significantly reduced the tonic extensor convulsion induced by strychnine and maximum electroshock-induced convulsions. The data obtained suggest that gossypin have anticonvulsant property and may probably be affecting both GABA aminergic and glycine inhibitory mechanism.

Protective effect of porphyran isolated from discolored nori (Porphyra yezoensis) on lipopolysaccharide-induced endotoxin shock in mice.

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Nishiguchi, Tomoki; Cho, Kichul; Isaka, Shogo; Ueno, Mikinori; Jin, Jun-O; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

2016-12-01

Porphyran, a sulfated polysaccharide, isolated from discolored nori (Porphyra yezoensis) (dc-porphyran) and one fraction (F1) purified from dc-porphyran by DEAE-chromatography showed the protective effects on LPS-induced endotoxin shock in mice. Intraperitoneal (i.p.) treatment with dc-porphyran or F1 (100mg/kg) 60min prior to i.p. injection of LPS (30mg/kg) completely protected mice from LPS lethality. At 10mg/kg concentration, F1 demonstrated more protection than dc-porphyran. Intravenous (i.v.) challenge of LPS, even at 20mg/kg, was more lethal than i.p. administration; i.v. injection of F1 (100mg/kg) with LPS significantly improved the survival rate. However, i.v. dc-porphyran (100mg/kg) produced an even lower survival rate than that of LPS alone. We examined pro-inflammatory mediators such as NO and TNF-α in serum. F1 significantly reduced the levels of these markers. Additionally, F1 significantly decreased the malondialdehyde level in the liver, a marker of oxidative stress, while dc-porphyran had almost no effect. Furthermore, F1 significantly decreased the production of TNF-α and NO in peritoneal exudate cells harvested from LPS-challenged mice, while dc-porphyran treatment showed a lesser decrease. Our results suggest that porphyran isolated from discolored nori, especially F1, is capable of suppressing LPS-induced endotoxin shock in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

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Yutaka Yonemura

2012-01-01

Full Text Available Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m2 of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m2 of Taxotere and 30 mg/m2 of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69% patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8% patients. Stage migration was experienced in 12 patients (14.6%. Complete cytoreduction was achieved in 58 patients (70.7%. By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI≤6, which are supposed to be removed completely by peritonectomy.

Naltrexone potentiates 4-aminopyridine seizures in the rat.

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Mihály, A; Bencsik, K; Solymosi, T

1990-01-01

The effects of a pharmacological blockade of the mu opiate receptors on the manifestation of tonic-clonic seizures were investigated in freely moving animals. 4-aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult rats with 1 mg/kg naltrexone HCl, 3, 5, 7, 9, 14 mg/kg 4-aminopyridine was injected intraperitoneally, and the latencies of the symptoms generated by 4-aminopyridine were measured. Naltrexone HCl decreased these latencies and enhanced the seizures significantly. The experiments provided further evidence for the existence of a tonic anticonvulsant opioid system in the brain.

The effects of thiamin on lead metabolism: organ distribution of lead 203.

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Kim, J S; Hamilton, D L; Blakley, B R; Rousseaux, C G

1992-01-01

The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi lead 203. They were treated with either thiamin (25 or 50 mg/kg body weight), calcium ethylenediaminetetraacetic acid (CaEDTA) (50 mg/kg body weight), or combinations of thiamin and CaEDTA. The whole body retention and the organ distribution of lead 203 varied depending upon the route of lead administration, dose of thiamin and the specific treatment combination. Thiamin (25 or 50 mg/kg) treatment increased the whole body retention of both intragastric and intraperitoneal lead by approximately 10% in each instance. Calcium ethylenediaminetetraacetic acid, either alone or in combination with thiamin (50 mg/kg) reduced the whole body retention of lead by as much as 14% regardless of route of lead exposure. The relative retention of lead by the liver, kidney and spleen was greater in mice exposed to lead by the intragastric route. Regardless of route, CaEDTA in the combined treatment reduced the relative retention of lead in both the liver and kidney, whereas thiamin alone only reduced the retention of lead in the kidney. The results of this study indicate that thiamin in combination with CaEDTA alters the distribution and retention of lead in a manner which may have therapeutic application as it relates to chelation therapy. PMID:1423063

Uric acid and allopurinol aggravate absence epileptic activity in Wistar Albino Glaxo Rijswijk rats.

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Lakatos, Renáta Krisztina; Dobolyi, Árpád; Kovács, Zsolt

2018-05-01

Uric acid has a role in several physiological and pathophysiological processes. For example, uric acid may facilitate seizure generalization while reducing uric acid level may evoke anticonvulsant/antiepileptic effects. Allopurinol blocks the activity of xanthine oxidase, by which allopurinol inhibits catabolism of hypoxanthine to xanthine and uric acid and, as a consequence, decreases the level of uric acid. Although the modulation of serum uric acid level is a widely used strategy in the treatment of certain diseases, our knowledge regarding the effects of uric acid on epileptic activity is far from complete. Thus, the main aim of this study was the investigation of the effect of uric acid on absence epileptic seizures (spike-wave discharges: SWDs) in a model of human absence epilepsy, the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. We investigated the influence of intraperitoneally (i.p.) injected uric acid (100 mg/kg and 200 mg/kg), allopurinol (50 mg/kg and 100 mg/kg), a cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitor indomethacin (10 mg/kg) and inosine (500 mg/kg) alone and the combined application of allopurinol (50 mg/kg) with uric acid (100 mg/kg) or inosine (500 mg/kg) as well as indomethacin (10 mg/kg) with uric acid (100 mg/kg) and inosine (500 mg/kg) with uric acid (100 mg/kg) on absence epileptic activity. We demonstrated that both uric acid and allopurinol alone significantly increased the number of SWDs whereas indomethacin abolished the uric acid-evoked increase in SWD number. Our results suggest that uric acid and allopurinol have proepileptic effects in WAG/Rij rats. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of near-infrared fluorescence conjugation on the anti-cancer potential of cetuximab.

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Yun, Ji Young; Hyun, Byung-Hwa; Nam, Sang Yoon; Yun, Young Won; Lee, Hu-Jang; Lee, Beom-Jun

2018-03-01

This study investigated the anti-cancer potential of a near-infrared fluorescence (NIRF) molecule conjugated with Cetuximab (Cetuximab-NIRF) in six-week-old female BALB/c athymic (nu+/nu+) nude mice. A431 cells were cultured and injected into the animals to induce solid tumors. Paclitaxel (30 mg/kg body weight (BW)), Cetuximab (1 mg/kg BW), and Cetuximab-NIRF (0.25, 0.5 and 1.0 mg/kg BW) were intraperitoneally injected twice a week into the A431 cell xenografts of the nude mice. Changes in BW, tumor volume and weight, fat and lean mass, and diameter of the peri-tumoral blood vessel were determined after two weeks. Tumor volumes and weights were significantly decreased in the Cetuximab-NIRF (1 mg/kg BW) group compared with the control group ( P <0.001). Lean mass and total body water content were also conspicuously reduced in the Cetuximab-NIRF (1 mg/kg BW) group compared with the vehicle control group. Peri-tumoral blood vessel diameters were very thin in the Cetuximab-NIRF groups compared with those of the paclitaxel group. These results indicate that the conjugation of Cetuximab with NIRF does not affect the anti-cancer potential of Cetuximab and NIRF can be used for molecular imaging in cancer treatments.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

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Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

2017-12-11

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

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A. Caires

2017-12-01

Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

The stimulatory effects of caffeine with oseltamivir (Tamiflu) on light-dark behavior and open-field behavior in mice.

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Uchiyama, Hidemori; Toda, Akihisa; Imoto, Masumi; Nishimura, Satoko; Kuroki, Hiroaki; Soeda, Shinji; Shimeno, Hiroshi; Watanabe, Shigenori; Eyanagi, Reiko

2010-01-22

Abnormal behaviors and death associated with the use of oseltamivir (Tamiflu) have emerged as a major issue in influenza patients taking the drug. Here, we investigated the mechanisms underlying the effects of oseltamivir on the behavior of mice using light-dark and open-field preference tests. Oseltamivir (75 and 150 mg/kg, intraperitoneally (i.p.)) alone affected neither time spent in the open area in the light-dark preference test nor ambulation in the open-field test at 2h post-injection. However, a non-selective adenosine A(1)/A(2) receptor antagonist, caffeine (10mg/kg, i.p.) in combination with oseltamivir (150 mg/kg, i.p.) increased time spent in the open area in the light-dark preference test. This enhancement was not inhibited by a benzodiazepine receptor antagonist, flumazenil (10-20mg/kg, subcutaneously (s.c.)). Enhancement of ambulation in the open-field test was also observed when caffeine (10mg/kg, i.p.) was combined with oseltamivir (150 mg/kg, i.p.). This enhancement was inhibited by a dopamine D(2) receptor antagonist, haloperidol (0.1mg/kg, s.c.). Furthermore, an adenosine A(2) receptor antagonist, SCH58261 (3mg/kg, i.p.) in combination with oseltamivir (150 mg/kg, i.p.) increased ambulation in the open-field test, while an adenosine A(1) receptor antagonist, DPCPX (1-3mg/kg, i.p.) did not. These findings suggest that the actions of oseltamivir may involve the dopamine and adenosine systems. Our findings suggest that due to the interaction between central blockade of adenosine A(2) receptors by caffeine, and oseltamivir-induced behavioral changes, patients being treated with oseltamivir should be closely monitored. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Transcriptomic responses of European flounder (Platichthys flesus) to model toxicants

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Williams, Tim D. [School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)], E-mail: t.d.williams@bham.ac.uk; Diab, Amer [Institute of Aquaculture, University of Stirling, Stirling, Scotland FK9 4LA (United Kingdom); Ortega, Fernando [School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Sabine, Victoria S. [Institute of Aquaculture, University of Stirling, Stirling, Scotland FK9 4LA (United Kingdom); Godfrey, Rita E.; Falciani, Francesco; Chipman, J. Kevin [School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); George, Stephen G. [Institute of Aquaculture, University of Stirling, Stirling, Scotland FK9 4LA (United Kingdom)

2008-11-11

The temporal transcriptomic responses in liver of Platichthys flesus to model environmental pollutants were studied over a 16-day time span after intraperitoneal injection with cadmium chloride (50 {mu}g/kg in saline), 3-methylcholanthrene (25 mg/kg in olive oil), Aroclor 1254 (50 mg/kg in olive oil), tert-butyl-hydroperoxide (5 mg/kg in saline), Lindane (25 mg/kg in olive oil), perfluoro-octanoic acid (100 mg/kg in olive oil) and their vehicles, olive oil (1 ml/kg) or saline (0.9%). Statistical, gene ontology and supervised analysis clearly demonstrated the progression from acute effects, biological responses to and recovery from the treatments. Key biological processes disturbed by the individual treatments were characterised by gene ontology analyses and individual toxicant-responsive genes and pathways were identified by supervised analyses. Responses to the polyaromatic and chlorinated aromatic compounds showed a degree of commonality but were distinguishable and they were clearly segregated from the responses to the pro-oxidants cadmium and the organic hydroperoxide, as well as from the peroxisomal proliferator, perfluoro-octanoic acid. This study demonstrated the utility of the microarray technique in the identification of toxicant-responsive genes and in discrimination between modes of toxicant action.

Transcriptomic responses of European flounder (Platichthys flesus) to model toxicants

International Nuclear Information System (INIS)

Williams, Tim D.; Diab, Amer; Ortega, Fernando; Sabine, Victoria S.; Godfrey, Rita E.; Falciani, Francesco; Chipman, J. Kevin; George, Stephen G.

2008-01-01

The temporal transcriptomic responses in liver of Platichthys flesus to model environmental pollutants were studied over a 16-day time span after intraperitoneal injection with cadmium chloride (50 μg/kg in saline), 3-methylcholanthrene (25 mg/kg in olive oil), Aroclor 1254 (50 mg/kg in olive oil), tert-butyl-hydroperoxide (5 mg/kg in saline), Lindane (25 mg/kg in olive oil), perfluoro-octanoic acid (100 mg/kg in olive oil) and their vehicles, olive oil (1 ml/kg) or saline (0.9%). Statistical, gene ontology and supervised analysis clearly demonstrated the progression from acute effects, biological responses to and recovery from the treatments. Key biological processes disturbed by the individual treatments were characterised by gene ontology analyses and individual toxicant-responsive genes and pathways were identified by supervised analyses. Responses to the polyaromatic and chlorinated aromatic compounds showed a degree of commonality but were distinguishable and they were clearly segregated from the responses to the pro-oxidants cadmium and the organic hydroperoxide, as well as from the peroxisomal proliferator, perfluoro-octanoic acid. This study demonstrated the utility of the microarray technique in the identification of toxicant-responsive genes and in discrimination between modes of toxicant action

The protective effect of Sambucus ebulus against lung toxicity induced by gamma irradiation in mice

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Mohammad Karami

2015-01-01

Full Text Available The aim of present study was to investigate the potential antioxidant and lung protective activities of Sambucus ebulus (SE against toxicity induced by gamma irradiation. Hydroalcoholic extract of SE (20, 50 and 100 mg/kg was studied for its lung protective activity. Phenol and flavonoid contents of SE were determined. Male C57 mice were divided into ten groups with five mice per group. Only the first and second groups (as negative control received intraperitoneally normal saline fluid. Groups 3 to 5 received only SE extract at doses of 20 mg/kg, 50 mg/kg and 100 mg/kg intraperitoneally; three groups were repeatedly injected for 15 days as chronic group. Groups 6 to 8 received a single-dose of gamma irradiation just 2 hours before irradiation as acute group. The ninth and tenth groups (as positive control received only gamma rays. Animal was exposed whole-body to 6 Gy gamma radiation. After irradiation, tissue sections of lung parenchyma were examined by light microscope for any histopathologic changes. SE at doses 50 and 100 mg/kg improved markedly histopathological changes induced by gamma irradiation in lung. Lung protective effect of SE could be due to attention of lipid peroxidation. Our study demonstrated that SE as a natural product has a protective effect against lung toxicity induced by   gamma irradiation in animal.

Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

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Woźny, Maciej, E-mail: maciej.wozny@uwm.edu.pl [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland); Lewczuk, Bogdan; Ziółkowska, Natalia [Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 13, 10-713 Olsztyn (Poland); Gomułka, Piotr [Department of Ichthyology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 5, 10-719 Olsztyn (Poland); Dobosz, Stefan [Department of the Salmonid Research in Rutki, Inland Fisheries Institute in Olsztyn, Rutki, 83-330 Żukowo (Poland); Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland)

2016-12-15

To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg{sup −1}) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg{sup −1}) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

Plants used in Guatemala for the treatment of protozoal infections. I. Screening of activity to bacteria, fungi and American trypanosomes of 13 native plants.

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Cáceres, A; López, B; González, S; Berger, I; Tada, I; Maki, J

1998-10-01

Extracts were prepared from 13 native plants used for the treatment of protozoal infections. Activity against bacteria and fungi was demonstrated by dilution procedures; Trypanosoma cruzi was evaluated in vitro against epimastigote and trypomastigotes and in vivo against trypomastigotes. In active extracts, toxicity was evaluated by Artemia salina nauplii, oral acute toxicity (1-5 g/kg) and oral and intraperitoneal subacute toxicity in mice (500 mg/kg). From the plants screened, six showed activity (Neurolaena lobata and Solanum americanum; in vitro or in vivo activity was shown by Acalypha guatemalensis, Petiveria alliacea and Tridax procumbens. Toxicity studies showed that extracts from S. americanum are toxic to A. salina (aqueous, 160 ppm). None showed acute or oral toxicity to mice; S. americanum showed intraperitoneal subacute toxicity.

Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation.

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Mouro, Francisco M; Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Baqi, Younis; Müller, Christa E; Lopes, Luísa V; Ribeiro, Joaquim A; Sebastião, Ana M

2017-05-01

Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes of Tc-99m sestamibi uptake in P-glycoprotein expressing leukaemia cells treated in vivo with antisense oligodeoxynucleotide complementary to mdr1 mRNA

International Nuclear Information System (INIS)

Kinuya, S.; Yokoyama, K; Fukuoka, M.; Michigishi, T.; Tonami, N.; Shiba, K.; Mori, H.; Watanabe, N.; Shuke, N.

2006-01-01

We examined the feasibility of Tc-99m sestamibi to monitor changes of mRNA expression of MDRl/P-glycoprotein (Pgp) following antisense oligodeoxynucleotide (AS-ODN) treatment in vivo. Three days after the intraperitoneal inoculation of murine leukaemia P388/R cells expressing MDR1/P-gp in CDFI mice, 15-mer phosphorothioate ASODN to the initiation codon of mouse mdr1 mRNA was administered intraperitoneally at 10 mg/kg daily for 3 or 4 days. Cells collected from ascites were suspended in medium for Tc-99m sestamibi uptake studies. To know the duration of antisense effects, cells were harvested 2 days later after the 3-day treatment. AS-ODN treatment increased Tc-99m sestamibi uptake. Effects of 3-day treatment and 4-day treatment were the same. Treatment effects were not detected when uptake was observed 2 days after 3-day treatment. Based on the results it was concluded that in vivo treatment with AS-ODN specific to the coding portion of mdr1 mRNA increased Tc-99m sestamibi uptake in leukaemia cells possessing MDR function. (author)

Hypocretin/orexin signaling in the hypothalamic paraventricular nucleus is essential for the expression of nicotine withdrawal.

Science.gov (United States)

Plaza-Zabala, Ainhoa; Flores, África; Maldonado, Rafael; Berrendero, Fernando

2012-02-01

Hypocretin (orexin) signaling is involved in drug addiction. In this study, we investigated the role of these hypothalamic neuropeptides in nicotine withdrawal by using behavioral and neuroanatomical approaches. Nicotine withdrawal syndrome was precipitated by mecamylamine (2 mg/kg, subcutaneous) in C57BL/6J nicotine-dependent mice (25 mg/kg/day for 14 days) pretreated with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 (5 and 10 mg/kg, intraperitoneal), the hypocretin receptor 2 antagonist TCSOX229 (5 and 10 mg/kg, intraperitoneal), and in preprohypocretin knockout mice. c-Fos expression was analyzed in several brain areas related to nicotine dependence by immunofluorescence techniques. Retrograde tracing with rhodamine-labeled fluorescent latex microspheres was used to determine whether the hypocretin neurons project directly to the paraventricular nucleus of the hypothalamus (PVN), and SB334867 was locally administered intra-PVN (10 nmol/side) to test the specific involvement of Hcrtr-1 in this brain area during nicotine withdrawal. Somatic signs of nicotine withdrawal were attenuated in mice pretreated with SB334867 and in preprohypocretin knockout mice. No changes were found in TCSOX229 pretreated animals. Nicotine withdrawal increased the percentage of hypocretin cells expressing c-Fos in the perifornical, dorsomedial, and lateral hypothalamus. In addition, the increased c-Fos expression in the PVN during withdrawal was dependent on hypocretin transmission through Hcrtr-1 activation. Hypocretin neurons directly innervate the PVN and the local infusion of SB334867 into the PVN decreased the expression of nicotine withdrawal. These data demonstrate that hypocretin signaling acting on Hcrtr-1 in the PVN plays a crucial role in the expression of nicotine withdrawal. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Non-Competitive NMDA Receptor Antagonist Hemantane Reduces Ethanol Consumption in Long-Term Alcohol Experienced Rats.

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Kolik, L G; Nadorova, A V; Seredenin, S B

2017-12-01

Activity of hemantane, an amino adamantane derivative, exhibiting the properties of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in experimental in vivo models of alcoholism. Hemantane had no effects on the formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice. Under conditions of free choice between 10% ethanol and water, hemantane (20 mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol intake in random-bred male rats with formed alcohol motivation (>4 g/kg of ethanol). During modelling of withdrawal syndrome, hemantane administered intraperitoneally in doses of 5-20 mg/kg dose-dependently attenuated alcohol-deprivation effect after acute withdrawal with no effects on protracted abstinence. It was found that hemantane suppressed alcohol drinking behavior in long-term ethanol experienced rats and attenuated alcohol-seeking behavior after acute withdrawal.

Anti-inflammatory and antinociceptive activities of Phyllanthus niruri spray-dried standardized extract

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Cínthia R. C. Porto

2013-02-01

Full Text Available Phyllanthus niruri L., Euphorbiaceae, spray-dried standardized extract was studied for its anti-inflammatory and antinociceptive activities in adult albino rats and mice. The anti-inflammatory effect of spray-dried standardized extract was observed in carrageenan-induced paw edema and thioglycolate-induced leukocyte migration, while antinociceptive effects were observed using Randall & Selitto, tail flick, and hot plate tests. This study showed that intraperitoneal spray-dried standardized extract at 100, 200, 800, or 1600 mg/kg reduced the vascular response in the inflammatory process of paw edema induced by 1% carrageenan. Oral spray-dried standardized extract at 100 or 200 mg/kg inhibited leukocyte migration to the site of inflammation induced by 3% thioglycolate. In rats, at 100 and 200 mg/kg intraperitoneally, the extract exhibited a marked peripheral analgesic effect in a Randall & Selitto assay and showed significant central analgesic activity in a hot plate and tail flick assay. In conclusion, this study suggested that Phyllanthus niruri spray-dried standardized extract has potent inflammatory and antinociceptive activities and that these activities are not modified by standard drying process, making it feasible to use the dry extract standardized to obtain a phytotherapic preparation and thus validating its use for the treatment of pain and inflammation disorders.

Intraperitoneal stone migration during percutaneos nephrolithotomy

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Akif Diri

2014-12-01

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

Doxorubicin induced neuro- and cardiotoxicities in experimental rats: Protection against oxidative damage by Theobroma cacao Stem bark

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A.M. Kosoko

2017-07-01

Full Text Available 80 rats, randomly selected, were divided into 3 treatment groups: pre-, co- and post-treatment; consisting of 6 sub-groups each (5 rats per sub-group: baseline, normal saline (2 mL, α-lipoic acid (20 mg/kg body weight, 200 mg/kg, 400 mg/kg or 800 mg/kg body weight Theobroma cacao stem bark aqueous extract (TCAE. All rats except for baseline group were intoxicated with 20 mg/kg body weight doxorubicin (DOX intraperitoneally. The animals in pre- or post-treatment group received a single dose of DOX (20 mg/kg body weight intraperitoneally 24 h before or after 7 days’ oral administration with TCAE respectively while those in co-treatment group were co-administered 2.86 mg/kg body weight of DOX with either normal saline, α- lipoic acid or TCAE orally for 7 days. Animals were sacrificed (pre- and post- treatment groups were sacrificed on the ninth day while the co-treatment group sacrificed on the 8th day. Brain and heart tissue samples were harvested for enzyme markers of toxicity, oxidative stress and histopathological examinations. DOX intoxication caused significant decrease in activities of LDH and ACP, and increase in γGT and ALP activities in brain tissues while causing a significant increase in LDH, ACP, γGT activities and decrease in ALP activity in the cardiac tissues. DOX intoxication caused a significant increase in concentrations of H2O2 generated, MDA and PC, XO, MPx and NOX activities with concomitant decrease in CAT, SOD, GPx and GST activities, and in concentrations of GSH, AsA and α-Toc in brain and cardiac tissues. Pre-, co- and post-treatment with TCAE at either 200 mg/kg, 400 mg/kg or 800 mg/kg body weight significantly reversed the oxidative damage to the organs induced by DOX-intoxication. The result affirmed that T. cacao stem bark aqueous extract protected against DOX induced oxidative damage in brain and cardiac tissues of experimental rats.

Effects on proliferation and cell cycle of irradiated KG-1 cells stimulated by CM-CSF

International Nuclear Information System (INIS)

Guo Dehuang; Dong Bo; Wen Gengyun; Luo Qingliang; Mao Bingzhi

2000-01-01

In order to explore the variety of cell proliferation and cell cycle after exposure to ionizing radiation, the responses of irradiated KG-1 cells of the human myeloid leukemia stimulated by GM-CSF, the most common used cytokine in clinic, were investigated. The results showed that GM-CSF enhance KG-1 cells proliferation, reduce G0/G1 block, increase S phase and G2/M phase. The stimulation effects of the GM-CSF are more effective in irradiated group than in control group

Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling.

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Zhang, Wen-zhou; Jiang, Zheng-kui; He, Bao-xia; Liu, Xian-ben

2015-08-01

Arctigenin, a bioactive component of Arctium lappa (Nubang), has anti-inflammatory activity. Here, we investigated the effects of arctigenin on lipopolysaccharide (LPS)-induced acute lung injury. Mice were divided into four groups: control, LPS, LPS + DMSO, and LPS + Arctigenin. Mice in the LPS + Arctigenin group were injected intraperitoneally with 50 mg/kg of arctigenin 1 h before an intratracheal administration of LPS (5 mg/kg). Lung tissues and bronchoalveolar lavage fluids (BALFs) were collected. Histological changes of the lung were analyzed by hematoxylin and eosin staining. Arctigenin decreased LPS-induced acute lung inflammation, infiltration of inflammatory cells into BALF, and production of pro-inflammatory cytokines. Moreover, arctigenin pretreatment reduced the malondialdehyde level and increased superoxide dismutase and catalase activities and glutathione peroxidase/glutathione disulfide ratio in the lung. Mechanically, arctigenin significantly reduced the production of nitric oxygen and inducible nitric oxygen synthase (iNOS) expression, enhanced the expression of heme oxygenase-1, and decreased the phosphorylation of mitogen-activated protein kinases (MAPKs). Arctigenin has anti-inflammatory and antioxidative effects on LPS-induced acute lung injury, which are associated with modulation of MAPK, HO-1, and iNOS signaling.

Protective Effects of Agmatine against Chlorpromazine- Induced Toxicity in the Liver of Wistar Rats

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Dejanović Bratislav

2016-03-01

Full Text Available The metabolic pathways of chlorpromazine (CPZ toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p. for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution, the CPZ group (CPZ, 38.7 mg/kg b.w., the CPZ+AGM group (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p. and the AGM group (AGM, 75 mg/kg b.w..

Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

Science.gov (United States)

Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

2013-04-01

The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

International Nuclear Information System (INIS)

Amirshahrokhi, K.; Dehpour, A.R.; Hadjati, J.; Sotoudeh, M.; Ghazi-Khansari, M.

2008-01-01

Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of β cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a μ-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of β cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of β cells and insulitis in the MLDS model of type 1 diabetes

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

Science.gov (United States)

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

2014-04-01

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

Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

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Anders Lyngvi Fougner

2016-04-01

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

Systemic modulation of serotonergic synapses via reuptake blockade or 5HT1A receptor antagonism does not alter perithreshold taste sensitivity in rats.

Science.gov (United States)

Mathes, Clare M; Spector, Alan C

2014-09-01

Systemic blockade of serotonin (5HT) reuptake with paroxetine has been shown to increase sensitivity to sucrose and quinine in humans. Here, using a 2-response operant taste detection task, we measured the effect of paroxetine and the 5HT1A receptor antagonist WAY100635 on the ability of rats to discriminate sucrose, NaCl, and citric acid from water. After establishing individual psychometric functions, 5 concentrations of each taste stimulus were chosen to represent the dynamic portion of the concentration-response curve, and the performance of the rats to these stimuli was assessed after vehicle, paroxetine (7mg/kg intraperitoneally), and WAY100635 (0.3mg/kg subcutaneously; 1mg/kg intravenously) administration. Although, at times, overall performance across concentrations dropped, at most, 5% from vehicle to drug conditions, no differences relative to vehicle were seen on the parameters of the psychometric function (asymptote, slope, or EC50) after drug administration. In contrast to findings in humans, our results suggest that modulation of 5HT activity has little impact on sucrose detectability at perithreshold concentrations in rats, at least at the doses used in this task. In the rat model, the purported paracrine/neurocrine action of serotonin in the taste bud may work in a manner that does not impact overt taste detection behavior. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hydroethanolic extract of Carthamus tinctorius induces antidepressant-like effects: modulation by dopaminergic and serotonergic systems in tail suspension test in mice.

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Abbasi-Maleki, Saeid; Mousavi, Zahra

2017-09-01

Studies indicate that major deficiency in the levels of monoaminergic transmitters is a reason for severe depression. On the other hand, it is shown that Carthamus tinctorius L. (CT) may improve neuropsychological injuries by regulation of the monoamine transporter action. Hence, the present study was undertaken to evaluate the involvement of monoaminergic systems in antidepressant-like effect of CT extract in the tail suspension test (TST) in mice. The mice were intraperitoneally (IP) treated with CT extract (100-400 mg/kg) 1 hr before the TST. To investigate the involvement of monoaminergic systems in antidepressant-like effect, the mice were treated with receptor antagonists 15 min before CT extract treatment (400 mg/kg, IP) and 1 hr before the TST. Findings showed that CT extract (100-400 mg/kg, IP), dose-dependently induced antidepressant-like effect ( P open-field test. Pretreatment of mice with SCH23390, sulpiride, haloperidol, WAY100135, cyproheptadine, ketanserin and p-chlorophenylalanine (PCPA) inhibited the antidepressant-like effect of CT extract (400 mg/kg, IP), but not with prazosin and yohimbine. Co-administration of CT extract (100 mg/kg, IP) with sub-effective doses of fluoxetine (5 mg/kg, IP) or imipramine (5 mg/kg, IP) increased their antidepressant-like response. Our findings firstly showed that components (especially N-Hexadecanoic acid) of CT extract induce antidepressant-like effects by interaction with dopaminergic (D1 and D2) and serotonergic (5HT1A, 5-HT2A receptors) systems. These findings validate the folk use of CT extract for the management of depression.

Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

OpenAIRE

Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.

2008-01-01

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8–14 (E8–E14) to 100 mg/kg/day vinclozolin or flutamide at either 5mg or 20 mg/kg/day. As previously observed, vinclozolin i...

Feasibility and antitumor efficacy in vivo, of simultaneously targeting glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6-diazo-5-oxo-L-norleucine and orlistat in colon cancer.

Science.gov (United States)

Cervantes-Madrid, Diana; Dominguez-Gomez, Guadalupe; Gonzalez-Fierro, Aurora; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Trejo-Becerril, Catalina; Duenas-Gonzalez, Alfonso

2017-03-01

The aim of the present study was to investigate in vivo the feasibility and efficacy of the combination of lonidamine (LND), 6-diazo-5-oxo-L-norleucine (DON) and orlistat to simultaneously target glycolysis, glutaminolysis and de novo synthesis of fatty acids, respectively. The doses of LND and DON used in humans were translated to mouse doses (77.7 mg/kg and 145.5 mg/kg, respectively) and orlistat was used at 240 mg/kg. Three schedules of LND, DON and orlistat at different doses were administered by intraperitoneal injection to BALB/c mice in a 21-day cycle (schedule 1: LND, 0.5 mg/day; DON, 0.25 mg/day 1, 5 and 9; orlistat, 240 mg/kg/day; schedule 2: LND, 0.1 mg/day; DON, 0.5 mg/day 1, 5 and 9; orlistat, 240 mg/kg/day; schedule 3: LND, 0.5 mg/day; DON, 0.08 mg/day 1, 5 and 9; orlistat, 360 mg/kg/day) to assess tolerability. To determine the antitumor efficacy, a syngeneic tumor model in BALB/c mice was created using colon cancer CT26.WT cells, and a xenogeneic tumor model was created in nude mice using the human colon cancer SW480 cell line. Mice were treated with schedule 1. Animals were weighed, clinically inspected during the experiment and the tumor volume was measured at day 21. The 3 schedules assessed in the tolerability experiments were well tolerated, as mice maintained their weight and no evident clinical signs of toxicity were observed. Combination treatment with schedule 1 significantly decreased tumor growth in each mouse model. No evident signs of toxicity were observed and mice maintained their weight during treatment. The triple metabolic blockade of the malignant phenotype appears feasible and promising for cancer therapy.

Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats.

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Lakatos, Renáta Krisztina; Dobolyi, Árpád; Todorov, Mihail Ivilinov; Kékesi, Katalin A; Juhász, Gábor; Aleksza, Magdolna; Kovács, Zsolt

2016-06-01

The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system. Copyright © 2016 Elsevier Inc. All rights reserved.

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test.

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Nazari, Seyedeh Khadijeh; Nikoui, Vahid; Ostadhadi, Sattar; Chegini, Zahra Hadi; Oryan, Shahrbanoo; Bakhtiarian, Azam

2016-12-01

Previous study confirmed that the acute treatment with baclofen by inhibition of the l-arginine-nitric oxide (NO) pathway diminished the immobility behavior in the forced swimming test (FST) of mice. Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (K ATP ), in the present study we investigated the involvement of K ATP channels in antidepressant-like effect of baclofen in the forced swimming test (FST). After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of the antidepressant-like activity of baclofen in mice. Baclofen at different doses (0.1, 0.3, and 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of K ATP channels, after determination of sub-effective doses of glibenclamide as a K ATP channel blocker and cromakalim, as an opener of these channels, they were co-administrated with the sub-effective and effective doses of baclofen, respectively. Baclofen at dose 1mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20mg/kg). Co-administration of gelibenclamide sub-effective dose (1mg/kg) with baclofen (0.1mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1mg/kg) inhibited the antidepressant-like effect of baclofen (1mg/kg) in the FST. All aforementioned treatments had not any impact on the locomotor movement of mice in OFT. Our study for the first time revealed that antidepressant-like effect of baclofen on mice is K ATP -dependent, and baclofen seems that exert this effect by blocking the K ATP channels. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The protective effect of Physalis peruviana L. against cadmium-induced neurotoxicity in rats.

Science.gov (United States)

Abdel Moneim, Ahmed E; Bauomy, Amira A; Diab, Marwa M S; Shata, Mohamed Tarek M; Al-Olayan, Ebtesam M; El-Khadragy, Manal F

2014-09-01

The present study was carried out to investigate the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced neurotoxicity in rats. Adult male Wistar rats were randomly divided into four groups. Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg bwt of cadmium chloride for 5 days. Group 3 was treated with 200 mg/kg bwt of methanolic extract of Physalis (MEPh). Group 4 was pretreated with MEPh 1 h before cadmium for 5 days. Cadmium treatment induced marked disturbances in neurochemical parameters as indicating by significant (p Physalis has a beneficial effect in ameliorating the cadmium-induced oxidative neurotoxicity in the brain of rats.

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice.

Science.gov (United States)

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

2015-01-01

The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), and bupropion + duloxetine (5 mg/kg, each) were given to groups I-VII, respectively. Elevated plus maze was used to evaluate transfer latency (TL) and Morris water maze was used to estimate the time spent in target quadrant. Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded. Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies.

Comparison of the effects of NG-nitro-L-arginine and indomethacin on the hypercapnic cerebral blood flow increase in rats

DEFF Research Database (Denmark)

Wang, Qian; Pelligrino, D A; Paulson, O B

1994-01-01

The effects of NG-nitro-L-arginine (NOLAG), an inhibitor of nitric oxide synthase (NOS), and of indomethacin, an inhibitor of cyclooxygenase, on the rise in cerebral blood flow (CBF) accompanying increasing levels of hypercapnia (paCO2 = 40-135 mmHg) were studied in anesthetized rats. CBF...... with additional step increase in paCO2. Intracarotid infusion of 7.5 mg/kg NOLAG significantly attenuated the CO2-elicited CBF increase by about 45-65% at paCO2 values below 115 mmHg. Beyond this level, there was a lesser inhibition of about 27-35%. 30 mg/kg NOLAG had essentially the same effect as 7.5 mg....../kg NOLAG. 50 mg/kg NOLAG, given intraperitoneally (i.p.) twice daily for 4 days, also caused an attenuated CBF response to CO2, but the inhibitory effect was significantly less than with acute NOLAG administration in the paCO2 range of 61-90 mmHg. Infusion of L-arginine, 1 g/kg/h, prevented the effect of 7...

The effect of ethyl pyruvate on oxidative stress in intestine and bacterial translocation after thermal injury.

Science.gov (United States)

Karabeyoğlu, Melih; Unal, Bülent; Bozkurt, Betül; Dolapçi, Iştar; Bilgihan, Ayşe; Karabeyoğlu, Işil; Cengiz, Omer

2008-01-01

Thermal injury causes a breakdown in the intestinal mucosal barrier due to ischemia reperfusion injury, which can induce bacterial translocation (BT), sepsis, and multiple organ failure in burn patients. The aim of this study was to investigate the effect of ethyl pyruvate (EP) on intestinal oxidant damage and BT in burn injury. Thirty-two rats were randomly divided into four groups. The sham group was exposed to 21 degrees C water and injected intraperitoneal with saline (1 mL/100 g). The sham + EP group received EP (40 mg/kg) intraperitoneally 6 h after the sham procedure. The burn group was exposed to thermal injury and given intraperitoneal saline injection (1 mL/100 g). The burn + EP group received EP (40 mg/kg) intraperitoneally 6 h after thermal injury. Twenty-four hours later, tissue samples were obtained from mesenteric lymph nodes, spleen, and liver for microbiological analysis and ileum samples were harvested for biochemical analysis. Thermal injury caused severe BT in burn group. EP supplementation decreased BT in mesenteric lymph nodes and spleen in the burn + EP group compared with the burn group (P < 0.05). Also, burn caused BT in liver, but this finding was not statistically significant among all groups. Thermal injury caused a statistically significant increase in malondialdehyde and myeloperoxidase levels, and EP prevented this effects in the burn + EP group compared with the burn group (P < 0.05). Our data suggested that EP can inhibit the BT and myeloperoxidase and malondialdehyde production in intestine following thermal injury, suggesting anti-inflammatory and anti-oxidant properties of EP.

Evaluation of Eucalyptus citriodora essential oil on goat gastrointestinal nematodes Avaliação do óleo essencial de Eucalyptus citriodora sobre nematóides gastrintestinais de caprinos

Directory of Open Access Journals (Sweden)

Iara Tersia Freitas Macedo

2011-09-01

Full Text Available Phytotherapy may be an alternative strategy for controlling gastrointestinal parasites. This study evaluated the anthelmintic efficacy of Eucalyptus citriodora essential oil (EcEO. The in vitro effects of EcEO were determined through testing the inhibition of egg hatching and larval development of Haemonchus contortus. EcEO was subjected to acute toxicity testing on mice, orally and intraperitoneally. The in vivo effects of EcEO were determined by the fecal egg count reduction test (FECRT in goats infected with gastrointestinal nematodes. The results showed that 5.3 mg.mL-1 EcEO inhibited egg hatching by 98.8% and 10.6 mg.mL-1 EcEO inhibited H. contortus larval development by 99.71%. The lethal doses for 50% of the mice were 4153 and 622.8 mg.kg-1, for acute toxicity orally and intraperitoneally. In the FECRT, the efficacy of EcEO and ivermectin was 66.25 and 79.16% respectively, on goat gastrointestinal nematodes eight days after treatment. EcEO showed in vitro and in vivo anthelmintic activity.Fitoterapia pode ser uma estratégia alternativa para o controle de parasitas gastrintestinais. Este estudo avaliou a eficácia anti-helmintica do óleo essencial de Eucalyptus citriodora (OeEc. Os efeitos in vitro do OeEc foram determinados através do teste de eclosão de ovos e inibição do desenvolvimento larvar de Haemonchus contortus. O OeEc foi submetido ao teste de toxicidade aguda oral e intraperitoneal, em camundongos. Os efeitos in vivo do OeEc foram avaliados através do teste de redução da contagem de ovos nas fezes (FECRT com caprinos infectados com nematóides gastrintestinais. Os resultados mostraram que 5,3 mg.mL-1 OeEc inibiram 98,8% a eclosão de ovos e 10,6 mg.mL-1 OeEc inibiram 99,71% o desenvolvimento larvar de H. contortus. As doses letais para 50% dos camundongos foram de 4153 e 622,8 mg.kg-1 pela via oral e intraperitoneal. No FECRT, a eficácia de OeEc e ivermectina foi de 66,25 e 79,16%, respectivamente, em caprinos 8 dias

CT diagnosis of intraperitoneal bladder rupture with blunt abdominal trauma

International Nuclear Information System (INIS)

Kong Fanbin

2000-01-01

Objective: To evaluate CT examination in the diagnosis of intraperitoneal bladder rupture (IPBR) caused by blunt abdominal trauma. Methods: All CT and clinical data of 9 patients with IPBR were reviewed retrospectively. Results: IPBR was detected on CT scans in all 9 patients. CT findings of IPBR included low -attenuation free intraperitoneal fluid collections in the lateral paravesical fossae, the pericolic space, the culde-sac of the pelvis, Morison's pouch, the peri-hepatic space, the perisplenic space and interspace of bowel loops in 9 cases with a lower CT density compared with pure blood. The disruption of the bladder wall was located by CT scan in 5 cases: high-attenuation bladder wall with focal defect in 3 cases and a tear drop-like deformity of the bladder in 2 cases. Other CT findings supporting the diagnosis of IPBR included an underfilled bladder in 8 cases, bladder contusion in 4 cases, and blood clots within the bladder in 6 cases. Conclusion: The presence of intraperitoneal fluid with a CT density less than that of pure blood strongly suggests extravasated urine in the trauma. Intraperitoneal and extraperitoneal rupture can be distinguished based on location of extravasated urine seen on CT scans. The precise localization of the ruptured bladder wall may be demonstrated by CT scan, which is valuable for surgical treatment

Potential effects of Cramoll 1,4 lectin on murine Schistosomiasis mansoni.

Science.gov (United States)

Melo, Cristiane Moutinho Lagos de; de Lima, Amanda Lucena Rosendo; Beltrão, Eduardo Isidoro Carneiro; Cavalcanti, Carmelita C Bezerra; de Melo-Júnior, Mário Ribeiro; Montenegro, Silvia Maria L; Coelho, Luana Cassandra B Barroso; Correia, Maria Tereza dos Santos; Carneiro-Leão, Ana Maria dos Anjos

2011-05-01

Cratylia mollis is a natural forage plant from the Northeast of Brazil. C. mollis seed lectin (Cramoll) containing molecular forms 1 and 4 (Cramoll 1,4) has shown anti-inflammatory and wound-healing activities. This work analyzed the effect of Cramoll 1,4 on experimental schistosomiasis in mice. Experimental groups (n=15/group) were composed of female albino Swiss mice, which were subcutaneously and caudally infected with Schistosoma mansoni (BH strain, 100 cercariae/mouse) and were treated with an intraperitoneal dose after infection as follows: (1) Cramoll 1,4 (50 mg kg(-1) single dose - after 40 days of infection), (2) Cramoll 1,4 (7 mg kg(-1) daily dose - for 7 days after infection) and control (untreated mice). Mice were sacrificed 8 weeks after infection and adult worms were recovered from the portal-hepatic system. Livers were fixed in 10% (v/v) formaldehyde/0.15M NaCl and tissue sections were processed for haematoxilin and Masson's trichrome stainings. Mice infected subcutaneously harboured no or very few worms and hence the effect of Cramoll 1,4 could not be assessed. Results (P≤0.05) were obtained with Cramoll 1,4 using the two treatments, with reduction of: egg excretion (79 and 80%), adult worm recovery (71 and 79%) and liver granulomas (40 and 73.5%) in relation to control. This study showed the potential anti-helminthic activity of Cramoll 1,4 when tested against Schistosomiasis mansoni infection in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Intra-individual comparison of different contrast media concentrations (300 mg, 370 mg and 400 mg iodine) in MDCT

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Behrendt, Florian F.; Keil, Sebastian; Plumhans, Cedric; Guenther, Rolf W. [RWTH Aachen University, Department of Diagnostic Radiology, University Hospital, Aachen (Germany); Pietsch, Hubertus; Jost, Gregor; Sieber, Martin A.; Seidensticker, Peter [Bayer Schering Pharma AG, Berlin (Germany); Mahnken, Andreas H. [RWTH Aachen University, Department of Diagnostic Radiology, University Hospital, Aachen (Germany); RWTH Aachen University, Applied Medical Engineering, Helmholtz-Institute for Biomedical Engineering, Aachen (Germany)

2010-07-15

To compare intra-individual contrast enhancement in multi-detector-row computed tomography (MDCT) using contrast media (CM) containing 300, 370 and 400 mg iodine per ml (mgI/ml). Six pigs underwent repeated chest MDCT using three different CM (iopromide 300, iopromide 370, iomeprol 400). An identical iodine delivery (IDR) rate of 1.5 gI/s and a constant total iodine dose of 300 mg/kg body weight were used. Dynamic CT were acquired at the level of the pulmonary artery, and the ascending and descending aorta. After the time enhancement curves were computed, the pulmonary and aortic peak enhancement, time to peak and plateau time above 300 HU were calculated. Intra-individual peak contrast enhancement was significantly higher for the 300 mgI/ml contrast medium compared with the 370 and 400 mgI/ml media: pulmonary trunk 595 HU vs 516 HU (p = 0.0093) vs 472HU (p = 0.0005), and aorta 505 HU vs 454 HU (p = 0.0008) vs 439 HU (p = 0.0001), respectively. Comparison of time to peaks showed no significant difference. Plateau times were significantly longer for the 300 mgI/ml than for the 370 and 400 mgI/ml CM at all anatomical sites. Given normalised IDR and total iodine burden, the use of CM with a standard concentration with 300 mg iodine/ml provides improved contrast enhancement compared with highly concentrated CM in the chest. (orig.)

Protective Effect of Astaxanthin on Liver Fibrosis through Modulation of TGF-β1 Expression and Autophagy

Directory of Open Access Journals (Sweden)

Miao Shen

2014-01-01

Full Text Available Liver fibrosis is a common pathway leading to cirrhosis and a worldwide clinical issue. Astaxanthin is a red carotenoid pigment with antioxidant, anticancer, and anti-inflammatory properties. The aim of this study was to investigate the effect of astaxanthin on liver fibrosis and its potential protective mechanisms. Liver fibrosis was induced in a mouse model using CCL4 (intraperitoneal injection, three times a week for 8 weeks, and astaxanthin was administered everyday at three doses (20, 40, and 80 mg/kg. Pathological results indicated that astaxanthin significantly improved the pathological lesions of liver fibrosis. The levels of alanine aminotransferase aspartate aminotransferase and hydroxyproline were also significantly decreased by astaxanthin. The same results were confirmed in bile duct liagtion, (BDL model. In addition, astaxanthin inhibited hepatic stellate cells (HSCs activation and formation of extracellular matrix (ECM by decreasing the expression of NF-κB and TGF-β1 and maintaining the balance between MMP2 and TIMP1. In addition, astaxanthin reduced energy production in HSCs by downregulating the level of autophagy. These results were simultaneously confirmed in vivo and in vitro. In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

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...

Suggesting a possible role of CA1 histaminergic system in harmane-induced amnesia.

Science.gov (United States)

Nasehi, Mohammad; Mashaghi, Elham; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2013-11-27

A number of tremorogenic β-carboline alkaloids such as harmane are naturally present in the human food chain. They are derived from medicinal plants such as Peganum harmala that have been used as folk medicine in anticancer therapy. In the present study, effects of the histaminergic system of the dorsal hippocampus (CA1) on harmane-induced amnesia were examined. One-trial step-down was used to assess memory retention in adult male mice. The results showed that pre-training intra-CA1 administration of histamine (5μg/mouse), ranitidine (H2 receptor antagonist; at the doses of 0.25 and 0.5μg/mouse) and pyrilamine (H1 receptor antagonist; at the dose of 5μg/mouse) decreased memory formation. Pre-training intraperitoneal (i.p.) administration of harmane (12mg/kg) also decreased memory formation. Moreover, pre-training intra-CA1 injection of a sub-threshold dose of histamine (2.5μg/mouse) could reverse harmane (12mg/kg, i.p.)-induced impairment of memory. On the other hand, pre-training intra-CA1 injection of sub-threshold doses of ranitidine (0.0625μg/mouse) and pyrilamine (2.5μg/mouse) increased harmane-induced impairment of memory. In conclusion, the present findings suggest the involvement of the CA1 histaminergic system in harmane-induced impairment of memory formation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Baicalein administration protects against pentylenetetrazole ...

African Journals Online (AJOL)

normal control, model (untreated epilepsy) and four treatment groups that received separately, intraperitoneal ... pentylenetetrazole-induced convulsions by baicalein treatment at a dose of 50 mg/kg. .... baicalein groups vs. model group ...

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

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

NARCIS (Netherlands)

de Vos, P; Vegter, D; de Haan, B.J; Strubbe, J.H.; Bruggink, J.E.; van Schilfgaarde, R

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

Fatal cardiac arrhythmia after repeated exposure to 1,1-difluoroethane (DFE).

Science.gov (United States)

Avella, Joseph; Wilson, James C; Lehrer, Michael

2006-03-01

A 42-year-old man was found dead after repeated exposure to 1,1-difluoroethane (DFE, Freon 152a), a propellant found in CRC Duster, a product intended for the removal of dust and lint. Toxicologic analysis detected DFE in femoral blood 136.3 mg/L, brain 117.5 mg/kg, liver 87.6 mg/kg, lung 60.3 mg/kg, adipose 235.7 mg/kg, and vitreous fluid 25.1 mg/L. The cause of death was determined to be a fatal cardiac arrhythmia due to intoxication with 1,1-difluoroethane. After comparison to previously published cases involving DFE, we suggest that analysis of adipose tissue for DFE and similar compounds, along with blood and other tissues, may be useful in distinguishing between acute versus chronic exposure. Adipose may also be a valuable alternate specimen for detection in cases where loss or elimination from blood is likely to have occurred.

Acute oral Toxicity and Antioxidant Activity of Neoglaziovia variegata

African Journals Online (AJOL)

fisiologia

2012-09-18

Sep 18, 2012 ... In the acute toxicity of Nv-EtOH, behavioral and physiological alterations were not observed neither animal's death in the doses of 2.0 g/kg intraperitoneally and 5.0 g/kg orally, respectively indicating low toxicity of the extract. In this experiment, it was observed that the. Nv-EtOH has LD50 > 5000 mg/kg.

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

Science.gov (United States)

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

Evaluation of analgesic and anti-inflammatory effects of ethanol extract of Ficus iteophylla leaves in rodents.

Science.gov (United States)

Abdulmalik, I A; Sule, M I; Musa, A M; Yaro, A H; Abdullahi, M I; Abdulkadir, M F; Yusuf, H

2011-01-01

This study was undertaken to investigate the leaf part of the plant for analgesic and anti-inflammatory. The ethanol extract of Ficus iteophylla leaves (100, 200, and 400 mg kg(-1), i.p) was evaluated for analgesic and anti-inflammatory activities. The analgesic effect was studied using acetic acid-induced abdominal constriction and hot plate test in mice, while the anti-inflammatory effect was investigated using carrageenan induced paw oedema in rats. The ethanol extract at 100 mg kg(-1), 200 mg kg(-1), and 400 mg kg(-1) significantly (Pacetic acid induced writhes by 1.50 ± 0.43, 3.0 ± 0.82 and 1.0 ± 0.82 respectively. It also exhibited significantly (Pscreening of the plant extract revealed the presence of flavonoids, steroids, tannins and saponins while the effect of flavonoids, steroids and tannins on analgesic and inflammatory has been reported. The intraperitoneal median lethal dose (LD(50)) value of the extract was found to be 3807.8 mgkg(-1) body weights. The result obtained from this study shows that the extract of Ficus iteophylla contained phytochemical constituents with analgesic and anti-inflammatory activities, therefore the leaf part of the plant could be used in the management of pain and inflammatory conditions.

Effect of Purine Nucleoside Analogue-Acyclovir on The Sperm Parameters and Testosterone Production in Rats

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Vahid Nejati

2013-01-01

Full Text Available Background: Acyclovir (ACV, a synthetic purine nucleoside analogue derived fromguanosine, is known to be toxic to gonads and the aim of this study was to evaluate theeffect of ACV on the sperm parameters and testosterone production in rat.Materials and Methods: In this experimental study, forty adult male Wistar rats (220± 20 g were randomly divided into five groups (n=8 for each group. One groupserved as control and one group served as sham control [distilled water was intraperitoneally(i.p. injected]. ACV was administered intraperitoneally in the drugtreatment groups (4, 16 and 48 mg/kg/day for 15 days. Eighteen days after the lastinjection, rats were sacrificed by CO2 inhalation. After that, cauda epididymideswere removed surgically. At the end, sperm concentrations in the cauda epididymis,sperm motility, morphology, viability, chromatin quality and DNA integrity wereanalyzed. Serum testosterone concentrations were determined.Results: The results showed that ACV did not affect sperm count, but decreased spermmotility and sperm viability at 16 and 48 mg/kg dose-levels. Sperm abnormalities increasedat 48 mg/kg dose-level of ACV. Further, ACV significantly increases DNA damageat 16 and 48 mg/kg dose-levels and chromatin abnormality at all doses. Besides, asignificant decrease in serum testosterone concentrations was observed at 16 and 48 mg/kg doses.Conclusion: The present results highly support the idea that ACV induces testicular toxicityby adverse effects on the sperm parameters and serum level of testosterone in malerats.

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

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.

AY Bala, T. Adamu, U. Abubakar, MJ Ladan and MG Abubakar

African Journals Online (AJOL)

acer

About 20 – 25 parasites per microscope field were dosed with 1, 2 and 4mg/ml of aqueous extracts of .... brucei as test organisms. It is hoped ... in open air in the laboratory to avoid denaturing .... extract of Terminalia spp at 150mg/kg in mice.

Effects of crocin and safranal, saffron constituents, on the formalin-induced orofacial pain in rats

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Amir Erfanparast

2015-08-01

Full Text Available Objective: Crocin and safranal are the main components of saffron, and have many biological functions such as anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of crocin, safranal, morphine, diclofenac and naloxone in combined and separately on formalin-induced orofacial pain in rats. Materials and Methods: Subcutaneous injection of a diluted formalin solution (50 µl, 1.5% into the upper lip region produced a biphasic pattern of pain response (a neurogenic phase: 0-3 min and an inflammatory phase: 15-33 min. The time each animal spent face rubbing with ipsilateral forepaw was recorded and considered as an index of nociception Results: Intraperitoneal injections of crocin (12.5 and 25 mg/kg, safranal (0.25 and 0.5 mg/kg, diclofenac (5 and 10 mg/kg and morphine (1 and 2 mg/kg suppressed the second phase of pain. The second phase of pain was also reduced when low (ineffective doses of crocin (6.25 mg/kg and safranal (0.125 mg/kg were co-administered with low doses of diclofenac (2.5 mg/kg and morphine (0.5 mg/kg. The more antinociceptive effects were observed when the medium doses of the above-mentioned chemicals used together. Naloxone prevented morphine-induced antinociception, but did not inhibit the suppressive effects of crocin and safranal. Safranal at a high dose (0.5 mg/kg suppressed locomotor activity. Conclusion: The present results showed antinociceptive effects for crocin and safranal in inflammatory pain. Opioid receptors may not be involved in the antinociceptive effect of crocin and safranal. Crocin and safranal increased diclofenac-induced antinociception.

Increase in tumor oxygen tension and radiosensitivity after administration of pentoxifylline

International Nuclear Information System (INIS)

Hasegawa, Takeo; Gu, Yeun Hwa; Nagao, Takashi; Miyata, Katsuyuki; Song, Chang W.; Tanake, Yoshimasa; Hasegawa, Takashi

1999-01-01

The effects of pentoxifylline (PTX) on the pO2 and radioresponse in SCK tumors of A/J mice were investigated. When the mice were injected intraperitoneally with 5 mg/kg of PTX, the tumor pO2 increased slowly, peaked 20-50 min postinjection, and returned to its original level in 70-90 min. The magnitude of the changes in tumor pO2 after on ip injection of 25 or 50 mg/kg PTX was similar to that caused by 5 mg/kg PTX. When the A/J mice bearing SCK tumors in the legs were injected ip with 50 mg/kg PTX and the tumors were X ray irradiated 20 min later, the tumor growth delay was greater than that of radiation alone

Corrigendum to “Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain" [Neurosci.Lett. 580 (2014) 12–16] A possible new animal model of autism

DEFF Research Database (Denmark)

Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

2015-01-01

The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20 mg/kg or 100 mg/kg) continuously during the last 9......–12 days of pregnancy and during the lactation period until sacrifice on the 23rd postnatal day. Total number of neocortical neurons was estimated using the optical fraction at or and frontal cortical thicknesses were sampled in VPA exposed pups compared with an unexposed control group. We found that pups....... Pups exposed to 100 mg/kg, but not to 20 mg/kg VPA displayed a significant (p brain development by disturbing neocortical organization...

A COMBINED EFFECT OF DEXTROMETHORPHAN AND MELATONIN ON NEUROPATHIC PAIN BEHAVIOR IN RATS

Science.gov (United States)

Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-01-01

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain. PMID:19595681

Changes in Glutamate/NMDA Receptor Subunit 1 Expression in Rat Brain after Acute and Subacute Exposure to Methamphetamine

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Walailuk Kerdsan

2009-01-01

Full Text Available Methamphetamine (METH is a psychostimulant drug of abuse that produces long-term behavioral changes including behavioral sensitization, tolerance, and dependence. METH has been reported to induce neurotoxic effects in several areas of the brain via the dopaminergic system. Changes of dopamine function can induce malfunction of the glutamatergic system. Therefore, the aim of the present study was to examine the effects of METH administration on the expression of glutamate N-methyl-D-aspartate receptor subunit 1 (NMDAR1 in frontal cortex, striatum, and hippocampal formation after acute and subacute exposure to METH by western blotting. Male Sprague-Dawley rats were injected intraperitoneally with a single dose of 8 mg/kg METH, 4 mg/kg/day METH for 14 days and saline in acute, subacute, and control groups, respectively. A significant increase in NMDAR1 immunoreactive protein was found in frontal cortex in the subacute group (P=.036 but not in the acute group (P=.580. Moreover, a significant increase in NMDAR1 was also observed in striatum in both acute (P=.025 and subacute groups (P=.023. However, no significant differences in NMDAR1 in hippocampal formation were observed in either acute or subacute group. The results suggest that an upregulation of NMDA receptor expression may be a consequence of glutamatergic dysfunction induced by METH.

Direct Renin Inhibition with Aliskiren Improves Ischemia-Induced Neovasculogenesis in Diabetic Animals via the SDF-1 Related Mechanism.

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Ting-Ting Chang

Full Text Available Aliskiren is a direct renin inhibitor which is suggested to modify proangiogenic cells in addition to lower blood pressure. Given that angiogenesis is impaired in the presence of diabetes mellitus, we would like to investigate whether and how aliskiren enhances endothelial progenitor cells (EPCs and improves ischemic-induced neovasculogenesis by an effect independent of blood pressure reduction in diabetic animals.Streptozotocin-induced diabetic mice were administered with either aliskiren (5 or 25 mg/kg/day using an osmotic pump or hydralazine (2 or 10 mg/kg/day given in drinking water for two weeks prior to a hind-limb ischemia surgery. Laser Doppler imaging and flow cytometry were used to evaluate the degree of neovasculogenesis and the circulating levels of EPCs, respectively.In streptozotocin-induced diabetic mice, aliskiren enhanced the recovery of limb perfusion and capillary density, increased the number of circulating Sca-1+/Flk-1+ EPC-like cells, and elevated the levels of the plasma vascular endothelial growth factor (VEGF and stromal cell-derived factor (SDF-1α in a dose-dependent manner, whereas there were no such effects in hydralazine-treated mice. Intraperitoneal administration of anti-SDF-1 neutralizing monoclonal antibodies abolished the effects of aliskiren.Independent of the reduction of blood pressure, aliskiren enhanced ischemia-induced neovasculogenesis in a dose-dependent manner via VEGF/SDF-1α related mechanisms in diabetic mice.

Shenfu injection reduces toxicity of bupivacaine in rats

Institute of Scientific and Technical Information of China (English)

王强; 刘艳红; 雷毅; 杨静; 陈绍洋; 陈敏; 熊利泽

2003-01-01

Objective To investigate the effects of injecting Shenfu, an extract of traditional Chinese herbal medicines, on the central nervous system (CNS) and the cardiac toxicity of bupivacaine in rats. Methods Sixteen male Sprague-Dawley rats, weighing form 280 to 320 g, were randomly assigned to two groups (n=8 in each group). Animals in the control group received a saline injection 10 ml/kg while animals in the Shenfu group received an injection of Shenfu 10 ml/kg intraperitoneally 30 minutes before intravenous infusion of bupivacaine. Lead Ⅱ of an electrocardiogram (EEG) was continuously monitored after 3 needles were inserted into the skin of both forelimbs and the left hind-leg of each rat. The femoral artery was cannulated for measurement of arterial blood pressure and blood sampling. The femoral vein was cannulated for the infusion of bupivacaine. After baseline measurement (arterial blood pressure, heart rate and arterial blood gas), 0.5% bupivacaine was infused intravenously at a rate of 2 mg*kg-1*min-1 to all animals until asystole occurred. The time of bupivacaine-induced convulsions, arrhythmia and asystole were determined. The dose of bupivacaine was then calculated at the corresponding time point. Results The doses of bupivacaine that induced convulsions, arrhythmia and cardiac arrest were remarkably larger in Shenfu injection-treated animals than in saline-treated rats ［convulsions, (10.5±1.9) mg/kg vs (7.2±1.5) mg/kg; arrhythmia (10.5±2.0) mg/kg vs (7.2±1.9) mg/kg; asystole, (32.8±8.5) mg/kg vs (25.0±5.0) mg/kg; P=0.006, 0.009 and 0.044, respectively］. Conclusion The Shenfu injection is able to reduce the toxicity of bupiralaine to CNS and cardiac system in rats.

Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction.

Science.gov (United States)

Fetoni, Anna R; Eramo, Sara L M; Paciello, Fabiola; Rolesi, Rolando; Podda, Maria Vittoria; Troiani, Diana; Paludetti, Gaetano

2014-06-01

To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1. Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities. In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection. Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression. This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.

Involvement of NMDA receptors in the antidepressant-like effect of tramadol in the mouse forced swimming test.

Science.gov (United States)

Ostadhadi, Sattar; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Akbarian, Reyhaneh; Imran-Khan, Muhammad; Ghasemi, Mehdi; Dehpour, Ahmad-Reza

2017-09-01

Tramadol is an analgesic agent that is mainly used to treat moderate to severe pain. There is evidence that tramadol may have antidepressant property. However, the mechanisms underlying the antidepressant effects of tramadol have not been elucidated yet. Considering that fact that N-methyl-d-aspartate (NMDA) receptor signaling may play an important role in the pathophysiology of depression, the aim of the present study was to investigate the role of NMDA receptor signaling in the possible antidepressant-like effects of tramadol in the mouse forced swimming test (mFST). We found that tramadol exerted antidepressant-like effects at high dose (40mg/kg, intraperitoneally [i.p.]) in the mFST. Co-administration of non-effective doses of NMDA receptor antagonists (ketamine [1mg/kg, i.p.], MK-801 [0.05mg/kg, i.p.], or magnesium sulfate [10mg/kg, i.p.]) with sub-effective dose of tramadol (20mg/kg, i.p.) exerted significant antidepressant-like effects in the mFST. The antidepressant-like effects of tramadol (40mg/kg) was also inhibited by pre-treatment with non-effective dose of the NMDA receptor agonist NMDA (75mg/kg, i.p.). Our data suggest a role for NMDA receptor signaling in the antidepressant-like effects of tramadol in the mFST. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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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

The antidepressant-like effect of 7-fluoro-1,3-diphenylisoquinoline-1-amine in the mouse forced swimming test is mediated by serotonergic and dopaminergic systems.

Science.gov (United States)

Pesarico, Ana Paula; Sampaio, Tuane Bazanella; Stangherlin, Eluza Curte; Mantovani, Anderson C; Zeni, Gilson; Nogueira, Cristina Wayne

2014-10-03

The aim of the present study was to investigate the role of monoaminergic system in the antidepressant-like action of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a derivative of isoquinoline class, in Swiss mice. The antidepressant-like effect of FDPI was characterized in the modified forced swimming test (FST) and the possible mechanism of action was investigated by using serotonergic, dopaminergic and noradrenergic antagonists. Monoamine oxidase (MAO) activity and [(3)H]serotonin (5-HT) uptake were determined in prefrontal cortices of mice. The results showed that FDPI (1, 10 and 20mg/kg, i.g.) reduced the immobility time and increased the swimming time but did not alter climbing time in the modified FST. These effects were similar to those of paroxetine (8mg/kg, i.p.), a positive control. Pretreatments with p-chlorophenylalanine (100mg/kg, i.p., an inhibitor of 5-HT synthesis), WAY100635 (0.1mg/kg, s.c., 5-HT1A antagonist), ondansetron (1mg/kg, i.p., a 5-HT3 receptor antagonist), haloperidol (0.2mg/kg, i.p., a non-selective D2 receptor antagonist) and SCH23390 (0.05mg/kg, s.c., a D1 receptor antagonist) were effective to block the antidepressant-like effect of FDPI at a dose of 1mg/kg in the FST. Ritanserin (1mg/kg, i.p., a 5-HT2A/2C receptor antagonist), sulpiride (50mg/kg, i.p., a D2 and D3 receptor antagonist), prazosin (1mg/kg, i.p., an α1 receptor antagonist), yohimbine (1mg/kg, i.p., an α2 receptor antagonist) and propranolol (2mg/kg, i.p., a β receptor antagonist) did not modify the effect of FDPI in the FST. FDPI did not change synaptosomal [(3)H]5-HT uptake. At doses of 10 and 20mg/kg FDPI inhibited MAO-A and MAO-B activities. These results suggest that antidepressant-like effect of FDPI is mediated mostly by serotonergic and dopaminergic systems. Copyright © 2014 Elsevier Inc. All rights reserved.

Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test.

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Ostadhadi, Sattar; Ahangari, Mohammad; Nikoui, Vahid; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Jazaeri, Farahnaz; Chamanara, Mohsen; Akbarian, Reyhaneh; Dehpour, Ahmad-Reza

2016-08-01

Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (P<0.01) without any effect on locomotor activity in the open-field test (OFT), while higher dose of lamotrigine (30mg/kg) reduced the immobility time in the FST (P<0.001) as well as the number of crossings in the OFT. Pretreatment of animals with NMDA (75mg/kg), l-arginine (750mg/kg, a substrate for nitric oxide synthase [NOS]) or sildenafil (5mg/kg, a phosphodiesterase [PDE] 5 inhibitor) reversed the antidepressant-like effect of lamotrigine (10mg/kg) in the FST. Injection of l-nitroarginine methyl ester (l-NAME, 10mg/kg, a non-specific NOS inhibitor), 7-nitroindazole (30mg/kg, a neuronal NOS inhibitor), methylene blue (20mg/kg, an inhibitor of both NOS and soluble guanylate cyclase [sGC]), or MK-801 (0.05mg/kg), ketamine (1mg/kg), and magnesium sulfate (10mg/kg) as NMDA receptor antagonists in combination with a sub-effective dose of lamotrigine (5mg/kg) diminished the immobility time of animals in the FST compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the OFT. Based on our findings, it is suggested that the antidepressant-like effect of lamotrigine might mediated through inhibition of either NMDA receptors or NO-cGMP synthesis. Copyright © 2016. Published by Elsevier Masson SAS.

Toxicity status and anti-ulcerative potential of Sanseviera trifasciata leaf extract in wistar rats

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Osaseaga Macdonald Ighodaro

2017-06-01

Full Text Available Aims: The lethal dose (LD50 and anti-ulcerative potentials of Sansevieria trifasciata (ST leaf extract were investigated. Methods: LD50 was determined through two routes of administration (intraperitoneal and oral using the method of Lorke. The anti-ulcerative activity was evaluated in indomethacin-induced ulcer model (40 mg/kg BW, i.p, single dose against a reference drug, Cimetidine (100 mg/kg BW, per ox (p.o. ST was assessed at two different doses (200 and 400 mg/kg BW, p.o. Treatments were done twice daily at 8 h interval for 7 days prior to indomethacin injection. Results: The intraperitoneal (i.p LD50 was determined as 774.60 mg/kg BW and oral administration of the extract at 18,000 mg/kg BW dosage did not cause any negative behavioral changes in the animals, and no mortality was recorded after 24h of the experiment. ST- pre-treated animals showed some improvement against indomethacin-induced ulceration. The extract was able to an extent prevent indomethacin-induced reduction in gastric volume (36.1 %, free acidity (55.3 %, total acidity (35.6 % while minimizing increase in pH by (13.3 %. Moreover, the extract showed 17.92% and 14.96 % ulcer-protective ability at 200 and 400 mg/kg BW respectively. The phytochemical analysis of ST extract revealed the presence of phytoconstituents such as glycosides, saponins, flavonoids, terpenoids, alkaloids, tannins, Anthraquinone and glycosides. Conclusions: Sansevieria trifasciata apparently has a promising anti-ulcerative potential, and is safe for use in folk medicine. This valuable medicinal property is probably due to the array of important phytochemicals contained in the plant as observed in this study. However, further study involving bioassay-guided identification of the main anti-ulcerative compound in ST is required to establish the use of the plant as a viable anti-ulcerative agent. [J Complement Med Res 2017; 6(2.000: 234-239

Comparative antioxidant and hypoglycaemic effects of aqueous ...

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DEYAKS PLC

2013-10-02

Oct 2, 2013 ... rats. Diabetes was induced intraperitoneally using 50 mg/kg streptozotocin, while ... causes long-term complications in many organs. ..... Iwueke AV, Nwodo OFC, Okoli CO (2006) not cited. ... Regulation of geneexpression by.

Pros and cons of intraperitoneal chemotherapy in the treatment of epithelial ovarian cancer.

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Zeimet, Alain G; Reimer, Daniel; Radl, Alice C; Reinthaller, Alexander; Schauer, Christian; Petru, Edgar; Concin, Nicole; Braun, Stephan; Marth, Christian

2009-07-01

Development of the pros and cons of intraperitoneal (IP) chemotherapy in the treatment of epithelial ovarian cancer based on the most prominent data published on the evolution of IP chemotherapy and on experience with this therapeutic strategy in clinical routine. The literature published on IP chemotherapy in ovarian cancer between 1970 and 2008 was identified systematically by computer-based searches in MEDLINE and the Cochrane Library. Furthermore, a preliminary analysis of data recorded during an observational nationwide multicenter study of the Austrian AGO on IP-IV chemotherapy using the GOG-172 treatment regimen was performed. The literature review unequivocally revealed a significantly greater toxicity for IP than for intravenous (IV) cisplatin-based chemotherapy. However, according to a Cochrane meta-analysis, IP-IV administration of chemotherapy is associated with a 21.6% decrease in the risk for death. In agreement with earlier reports, the most frequently mentioned side-effects in the Austria-wide observational study were long-lasting neurotoxicity, abdominal pain, fatigue, gastrointestinal and metabolic toxicities, and catheter-related complications. Most of these toxicities were identified as mirroring the toxicity profile of high-dose IV cisplatin (>or=100 mg/m(2)). In some patients, the classic IP-IV regimen with cisplatin/paclitaxel was changed to an alternative schedule comprising carboplatin AUC 5 (d1) and weekly paclitaxel 60 mg/m(2) (d1, 8, 15) completely administered via the IP route. This treatment was better tolerated and quality of life was significantly less compromised. However, neutropenia and thrombocytopenia were the limiting side-effects of this IP regimen. In cases where optimal cytoreduction with residual disease 1 cm was achieved during primary surgery and disease was confined to the peritoneal cavity, IP chemotherapy should be given serious consideration, even at the expense of significantly increased, but manageable toxicity.

Antidepressant effect of pramipexole in mice forced swimming test: A cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway.

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Ostadhadi, Sattar; Imran Khan, Muhammad; Norouzi-Javidan, Abbas; Dehpour, Ahmad-Reza

2016-07-01

Pramipexole is a dopamine D2 receptor agonist indicated for treating Parkinson disorder. This study was aimed to investigate the effect of pramipexole in forced swimming test (FST) in mice and the possible involvement of activation of D2 receptors and inhibition of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) on this effect. Intraperitoneal administration of pramipexole (1-3mg/kg) reduced the immobility time in the FST similar to fluoxetine (20mg/kg, i.p.). This effect of pramipexole (1mg/kg, i.p.) was ceased when mice were pretreated with haloperidol (0.15mg/kg, i.p,) and sulpiride (5mg/kg, i.p) as D2 receptor antagonists, NMDA (75mg/kg,i.p.), l-arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.05mg/kg, i.p., a NMDA receptor antagonist) l-NG-Nitro arginine methyl ester (l-NAME, 10mg/kg, i.p., a non-specific nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (30mg/kg, i.p., a neuronal NOS inhibitor) and methylene blue (10mg/kg, i.p.), an inhibitor of both NOS and soluble guanylyl cyclase (sGC) in combination with the sub-effective dose of pramipexole (0.3mg/kg, i.p.) reduced the immobility. Altogether, our data suggest that the antidepressant-like effect of pramipexole is dependent on the activation of D2 receptor and inhibition of either NMDA receptors and/or NO-cGMP synthesis. These results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of pramipexole and reinforce the role of D2 receptors, NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant mechanism of this agent. Copyright © 2016. Published by Elsevier Masson SAS.

Anticonvulsant effect of Uncaria rhynchophylla (Miq) Jack. in rats with kainic acid-induced epileptic seizure.

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Hsieh, C L; Chen, M F; Li, T C; Li, S C; Tang, N Y; Hsieh, C T; Pon, C Z; Lin, J G

1999-01-01

This study investigated the anticonvulsant effect of Uncaria rhynchophylla (UR) and the physiological mechanisms of its action in rats. A total of 70 male Sprague-Dawley (SD) rats were selected for study. Thirty four of these rats were divided into 5 groups as follows: 1) CONTROL GROUP (n = 6): received intraperitoneal injection (i.p.) of kainic acid (KA, 12 mg/kg); 2) UR1000 group (n = 10), 3) UR500 group (n = 6) 4) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 5) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Behavior and EEG were monitored from 15 min prior to drug administration to 3 hours after KA administration. The number of wet dog shakes were counted at 10 min intervals throughout the experimental course. The remaining 36 rats were used to measure the lipid peroxide level in the cerebral cortex one hour after KA administration. These rats were divided into 6 groups of 6 rats as follows: 1) Normal group: no treatment was given; 2) CONTROL GROUP: received KA (12 mg/kg) i.p.; 3) UR1000 group, 4) UR500 group, 5) UR250 group, received UR 1000, 500, 250 mg/kg i.p. 30 min prior to KA administration, respectively; 6) Contrast group: received carbamazepine 20 mg/kg i.p. 30 min prior to KA administration. Our results indicated that both UR 1000 and 500 mg/kg decreased the incidence of KA-induced wet dog shakes, no similar effect was observed in the UR 250 mg/kg and carbamazepine 20 mg/kg group. Treatment with UR 1000 mg/kg, 500 mg/kg, or 250 mg/kg and carbamazepine 20 mg/kg decreased KA-induced lipid peroxide level in the cerebral cortex and was dose-dependent. These findings suggest that the anticonvulsant effect of UR possibly results from its suppressive effect on lipid peroxidation in the brain.

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

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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.

Effect of interleukin-1beta on the behavior of rats during mild stress in the open-field test.

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Pertsov, S S; Koplik, E V; Simbirtsev, A S; Kalinichenko, L S

2009-11-01

We studied the effect of interleukin-1beta on the behavior of rats with different individual typological characteristics during mild stress in the open-field test. Intraperitoneal injection of interleukin-1beta (5 microg/kg, 108 U/mg) was followed by a decrease in orientation and exploratory activity of passive and, particularly, of active animals in the open field. As differentiated from rats receiving physiological saline, the initial differences in behavioral characteristics of active and passive animals were not revealed in the repeated test after injection of interleukin-1beta. We conclude that interleukin-1beta abolishes the behavioral differences between active and passive specimens in the open field. These data suggest that administration of interleukin-1beta to rats leads to reorganization of the mechanisms for emotional evaluation of adverse emotiogenic factors under conditions of mild stress in the open-field test.

In vitro and mouse in vivo characterization of the potent free fatty acid 1 receptor agonist TUG-469

DEFF Research Database (Denmark)

Urban, C; Hamacher, A; Partke, H J

2013-01-01

in vitro potency of TUG-469 compared to the reference FFA1 agonist GW9508 and to prove in vivo activity in a pre-diabetic mouse model. The in vitro pharmacology of TUG-469 was studied using Ca(2+)-, cAMP-, and impedance-based assays at recombinant FFA1 and free fatty acid receptor 4, formerly known as GPR......120 (FFA4) expressing 1321N1 cells and the rat insulinoma cell line INS-1. Furthermore, we investigated the systemic effect of TUG-469 on glucose tolerance in pre-diabetic New Zealand obese (NZO) mice performing a glucose tolerance test after intraperitoneal administration of 5 mg/kg TUG-469...... significantly improved glucose tolerance in pre-diabetic NZO mice. TUG-469 turned out as a promising candidate for further drug development of FFA1 agonists for treatment of type 2 diabetes mellitus....

Detection of Respiratory Adverse Events in Pediatric Dental Patients Sedated With 0.75mg/Kg of Midazolam and Oxygen by Continuous Pretracheal Auscultation: A Prospective Randomized Controlled Trial.

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Somri, Mostafa; Matter, Ibrahim; Hadjittofi, Christopher; Hoash, Naser; Moaddi, Bian; Kharouba, Johnny; Parisinos, Constantinos A; Peretz, Benjamin

Sedation is becoming more commonplace for pediatric patients undergoing minor procedures. Fortunately, electronic monitors have contributed to a reduction in the associated respiratory adverse events (RAEs). To test the hypothesis that adding the pretracheal stethoscope (PTS) to standard monitoring methods (SMMs) may improve RAE detection in sedated pediatric dental patients, the frequency of RAEs detected by SMMs (i.e. visual observation, capnography, and pulse oximetry) was compared to that detected by SMMs alongside continuous PTS auscultation. A prospective, randomised, controlled trial was performed with 100 pediatric patient participants of ASA≤2, who were scheduled to receive dental treatment under 0.75 mg/kg and oxygen. Patients were randomised into Groups A (n=50; SMMs) and B (n=50; SMMs+PTS). Inclusion criteria were behavioral management problems and intolerance to dental treatment despite behavioral management techniques or nitrous oxide administration. Exclusion criteria were high-risk conditions for RAEs, altered mental status, gastrointestinal disorders, parental refusal of conscious sedation and failure of previous conscious sedation. An anesthesist was present throughout the dental treatments. RAEs were detected in 10 (20%) and 22(44%) Group A and B patients respectively (p=0.01). The majority of RAEs within Group B were detected by PTS auscultation (n=19). Capnography produced 13 and 15 false-positive results in Groups A and B respectively, whereas the PTS produced 4(8%) false-positive results in Group B (p=0.009). PTS was found to be useful for detecting RAEs during pediatric dental sedation with 0.75mg/kg midazolam and oxygen, in the presence of an anesthesist.

Salvianolic Acid A Protects the Peripheral Nerve Function in Diabetic Rats through Regulation of the AMPK-PGC1α-Sirt3 Axis

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Guanhua Du

2012-09-01

Full Text Available Salvianolic acid A (SalA is one of the main efficacious, water-soluble constituents of Salvia miltiorrhiza Bunge. This study investigated the protective effects of SalA on peripheral nerve in diabetic rats. Administration of SalA (0.3, 1 and 3 mg/kg, ig was started from the 5th week after strepotozotocin (STZ60 mg/kg intraperitoneal injection and continued for 8 weeks. Paw withdrawal mechanical threshold (PWMT and motor nerve conduction velocity (MNCV were used to assess peripheral nerve function. The western blot methods were employed to test the expression levels of serine-threonine liver kinase B1 (LKB1, AMP-activated protein kinase (AMPK, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α, silent information regulator protein3 (sirtuin 3/Sirt3 and neuronal nitric oxide synthase (nNOS in sciatic nerve. Results showed that SalA administration could increase PWMT and MNCV in diabetic rats; reduce the deterioration of sciatic nerve pathology; increase AMPK phosphorylation level, up-regulate PGC-1α, Sirt3 and nNOS expression, but had no influence on LKB1. These results suggest that SalA has protective effects against diabetic neuropathy. The beneficial effects of SalA on peripheral nerve function in diabetic rats might be attributed to improvements in glucose metabolism through regulation of the AMPK-PGC1α-Sirt3 axis.

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

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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

GABA(A) receptor antagonism in the ventrocaudal periaqueductal gray increases anxiety in the anxiety-resistant postpartum rat.

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Miller, Stephanie M; Piasecki, Christopher C; Peabody, Mitchell F; Lonstein, Joseph S

2010-06-01

Postpartum mammals show suppressed anxiety, which is necessary for their ability to appropriately care for offspring. It is parsimonious to suggest that the neurobiological basis of this reduced anxiety is similar to that of non-parturient animals, involving GABA(A) receptor activity in sites including the midbrain periaqueductal gray (PAG). In Experiment 1, postpartum and diestrous virgin female rats received an intraperitoneal injection of the GABA(A) receptor antagonist (+)-bicuculline (0, 2 and 4 mg/kg) and anxiety-related behavior was assessed with an elevated plus maze. The 4 mg/kg dose of (+)-bicuculline significantly increased anxiety-related behavior, particularly in the postpartum females. Experiment 2 revealed that bicuculline's action was within the central nervous system, because anxiety in neither dams nor virgins was significantly affected by intraperitoneal injection of bicuculline methiodide (0, 2 and 6 mg/kg), which does not readily cross the blood-brain-barrier. In Experiment 3, bicuculline methiodide (2.5 ng/side) was directly infused into the ventrocaudal PAG (cPAGv) and significantly increased dams' anxiety compared to saline-infused controls. These studies expand our knowledge of how GABA(A) receptor modulators affect anxiety behaviors in postpartum rats to the widely-used elevated plus maze, and indicate that the postpartum suppression of anxiety is in part a consequence of elevated GABAergic neurotransmission in the cPAGv. Copyright 2010 Elsevier Inc. All rights reserved.

The effect of O-1602, an atypical cannabinoid, on morphine-induced conditioned place preference and physical dependence.

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Alavi, Mohaddeseh Sadat; Hosseinzadeh, Hossein; Shamsizadeh, Ali; Roohbakhsh, Ali

2016-06-01

Previous studies show that some non-CB1/non-CB2 effects of cannabinoids are mediated through G protein coupled receptor 55 (GPR55). As this receptor is activated by some of cannabinoid receptor ligands and is involved in the modulation of pain, it was hypothesized that this receptor may also interact with opioids. This study examined the effect of atypical cannabinoid O-1602 as a GPR55 agonist on morphine-induced conditioned place preference (CPP) and physical dependence. We used a biased CPP model to evaluate the effect of O-1602 (0.2, 1 and 5mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP in male mice. The locomotor activities of mice were also recorded. Moreover, repeated administration of morphine (50, 50 and 75mg/kg/day) for three days, induced physical dependence. The withdrawal signs such as jumps and diarrhea were precipitated by administration of naloxone (5mg/kg, ip). The effect of O-1602 on the development of morphine physical dependence was assessed by injection of O-1602 (0.2, 1 and 5mg/kg) before morphine administrations. Morphine (40mg/kg, subcutaneous; sc), but not O-1602 (5mg/kg) elicited significant preference in the post-conditioning phase. O-1602 at the doses of 0.2 and 1mg/kg, but not 5mg/kg reduced acquisition of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 at the doses of 0.2, 1 and 5mg/kg also reduced expression of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 had a significant inhibitory effect on development of morphine-induced physical dependence at the dose of 5mg/kg by decreasing jumps and diarrhea during withdrawal syndrome. The present results indicate that O-1602 decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

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Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

2014-04-01

The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Lithium attenuates cannabinoid-induced dependence in the animal model: involvement of phosphorylated ERK1/2 and GSK-3β signaling pathways.

Directory of Open Access Journals (Sweden)

Hamid Reza Rahimi

2014-09-01

Full Text Available Cannabis is one of the most banned drugs in the world. Cannabinoid-induced dependence or withdrawal signs are indicated by the result of complex molecular mechanisms including upstream protein kinases (PKs, such as an extracellular signal regulated kinase1/2 (ERK1/2 and downstream glycogen synthase kinase-3β (GSK-3β, which lead to neuronal plasticity. In this study, we examined the protective effect of lithium (Li as a potent ERK1/2 and GSK-3β modulator to prevent the development of dependence on cannabinoids. For this purpose, rats were treated twice daily with increasing doses of WIN 55,212-2 (WIN, 2-8 mg/kg, intraperitoneally (i.p., for five consecutive days. AM251 (AM, 2 mg/kg, a cannabinoid antagonist, was injected i.p to induce manifestations of abstinence in rat dependency on WIN, and the subsequent withdrawal signs were recorded. To evaluate the preventive effect of Li, the rats were pre-treated with Li (10 mg/kg, i.p. twice daily, 30 minutes before every injection of WIN. SL327, as an ERK1/2 inhibitor, was also injected (SL, 50 mg/kg, i.p. 30 minutes before the last doses of WIN in separate groups. The p-ERK1/2, total ERK1/2, p-GSK-3β and total GSK-3β expressions were determined with Western blot method after 60 minutes, prior to the Li, WIN or AM injections. Li and SL pre-treatment attenuated the global withdrawal signs in regarding their modulation effect on the up-regulation of p-ERK1/2 cascade enhanced by AM injection. Furthermore, the p-GSK-3β expression was up-regulated with SL and Li pre-treatment against AM injection, without alteration on the total contents of ERK1/2 and GSK-3β level. Therefore, p-ERK1/2 and p-GSK-3β pathways are involved in the cannabinoid-induced dependence. However, no crosstalk was indicated between these two pathways. In conclusion, Li neuroprotectionwith regard to cannabinoid abstinence may occur through the regulation of the p-ERK1/2 cascade inconsequent of p-GSK-3β signaling pathways in rats.

Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice.

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Ghumatkar, Priya J; Patil, Sachin P; Jain, Pankaj D; Tambe, Rufi M; Sathaye, Sadhana

2015-08-01

Phloretin (PHL), a dihydrochalcone flavonoid usually present in the roots and leaves of apple tree. In vitro study on GT1-7 immortalized hypothalamic neurons exposed to amyloid beta (25-35), demonstrated that PHL significantly influenced membrane fluidity and potential. PHL also significantly decreased excitotoxicity by restoring the calcium homeostasis in the same. Thus, PHL proves to be a promising therapeutic moiety which should be further screened in the treatment of Alzheimer's disease. The objective of the present study was to evaluate the nootropic, neuroprotective and neurotrophic roles of PHL in the subacute scopolamine induced amnesia in mice. In this study, mice were pretreated with PHL 2.5mg/kg, 5mg/kg, 10mg/kg and Donepezil (DON) 1mg/kg intraperitoneally (i.p) for 14days. The last 7days of treatment regimen included daily injection of SCP 1.5mg/kg to induce cognitive deficits. Mice were subjected to behavioral analysis. Biochemical estimation of the brain homogenates for acetylcholinesterase and oxidative stress biomarkers were conducted. Furthermore, immunohistochemical analysis for the brain derived neurotrophic factor (BDNF) was carried out particularly in the hippocampus. PHL was found to significantly improve the performance of mice in Morris water maze test (Pnootropic, neuroprotective and neurotrophic activities in SCP induced memory impaired mice and hence, is a promising therapeutic moiety in the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Interference-free determination of sub ng kg-1 levels of long-lived 93Zr in the presence of high concentrations (μg kg-1) of 93Mo and 93Nb using ICP-MS/MS.

Science.gov (United States)

Petrov, Panayot; Russell, Ben; Douglas, David N; Goenaga-Infante, Heidi

2018-01-01

Long-lived high abundance radionuclides are of increasing interest with regard to decommissioning of nuclear sites and longer term nuclear waste storage and disposal. In many cases, no routine technique is available for their measurement in nuclear waste and low-level (ng kg -1 ) environmental samples. Recent advances in ICP-MS technology offer attractive features for the selective and sensitive determination of a wide range of long-lived radionuclides. In this work, inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS)-based methodology, suitable for accurate routine determinations of 93 Zr at very low (ng kg -1 ) levels in the presence of high levels (μg kg -1 ) of the isobaric interferents 93 Nb and 93 Mo (often present in nuclear waste samples), is reported for the first time. Additionally, a novel and systematic strategy for method development based on the use of non-radioactive isotopes is proposed. It relies on gas-phase chemical reactions for different molecular ion formation to achieve isobaric interference removal. Using cell gas mixtures of NH 3 /He/H 2 or H 2 /O 2 , and suitable mass shifts, the signal from the 93 Nb and 93 Mo isobaric interferences on 93 Zr were suppressed by up to 5 orders of magnitude. The achieved limit of detection for 93 Zr was 1.3 × 10 -5  Bq g -1 (equivalent to 0.14 ng kg -1 ). The sample analysis time is 2 min, which represents a significant improvement in terms of sample throughput, compared to liquid scintillation counting methods. The method described here can be used for routine measurements of 93 Zr at environmentally relevant levels. It can also be combined with radiometric techniques for use towards the standardisation of 93 Zr measurements. Graphical abstract Interference-free determination of 93 Zr in the presence of high concentrations of isobaric 93 Mo and 93 Nb by ICP-MS/MS.

Uso de sal durante o transporte de juvenis (1kg de pirarucu (Arapaima gigas Use of salt during the transportation of pirarucu juveniles (1kg (Arapaima gigas

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Franmir Rodrigues Brandão

2008-12-01

Full Text Available O pirarucu é um peixe nativo da bacia Amazônica cuja criaçãovem sendo estudada em algumas partes do Brasil. O objetivo desse trabalho foi testar o sal de cozinha como mitigador de estresse durante o transporte de juvenis de pirarucu (1 kg. Para isso, os peixes foram transportados em dois diferentes sistemas: caixas sem adição de oxigênio (transporte aberto e sacos plásticos com injeção de oxigênio e lacrado (transporte fechado. Nos dois sistemas os peixes foram transportados em três diferentes tratamentos: controle e duas concentrações de sal na água (3 e 6 g.L-1. Após o transporte os peixes foram colocados em viveiros para avaliação da recuperação. Foram analisados parâmetros do metabolismo energético (cortisol, glicose e lactato e de hematologia (hematócrito. O sal de cozinha não foi eficiente em mitigar as respostas de estresse no transporte em nenhum dos dois sistemas de transporte estudados.Pirarucu is a native fish of the Amazon basin, widely used in culture systems in some parts of Brazil. The objective of this work was to test table salt as a stress mitigator during transportation of pirarucu juveniles (1kg. Fish were transported by two different systems: boxes without addition of oxygen (open system and closed oxygen filled plastic bags (closed system. To both systems fish were transported at three different treatments: control and two table salt concentration (3 and 6 gL-1. After transportation, fish were stocked in ponds to monitor recovery. Metabolic (cortisol, glucose and lactate and hematological (hematocrit parameters were analyzed. The table salt was not efficient in mitigating stress response during the both tested transport system.

Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

International Nuclear Information System (INIS)

Shaker, Mohamed E.; Zalata, Khaled R.; Mehal, Wajahat Z.; Shiha, Gamal E.; Ibrahim, Tarek M.

2011-01-01

Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl 4 ) rat model. Male Wistar rats received intraperitoneal injections of CCl 4 twice weekly for 8 weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20 mg/kg), nilotinib (10 and 20 mg/kg) and silymarin (100 mg/kg) during the last 4 weeks of CCl 4 -intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20 mg/kg) was the most effective treatment to counteract CCl 4 -induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10 mg/kg), nilotinib (20 mg/kg) and silymarin (100 mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl 4 -treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl 4 -induced fibrosis was ameliorated significantly by nilotinib (20 mg/kg) and imatinib (20 mg/kg). Unlike nilotinib, imatinib (20 mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans. - Graphical abstract: Display Omitted Research Highlights: → The anti-fibrotic effects of imatinib, nilotinib and silymarin were compared. → These effects were