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Sample records for cimetidine

  1. Cimetidin og kreatininclearance

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Ladefoged, S D; Feldt-Rasmussen, B F;

    1989-01-01

    Cimetidine lowers secretion of creatinine in the renal tubuli in healthy individuals and persons with chronic renal disease. The conditions in patients with renal transplants have hitherto been unknown. The renal clearance of endogenic creatinine (CKrea) was investigated prior to and after....... The fractionated creatinine clearance (CKrea/CTh) fell therefore from 1.43 (median) to 1.03 (p less than 0.01). It is concluded that cimetidine reduces creatinine secretion in patients with renal transplants and this should be borne in mind when the function of the graft is assessed solely with CKrea....

  2. Compound list: cimetidine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available cimetidine CIM 00035 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/cimetidin...e.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/cimetidin...e.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/cimetidin...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/cimetidine.Rat.in_vivo.Liver.Repeat.zip ...

  3. Treatment of hirsutism with cimetidine.

    Science.gov (United States)

    Golditch, I M; Price, V H

    1990-06-01

    We evaluated the efficacy of long-term cimetidine in treating hirsutism by monitoring four indices: subjective hair removal practice, grading of hair growth by the Lorenzo scale, photography, and hair weight measurement. Of 20 women with moderate to severe facial hirsutism treated with cimetidine, 300 mg four times daily, nine were followed for 48 weeks or longer. Of these nine subjects who completed 48-72 weeks of treatment, only two showed a decrease in hirsutism. None of the 11 subjects treated for less than 48 weeks had any decrease in hirsutism. We conclude that cimetidine, a weak antiandrogen, is not sufficiently effective to use in the treatment of hirsutism.

  4. Effects of cimetidine on haematopoiesis in vitro.

    Science.gov (United States)

    Calzado, M. C.; Garcia-Castellano, J. M.; Manzanares, R. M.; Martinez, F.; Prieto, B.; Torres, A.

    1982-01-01

    The possible modifications in haematopoiesis induced by cimetidine were studied in normal bone marrow cultures in vitro. When cimetidine was added in the therapeutic range, there was no significant change in either granulocytic-macrophagic (CFU-GM) or erythroid (BFU-E) colony growth. However, when cimetidine was added to the culture at 2 to 25 times the therapeutic range, a small but significant inhibition of both types of colony growth was found. We conclude that cimetidine in the therapeutic range does not induce inhibition of haematopoiesis in vitro but does in doses above the therapeutic range when inhibition is dose-dependent. PMID:7186818

  5. Cimetidine

    Science.gov (United States)

    ... nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); chlordiazepoxide (Librium); clopidogrel (Plavix), diazepam (Valium); lidocaine (Xylocaine); metronidazole (Flagyl); nifedipine (Adalat, Procardia); ...

  6. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    OpenAIRE

    Jantratid, E; Prakongpan, S.; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K.K.; Barends, D M

    2006-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned to Class III. Cimetidine's therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA) pr...

  7. Reduction of metformin renal tubular secretion by cimetidine in man.

    OpenAIRE

    Somogyi, A.; Stockley, C; Keal, J; Rolan, P; Bochner, F

    1987-01-01

    To determine whether cimetidine altered the renal handling of metformin, seven subjects took 0.25 g metformin daily with and without cimetidine 0.4 g twice daily. Blood and urine samples were collected and assayed for metformin, cimetidine and creatinine by h.p.l.c. Cimetidine significantly increased the area under the plasma metformin concentration-time curve by an average of 50% and reduced its renal clearance over 24 h by 27% (P less than 0.008). There was no alteration in the total urinar...

  8. Effect of cimetidine on survival after gastric cancer

    DEFF Research Database (Denmark)

    Tønnesen, H; Knigge, U; Bülow, Steffen

    1988-01-01

    The effect of cimetidine on survival was investigated in 181 patients with gastric cancer. Immediately after operation or the decision not to operate, the patients were randomised in double-blind fashion to placebo or cimetidine 400 mg twice daily for two years or until death, with review every...

  9. Reversible agranulocytosis in association with cimetidine and hepatic failure

    OpenAIRE

    Lewis, D. S.; Beck, E. R.

    1982-01-01

    A patient is described who developed agranulocytosis in the context of hepatic failure and cimetidine therapy. The close temporal relationship between discontinuation of the drug and granulopoietic recovery is considered to imply a role for cimetidine in the mechanism of the agranulocytosis.

  10. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    NARCIS (Netherlands)

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned

  11. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    Science.gov (United States)

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned to Class III. Cimetidine's therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA) problems were also taken into consideration. On the basis of the overall evidence, a biowaiver can be recommended for cimetidine IR products, provided that the test product contains only those excipients reported in this paper in their usual amounts, and that the test and the comparator drug products both are "rapidly dissolving" as per BCS.

  12. Effect of misoprostol and cimetidine on gastric cell labeling index

    Energy Technology Data Exchange (ETDEWEB)

    Fich, A.; Arber, N.; Sestieri, M.; Zajicek, G.; Rachmilewitz, D.

    1985-07-01

    The effect of misoprostol and cimetidine on gastric cell turnover was studied. Endoscopic biopsy specimens of fundic and antral mucosa were obtained from duodenal ulcer patients before and after 4 wk of therapy with cimetidine 1.2 g/day or misoprostol 800 micrograms/day. Biopsy specimens were incubated with (/sup 3/H)thymidine. Glandular column length and number of labeled cells were determined after autoradiography. There was no significant difference in column length of antral or fundic glands before or after therapy with cimetidine and misoprostol. The number of antral and fundic labeled cells was significantly decreased after misoprostol treatment (3.6 +/- 0.3 and 4.6 +/- 0.4, mean +/- SE), as opposed to their respective number before therapy (6.9 +/- 0.5 and 8.3 +/- 0.8) (p less than 0.01). On the other hand, after treatment with cimetidine, the number of antral and fundic labeled cells was significantly higher (11.8 +/- 0.9 and 7.5 +/- 1.0, respectively) as compared with their number before therapy (5.7 +/- 0.5 and 5.6 +/- 0.6, respectively). The decreased gastric cell turnover induced by misoprostol indicates that the trophic effect of prostanoids on gastric mucosa is not due to an increase in cellular kinetics. The increased gastric cell turnover induced by cimetidine may contribute to its therapeutic effect in peptic ulcer disease.

  13. Effect of cimetidine on pentamidine induced hyperglycemia in rats.

    Science.gov (United States)

    Arino, Toru; Karakawa, Seiji; Ishiwata, Yasuyoshi; Nagata, Masashi; Yasuhara, Masato

    2012-10-15

    The antiprotozoal agent pentamidine, used for the treatment of Pneumocystis jirovecii pneumonia (PCP), is known to cause abnormalities in blood glucose homeostasis, such as hypoglycemia and hyperglycemia. Pentamidine has been reported to be a substrate of organic cation transporter 1 (OCT1). We investigated the combination effects of cimetidine, an OCT1 inhibitor, on the pharmacokinetics of pentamidine and on pentamidine-induced hyperglycemia. Pentamidine was infused intravenously to rats for 20 min at a dose of 7.5 or 15 mg/kg and serum samples were obtained periodically. The serum concentration of glucose did not change significantly after pentamidine infusion at 7.5mg/kg, while it increased with pentamidine at 15 mg/kg, and the maximal concentration of glucose was 167 ± 36 mg/dl, 30 min after the start of pentamidine infusion. Cimetidine (50mg/kg) enhanced the pentamidine-induced elevation of glucose concentration and the maximal concentration of glucose was 208 ± 33 mg/dl in the pentamidine 15 mg/kg treated group. Cimetidine combination significantly reduced total body clearance of pentamidine and increased pentamidine concentrations in the liver, kidneys, and lungs. A significant correlation was found between changes in serum glucose concentrations and serum concentrations of pentamidine 30 min after the start of pentamidine infusion. These results suggest that the hyperglycemic effect of pentamidine is dependent on the concentration of pentamidine and can be enhanced by cimetidine combination.

  14. Photochemical fate of pharmaceuticals in the environment: cimetidine and ranitidine.

    Science.gov (United States)

    Latch, Douglas E; Stender, Brian L; Packer, Jennifer L; Arnold, William A; McNeill, Kristopher

    2003-08-01

    The photochemical fates of the histamine H2-receptor antagonists cimetidine and ranitidine were studied. Each of the two environmentally relevant pharmaceuticals displayed high rates of reaction with both singlet oxygen (1O2, O2(1delta(g))) and hydroxyl radical (*OH), two transient oxidants formed in sunlit natural waters. For cimetidine, the bimolecular rate constant for reaction with *OH in water is 6.5 +/- 0.5 x 10(9) M(-1) s(-1). Over the pH range 4-10, cimetidine reacts with 1O2 with bimolecular rate constants ranging from 3.3 +/- 0.3 x 10(6) M(-1) s(-1) at low pH to 2.5 +/- 0.2 x 10(8) M(-1) s(-1) in alkaline solutions. The bimolecular rate constants for ranitidine reacting with 1O2 in water ranges from 1.6 +/- 0.2 x 10(7) M(-1) s(-1) at pH 6-6.4 +/- 0.2 x 10(7) M(-1) s(-1) at pH 10. Reaction of ranitidine hydrochloride with *OH proceeds with a rate constant of 1.5 +/- 0.2 x 10(10) M(-1) s(-1). Ranitidine was also degraded in direct photolysis experiments with a half-life of 35 min under noon summertime sunlight at 45 degrees latitude, while cimetidine was shown to be resistant to direct photolysis. The results of these experiments, combined with the expected steady-state near surface concentrations of 1O2 and *OH, indicate that photooxidation mediated by 1O2 is the likely degradation pathway for cimetidine in most natural waters, and photodegradation by direct photolysis is expected to be the major pathway for ranitidine, with some degradation caused by 1O2. These predictions were verified in studies using Mississippi River water. Model compounds were analyzed by laser flash photolysis experiments to assess which functionalities within ranitidine and cimetidine are most susceptible to singlet-oxygenation and direct photolysis. The heterocyclic moieties of the pharmaceuticals were clearly implicated as the sites of reaction with 1O2, as evidenced by the high relative rate constants of the furan and imidazole models. The nitroacetamidine portion of ranitidine

  15. Cimetidine Pharmacodynamics and Pharmacokinetics in Healthy Subjects: A Comparison of Tablets and Suspension

    Directory of Open Access Journals (Sweden)

    ABR Thomson

    1994-01-01

    Full Text Available The objective of this study was to compare the effect of cimetidine 200 mg tablet with that of cimetidine suspension (200 mg/10 mL, a 20 mL suspension of 800 mg magnesium hydroxide and 912 mg aluminum hydroxide, and matching placebo on intragastric pH of healthy volunteers. There were 13 males and seven females, mean age 23 years (range 20 to 32 and mean weight 72 kg (range 55 to 89. The intragastric pH of each subject was measured over 6 h starting immediately before dosing on each of five study days. Cimetidine plasma levels were measured for 6 h after dosing on each of the cimetidine study days. Cimetidine tablet and suspension were superior to placebo tablet or suspension or to the magnesium hydroxide/aluminum hydroxide suspension in the area under the pH time curve from 0 to 6 h, percentage time pH of at least 3.5, change from pretreatment pH area under the pH time curve (0 to 6 h and maximum increase in pH. Mean plasma cimetidine levels were significantly and positively correlated to mean intragastric pH for both cimetidine tablets and cimetidine suspension. Comparing cimetidine concentration (Cmax and lower percentage time plasma cimetidine concentration was at least 0.5 μg/mL (the minimum therapeutic level. These pharmacokinetic variations between cimetidine suspension and tablets may have partially explained the pharmacodynamic differences of the lower area under the pH time curve (0 to 6 h. The results indicate that both cimetidine tablets and cimetidine suspension significantly increase intragastric pH relative to the magnesium hydroxide/aluminum hydroxide suspension, placebo tablets or placebo suspension. Based on the assumption that elevation of intragastric pH is an important factor for alleviation of the symptoms and for the healing of peptic disorders, the results of this study suggest that both cimetidine tablets and cimetidine suspension should be effective treatment.

  16. Cimetidine as pre-anesthetic agent for cesarean section

    DEFF Research Database (Denmark)

    Qvist, N; Storm, K; Holmskov, A

    1985-01-01

    In a prospective randomized study of 39 consecutive cesarean sections, 20 patients received cimetidine 400 mg intramuscularly as a pre-anesthetic, an 19 control patients were given NaCl. No perinatal effects on the infants were observed by cardiotocography before delivery, and K, Na, pH, PCO2, HCO......-3 and glucose values in capillary blood were nearly identical in the two groups 2 hours after birth, the difference being non-significant (p greater than 0.05). No respiratory effects or arrhythmias were observed. In another study comprising 8 elective cesarean sections in patients...

  17. Ranitidine versus cimetidine prior to emergency obstetric anesthesia.

    Science.gov (United States)

    Osman, H

    1995-06-01

    Twenty parturients in labour received emergency obstetric anesthesia were randomly divided into two equal groups. Group "R" received 150 mg oral ranitidine tablet on admission, followed by 50 mg infusion in 250 ml dextrose 5% over 30 minutes prior to anesthetic induction. Group "Ce" received 400 mg cimetidine oral tablet and 100 mg infusion in 250 ml dextrose 5% over 30 minutes. Ten parturients were considered as control. Ranitidine significantly reduced the maternal gastric volume with marked alkalinization of gastric pH. No significant changes were detected in the height, frequency or amplitude of uterine contraction or neonatal assessment.

  18. Binding of Cimetidine to Balb/C Mouse Liver Catalase; Kinetics and Conformational Studies.

    Science.gov (United States)

    Jahangirvand, Mahboubeh; Minai-Tehrani, Dariush; Yazdi, Fatemeh; Minai-Tehrani, Arash; Razmi, Nematollah

    2016-01-01

    Catalase is responsible for converting hydrogen peroxide (H2O2) into water and oxygen in cells. This enzyme has high affinity for hydrogen peroxide and can protect the cells from oxidative stress damage. Catalase is a tetramer protein and each monomer contains a heme group. Cimetidine is a histamine H2 receptor blocker which inhibits acid release from stomach and is used for gasterointestinal diseases. In this research, effect of cimetidine on the activity of liver catalase was studied and the kinetic parameters of this enzyme and its conformational changes were investigated. Cell free extract of mouse liver was used for the catalase assay. The activity of the catalase was detected in the absence and presence of cimetidine by monitoring hydrogen peroxide reduction absorbance at 240 nm. The purified enzyme was used for conformational studies by Fluorescence spectrophotometry. The data showed that cimetidine could inhibit the enzyme in a non-competitive manner. Ki and IC50 values of the drug were determined to be about 0.75 and 0.85 uM, respectively. The Arrhenius plot showed that activation energy was 6.68 and 4.77 kJ/mol in the presence and absence of the drug, respectively. Fluorescence spectrophotometry revealed that the binding of cimetidine to the purified enzyme induced hyperchromicity and red shift which determined the conformational change on the enzyme. Cimetidine could non-competitively inhibit the liver catalase with high affinity. Binding of cimetidine to the enzyme induced conformational alteration in the enzyme.

  19. [Effect of calcitonin, somatostatin and cimetidine on stress ulcer in rats].

    Science.gov (United States)

    Jakesz, R; Hofbauer, F; Lehr, L; Schiessel, R

    1978-05-01

    The prophylactic effect of calcitonin, somatostatin and cimetidine on stress ulcer formation in rats was investigated in two stress models: restraint + ketamin (4 h) and hypovolemia (4 h). The basis of the comparative study was a 70% inhibition of acid secretion for 4 h in pyloric ligated animals. This was achieved with 1000 microgram/kg somatostatin s.c., 10 microgram/kg calcitonin s.c., and 2 X 100 mumol/kg cimetidine s.c. In restraint stress and ketamin with calcitonin and cimetidine a significantly lower frequency of gastric lesions was found than with somatostatin. The most potent substance in hypovolemia was calcitonin, with a significant difference in the frequency of mucosal lesions to the groups with cimetidine and somatostatin.

  20. The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam.

    OpenAIRE

    1987-01-01

    The effect of cimetidine on the single dose pharmacokinetics of orally administered clobazam and N-desmethylclobazam (NDMC) was studied in volunteers. Cimetidine inhibited the elimination of both clobazam and NDMC and inhibited the rate of formation of NDMC from clobazam. The increase in the AUC for NDMC generated from clobazam was relatively greater than that for clobazam itself. This suggests that NDMC elimination is inhibited to a relatively greater extent than clobazam elimination. The in...

  1. Anti-inflammatory and ulcerogenic effects of indomethacin and tenoxicam in combination with cimetidine.

    Science.gov (United States)

    Maciel, Hermelinda P F; Cardoso, Luiz G V; Ferreira, Luciano R; Perazzo, Fábio F; Carvalho, José Carlos T

    2004-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the modulation of the inflammatory response. However, a number of facts involving the occurrence of gastrointestinal lesions have limited the chronic use of NSAIDs. In order to diminish the occurrence of gastrointestinal damage caused by NSAIDs, the combination of NSAIDs with the H2 receptor blocker, cimetidine, has been evaluated. The anti-inflammatory and ulcerogenic effects of indomethacin and tenoxicam in association with or without cimetidine were determined at pre-clinical levels. It was observed that the group of animals treated with indomethacin and cimetidine, or tenoxicam and cimetidine (10 mg/kg, p.o.) demonstrated a significant reduction (P < 0.05, ANOVA followed by Tukey-Kramer multiple comparison test) of type-III gastric ulcers. Furthermore, indomethacin or tenoxicam (10 mg/kg, p.o.) in association with cimetidine increased the anti-inflammatory activity. The group, which received indomethacin and cimetidine presented the best performance in decreasing the inflammatory process (P < 0.05, ANOVA followed by Tukey-Kramer multiple comparison test).

  2. Functional and structural changes of human erythrocyte catalase induced by cimetidine: proposed model of binding.

    Science.gov (United States)

    Yazdi, Fatemeh; Minai-Tehrani, Dariush; Jahngirvand, Mahboubeh; Almasirad, Ali; Mousavi, Zahra; Masoud, Masoudeh; Mollasalehi, Hamidreza

    2015-06-01

    In erythrocyte, catalase plays an important role to protect cells from hydrogen peroxide toxicity. Hydrogen peroxide is a byproduct compound which is produced during metabolic pathway of cells. Cimetidine, a histamine H2 receptor antagonist, is used for gastrointestinal tract diseases and prevents the extra release of gastric acid. In this study, the effect of cimetidine on the activity of human erythrocyte catalase was investigated. Erythrocytes were broken by hypotonic solution. The supernatant was used for catalase assay and kinetics study. Lineweaver-Burk plot was performed to determine the type of inhibition. The kinetics data revealed that cimetidine inhibited the catalase activity by mixed inhibition. The IC50 (1.54 μM) and Ki (0.45 μM) values of cimetidine determined that the drug was bound to the enzyme with high affinity. Circular dichroism and fluorescence measurement showed that the binding of cimetidine to the enzyme affected the content of secondary structure of the enzyme as well as its conformational changes. Docking studies were carried out to detect the site in which the drug was bound to the enzyme. Molecular modeling and energy calculation of the binding showed that the cyanoguanidine group of the drug connected to Asp59 via two hydrogen bonds, while the imidazole group of the drug interacted with Phe64 in the enzyme by a hydrophobic interaction. In conclusion, cimetidine could bind to human erythrocyte catalase, and its interaction caused functional and conformational changes in the enzyme.

  3. Effects of cimetidine on adenylate cyclase activity of guinea pig gastric mucosa stimulated by histamine, sodium fluoride and 5'-guanylylimidodiphosphate.

    Science.gov (United States)

    Anttila, P; Westermann, E

    1976-08-01

    Cimetidine, a recently developed histamine H2-receptor blocking agent has been shown to be a potent inhibitor of histamine-stimulated gastric acid secretion in rat, cat, dog and man. To study the mode of action of cimetidine the modification of stimulatory effects of histamine, sodium flouride and 5'-guanylylimidodiphosphate by cimetidine on the adenylate cyclase activity of guinea pig gastric mucosa was studied. The effect of cimetidine was also compared to that of metiamide, an older histamine H2-receptor antagonist. The effect of cimetidine was qualitatively similar to that of metiamide, i.e. a selective blockade of histamine H2-receptors. Quantitatively cimetidine was about 10-fold more potent than metiamide.

  4. Lack of effect of cimetidine on the pharmacokinetics and metabolism of a single oral dose of metronidazole

    DEFF Research Database (Denmark)

    Loft, S; Døssing, M; Sonne, J

    1988-01-01

    The time course of the effect of cimetidine on the pharmacokinetics of metronidazole was investigated in 6 healthy volunteers. Cimetidine 1.0 g/day was administered for 9-days and metronidazole 500 mg was administered orally on the second and eighth days, and in a control experiment. During...... cimetidine treatment the plasma kinetics of metronidazole and its partial clearance by renal excretion of the unchanged compound, glucuronidation, hydroxylation and oxidation to its acetic acid metabolite were not significantly different from the control values. The results indicate that cimetidine does...

  5. Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion

    Institute of Scientific and Technical Information of China (English)

    Nan-Hong Tang; Yan-Ling Chen; Xiao-Qian Wang; Xiu-Jin Li; Feng-Zhi Yin; Xiao-Zhong Wang

    2004-01-01

    AIM: To explore the cooperative effects of antisense oligonucleotide (ASON) of cell adhesion molecules and cimetidine on the expression of E-selectin and ICAM-1 in endothelial cells and their adhesion to tumor cells.METHODS: After treatment of endothelial cells with ASON and/or cimetidine and induction with TNF-α, the protein and mRNA changes of E-selectin and ICAM-1 in endothelial cells were examined by flow cytometry and RT-PCR,respectively. The adhesion rates of endothelial cells to tumor cells were measured by cell adhesion experiment.RESULTS: In comparison with TNF-α inducing group, lipoASON and lipo-ASON/cimetidine could significantly decrease the protein and mRNA levels of E-selectin and ICAM-1 in endothelial cells, and lipo-ASON/cimetidine had most significant inhibitory effect on E-selectin expression (from 36.37±1.56% to 14.23±1.07%, P<0.001). Meanwhile,cimetidine alone could inhibit the expression of E-selectin (36.37±1.56% vs 27.2±1.31%, P<0.001), but not ICAM-1 (69.34±2.50% vs68.07±2.10%,P>O.05)and the two kinds of mRNA, either. Compared with TNF-αα inducing group, the rate of adhesion was markedly decreased in lipo-E-selectin ASON and lipo-E-selectin ASON/cimetidine treated groups(P<0.05),and Jipo-E-selectin ASON/cimetidine worked better than lipo-E-selectin ASON alone except for HepG2/ECV304 group(P<0.05). However, the decrease of adhesion was not significant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidine treated groups except for HepG2/ECV304 group (P >0.05).CONCLUSION: These data demonstrate that ASON in combination with cimetidine in vitro can significantly reduce the adhesion between endothelial cells and hepatic or colorectal cancer cells, which is stronger than ASON or cimetidine alone. This study provides some useful proofs for gene therapy of antiadhesion.

  6. Effects of roxatidine acetate hydrochloride and cimetidine on the pharmacokinetics of theophylline in healthy subjects.

    Science.gov (United States)

    Yoshimura, N; Takeuchi, H; Ogata, H; Ishioka, T; Aoi, R

    1989-06-01

    The effects of roxatidine acetate hydrochloride and cimetidine during multiple dosing on the pharmacokinetics of theophylline was studied in nine healthy volunteers, five smokers and four non-smokers, in comparison with placebo treatment. Cimetidine reduced the terminal elimination rate constant and the total body clearance of theophylline from 0.119 to 0.101 h-1 (p less than 0.05) and from 31.2 to 26.5 ml/min (p less than 0.05), respectively, in comparison with those of placebo. There was no significant change in the volume of distribution (16.3 l for placebo and 15.5 l for cimetidine) and the renal clearance (4.5 ml/min for placebo and 3.9 ml/min for cimetidine). Roxatidine acetate hydrochloride did not significantly influence theophylline disposition in comparison with placebo treatment. The interaction of cimetidine on theophylline disposition was observed in both smokers and non-smokers, but the degree was greater in smokers.

  7. The effect of cimetidine on platelet function: a study involving gastric fluid measurements.

    Science.gov (United States)

    Mikhailidis, D P; Christofides, J; Barradas, M A; Jeremy, J Y; Dilawari, J; Dandona, P

    1986-10-01

    Gastric fluid samples were aspirated 30 and 60 minutes after the ingestion of two 200 mg tablets of cimetidine. The concentration of cimetidine in these samples was measured and their effect on platelet aggregation assessed in vitro. Gastric fluid samples significantly inhibited adrenaline- and ADP-induced platelet aggregation in vitro. In a further series of experiments, cimetidine solutions, at concentrations found in gastric fluid, inhibited platelet aggregation and thromboxane A2 (TXA2) release, in vitro. Ranitidine, another H2-receptor antagonist, was a more potent inhibitor of platelet aggregation than cimetidine. Since ranitidine is also the more potent H2-receptor antagonist which, unlike cimetidine, does not include an imidazole group (which is known to inhibit TXA2 synthesis) in its structure, we conclude that H2 blockade mediates the observed inhibition of aggregation. This platelet anti-aggregatory effect may be relevant to haemostatic mechanisms involved in bleeding peptic ulcers or gastric erosions exposed to high local concentrations of H2-receptor antagonists.

  8. Pharmacokinetic interaction between ϵ-acetamidocaproic acid (AACA) and cimetidine in indomethacin-induced acute gastric ulcer and control rats: inhibition of active renal secretion of AACA by cimetidine.

    Science.gov (United States)

    Choi, Y H; Lee, U; Suh, J H; Kim, Y G; Lee, M; Oh, E; Lee, M G

    2011-05-01

    After both the intravenous and oral administration of zinc acexamate [ZAC; ion-pairing between zinc and ϵ-acetamidocaproic acid (AACA)] and cimetidine together, the areas under the curve (AUCs) of AACA were significantly greater [by 28.2 and 98.9% after the intravenous and oral administration, respectively, for control rats and 13.5 and 16.9% for indomethacin-induced acute gastric ulcer (IAGU) rats, respectively] than those of ZAC alone due to the significantly slower renal clearance (CL(R)). The significantly greater AUCs of AACA after both the intravenous and oral administration of ZAC and cimetidine together in control and IAGU rats could have been due to the inhibition of active renal tubular secretion of AACA by cimetidine. After the intravenous and oral administration of both drugs together, the AUCs of cimetidine in control and IAGU rats were not different compared with those with cimetidine alone.

  9. Influence of cimetidine and its metabolites on Cisplatin-Investigation of adduct formation by means of electrochemistry/liquid chromatography/electrospray mass spectrometry

    NARCIS (Netherlands)

    Brauckmann, Christine; Faber, Helene; Lanvers-Kaminsky, Claudia; Sperling, Michael; Karst, Uwe

    2013-01-01

    Cimetidine has been studied as an additive in cancer chemotherapy. It is claimed to reduce the side effects of Cisplatin. This study focuses on possible interactions between Cisplatin and cimetidine on the molecular level. Due to the fact that cimetidine is metabolized in the liver, interactions bet

  10. Effect of cimetidine on catalase activity of Pseudomonas aeruginosa: a suggested mechanism of action.

    Science.gov (United States)

    Masoud, Masoudeh; Ebrahimi, Farnoosh; Minai-Tehrani, Dariush

    2014-01-01

    Catalase is an important enzyme for the degradation of hydrogen peroxide in cells. Bacteria have potent catalase to deal with H2O2 in their medium culture. Any chemicals that inhibit catalase activity can be harmful for cells. Histamine H2 antagonist drugs such as cimetidine and ranitidine are used for the treatment of gastrointestinal tract disorders. The present results showed that cimetidine could inhibit the catalase activity of Pseudomonas aeruginosa in a competitive inhibition. The determination of IC50 value and Ki (6.5 μM) of cimetidine demonstrated that the enzyme binds to the drug with high affinity. Binding of the drug to the enzyme was pH-dependent and no binding was observed at basic pH (>9) and acidic pH (catalase activity.

  11. Protective effects of cimetidine on micronucleated polychromatic erythrocytes in mice irradiated with 0.7Gy

    Directory of Open Access Journals (Sweden)

    Jun-ling ZHANG

    2016-01-01

    Full Text Available Objective  To study the radioprotective effect of cimetidine on single low-dose irradiated mice with radiosensitive detection indexes. Methods  Forty-eight healthy male C57BL/6 mice were randomly divided into normal control group, model control group, positive group (200mg/kg WR2721 and cimetidine groups (7.5mg/kg, 15mg/kg and 30mg/kg. The mice were given intraperitoneal injection of cimetidine 2h before irradiation in cimetidine groups and WR2721 before irradiation once a day for two days in positive group. All the mice except those in normal control group were irradiated with 0.7Gy 60Co γ-ray at 5.83mGy/min rate. Peripheral blood cells, superoxide dismutase (SOD activity and malondialdehyde (MDA content both in serum and liver, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMPEs were determined 24h after irradiation. Results  Compared with normal control group, the peripheral white blood cells (WBCs of irradiated mice decreased significantly (P<0.01, and fMPEs increased significantly (P<0.01 after irradiation. Except for 15mg/kg cimetidine group, the bone marrow DNA content was decreased significantly after irradiation (P<0.01, P<0.05. The SOD activity and MDA content in irradiated mice showed no significant difference compared with that of normal mice. Compared with model control group, peripheral WBCs and bone marrow DNA content showed no significant changes in treatment groups. The f MPE of 7.5mg/kg cimetidine group was 0.027‰, which was decreased significantly compared with that of model control group (P<0.01, and the dose reduction factor (DRF of 7.5mg/kg cimetidine group was 3.338. Conclusion  Cimetidine has good protective effect on micronucleated polychromatic erythrocytes (MPEs in mice irradiated by 0.7Gy in single low-dose. DOI: 10.11855/j.issn.0577-7402.2015.12.03

  12. The topological phase diagram of cimetidine: A case of overall monotropy.

    Science.gov (United States)

    Céolin, R; Rietveld, I B

    2017-03-01

    Cimetidine is a histamine H2-receptor antagonist used against peptic ulcers. It is known to exhibit crystalline polymorphism. Forms A and D melt within 0.35 degrees from each other and the enthalpies of fusion are similar as well. The present paper demonstrates how to construct a pressure-temperature phase diagram with only calorimetric and volumetric data available. The phase diagram provides the stability domains and the phase equilibria for the phases A, D, the liquid and the vapor. Cimetidine is overall monotropic with form D the only stable solid phase.

  13. Neither cimetidine nor probenecid affect the pharmacokinetics of tenoxicam in normal volunteers.

    Science.gov (United States)

    Day, R O; Geisslinger, G; Paull, P; Williams, K M

    1994-01-01

    The effect of pretreatment with cimetidine (1 g day-1, 7 days) and of probenecid (1 g twice daily, 4 days) on the pharmacokinetics of tenoxicam (single oral dose, 20 mg) was studied in six healthy volunteers. Cmax was increased significantly when tenoxicam was given with probenecid (2.8 micrograms ml-1 alone, 3.5 micrograms ml-1 after probenecid; P < 0.005). No other pharmacokinetic parameters were altered significantly by either drug. It is concluded that neither cimetidine nor probenecid affects the pharmacokinetics of tenoxicam in a clinically important way. PMID:8148224

  14. Factitious urticaria (dermographism): treatment by cimetidine and chlorpheniramine in a randomized double-blind study.

    Science.gov (United States)

    Kaur, S; Greaves, M; Eftekhari, N

    1981-02-01

    The HI-antihistamine chlorpheniramine and the H2-antihistamine cimetidine, given alone and in combination, have been compared with placebo in twenty patients with factitious urticaria (dermographism), in a double-blind, randomized cross-over trial. Of these regimes, the combination was the only treatment which significantly reduced weal size, flare size and duration of weal, compared with placebo, although other treatments approached statistical significance. Continuation of the most effective of the four treatments in nineteen of the patients for a further 3 months without breaking the randomization code provided further evidence of the great effectivness of combined cimetidine and chlorpheniramine. No significant side effects were note.

  15. Investigation of physical properties and stability of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems prepared by quench cooling, coprecipitation and ball milling

    DEFF Research Database (Denmark)

    Lim, Ai Wei; Löbmann, Korbinian; Grohganz, Holger;

    2016-01-01

    OBJECTIVES: The objective was to characterize the structural behaviour of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems (1 : 1 molar ratio) prepared by quench cooling, co-evaporation and ball milling. METHODS: Powder X-ray diffraction (PXRD) and DSC were used to characterise...... the samples. Structural relaxation (i.e. molecular mobility) behaviour was obtained from the Kohlrausch-Williams-Watts (KWW) relationship. KEY FINDINGS: A glass transition temperature (Tg ), on average 20 °C higher than the predicted Tg (calculated from the Fox equation), was observed in all samples...... by quench cooling (ln τ(β) = 2.4) and co-evaporation (ln τ(β) = 2.5). In contrast, molecular mobility of the naproxen-cimetidine samples followed the order co-evaporation (ln τ(β) = 0.8), quench cooling (ln τ(β) = 1.6) and ball milling (ln τ(β) = 1.8). CONCLUSION: The estimated relaxation times by the DSC...

  16. Roxatidine- and cimetidine-induced angiogenesis inhibition suppresses growth of colon cancer implants in syngeneic mice.

    Science.gov (United States)

    Tomita, Kazuyoshi; Izumi, Kazuki; Okabe, Susumu

    2003-11-01

    Cimetidine is known to suppress the growth of several tumors, including gastrointestinal cancer, in humans and animals. Nonetheless, whether other histamine H(2)-receptor antagonists exert such tumor suppressive effects remains unclear. The effect of roxatidine acetate hydrochloride (roxatidine), an H(2)-receptor antagonist, on the growth of colon cancer implanted in mice was examined and compared with that of cimetidine. Drugs were orally delivered for 26 - 29 days beginning before or after implantation of syngeneic colon cancer (Colon 38) in C57BL/6 mice. Tumor volume was determined throughout and histochemical analysis was also performed. Tumor tissue and serum vascular endothelial growth factor (VEGF) levels were measured. In vitro cell growth was assessed by the MTT assay. Both roxatidine and cimetidine significantly suppressed the growth of Colon 38 tumor implants. Histologic analysis revealed that such antagonists markedly increased necrotic areas and decreased the density of microvessels in tumor tissue. Both H(2)-receptor antagonists suppressed VEGF levels in tumor tissue and significantly decreased serum VEGF levels in Colon 38-bearing mice. Such drugs, however, failed to suppress in vitro growth of the cell line. In conclusion, both roxatidine and cimetidine were found to exert suppressive effects on the growth of colon cancer implants in mice by inhibiting angiogenesis via reducing VEGF expression.

  17. Cimetidine suspension as adjuvant to energy restricted diet in treating obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Andersen, T; Breum, Leif;

    1993-01-01

    OBJECTIVE--To study the effect of cimetidine suspension compared with placebo suspension on weight loss in moderately obese patients taking a 5 MJ/day diet supplemented with dietary fibre. To determine the relation between the effectiveness of the blinding and weight loss. DESIGN--Randomised doub...

  18. Ascorbic acid prevents cimetidine-induced decrease of serum hydrocortisone concentrations

    NARCIS (Netherlands)

    M.P. Boidin (Marinus Pieter); A. Stuurman (Arie); W. Erdmann (Wilhelm)

    1990-01-01

    markdownabstractAbstract A blind, parallel, prospective, clinical study was conducted to investigate the effect of ascorbic acid on human serum hydrocortisone concentrations which were decreased by the administration of cimetidine. The study population included 16 male adults scheduled for major a

  19. Effect of immunomodulator pyrimethamine and cimetidine on immunosuppression induced by burn blister fluid.

    Science.gov (United States)

    Gharegozloo, Behnaz; Hassan, Zuhair M; K Ardestani, Sussan; Tavassoli, Nasser

    2004-09-01

    Despite recent advances in burn wound management, sepsis remains the main cause of death in patients resuscitated after major thermal injury. Increased susceptibility to infections has been related to severe suppression of the immune system.The aim of this study was to induce immune suppression with blister fluid injection, and to modulate immune response by use of cimetidine and pyrimethamine in animal model.Male Balb/c mice were injected with blister fluid intrapritoneally (ip). Fluids were collected from parital-thickness burn blisters and then the delayed type hypersensitivity (DTH) to sheep red blood cell (SRBC) and the effects of different doses of immunomodulators (Cimetidine and Pyrimethamine) on this response were quantitated.A marked suppression of DTH was observed in mice injected with blister fluid. Pyrimethamine and Cimetidine at all three doses caused a significant enhancement of DTH response to SRBC compared with blister fluid injected in control group.This finding represents evidence of a host defense defect within the burn wound and also indicates the blister fluid exhibit immunosuppressor factor that can modulate with immunomadulatory drugs like cimetidine and pyrimethamine.

  20. A comparison of oral omeprazole and intravenous cimetidine in reducing complications of duodenal peptic ulcer

    Directory of Open Access Journals (Sweden)

    Khaleghian Farzaneh

    2006-01-01

    Full Text Available Abstract Background Gastrointestinal bleeding is a common problem and its most common etiology is peptic ulcer disease. Ulcer rebleeding is considered a perilous complication for patients. To reduce the rate of rebleeding and to fasten the improvement of patients' general conditions, most emergency departments in Iran use H2-blockers before endoscopic procedures (i.e. intravenous omeprazole is not available in Iran. The aim of this study was to compare therapeutic effects of oral omeprazole and intravenous cimetidine on reducing rebleeding rates, duration of hospitalization, and the need for blood transfusion in duodenal ulcer patients. Methods In this clinical trial, 80 patients with upper gastrointestinal bleeding due to duodenal peptic ulcer and endoscopic evidence of rebleeding referring to emergency departments of Imam and Sina hospitals in Tabriz, Iran were randomly assigned to two equal groups; one was treated with intravenous cimetidine 800 mg per day and the other, with 40 mg oral omeprazole per day. Results No statistically significant difference was found between cimetidine and omeprazole groups in regards to sex, age, alcohol consumption, cigarette smoking, NSAID consumption, endoscopic evidence of rebleeding, mean hemoglobin and mean BUN levels on admission, duration of hospitalization and the mean time of rebleeding. However, the need for blood transfusion was much lower in omeprazole than in cimetidine group (mean: 1.68 versus 3.58 units, respectively; p Conclusion This study demonstrated that oral omeprazole significantly excels intravenous cimetidine in reducing the need for blood transfusion and lowering rebleeding rates in patients with upper gastrointestinal bleeding. Though not statistically significant (p = 0.074, shorter periods of hospitalization were found for omeprazole group which merits consideration for cost minimization.

  1. Drug interactions between theophylline and H2-antagonists, roxatidine acetate hydrochloride and cimetidine: pharmacokinetic analysis in rats in vivo.

    Science.gov (United States)

    Nagai, N; Furuhata, M; Ogata, H

    1995-11-01

    The effects of roxatidine acetate hydrochloride (Rox) on the pharmacokinetics of theophylline were compared to those of cimetidine in rats in vivo, Cimetidine or Rox was maintained at a steady state level using continuous infusion, then theophylline was injected into the rats as a bolus (7.5 mg/kg). Cimetidine showed competitive inhibition of theophylline elimination in vivo, with an inhibition constant (Ki) of 28.5 microM. Cimetidine significantly decreased the total body clearance and extended the plasma half-life of theophylline, but did not change its volume of distribution. In contrast, Rox did not significantly influence the pharmacokinetics of theophylline in rats. The in vivo animal model used in the present study for investigating the mechanism of the drug interaction showed good agreement with the results obtained in clinical and in vitro studies.

  2. Potentiometric and spectrophotometric studies of Mn{sup II} and Ni{sup II} cimetidine complexes

    Energy Technology Data Exchange (ETDEWEB)

    Kanumfre, Francieli; Lima, Eliane M. de; Scheidt, Gabriele; Carneiro, Paulo I.B.; Rosso, Neiva D., E-mail: ndrosso@uepg.b [Universidade Estadual de Ponta Grossa, PR (Brazil). Dept. de Quimica

    2010-07-01

    Cimetidine is an important hydrogen histamine receptor which has the ability to chelate metal ions in blood plasma and in different tissues. This study aimed to determine the stability constants for the cimetidine ligand with Mn{sup II} and Ni{sup II} metallic ions, synthesizing complexes and characterizing them by infrared spectroscopy, IR, and hydrogen nuclear magnetic resonance, {sup 1}H NMR. Cimetidine protonation constant regarding to the imidazole group was log K 7.05 and the stability constants for Mn{sup II} and Ni{sup II} complexes, ML{sub 2} species were log K 3.75 and 2.97, respectively, in 0.100 mol L{sup -1} KCl. The interpretation of IR and {sup H}1 NMR spectra for complexes Mn{sup II}-cim{sub 2} and Ni{sup II}-cim{sub 2} indicated that their formation occurs through the sulfur atoms in the thiol group, nitrogen atoms of imidazole ring, and nitrogen atoms of secondary amine. The nitrile group seems to be involved in the complexation of the Ni{sup II}-cim{sub 2} complex. (author)

  3. EFFECTS OF PERIOPERATIVE CIMETIDINE ADMINISTRATION ON NATURAL KILLER CELLS IN PATIENTS WITH GASTROINTESTINAL CANCER

    Institute of Scientific and Technical Information of China (English)

    LI Yan; BAI De-jiao; WANG Kun; YANG Guo-liang; YUAN Hong-yin; SHAO Hua

    1999-01-01

    Objective: To study the effects of perioperative use of cimetidine on natural killer (NK) cells in gastrointestinal (GI) cancer patients. Methods: 49 GI cancer patients were randomized into treatment group which took cimetidine in the perioperative period, and control group which did not take the drug. NK cells were measured by immunocytochemical method, using mouse-anti-human CD57 monoclonal antibody as the primary antibody. Blood samples from 20 healthy volunteers were treated in the same way as normal control. Comparisons were made within and between groups. Results: The NK cell percentage of normal control was 18.50±2.31. Both groups of patients had significantly lower than normal NK percentages before treatment (P<0.05). NK cell percentages at admission,before operation, on the 2nd and the 10th postoperative days were 14.60±3.91, 15.64±3.61, 17.40±3.28, 20.68±4.13, respectively, for the treatment group, and 14.88±2.76, 13.17±2.93, 14.50±2.77, 15.67±2.55, respectively,for control group. The difference between the two groups was statistically significant. Conclusion: Perioperative cimetidine application can help restore NK cells. The drug may be useful to reverse postoperative immuno-depression in GI cancer patients.

  4. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B;

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

  5. The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

    Science.gov (United States)

    Tanaka, E; Nakamura, K

    1989-08-01

    The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t1/2) of AP was significantly increased. The volumes of distribution (V) of AP and TMO were not affected. After roxatidine acetate, the pharmacokinetics of AP and TMO were unchanged. The cumulative renal excretion (% dose) and formation clearance of 3-hydroxymethyl-3-nor-antipyrine (NORA) were lowered by cimetidine treatment, but not following the administration of roxatidine acetate. ICG clearance was not changed significantly by either pretreatment. The results of this study show that roxatidine acetate does not impair the metabolism of three model substrates used to assess hepatic drug clearance.

  6. Effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1988-01-01

    The effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion was investigated in rats. The effect of three doses of omeprazole given orally once daily for 25 days was investigated. In controls median ulcer healing was 19.6% after 25 days. Omeprazole...... increased median ulcer healing from 36% at 145 mumole/kg/day to 80% at 580 mumole/kg/day. Basal and pentagastrin stimulated gastric acid secretion decreased dose-dependently by nearly 90% at a dose of 580 mumole/kg/day 22-24 hr after the last dose of omeprazole. Cimetidine given twice daily, in a dose...... that initially inhibits gastric acid secretion by 95%, reduced acid secretion by only 50% 11 hr after the last dose. Median ulcer healing after treatment with cimetidine for 25 days was 41%. This study demonstrates that omeprazole has a more long-acting inhibitory effect on gastric acid secretion compared...

  7. Effect of ethanol, cimetidine and propranolol on toluene metabolism in man

    DEFF Research Database (Denmark)

    Døssing, M; Bælum, Jesper; Hansen, S H

    1984-01-01

    of exposure the increase was by 3.3. Neither cimetidine nor propranolol changed toluene metabolism significantly. The results indicate that ethanol may prolong the time interval in which toluene is retained in the human body in persons simultaneously exposed to ethanol and toluene. When using o...... performed. Ethanol inhibited toluene metabolism by 0.5 as expressed by the urinary excretion of two of the metabolites of toluene, namely o-cresol and hippuric acid. In agreement with this, the mean alveolar concentration of toluene was greater by 1.7 during ethanol exposure; 45 min after discontinuation...

  8. The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

    OpenAIRE

    1989-01-01

    The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t1/2) of AP was significantly increased. The volumes of distribution (V) of AP and TMO were not af...

  9. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Ladefoged, S D; Feldt-Rasmussen, B;

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

  10. EFFECTS OF PERIOPERATIVE CIMETIDINE ADMINISTRATION ON TUMOR CELL NUCLEAR MORPHOMETRY AND DNA CONTENT IN PATIENTS WITH GASTROINTESTINAL CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastrointestinal adenocarcinoma. Methods: 49 patients with pathologically confirmed gastrointestinal adenocarcinoma were randomized into test group (n=25) and control group (n=24). The test group started oral cimetidine intake 400 mg, tid, 7-10d before operation, followed by standard curative operation. The control group did not receive cimetidine. Tumor specimens were paraffin embedded for microsection and stained with hematoxylin and eosin (HE) and Feulgen stain. Morphometric studies and DNA content of tumor nuclei were performed on IBAS Image Analyzer. Results: The tumor cell nuclear area (m m2), nuclear perimeter (m m), maximal nuclear diameter (m m) for test group/control group were 23.54 ± 5.08/34.69± 10.08 (Pquintuple ploidy tumor cells for test group/control group were 16.64± 2.58/5.33± 2.14 (P0.50), 12.42± 5.00/14.48± 0.74 (P>0.20), 31.11± 6.86/ 45.97± 3.82 (P<0.005), respectively. Conclusion: Perioperative administration of cimetidine in gasgtrointestinal cancer patients could decrease the nuclear size and raise the percentage of diploid tumor cells, and convert high aneuploid tumor cells into low-aneuploid tumor cells, which might help reduce the invasiveness of tumor cells.

  11. Cimetidine Injection

    Science.gov (United States)

    ... effects of your treatment using laboratory tests and physical examinations. It is important to keep all appointments ... health care provider as soon as possible: tenderness warmth irritation drainage redness swelling pain ¶ These branded products ...

  12. Simultaneous determination of cimetidine, famotidine, nizatidine, and ranitidine in tablets by capillary zone electrophoresis.

    Science.gov (United States)

    Wu, S M; Ho, Y H; Wu, H L; Chen, S H; Ko, H S

    2001-08-01

    A simple capillary zone electrophoresis (CZE) method is described for the simultaneous determination of cimetidine (CIM), famotidine (FAM), nizatidine (NIZ), and ranitidine (RAN). The analysis of these drugs was performed in a 100 mM phosphate buffer, pH 3.5. Several parameters were studied, including wavelength for detection, concentration and pH of phosphate buffer, and separation voltage. The quantitative ranges were 100-1,000 microM for each analyte. The intra- and interday relative standard deviations (n = 5) were all less than 4%. The detection limits were found to be about 10 microM for CIM, 20 microM for RAN, 20 microM for NIZ, and 10 microM for FAM (S/N = 3, injection 1 s) at 214 nm. All recoveries were greater than 92%. Applications of the method to the assay of these drugs in tablets proved to be feasible.

  13. Cimetidine down-regulates stability of Foxp3 protein via Stub1 in Treg cells.

    Science.gov (United States)

    Zhang, Yizhi; Chen, Zhoujia; Luo, Xuerui; Wu, Bin; Li, Bin; Wang, Bin

    2016-10-02

    Foxp3-expressing Treg cells have been well documented to provide immune regulation by promoting immune tolerance and suppressing immune over-reaction. Cimetidine (CIM), used to inhibit stomach acid secretion, has been reported to promote immune responses and suppress Treg cell function in several studies. However, the underlying mechanism is unknown. To investigate CIM effects on the suppressive function of Treg and Foxp3, here we used CIM to stimulate human CD4(+)CD25(+) Treg cells and Jurkat T cells and evaluated changes of Foxp3 expression and stability. Our data showed that CIM leads to a reduction of Foxp3 via E3 ligase Stub1-mediated proteosomal degradation, which is dependent on an activated PI3K-AKT-mTOR pathway. Thus, CIM affects the suppressive function of Treg cells by destabilizing their Foxp3 expression.

  14. Comparison of omeprazole with cimetidine for prophylaxis of acid aspiration in elective surgery.

    Science.gov (United States)

    Bouly, A; Nathan, N; Feiss, P

    1993-05-01

    Gastric pH and volume were measured in four groups of 15 patients scheduled for elective surgery. The patients were randomly allocated to receive either no antacid, oral omeprazole 40 mg the evening before surgery, oral omeprazole 40 mg 2 h before surgery, or effervescent cimetidine 800 mg, 2 h before surgery. Anaesthesia was induced with thiopentone (4-6 mg kg-1), fentanyl (0.03 mg kg-1) and vecuronium (0.1 mg kg-1) and maintained with nitrous oxide in oxygen (50/50) and isoflurane. After induction of anaesthesia and on completion of surgery, gastric pH (mean +/- SEM) and volume were measured using a glass electrode and a phenol red dilution technique. Gastric pH were significantly higher in the three treated groups than in control (P 25 ml).

  15. Open trial of cimetidine in the prevention of upper gastro-intestinal haemorrhage in patients with severe intracranial injury.

    Science.gov (United States)

    Mouawad, E; Deloof, T; Genette, F; Vandesteene, A

    1983-01-01

    The present study evaluates the efficacy of Cimetidine in the prevention of clinically important gastro-intestinal haemorrhage in patients suffering from severe head injury. Fifty patients (39 males and 11 females) were included in the study. We excluded from the trial patients on anticoagulant therapy or concomitant non-steroid anti-inflammatory agents, pregnant and lactating women, and patients with previous histories of peptic ulcer disease.

  16. Determination of ranitidine, nizatidine, and cimetidine by a sensitive fluorescent probe.

    Science.gov (United States)

    Chang, Yin-Xia; Qiu, Yue-Qin; Du, Li-Ming; Li, Chang-Feng; Guo, Min

    2011-10-21

    A validated, simple, and sensitive fluorescence quenching method for the determination of ranitidine, nizatidine, and cimetidine in tablets and biological fluids is presented. This is the first single fluorescence method reported for the analysis of all three H(2) antagonists. The competitive reaction between the investigated drug and the palmatine probe for the occupancy of the cucurbit[7]uril (CB[7]) cavity was studied using spectrofluorometry. CB[7] was found to react with the probe to form a stable complex. The fluorescence intensity of the complex was also enhanced greatly. However, the addition of the drug dramatically quenched the fluorescence intensity of the complex. Accordingly, a new fluorescence quenching method for the determination of the studied drugs was established. The different experimental parameters affecting the fluorescence quenching intensity were studied carefully. At optimum reaction conditions, the rectilinear calibration graphs between the fluorescence quenching values (ΔF) and the medicament concentration were obtained in the concentration range of 0.04-1.9 μg mL(-1) for the investigated drugs. The limits of detection ranged from 0.013 to 0.030 μg mL(-1) at 495 nm using an excitation wavelength of 343 nm. The proposed method can be used for the determination of the three H(2) antagonists in raw materials, dosage forms and biological fluids.

  17. FORMULATION AND EVALUATION OF FLOATING IN SITU GEL BASED GASTRO RETENTIVE DRUG DELIVERY OF CIMETIDINE

    Directory of Open Access Journals (Sweden)

    Bhargav D. Jayswal

    2012-05-01

    Full Text Available The present investigation deals with the formulation and evaluation of sodium alginate and pectin basedIn situ gel of Cimetidine. Sodium alginate and pectin were used as a polymer and CaCO3 was used as across-linking agent. In-situ forming polymeric formulations drug delivery systems is in sol form beforeadministration in the body, but once administered, undergoes gelation in-situ to form a gel. Theformulation of gel depends upon factors like temperature modulation, pH changes, presence of ions andultra-violet irradiation, from which drug gets released in sustained and controlled manner. The objectiveof this study was to develop a novel in- situ gel system for sustained drug delivery using naturalbiodegradable polymers. The system utilizes polymers that exhibit sol-to-gel phase transition due tochange in specific physico-chemical parameters. In-situ gel was formed at a biological pH. In vitrorelease studies were conducted in simulated gastric fluid and cumulative amount of drug release wasanalyzed by spectrophotometry. From designed set of experiments, it was evident that formulationcontaining 1.2% of sodium alginate and 1.5% of pectin control the release of drug for longer duration.The in-situ gel exhibited the expected, viscosity, drug content, pH, in vitro gelling capacity, in vitrofloating ability, water uptake ability and sustained drug release.The drug release from the in situ gelsfollows the fickian diffusion type of release.

  18. Continuous intragastric pH monitoring in the evaluation of ebrotidine, cimetidine and placebo on gastric acidity in healthy volunteers.

    Science.gov (United States)

    Muñoz-Navas, M; Honorato, J; Reina-Ariño, M; Márquez, M; Herrero, E; Villamayor, F; Torres, J; Roset, P N; Fíllat, O; Camps, F; Ortiz, J A

    1997-04-01

    This study was conducted to determine the efficacy and tolerance of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl) methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43.9, FI-3542), a new H2-receptor antagonist, on reducing gastric acidity after a single 800 mg dose, compared with cimetidine 800 mg once daily and placebo by means of a continuous intragastric pH monitoring. A total of 30 healthy volunteers were allocated to receive in a double blind, parallel design the study medication. Clinical observations, physical examinations and visual analogue scales (VAS) were performed during the study to assess the tolerability of the three treatments. Ebrotidine and cimetidine caused a greater and longer-lasting gastric acid inhibition than placebo. With ebrotidine, significantly (p < 0.05) higher median pH values (and interquartile range, IQR) were reached in the post-administration (2.61, IQR 2.02-3.93), postprandial (3.38, IQR 2.82-3.91) and nocturnal (2.83, IQR 1.69-3.77) periods than with placebo: 1.82 (IQR, 1.66-2.09), 2.81 (IQR, 2.02-3.28), and 1.89 (IQR, 1.44-2.13), respectively. Cimetidine showed significant differences compared to placebo in the post-administration (2.36, IQR 1.89-3.46) and nocturnal (2.46, IQR 1.88-4.33) periods. No statistical differences were observed between the active treatments. Ebrotidine caused a significantly higher percentage of time above pH 2.0 in the post-administration and nocturnal periods compared to placebo (p < 0.05), and above pH 3.0 in the post-administration, postprandial and nocturnal periods. No serious adverse effects, or disturbances in the VAS or in the vital signs were reported, and all medications were well tolerated. It is concluded that a single dose of ebrotidine 800 mg is as effective as cimetidine 800 mg in reducing total and nocturnal intragastric acidity. The study also confirms the excellent safety profile of the new drug.

  19. Comparative investigation of the influence of nizatidine, ranitidine, and cimetidine on the steady-state pharmacokinetics of theophylline in COPD patients.

    Science.gov (United States)

    Bachmann, K; Sullivan, T J; Mauro, L S; Martin, M; Jauregui, L; Levine, L

    1992-05-01

    The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.

  20. An Overview of Analytical Determination of Diltiazem, Cimetidine, Ranitidine, and Famotidine by UV Spectrophotometry and HPLC Technique

    Directory of Open Access Journals (Sweden)

    Nighat Shafi

    2013-01-01

    Full Text Available This review article recapitulates the analytical methods for the quantitative determinations of diltiazem and three H2 receptor antagonists (cimetidine, ranitidine, and famotidine by one of the spectroscopic technique (UV spectrophotometery and separation technique such as high-performance liquid chromatography (HPLC. The clinical and pharmaceutical analysis of these drugs requires effective analytical procedures for quality control, pharmaceutical dosage formulations, and biological fluids. An extensive survey of the literature published in various analytical and pharmaceutical chemistry-related journals has been compiled in its review. A synopsis of reported spectrophotometric and high-performance liquid chromatographic methods for individual drug is integrated. This appraisal illustrates that majority of the HPLC methods reviewed are based on the quantitative analysis of drugs in biological fluids, and they are appropriate for therapeutic drug monitoring purpose.

  1. Synergistic and additive effects of cimetidine and levamisole on cellular immune responses to hepatitis B virus DNA vaccine in mice.

    Science.gov (United States)

    Niu, X; Yang, Y; Wang, J

    2013-02-01

    We and others have previously shown that both cimetidine (CIM) and levamisole (LMS) enhance humoral and cellular responses to DNA vaccines via different mechanisms. In this study, we investigated the synergistic and additive effects of CIM and LMS on the potency of antigen-specific immunities generated by a DNA vaccine encoding the hepatitis B surface antigen (HBsAg, pVax-S2). Compared with CIM or LMS alone, the combination of CIM and LMS elicited a robust HBsAg-specific cellular response that was characterized by higher IgG2a, but did not further increase HBsAg-specific antibody IgG and IgG1 production. Consistent with these results, the combination of CIM and LMS produced the highest level of IL-2 and IFN-γ in antigen-specific CD4(+) T cells, whereas the combination of CIM and LMS did not further increase IL-4 production. Significantly, a robust HBsAg-specific cytotoxic response was also observed in the animals immunized with pVax-S2 in the presence of the combination of CIM and LMS. Further mechanistic studies demonstrated that the combination of CIM and LMS promoted dendritic cell (DC) activation and blocked anti-inflammatory cytokine IL-10 and TGF-β production in CD4(+) CD25(+) T cells. These findings suggest that CIM and LMS have the synergistic and additive ability to enhance cellular response to hepatitis B virus DNA vaccine, which may be mediated by DC activation and inhibition of anti-inflammatory cytokine expression. Thus, the combination of cimetidine and levamisole may be useful as an effective adjuvant in DNA vaccinations for chronic hepatitis B virus infection.

  2. Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney.

    Science.gov (United States)

    Ito, Sumito; Kusuhara, Hiroyuki; Yokochi, Miyu; Toyoshima, Junko; Inoue, Katsuhisa; Yuasa, Hiroaki; Sugiyama, Yuichi

    2012-02-01

    Cimetidine, an H₂ receptor antagonist, has been used to investigate the tubular secretion of organic cations in human kidney. We report a systematic comprehensive analysis of the inhibition potency of cimetidine for the influx and efflux transporters of organic cations [human organic cation transporter 1 (hOCT1) and hOCT2 and human multidrug and toxin extrusion 1 (hMATE1) and hMATE2-K, respectively]. Inhibition constants (K(i)) of cimetidine were determined by using five substrates [tetraethylammonium (TEA), metformin, 1-methyl-4-phenylpyridinium, 4-(4-(dimethylamino)styryl)-N-methylpyridinium, and m-iodobenzylguanidine]. They were 95 to 146 μM for hOCT2, providing at most 10% inhibition based on its clinically reported plasma unbound concentrations (3.6-7.8 μM). In contrast, cimetidine is a potent inhibitor of MATE1 and MATE2-K with K(i) values (μM) of 1.1 to 3.8 and 2.1 to 6.9, respectively. The same tendency was observed for mouse Oct1 (mOct1), mOct2, and mouse Mate1. Cimetidine showed a negligible effect on the uptake of metformin by mouse kidney slices at 20 μM. Cimetidine was administered to mice by a constant infusion to achieve a plasma unbound concentration of 21.6 μM to examine its effect on the renal disposition of Mate1 probes (metformin, TEA, and cephalexin) in vivo. The kidney- and liver-to-plasma ratios of metformin both were increased 2.4-fold by cimetidine, whereas the renal clearance was not changed. Cimetidine also increased the kidney-to-plasma ratio of TEA and cephalexin 8.0- and 3.3-fold compared with a control and decreased the renal clearance from 49 to 23 and 11 to 6.6 ml/min/kg, respectively. These results suggest that the inhibition of MATEs, but not OCT2, is a likely mechanism underlying the drug-drug interactions with cimetidine in renal elimination.

  3. Simultaneous determination of metformin, cimetidine, famotidine, and ranitidine in human serum and dosage formulations using HPLC with UV detection.

    Science.gov (United States)

    Arayne, M Saeed; Sultana, Najma; Zuberi, M Hashim; Siddiqui, Farhan Ahmed

    2010-10-01

    A new, simple, and reliable reversed-phase high-performance liquid chromatographic method has been developed and validated for the simultaneous determination of metformin (Metf), cimetidine (Cimt), famotidine (Famt), and ranitidine (Rant) in their synthetic mixtures and tablet formulations. These drugs were separated on a Purospher Star RP18 endcapped (250 mm × 4.6 mm i.d.) column packed with 5-μm particles. The mobile phase, optimized through an experimental design, consisted of methanol-water-triethylamine (20:80:0.05), whose pH was adjusted to 3.0 with phosphoric acid (85%) pumped at a flow rate of 1.0 mL/min. UV detection was performed at 229 nm. The method was validated in the sample concentration range of 5-25 μg/mL for all the drugs, where it demonstrated good linearity with r = 0.9998, 0.9979, 0.9997, and 0.9987 (n = 6), respectively. For independent 100% level samples, the intra-day and inter-day precision was in the range i.e. < 2.0 for all the drugs. The method demonstrated robustness, resisting to small deliberate changes in pH, flow rate, and composition (organic:aqueous ratio) of the mobile phase. The limit of detection values were 0.071, 0.116, 0.134, and 0.110 μg/mL, while the limit of quantitation were 0.217, 0.352, 0.405, and 0.368 μg/mL for Metf, Cimt, Famt, and Rant, respectively. The applicability of the method was demonstrated by determining the drug content in pharmaceutical formulations, where it exhibited good performance.

  4. Resposta cronotrópica ao teste cardiopulmonar após o uso de cimetidina Effects of cimetidine on chronotropic response to cardiopulmonary exercise t esting

    Directory of Open Access Journals (Sweden)

    Gicela Risso Rocha

    2006-03-01

    Full Text Available OBJETIVO: Testar a hipótese, por meio de ensaio clínico randomizado, de que a administração de cimetidina altera a resposta cronotrópica ao exercício. MÉTODOS: Foram selecionados 24 indivíduos saudáveis, com idade entre 20 e 68 anos, não-atletas, os quais concordaram em ser submetidos a testes cardiopulmonares, após uso de placebo e de cimetidina, 400 mg, duas vezes ao dia, durante uma semana. Os testes foram realizados em esteira rolante, com protocolo de rampa com análises diretas dos gases expirados. Foi avaliada freqüência cardíaca máxima atingida, além da freqüência cardíaca de repouso e do limiar anaeróbico. RESULTADOS: Os indivíduos estudados foram igualmente distribuídos por sexo, com idade média (± desvio padrão de 43 ±11 anos. Os exames com placebo e com cimetidina tiveram igual duração (578±90 seg vs 603±131 seg e igual VO2 pico (35±8 ml/kg.min vs 35±8 ml/kg.min. A administração de cimetidina não apresentou efeito significativo na freqüência cardíaca de repouso (75±10 vs 74±8 bpm, no pico do esforço (176±12 vs 176±11 bpm e, da mesma forma, também não houve diferença entre as variações das freqüências cardíacas (pico - repouso, nos dois estudos (101±14 vs 101±13 bpm. CONCLUSÃO: A administração de cimetidina por sete dias não altera a resposta cronotrópica ao exercício.OBJECTIVE: To test the hypothesis that the administration of cimetidine will modify the chronotropic response to exercise testing through a random clinical trial. METHODS: The study selected 24 eligible healthy subjects, ages between 20 and 68 years, not athletes, who agreed to undergo cardiopulmonary exercise testing after the administration of placebo and 400 mg of cimetidine twice a day for one week. The tests were performed on a treadmill using a ramp protocol and direct analysis of the expired gases. Peak, resting and anaerobic threshold heart rate were recorded. RESULTS: The twenty subjects studied were

  5. Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.

    Science.gov (United States)

    Sikiric, P; Seiwerth, S; Grabarevic, Z; Balen, I; Aralica, G; Gjurasin, M; Komericki, L; Perovic, D; Ziger, T; Anic, T; Prkacin, I; Separovic, J; Stancic-Rokotov, D; Lovric-Bencic, M; Mikus, D; Staresinic, M; Aralica, J; DiBiaggio, N; Simec, Z; Turkovic, B; Rotkvic, I; Mise, S; Rucman, R; Petek, M; Sebecic, B; Ivasovic, Z; Boban-Blagaic, A; Sjekavica, I

    2001-01-01

    Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were

  6. Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N{sub 3}-enamino tautomer

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, Natalia L.; Simonetti, Sebastian O.; Maggio, Rubén M.; Kaufman, Teodoro S., E-mail: kaufman@iquir-conicet.gov.ar

    2015-05-22

    Highlights: • Thermally stressed cimetidine above its melting point affords a stable N{sub 3} tautomer. • Multi-spectroscopic/chemometric approach developed to monitor tautomerization. • First combined use of NMR, UV and IR spectroscopies with chemometrics. • Solid cimetidine suffers first order degradation upon submission to dry heat. • Theoretical chemistry analysis confirmed the relative stability of cimetidine tautomer. - Abstract: Exposure of cimetidine (CIM) to dry heat (160–180 °C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics. One of the products was structurally characterized by mono- and bi-dimensional NMR experiments. It was found to be the N{sub 3}-enamino tautomer (TAU) of CIM, resulting from the thermal isomerization of the double bond of the cyanoguanidine moiety of the drug, from the imine form to its N{sub 3}-enamine state. The thus generated tautomer demonstrated to be stable for months in the glassy solid and in methanolic solutions. A theoretical study of CIM and TAU revealed that the latter is less stable; however, the energy barrier for tautomer interconversion is high enough, precluding the process to proceed rapidly at room temperature.

  7. Effect Observation of 40 Cases of Cimetidine Combined With Folic Acid in the Treatment of Infantile Diarrhea%西咪替丁联合叶酸治疗小儿腹泻40例效果观察

    Institute of Scientific and Technical Information of China (English)

    高佩军

    2015-01-01

    Objective To observe the effect of cimetidine combined with folic acid in treatment of infantile diarrhea effect. Methods 80 cases of diarrhoea in children were divided into two groups, the combined group treated with cimetidine and folic acid on the treatment, single drug group treated with cimetidine therapy, compared two groups of children with diarrhea stop time, the overall effect, recurrence. Results combined group diarrhea average stop time (3.96±1.38) d lower than the single drug group (5.74±1.42) d, (P0.05. Conclusion Combined with cimetidine folic acid phase treatment of infantile diarrhea effect is exact, can repair the damaged intestinal villi and epithelial cell damage synergistic therapeutic efifcacy.%目的:观察西咪替丁联合叶酸治疗小儿腹泻的效果。方法采用随机数字表法将80例腹泻患儿分为两组,联合组予西咪替丁联合叶酸治疗,单药组予西咪替丁治疗,对比两组患儿的腹泻停止时间、整体疗效、复发情况。结果联合组腹泻平均停止时间(3.96±1.38)d低于单药组(5.74±1.42)d,P<0.05;联合组有效率92.50%高于单药组75.00%,P<0.05;联合组复发率5.00%低于单药组12.50%,P>0.05。结论西咪替丁联合叶酸相治疗小儿腹泻效果确切,具有修复破损肠绒毛和受损上皮细胞等作用,协同治疗效果确切。

  8. Study on Bacterial Endotoxin Test of Cimetidine Raw Material%西咪替丁原料药细菌内毒素检查方法的探讨

    Institute of Scientific and Technical Information of China (English)

    金艳; 王益民

    2012-01-01

    Objective To establish a bacterial endotoxin test for cimetidine raw material. Methods According to the method of the bacteria endotoxin test in the Chinese Pharmacopoeia (edition 2010, Vol. II). Results When the mass concentration of sample was diluted to 4.0 mg/mL,no interference effect on the reaction of bacterial endotoxin and TAL was found. The limit value of the bacterial endotoxin was 0. 5 EU/mg. Conclusion It is feasible to detect the bacterial endotoxin of cimetidine raw material by the method of bacterial endotoxin test.%目的 建立西咪替丁原料药的细菌内毒素检查方法.方法 参照2010年版细菌内毒素检查法进行试验.结果 样品质量浓度稀释至4.0 g/L时,对鲎试剂与细菌内毒素的反应无干扰作用.其细菌内毒素限值定为0.5 EU/mg.结论 西咪替丁原料药采用内毒素检查法(鲎试剂法)是可行的.

  9. 外用西咪替丁、甲硝唑联合激光治疗智齿冠周炎疗效观察%Observe the efficacy of topical cimetidine, metronidazole combined laser treatment on pericoronitis

    Institute of Scientific and Technical Information of China (English)

    姚冬梅

    2014-01-01

    Objective:To observe treatment effect of cimetidine,metronidazole combined laser acute on pericoronitis.Methods:79 cases with acute pericoronitis were randomly divided into experimental group and control group.In experimental group,irradiation 5 minutes by Mandi Sen infrared laser treatment after cimetidine,metronidazole liquid alternately flushing,and then taken powder researched by two tablets into blind pouch.In the control group,also irradiated with infrared laser treatment for 5 minutes afer partial hydrogen peroxide and saline flush,then taken iodine glycerin into blind bag.1 time/day,evaluated the efficacy after 5 days.Results:The effective rate in the experimental group were higher than in the control group(P<0.01),and no adverse reactions occur.Conclusion:Cimetidine,metronidazole combined laser is an effective method of acute pericoronitis treatment.%目的:观察西咪替丁、甲硝唑联合激光治疗急性智齿冠周炎效果。方法:选取急性智齿冠周炎79例,随机分为试验组和对照组。试验组西咪替丁、甲硝唑液交替冲洗后,用曼迪森红外激光治疗仪照射5分钟,然后将两药片剂研成的药粉放进盲袋内;对照组局部双氧水、生理盐水冲洗后,也用红外激光治疗仪照射5分钟,盲袋内置入碘甘油,1次/日,5天后复诊评价疗效。结果:试验组的显效率均较对照组高(P<0.01),无不良反应发生。结论:西咪替丁、甲硝唑联合激光是一种治疗急性智齿冠周炎的有效方法。

  10. 阿苯达唑联合西咪替丁治疗肝包虫病的疗效观察%The curative effect of albendazole combined with cimetidine in the treatment of hepatic echinococcosis

    Institute of Scientific and Technical Information of China (English)

    盛篧; 汤治平; 周芳; 杨统升

    2016-01-01

    Objective To observe the clinical effect of albendazole combined with cimetidine in the treatment of hepatic hydatid disease.Methods 60 cases with liver hydatid disease from 2010 to 2014 wrer selected,and they were randomly divided into two groups,30 cases in each group.The control group was treated with albendazole tablets,2 times daily,2 capsules/time.The treatment group was intravenously injected cimetidine based on the treatment of the control group.Before and after treatment,the ultrasound imaging changes and clinical effect were observed.Results In the control group,the total effective rate was 83.33%(25 /30).In the treatment group, the total effective rate was 96.67%(29 /30).The total effective rate between the two groups had statistically signifi-cant difference(χ2 =9.842,P <0.01).Conclusion Albendazole combined with cimetidine in treatment of hepatic hydatid disease has good curative effect,which can be viewed as first choice in the treatment of hydatid disease.%目的:观察阿苯达唑联合西咪替丁治疗肝包虫病的临床效果。方法选取2010-2014年收治的肝包虫病患者60例,采用数字表法随机分为两组,每组各30例,对照组给予阿苯达唑片治疗,2次/d,2粒/次。治疗组在对照组的基础上联合西咪替丁静脉滴注治疗。观察治疗前后超声影像变化及临床效果。结果对照组总有效率为83.33%(25/30),治疗组总有效率96.67%(29/30),两组总有效率差异有统计学意义(χ2=9.842,P <0.01)。结论阿苯达唑联合西咪替丁治疗肝包虫病有较好疗效,可作为包虫病首选治疗药物。

  11. Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N3-enamino tautomer.

    Science.gov (United States)

    Calvo, Natalia L; Simonetti, Sebastian O; Maggio, Rubén M; Kaufman, Teodoro S

    2015-05-22

    Exposure of cimetidine (CIM) to dry heat (160-180°C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics. One of the products was structurally characterized by mono- and bi-dimensional NMR experiments. It was found to be the N3-enamino tautomer (TAU) of CIM, resulting from the thermal isomerization of the double bond of the cyanoguanidine moiety of the drug, from the imine form to its N3-enamine state. The thus generated tautomer demonstrated to be stable for months in the glassy solid and in methanolic solutions. A theoretical study of CIM and TAU revealed that the latter is less stable; however, the energy barrier for tautomer interconversion is high enough, precluding the process to proceed rapidly at room temperature.

  12. A comparison of the inhibitory effects of roxatidine acetate hydrochloride and cimetidine on cytochrome P-450-mediated drug-metabolism in mouse hepatic microsomes and in man in vivo.

    Science.gov (United States)

    Morita, K; Konishi, H; Ono, T; Shimakawa, H

    1987-07-01

    The inhibitory effects of roxatidine acetate hydrochloride (ROX), a new H2-receptor antagonist, on the oxidative drug-metabolizing enzyme system in mouse hepatic microsomes and in man in vivo were compared with those of cimetidine (CIM). CIM markedly inhibited testosterone 6 beta-, 7 alpha- and 16 alpha-hydroxylase, aminopyrine N-demethylase and aniline hydroxylase activities in mouse hepatic microsomes with inhibition constants (Ki) of 0.2-3.49 mM. ROX exhibited much weaker inhibitory effects on each enzyme activity with 12 to 100-fold higher values of Ki than those of CIM. CIM gave type II difference spectra with dissociation constants (Ks) of 10.4 and 111 microM while ROX gave reverse type I difference spectra with Ks of 55.6 microM. The ratio of 6 beta-hydroxycortisol (6 beta-OHF) to 17-hydroxy corticosteroids (17-OHCS) in urine, used as an indicator of oxidative drug-metabolizing capacity in man, was decreased by 25-35% of the original level on 1-3 d after oral treatment with 800 mg/d of CIM. The ratio was not significantly changed during oral treatment with 150 mg/d of ROX. These results indicate that ROX exhibits a lower affinity for cytochrome P-450 and a lower inhibitory potency on the drug-metabolizing enzymes in hepatic microsomes than does CIM.

  13. Comparação entre a eficácia da cimetidina e do sulfato de zinco no tratamento de verrugas múltiplas e recalcitrantes Efficacy comparison between cimetidine and zinc sulphate in the treatment of multiple and recalcitrant warts

    Directory of Open Access Journals (Sweden)

    Mariane Stefani

    2009-02-01

    Full Text Available FUNDAMENTOS: Verrugas são proliferações epiteliais na pele e mucosas causadas por diversos tipos de HPV. Elas podem involuir espontaneamente ou aumentar em número e tamanho de acordo com estado imunitário do paciente. A cimetidina e o sulfato de zinco têm importante efeito no sistema imune, sendo usados como imunomoduladores no tratamento de diversas doenças. OBJETIVO:Comparar a eficácia terapêutica de cimetidina e sulfato de zinco no tratamento de verrugas cutâneas de difícil tratamento. MÉTODOS: Estudo prospectivo duplo-cego randomizado. Dezoito pacientes com verrugas múltiplas foram divididos em dois grupos, um recebeu cimetidina 35mg/kg/dia (máximo 1.200mg/dia, e o outro, sulfato de zinco 10mg/kg/dia (máximo de 600mg/dia por três meses. RESULTADOS: Dos 18 pacientes do estudo, nove receberam cimetidina, e nove, sulfato de zinco; apenas um do grupo do sulfato de zinco não completou o tratamento devido a náuseas e vômitos. Cura foi obtida em cinco pacientes tratados com sulfato de zinco, e apenas um não obteve alteração das lesões. Do grupo da cimetidina cinco não apresentaram modificação, e quatro apresentaram diminuição inferior a 30% das lesões iniciais. CONCLUSÕES: Sulfato de zinco na dose de 10mg/kg/dia parece ser mais efetivo que cimetidina para o tratamento de crianças e adultos com verrugas múltiplas e de difícil manejo. A pequena casuística deste trabalho não permite, entretanto, conclusão categórica.BACKGROUND: Warts are epithelial proliferations on the skin and mucous membrane caused by various types of HPV. They can decrease spontaneously or increase in number and size according to patient's immune status. Cimetidine and zinc sulphate have important effects on the immune system and are used as immunomodulators in the treatment of various diseases. OBJECTIVE: To compare the efficacy of cimetidine and zinc sulphate in the treatment of multiple and recalcitrant warts. METHODS: A random double

  14. Curative effect and safety by cimetidine and interferon combined with zinc supplements in the treatment of pediatric rotavirus infected diarrhea%西咪替丁和干扰素联合补锌治疗小儿轮状病毒感染性腹泻的疗效和安全性

    Institute of Scientific and Technical Information of China (English)

    梁荣伟

    2016-01-01

    Objective To investigate curative effect and safety by cimetidine and interferon combined with zinc supplements in the treatment of pediatric rotavirus infected diarrhea. Methods A total of 100 children with pediatric rotavirus infected diarrhea were randomly divided into control group and observation group, with 50 cases in each group. The control group received interferon and cimetidine for treatment, and the observation group received additional zinc supplements for treatment. Their curative effects were observed. Results The observation group had much higher total effective rate as 94.0% than 78.0% of the control group, and their difference had statistical significance (P0.05). Conclusion On the basis of conventional treatment by interferon and cimetidine, implement of zinc supplements in treating pediatric rotavirus infected diarrhea provides satisfactory effect. This method is helpful for early rehabilitation in children patients, along with high safety of drug use. It is worth clinical promotion and application.%目的:探讨西咪替丁和干扰素联合补锌治疗小儿轮状病毒感染性腹泻的疗效和安全性。方法100例小儿轮状病毒感染性腹泻患儿,随机分为对照组和观察组,每组50例。对照组给予干扰素、西咪替丁治疗,观察组在此基础上联合补锌治疗。观察两组治疗效果。结果观察组治疗总有效率为94.0%,明显高于对照组的78.0%,差异有统计学意义(P0.05)。结论在常规给予干扰素、西咪替丁治疗的基础上联合补锌治疗小儿轮状病毒感染性腹泻可收到满意效果,有利于患儿早期恢复,且用药安全性较高,值得临床推广使用。

  15. Effect observation of cimetidine and interfer-on combined with zinc supplements in the treatment of children with rotavirus diarrhea%甲氰米胍、干扰素联合补锌治疗小儿轮状病毒感染性腹泻疗效观察

    Institute of Scientific and Technical Information of China (English)

    马超; 刘春枝; 任少敏

    2016-01-01

    AIM: To investigate the effect of cimetidine and interferon combined with zinc supplements in the treatment of children with rotavirus diarrhea. METHODS: A total of 120 children with rotavirus diarrhea admitted into Affiliated Hospital of Inner Mongolia Medical University from January 2015 to December 2015 were randomly divided into observation group and control group, with 60 cases in each group. Two groups of children were all given conventional symptomatic treatment. In addition, on the basis of this, the control group was treated with cimetidine combined with interferon treatment, while the observation group on the basis of the control group was treated with additional zinc gluconate oral liquid. The effects of the two groups were observed. RESULTS: The total effective rate in the observation group (96.7%) was higher than that of the control group(75%), and the difference was statistically significant ( P0. 05 ) . CONCLUSION:Cimetidine and interferon combined with zinc supplements in the treatment of children with rotavirus diarrhea provides satisfactory effect, with a shorter course of disease.%目的:探讨甲氰米胍、干扰素联合补锌治疗小儿轮状病毒感染性腹泻的疗效.方法:选择取内蒙古医科大学附属医院2015-01/2015-12收治的120例轮状病毒感染性腹泻患儿,按照随机数字表法分为观察组( n=60)和对照组( n=60).两组患儿均接受常规对症治疗,在此基础上,对照组给予甲氰米胍联合干扰素治疗,观察组在对照组基础上加用葡萄糖酸锌口服液,观察两组治疗效果.结果:观察组和对照组的总有效率分别为96.7%和75.0%,观察组的总有效率高于对照组,组间比较,差异具有统计学意义(P<0.05);观察组病毒转阴率为63.3%,对照组病毒转阴率为51.7%,观察组病毒转阴率明显高于对照组,差异具有统计学意义( P<0.05);观察组平均住

  16. Penetapan Kadar Cimetidin Pada Omekur Tablet Secara Spektrofotometri Di. PT Mutiara Mukti Farama Medan

    OpenAIRE

    Joshua Alexander G.

    2011-01-01

    Tablet adalah sediaan padat, dibuat secara kempa-cetak berbentuk rata atau cembung rangkap, umumnya bulat, mengandung satu jenis obat atau lebih dengan atau tanpa zat tambahan (Anief, 1999). Obat adalah semua bahan tunggal atau campuran yang digunakan oleh semua makhluk untuk bagian dalam maupun bagian luar, guna mencegah, meringankan, maupun menyembuhkan penyakit. Menurut undang-undang kesehatan, yang dimaksud dengan obat adalah suatu bahan atau campuran bahan yang dimaksudkan untuk digu...

  17. High-Resolution Solid-State NMR Spectroscopy: Characterization of Polymorphism in Cimetidine, a Pharmaceutical Compound

    Science.gov (United States)

    Pacilio, Julia E.; Tokarski, John T.; Quiñones, Rosalynn; Iuliucci, Robbie J.

    2014-01-01

    High-resolution solid-state NMR (SSNMR) spectroscopy has many advantages as a tool to characterize solid-phase material that finds applications in polymer chemistry, nanotechnology, materials science, biomolecular structure determination, and others, including the pharmaceutical industry. The technology associated with achieving high resolution…

  18. Human breast cancer resistance protein : Interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine

    NARCIS (Netherlands)

    Pavek, P; Merino, G; Wagenaar, E; Bolscher, E; Novotna, M; Jonker, JW; Schinkel, AH

    2005-01-01

    The breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette drug efflux transporter that extrudes xenotoxins from cells, mediating drug resistance and affecting the pharmacological behavior of many compounds. To study the interaction of human wild-type BCRP with steroid drugs, hormo

  19. In Vivo Effects of the H2 Receptor Antagonist Cimetidine on Anamnestic Response of Humoral Immunity in Chicks%西咪替丁对鸡回忆性体液免疫应答反应的作用

    Institute of Scientific and Technical Information of China (English)

    乔彦良; 盛英霞; 杨汉春; 李翠梅; 付兴伦; 原培勋

    2001-01-01

    本试验系统观察了西咪替丁对鸡回忆性体液免疫应答反应的作用,并与同类咪唑类化合物左旋咪唑进行了比较.28日龄鸡,免疫注射绵羊红细胞+牛血清白蛋白(SRBC+BSA)悬液,或稀释的布氏杆菌(BA)抗原.56日龄时,以10.0、100.0mg/kg西咪替丁或10.0mg/kg左旋咪唑饮水给药,连用3天,给药第二天同时进行第2次免疫注射.结果表明西咪替丁(10.0~100mg/kg)可使二次免疫鸡体内对颗粒性胸腺依赖性抗原SRBC和非胸腺依赖性抗原BA抗体滴度回忆性免疫应答反应明显升高;但使鸡对可溶性胸腺依赖性抗原BSA抗体滴度回忆性免疫应答反应明显降低.与西咪替丁比较,左旋咪唑(10.0mg/kg)也存在着非常类似的作用.

  20. Clinical efficacy of sodium cromoglycate combined with cimetidine in treatment of severe vernal conjunctivitis%色甘酸钠联合西米替丁治疗重症春季结膜炎的临床疗效

    Institute of Scientific and Technical Information of China (English)

    张姝

    2008-01-01

    目的 探讨色甘酸钠联合西米替丁治疗长期反复发作、眼部反应重、部分病例有Trantasdots小点、并发盾状溃疡的重症春季结膜炎的临床疗效.方法 36例随机分为实验组和对照组.实验组21例用色甘酸钠联合西米替丁,西米替丁每次400 mg,3次/d,口服,10~15 d为1个疗程,2%色甘酸钠滴眼液,6次/d滴眼;对照组15例用吲哚美辛口服或阿斯匹林口服,用0.5%可的松滴眼液,3次/d滴眼.结果 实验组治疗后,66.66%患眼病情缓解,28.57%患眼好转,总有效率95.23%;对照组治疗后13.33%患眼病情缓解,46.67%患眼好转,总有效率为60.00%,两组差异极其显著(P<0.01).结论 抗组胺H2受体的免疫调节剂西米替丁全身应用方法简单、经济,无不良反应,是选择应用于重症春季结膜炎的一种新的有效疗法.

  1. Effects of Cimetidine on portal hemodynamics in dogs with cirrhosis and portal hypertension%甲氰咪胍对肝硬化门脉高压症犬门脉血液动力学的影响

    Institute of Scientific and Technical Information of China (English)

    王延龄; 陈云波; 丁巍; 李桂英; 王淑敏; 李爱景

    2005-01-01

    目的:探讨甲氰咪胍对肝硬化门脉高压症犬门脉血液动力学的影响.方法:以胆总管结扎法成功制备胆汁性肝硬化门脉高压症模型犬11只,随机分为两组,即甲氰咪胍组(n=7)和盐水对照组(n=4);另取4只正常犬作正常对照组.经股动脉、股静脉、右颈外静脉分别插管,以多导生理记录仪、电磁流量计等检测门脉及全身血液动力学变化,使用RF-3000型荧光分光光度计测量血浆组织胺浓度.结果:甲氰咪胍组静脉注射甲氰咪胍(剂量0.012 g·kg-1)5、15、30、60、90和120 min后,自由门脉压平均值分别较注射前下降5.2%、14.1%、13.7%、12.9%、9.3%和6.5%(P<0.05,P<0.01,P<0.01,P<0.01,P<0.01,P<0.05),肝静脉楔入压、肝静脉压梯度、门静脉阻力均同步下降.肝动脉血流量无显著改变,门静脉血流量及全肝血流量轻度增多.肝静脉自由压、下腔静脉压、腹主动脉平均压及心率均无明显变化.自由门静脉压下降最大幅度与股静脉血血浆组织胺浓度呈显著正相关(r=0.787 4,P<0.05).盐水对照组及正常对照组上述各指标均无显著变化.结论:甲氰咪胍通过拮抗肝硬化门脉高压症犬血中异常升高的组织胺的作用,舒张肝血管床,降低门脉血流阻力,从而降低门脉压力,同时使门脉及全肝血流量轻度增加,而对全身血流动力学无不良影响.

  2. Delavirdine

    Science.gov (United States)

    ... and propafenone (Rythmol); medications for indigestion, heartburn, or ulcers such as cimetidine (Tagamet), famotidine (Pepcid), lansoprazole (Prevacid), nizatidine (Axid), omeprazole (Prilosec), and ranitidine (Zantac); ...

  3. Drug-induced diarrhea

    Science.gov (United States)

    ... cancer Drugs used to treat heartburn and stomach ulcers, such as omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (AcipHex), pantoprazole (Protonix), cimetidine (Tagamet), ranitidine ( ...

  4. Ceritinib

    Science.gov (United States)

    ... your blood pressure; medications for indigestion, heartburn, or ulcers such as cimetidine (Tagamet, in Duexis), esomeprazole (Nexium), famotidine (Pepcid), lansoprazole (Prevacid), nizatidine (Axid), omeprazole (Prilosec), pantoprazole (Protonix), rabeprazole ( ...

  5. Aluminum Hydroxide

    Science.gov (United States)

    ... and others), chloroquine (Aralen), cimetidine (Tagamet), clonazepam (Klonopin), clorazepate, dexamethasone (Decadron and others), diazepam (Valium, Valrelease, and Zetran), diflunisal (Dolobid), digoxin (Lanoxin), ...

  6. Tizanidine

    Science.gov (United States)

    ... cimetidine (Tagamet); clonidine (Catapres, Catapres-TTS); dantrolene (Dantrium); diazepam (Valium); famotidine (Pepcid, Pepcid AC); medications for anxiety, seizures, or high blood pressure; mexiletine (Mexitil); oral ...

  7. H2 blockers

    Science.gov (United States)

    ... Pepcid AC, Pepcid Oral) Cimetidine (Tagamet, Tagamet HB) Ranitidine (Zantac, Zantac 75, Zantac Efferdose, Zantac injection, and Zantac Syrup) Nizatidine Capsules (Axid AR, Axid Capsules, Nizatidine Capsules)

  8. Constitutive nitric oxide synthase inhibition combined with histamine and serotonin receptor blockade improves the initial ovalbumin-induced arterial hypotension but decreases the survival time in brown norway rats anaphylactic shock.

    Science.gov (United States)

    Bellou, Abdelouahab; Lambert, Henri; Gillois, Pierre; Montémont, Chantal; Gerard, Philippe; Vauthier, Eliane; Sainte-Laudy, Jean; Longrois, Dan; Guéant, Jean Louis; Mallié, Jean Pierre

    2003-01-01

    Anaphylactic shock accidents after allergen exposure are frequent. After immunization with ovalbumin (OVA), a common dietary constituent, we evaluated the efficacy of pretreatment with histamine-receptor or serotonin-receptor blockers administered alone or in combination with a nitric oxide synthase inhibitor (L-NAME) on OVA-induced anaphylactic shock in Brown Norway rats. Animals were allocated to the following groups (n = 6 each): control (0.9% saline); diphenydramine (15 mg kg(-1)); cimetidine (20 mg kg(-1)); diphenydramine + cimetidine; dihydroergotamine (50 microg kg(-1)); diphenydramine + cimetidine + dihydroergotamine; L-NAME (100 mg/kg) alone or associated with diphenydramine, cimetidine, diphenydramine + cimetidine, dihydroergotamine, or diphenydramine + cimetidine + dihydroergotamine. Mean arterial blood pressure (MABP), heart rate (HR), and survival time were monitored for 60 min following treatment. The shock was initiated with i.v. OVA. The MABP drop after i.v. OVA was worsened by diphenydramine and was modestly attenuated by cimetidine, dihydroergotamine, or both together. L-NAME potentiated slightly the effects of cimetidine and dihydroergotamine by lessening the initial MABP decrease, but this transient effect was not sufficient to prevent the final collapse or to improve survival time. Decreased vasodilatory (prostaglandins E2), increased vasoconstrictory (thromboxane B2) prostaglandins, and unchanged leukotriene C4 concentrations were contributory to the overall hemodynamic changes. Thus, the combined blockade of vasodilator mediators (histamine, serotonin, and nitric oxide) slowed the MABP drop in anaphylactic shock, but did not improve survival. More studies are needed to understand these discordant effects.

  9. New H2-receptor antagonist--roxatidine acetate--in treatment of duodenal ulcer.

    Science.gov (United States)

    Amarapurkar, D N; Parikh, S S; Desai, H G

    1993-08-01

    A double blind randomised trial, comparing a new H2-receptor antagonist, Roxatidine acetate, with Cimetidine was carried out in 47 patients of uncomplicated, endoscopically proven duodenal ulcer. Twenty seven patients were treated with Roxatidine 75 mg twice daily and 20 patients were treated with Cimetidine 200 mg 3 times a day and 400 mg at bed time for 4 weeks. At the end of 4 weeks, total pain relief was obtained in 74% and 70% patients receiving Roxatidine and Cimetidine respectively. Complete endoscopic healing at the end of 4 weeks was observed in 92.3% patients receiving Roxatidine and 85% patients receiving Cimetidine. These differences were statistically not significant. No significant side effects were observed in either group. We conclude that Roxatidine acetate is comparable to cimetidine in relieving pain and endoscopic healing of duodenal ulcer and has an excellent safety profile.

  10. The effect of H1 and H2 histamine antagonists on symptomatic dermographism.

    Science.gov (United States)

    Matthews, C N; Boss, J M; Warin, R P; Storari, F

    1979-07-01

    In ten patients suffering from symptomatic dermographism the combined administration of chlorpheniramine + cimetidine produced a greater reduction in the weal and flare response provoked by a standardized scratch than the administration of chlorpheniramine alone. There was a statistically significant improvement in the overall assessment of the patient's skin condition with the combined administration of chlorpheniramine + cimetidine. Chlorpheniramine given alone produced no significant benefit whilst cimetidine alone produced a marked exacerbation in itching in nearly half the patients who initially entered the study and was sufficient to require withdrawal.

  11. Efeitos hemodinâmicos do atracúrio e do cisatracúrio e o uso de difenidramina e cimetidina Efectos hemodinámicos del atracurio y del cisatracurio y el uso de la difenidramina y la cimetidina Hemodynamic effects of atracurium and cisatracurium and the use of diphenhydramine and cimetidine

    Directory of Open Access Journals (Sweden)

    Claudia Maria Nogueira Correa

    2010-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Haja visto que atracúrio pode causar hipotensão arterial no homem, investigaram-se os efeitos hemodinâmicos promovidos pelo atracúrio e pelo cisatracúrio e a proteção hemodinâmica conferida pela difenidramina e cimetidina em ratos. MÉTODO: 1 Ratos Wistar anestesiados com pentobarbital sódico e preparados de acordo com Brown e col. para avaliar doses de atracúrio e cisatracúrio para redução de T4/T1 da sequência de quatro estímulos maior ou igual a 95%. 2 Avaliação das alterações hemodinâmicas de atracúrio e cisatracúrio por injeção venosa, medindo-se a pressão arterial sistêmica da artéria carótida e eletrocardiograma de ratos. 3 Observação de proteção hemodinâmica pelo tratamento prévio com difenidramina (2 mg.kg-1 e/ou cimetidina (4 mg.kg-1 por injeção venosa. Análise estatística: teste t de Student, ANOVA. RESULTADOS: O atracúrio e o cisatracúrio não modificaram a pressão arterial média (PAM nas doses de 1 mg.kg-1 e 0,25 mg.kg-1, respectivamente. Doses de 4 mg.kg-1 promoveram diminuição da PAM de 62,8 ± 4,5% do controle para o atracúrio, e de 82,5 ± 2,3% do controle para o cisatracúrio. Com difenidramina e cimetidina, a pressão sistólica diminuiu 95,4 ± 2,5% do controle. Com cimetidina, pressão diastólica diminuiu 82,7 ± 8,4% do controle. O efeito conjunto sobre as pressões sistólica e diastólica refletiu-se nos valores observados da PAM. CONCLUSÕES: A difenidramina e a cimetidina, isoladamente, não impediram a diminuição da pressão arterial média induzida pelo atracúrio. No entanto, associação destes dois fármacos foi eficaz na prevenção dos efeitos hemodinâmicos induzidos pelo atracúrio. O cisatracúrio nas doses do experimento não promoveu diminuição da pressão arterial que justificasse as medidas preventivas aplicadas nos grupos onde se utilizou o atracúrio.JUSTIFICATIVA Y OBJETIVOS: Habida cuenta de que el atracurio puede causar hipotensión arterial en el hombre, se investigaron los efectos hemodinámicos promovidos por el atracurio y por el cisatracurio, y la protección hemodinámica dada por la difenidramina y la cimetidina en ratones. MÉTODO: 1 Ratones Wistar anestesiados con pentobarbital sódico y preparados de acuerdo con Brown y col. para evaluar las dosis de atracurio y cisatracurio para la reducción de T4/T1 de la secuencia de cuatro estímulos mayor o igual al 95%. 2 Evaluación de las alteraciones hemodinámicas del atracurio y el cisatracurio por inyección venosa, midiendo la presión arterial sistémica de la arteria carótida y electrocardiograma de ratones. 3 Observación de la protección hemodinámica por el tratamiento previo con difenidramina (2 mg.kg-1 y/o cimetidina (4 mg.kg-1 por inyección venosa. Análisis estadístico: test t de Student, ANOVA. RESULTADOS: El atracurio y el cisatracurio no modificaron la presión arterial promedio (PAP en las dosis de 1 mg.kg-1 y 0,25 mg.kg-1, respectivamente. Las dosis de 4 mg.kg-1 disminuyeron la PAP de 62,8 ± 4,5% del control para el atracurio, y de 82,5 ± 2,3% del control para el cisatracurio. Con la difenidramina y la cimetidina, la presión sistólica se redujo a 95,4 ± 2,5% del control. Con la cimetidina, la presión diastólica disminuyó 82,7 ± 8,4% del control. El efecto con-junto sobre las presiones sistólica y diastólica se reflejó en los valores observados de la PAP. CONCLUSIONES: La difenidramina y la cimetidina, aisladamente, no impidieron la disminución de la presión arterial promedio inducida por el atracurio. Sin embargo, la asociación de esos de los fármacos fue eficaz en la prevención de los efectos hemodinámicos inducidos por el atracurio. El cisatracurio, en las dosis del experimento, no promovió una disminución de la presión arterial que justificase las medidas preventivas aplicadas en los grupos donde se utilizó el atracurio.BACKGROUND AND OBJECTIVES: Since atracurium can cause hypotension in humans, the hemodynamic effects of atracurium and cisatracurium as well as the hemodynamic prote

  12. Cimetidine test in correcting creatinine clearance rate in chlidren with renal dysfunction and its evaluation%西咪替丁试验纠正肾功能不全患儿肌酐清除率方法及评价

    Institute of Scientific and Technical Information of China (English)

    孙良忠; 陈述枚

    2003-01-01

    1 使用肌酐清除率评价肾小球滤过率的偏差 肾小球滤过率(GFR)的检测对观察肾脏疾病的进展和预后、药物治疗疗效、透析充分性和移植肾的功能等均有重要意义.目前准确评价GFR的指标是菊粉清除率(Cin)或同位素51铬-乙二胺四乙酸(51Cr-EDTA)等的清除率;临床上用来评价GFR最常用的指标仍然是肌酐清除率(Ccr).Ccr与实际GFR存在一定的偏差.导致Ccr偏离GFR的主要原因是肾小管可分泌少量的肌酐,使Ccr高于GFR.血清肌酐(Scr)在正常水平时,肾小管分泌肌酐量很少,对Ccr影响不大,Ccr/GFR为1.1~1.4;且由于肾小管对肌酐的分泌存在昼夜规律,对肌酐的分泌主要集中在夜间,因此采用4h晨尿Ccr会比24h Ccr的偏差小.但是如果肾小球功能降低,Scr水平升高时,肾小管就会失去分泌肌酐的昼夜规律,分泌肌酐量会显著增多,使测得的Ccr远高于实际GFR;在GFR小于20mL*(min*1.73m2)-1时,Ccr/GFR比值可达到1.7[1,2].这样,用Ccr来反映GFR就会很不准确.

  13. Cimetidine inhibits production of interferon γ and tumor necrosis factor α by splenocytes in aplastic anemic mice%西咪替丁抑制再生障碍性贫血小鼠脾细胞产生干扰素γ和肿瘤坏死因子α

    Institute of Scientific and Technical Information of China (English)

    夏添; 王绮如; 徐有恒

    2001-01-01

    研究西咪替丁对免疫介导再生障碍性贫血小 鼠淋巴细胞产生IFN γ和TNF α的影响。方法:亚 致死量照射后输注异种淋巴细胞构建再障小鼠,用 LPS或PHA-P刺激脾脏细胞产生TNF α或IFN γ,夹 心ELISA法检测诱生的IFN γ浓度,用L929细胞毒 法测定TNF α水平。结果:(1)再障鼠淋巴细胞诱 生的IFN γ和TNF α浓度分别为(137±36)ng/L and (6±3)μg/L,均高于单纯放射组及对照组;(2)用 西咪替丁处理淋巴细胞后,再障小鼠淋巴细胞产生 的IFN γ和TNF α水平下降,分别为(14±8)ng/L 和(2.7±0.6)μg/L。结论:西咪替丁能有效减少 再障小鼠脾淋巴细胞IFN γ和TNF α的产生。

  14. 甲氰咪胍联合左旋咪唑预防肛门尖锐湿疣术后复发的效果%Effect of Cimetidine Combined with Levamisole in Prevention of Recurrence after Operation for Anal Condyloma Acuminatum

    Institute of Scientific and Technical Information of China (English)

    张志明

    2004-01-01

    观察甲氰咪胍联合左旋咪唑预防肛门尖锐湿疣(CA)术后复发的效果.选择尖锐湿疣患者36例,随机分为治疗组19例,在激光或手术切除疣体的基础上,采用甲氰咪胍(0 2g,3次/d,连用2个月)联合左旋咪唑(25mg,3次/d,服3d停4d,连用2个月)治疗;对照组17例,单纯激光或手术治疗.同时采用双联抗体夹心ELISA技术,检测CA患者治疗前后血清IL-2水平.观察比较2组治愈率、复发率及治疗前后IL-2变化,术后3个月评定疗效.结果:治疗组治愈率89.47%.对照组52.94%;治疗组复发率10.53%,对照组47.06%,两组治疗后复发率比较有显著性差异(P<0.05).两组患者IL-2水平均低于正常组.治疗组用药后血清IL-2水平明显升高(P<0.05).

  15. Treatment Option Overview (Pancreatic Neuroendocrine Tumors / Islet Cell Tumors)

    Science.gov (United States)

    ... NETs may include treatment for the following: Stomach ulcers may be treated with drug therapy such as: Proton pump inhibitor drugs such as omeprazole , lansoprazole , or pantoprazole. Histamine blocking drugs such as cimetidine , ...

  16. Stages of Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    ... NETs may include treatment for the following: Stomach ulcers may be treated with drug therapy such as: Proton pump inhibitor drugs such as omeprazole , lansoprazole , or pantoprazole. Histamine blocking drugs such as cimetidine , ...

  17. General Information about Pancreatic Neuroendocrine Tumors (Islet Cell Tumors)

    Science.gov (United States)

    ... NETs may include treatment for the following: Stomach ulcers may be treated with drug therapy such as: Proton pump inhibitor drugs such as omeprazole , lansoprazole , or pantoprazole. Histamine blocking drugs such as cimetidine , ...

  18. Atazanavir

    Science.gov (United States)

    ... are taking a medication for indigestion, heartburn, or ulcers such as cimetidine, esomeprazole (Nexium, in Vimovo), famotidine (Pepcid, in Duexis), lansoprazole (Prevacid, in Prevpac), nizatidine (Axid), omeprazole (Prilosec, in ...

  19. Treatment Options for Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    ... NETs may include treatment for the following: Stomach ulcers may be treated with drug therapy such as: Proton pump inhibitor drugs such as omeprazole , lansoprazole , or pantoprazole. Histamine blocking drugs such as cimetidine , ...

  20. Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human...... EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more...... effective than cimetidine alone. These results show that a combination of an agent inhibiting gastric acid secretion and the cytoprotective and growth-stimulating peptide EGF/URO seems to be more effective with regard to duodenal ulcer healing than individual administration of the two substances. Synthetic...

  1. Gynecomastia

    Science.gov (United States)

    ... men include: Cancer chemotherapy Hormone treatment for prostate cancer, such as flutamide (Proscar), or for enlarged prostate, such as finasteride (Propecia) Radiation treatment of the testicles HIV medicines Anabolic steroids Heartburn and ulcer medicines, such as cimetidine (Tagamet) ...

  2. Zidovudine Injection

    Science.gov (United States)

    ... severe side effects, such as liver damage, blood toxicities, and muscle disorders. If you experience any of ... prescription and nonprescription medications you are taking, especially acetaminophen, acyclovir (Zovirax), aspirin, cancer chemotherapy, cimetidine (Tagamet), fluconazole ( ...

  3. Therapeutic approach in patients with concomitant disease/drug--drug interactions (roxatidine acetate).

    Science.gov (United States)

    Collins, J D

    1988-01-01

    Possible mechanisms of drug interactions with H2-antagonists are outlined. The mode of action of roxatidine acetate on hepatic microsomal enzymes is contrasted with those of cimetidine and ranitidine, and their differing structure-activity relationships are discussed. In the light of the mechanisms of drug interactions with H2-antagonists, clinical studies with roxatidine acetate are contrasted with published interaction data of cimetidine and ranitidine. The therapeutic consequences of these data are considered.

  4. The physiology of the normal human breast: an exploratory study.

    Science.gov (United States)

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  5. H2-antagonist derangement of the kinetics of sustained-release oral theophylline.

    Science.gov (United States)

    Dal Negro, R; Turco, P; Zoccatelli, O; Trevisan, F; Pomart, C

    1985-06-01

    The authors have evaluated the interference of the H2-antagonists cimetidine and ranitidine with the elimination kinetics of sustained-release anhydrous theophylline, administered per os at the dose of 300 mg b.i.d. in two randomly selected groups of patients suffering from chronic obstructive lung disease. The plasma theophylline trends (obtained over a 12-hour period) were compared in the two groups in basal conditions (on reaching the theophylline steady state) and after 8 days treatment with cimetidine or ranitidine. In addition, the bronchodilator effect of theophylline was evaluated in these experimental conditions by means of FEV1 measurements. Simultaneous administration of ranitidine produced no changes in theophylline elimination, and the bronchodilator effect of theophylline proved both substantial and systematic in the patients treated with this H2-antagonist. On the other hand, the patients treated with cimetidine showed a marked, systematic increase in theophylline plasma levels, even exceeding the upper limit of its known therapeutic range in 4 cases. Despite this, no evidence of a bronchodilator effect was found in the cimetidine-treated patients, while significant effects attributable to theophylline toxicity were observed in the 4 cases with excessive theophylline plasma levels. The simultaneous administration of cimetidine in patients treated with sustained-release anhydrous theophylline thus proved capable of seriously undermining the strategy of theophylline usage precisely on account of the high degree of bioavailability of theophylline in the sustained-release formulation.

  6. Efficacy and safety of ecabet sodium on functional dyspepsia :A prospective, double-blinded, randomized, multi-center controlled trial

    Institute of Scientific and Technical Information of China (English)

    Jun Haeng Lee; Soo Teik Lee; Eun Hyun Lee; Jong Chul Rhee; Jae J Kim; Ki-Baik Hahm; Dong Ho Lee; Nayoung Kim; Sung Kook Kim; Jong Jae Park; Seok Reyol Choi; Jong Hun Lee

    2006-01-01

    AIM: To compare ecabet sodium and cimetidine in relieving symptoms of functional dyspepsia.METHODS: We performed a multi-center, prospective,randomized, double-blinded controlled trial to compare the clinical efficacy of ecabet sodium and cimetidine in patients with functional dyspepsia. Two-hundred and seventy-two patients with dyspeptic symptoms fulfilling the Rome-Ⅱ criteria were enrolled from 7 centers. In the study group (115 patients), 1.5 g ecabet sodium was given twice a day. In the control group (121 patients),400 mg cimetidine was given twice a day. Symptoms and parameters of quality of life were analyzed at baseline, 3,14, and 28 d after initiating the treatment.RESULTS: Two-hundred and thirty-six patients completed the clinical trial. After 4 wk of treatment,the rates of improvement in patients with dyspeptic symptoms were not different between two groups (77.4% in the ecabet group and 79.3% in the cimetidine group, respectively, P > 0.05). Likewise, the rates of symptomatic improvement were not different at 3 d and 14 d. The parameters of quality of life did not change significantly during the study period in both groups.There was no clinically significant adverse event in both groups.CONCLUSION: In patients with functional dyspepsia,ecabet sodium has similar clinical efficacy with cimetidine.

  7. Role of central histaminergic mechanism in behavioural depression (swimming despair) in mice.

    Science.gov (United States)

    Nath, C; Gulati, A; Dhawan, K N; Gupta, G P

    1988-01-01

    The role of the central histaminergic system in depression was studied by using swimming despair test in mice - a behavioural model of depression. In this test, immobility of mice reflects a state of depression. Intracerebral (ic) injection of histamine (50-200 micrograms) increased significantly the immobility. The H1-receptor blocker mepyramine (2.5-20 mg/kg ip) had no effect while H2-receptor blocker cimetidine (100-200 micrograms ic) caused a significant decrease in immobility. The histamine induced facilitation was blocked completely by cimetidine and antidepressant drugs-imipramine and desipramine, but remained unaffected in mice pretreated with mepyramine or atropine. The H2 agonist impromidine (20-40 micrograms ic) also enhanced significantly, the immobility which was blocked by cimetidine and antidepressant drugs. It has been concluded that central H2-receptors facilitate depression and antidepressant drugs block central H2-receptors.

  8. Radioprotective effect of cimitidine on acutely irradiated mice survival and hematopoietic system

    Directory of Open Access Journals (Sweden)

    Qing-rong WANG

    2017-02-01

    Full Text Available Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice. Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523 group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg. Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE were determined 30d after 6.0Gy irradiation. Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC and bone marrow DNA content were decreased significantly (P<0.01, P<0.05 in model group, and fMNPCE was increased significantly (P<0.05. Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01. In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 or P<0.05, and the fMNPCE was decreased significantly (P<0.01 or P<0.05and tended towards normal. Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system. DOI: 10.11855/j.issn.0577-7402.2017.01.12

  9. [The effect of two lubricants (magnesium stearate and pruv) in the formation of tablets of four anti-ulcer agents/ by means of direct compression].

    Science.gov (United States)

    Garcia Marquez, M A; Muñoz, A; Jiménez-Castellanos, M R

    1992-01-01

    In this research we study the influence of two lubricants-Magnesium Stearate and Pruv--on the tablets elaboration of Cimetidine, Ranitidine, Famotidine and Pirenzepine by direct compression. The presence of 0.5% of lubricants improved the flow of all the formulations, but especially the Famotidine's formulation. The formulations with Magnesium Stearate had the worst results in tests of friability and tensile strength. All tablets with drugs and Pruv had high data in indentation hardness. The tablets of Cimetidine, Famotidine and Pirenzepine with Magnesium Stearate had less time of disintegration.

  10. Longitudinal study of influence of Helicobacter pylori on current risk of duodenal ulcer relapse. The Hvidovre Ulcer Project Group

    DEFF Research Database (Denmark)

    Clausen, M R; Franzmann, M B; Holst, C;

    1992-01-01

    acid output, time of healing of the preceding ulcer, treatment of the present ulcer (cimetidine, antacids, or no treatment), or type and degree of gastritis. Thus, although H. pylori is prevalent in patients with duodenal ulcer disease, the present study indicates that H. pylori does not have...

  11. Tranexamic acid for upper gastrointestinal bleeding

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Klingenberg, Sarah Louise; Langholz, Ebbe

    2012-01-01

    Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. The present review includes updated searches of randomised trials on tranexamic acid versus placebo, cimetidine or lansoprazole....

  12. Tranexamic acid for upper gastrointestinal bleeding

    DEFF Research Database (Denmark)

    Bennett, Cathy; Klingenberg, Sarah Louise; Langholz, Ebbe;

    2014-01-01

    controlled trial from which data are not yet available. Control groups were randomly assigned to placebo (seven trials) or no intervention (one trial). Two trials also included a control group randomly assigned to antiulcer drugs(lansoprazole or cimetidine). The included studies were published from 1973...

  13. [Fluoroquinolones. Drug interactions].

    Science.gov (United States)

    Rusu, G; Dănilă, G

    2000-01-01

    This review summarizes clinically relevant drug-drug interactions for fluoroquinolones: antiacids containing aluminum and magnesium salts, iron or zinc preparations, sucralfate, cimetidine, ranitidine, warfarina, cyclosporin, rifampin, oral contraceptive steroids, benzodiazepine, probenecid, beta-lactam antibiotics, nonsteroidal anti-inflammatory drugs, metronidazole, theophylline, caffeine.

  14. Recalcitrant pharmaceuticals in the aquatic environment : a comparative screening study of their occurrence, formation of phototransformation products and their in vitro toxicity

    OpenAIRE

    2014-01-01

    Data allowing for a complete environmental risk assessment of pharmaceuticals and their photoderatives in the environment are still scarce. In the present study, in vitro toxicity and both bio- and photopersistence of various pharmaceuticals (aciclovir, allopurinol, cetirizine, cimetidine, fluconazole, hydrochlorothiazide, lisinopril, phenytoin, primidone, ranitidine, sotalol, sulpiride, tramadol and valsartane) as well as their phototransformation products were evaluated in order to fill dat...

  15. Human solvent exposure. Factors influencing the pharmacokinetics and acute toxicity

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1991-01-01

    . Normal therapeutic doses of cimetidine or propranolol have no measurable effect on toluene metabolism. Exposure to 100 ppm during 7 h causes irritation in the eyes and airways as well as feeling of intoxication, dizziness, and headache. There are signs of impairment in the performance in test concerning...

  16. Titanium dioxide nanofibers integrated stainless steel filter for photocatalytic degradation of pharmaceutical compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ramasundaram, Subramaniyan; Yoo, Ha Na; Song, Kyung Guen; Lee, Jaesang [Center for Water Resource Cycle Research, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Choi, Kyoung Jin [School of Mechanical and Material Science Engineering, Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of); Hong, Seok Won, E-mail: swhong@kist.re.kr [Center for Water Resource Cycle Research, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791 (Korea, Republic of)

    2013-08-15

    Highlights: • A photocatalytic metal filter was fabricated with electrospun nanofibrous TiO{sub 2}. • PVDF layer effectively acted as a binder between TiO{sub 2} nanofibers and metal filter. • The photocatalytic efficacy of P-SSF was evaluated against pharmaceuticals. • The photocatalytic efficacy was highly dependent on water flux thru P-SSF. •Almost 90% of cimetidine was removed at a flux of 10 L/m{sup 2} h and 0.1–0.2 kPa TMP. -- Abstract: A photocatalytically active stainless steel filter (P-SSF) was prepared by integrating electrospun TiO{sub 2} nanofibers on SSF surface through a hot-press process where a poly(vinylidene fluoride) (PVDF) nanofibers interlayer acted as a binder. By quantifying the photocatalytic oxidation of cimetidine under ultraviolet radiation and assessing the stability of TiO{sub 2} nanofibers integrated on the P-SSF against sonication, the optimum thickness of the TiO{sub 2} and PVDF layer was found to be 29 and 42 μm, respectively. At 10 L/m{sup 2} h flux, 40–90% of cimetidine was oxidized when the thickness of TiO{sub 2} layer increased from 10 to 29 μm; however, no further increase of cimetidine oxidation was observed as its thickness increased to 84 μm, maybe due to limited light penetration. At flux conditions of 10, 20, and 50 L/m{sup 2} h, the oxidation efficiencies for cimetidine were found to be 89, 64, and 47%, respectively. This was attributed to reduced contact time of cimetidine within the TiO{sub 2} layer. Further, the degradation efficacy of cimetidine was stably maintained for 72 h at a flux of 10 L/m{sup 2} h and a trans-filter pressure of 0.1–0.2 kPa. Overall, our results showed that it can potentially be employed in the treatment of effluents containing organic micropollutants.

  17. Effect of antisecretory agents and vagotomy on healing of "chronic" cysteamine-induced duodenal ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1986-01-01

    Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect...... of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference...... between treated and untreated groups decreased. The morphology of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably...

  18. Lipolytic responses induced by intracerebroventricular administration of histamine in the rat.

    Science.gov (United States)

    Bugajski, J; Janusz, Z

    1981-04-01

    Histamine (10-50 microgram) administered intraventricularly in conscious rats induced an increase in serum-free fatty acids. The maximum, significant increase appeared 30-60 min after administration. Histamine H1-receptor antagonists, mepyramine and chloropyramine, when injected 2 h prior to histamine, abolished considerably hyperlipaemic responses to histamine. H2-Receptor antagonists, metiamide and cimetidine, given i.c.v. only moderately diminished histamine-induced hyperlipaemia. Histamine injected i.c.v. also increased serum corticosterone levels considerably. This elevation was prevented significantly by the H1-receptor antagonist, mepyramine, but not by the H2-receptor blocker, cimetidine. It seems likely that histamine given i.c.v. induces lipolysis through the release of ACTH, one of the known lipid-mobilizing hormones. The central lipid-mobilizing mechanism after histamine depends more on activation of H1- than H2-receptors.

  19. Clinical studies on the use of roxatidine acetate for the treatment of peptic ulcer in Japan.

    Science.gov (United States)

    Inoue, M

    1988-01-01

    Roxatidine acetate is a novel H2-receptor antagonist with a chemical structure different to the earlier drugs of this type. It is a potent inhibitor of histamine-mediated gastric acid secretion and in animal models is 4 to 6 times as potent as cimetidine. In a multicentre double-blind clinical trial of over 700 patients with gastric or duodenal ulcers roxatidine acetate 75 mg twice daily and cimetidine 200mg four times daily produced endoscopically confirmed and subjective and objective healing rates in excess of 90% for both types of ulcer, with no significant difference between the treatments. Roxatidine acetate's efficacy in stomal ulcer (marginal ulcer) and reflux oesophagitis has been confirmed in non-comparative studies of up to 8 weeks' duration. The overall incidence of adverse reactions in 1623 patients treated with roxatidine acetate 75 mg twice daily was 1.7%, with skin rashes and constipation the most frequently reported side effects.

  20. Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands...... delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined...... administration of synthetic human EGF/URO and cimetidine further increased healing of gastric ulcers compared with administration of each substance. Neither synthetic human EGF/URO, nor removal of the submandibular glands had any influence on gastric acid secretion. This study showed that the submandibular...

  1. The role of colloidal bismuth subcitrate in the short-term treatment of duodenal ulcer.

    Science.gov (United States)

    Barbara, L; Corinaldesi, R; Rea, E; Paternicò, A; Stanghellini, V

    1986-01-01

    Colloidal bismuth subcitrate (CBS) is a drug used in the treatment of duodenal ulcer; it acts mainly by increasing mucosal resistance against endoluminal aggressive agents, without inhibiting gastric secretion. In previous clinical trials, CBS solution induced healing rates significantly higher than placebo and similar to those observed with cimetidine. In spite of these promising results, the drug has never been widely employed, mainly because of its unpleasant taste, which greatly reduced patient compliance. For this reason, chewing tablets have been introduced. CBS tablets have been reported to induce healing rates significantly higher than placebo and similar to those obtained with CBS solution, cimetidine, and ranitidine. CBS may therefore represent an important alternative to antisecretory drugs in the therapy of duodenal ulcer patients.

  2. Reply to "On the Effect of Common Excipients on the Oral Absorption of Class 3 Drugs".

    Science.gov (United States)

    Vaithianathan, Soundarya; Haidar, Sam H; Zhang, Xinyuan; Jiang, Wenlei; Avon, Christopher; Dowling, Thomas C; Shao, Changxing; Kane, Maureen; Hoag, Stephen W; Flasar, Mark H; Ting, Tricia Y; Polli, James E

    2016-04-01

    We previously concluded that 12 common excipients need not be qualitatively the same and quantitatively very similar to reference for Biopharmaceutics Classification System-based biowaivers. This conclusion for regulatory relief is based upon a series of bioequivalence studies in humans involving cimetidine and acyclovir. Limitations were also discussed. We understand the major concern of García-Arieta et al. is that "results obtained by Vaithianathan et al. should not be extrapolated to other drugs." We understand that individuals conducting their own risk/benefit analysis may reach that conclusion, and we reply to the concerns of García-Arieta et al. We continue to conclude that the 12 common excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather, simply be not more than the quantities studied in our manuscript for cimetidine and acyclovir, and potentially other class 3 drugs with similar properties.

  3. The first case of adult-onset PFAPA syndrome in Japan.

    Science.gov (United States)

    Kutsuna, Satoshi; Ohmagari, Norio; Tanizaki, Ryutaro; Hagino, Noboru; Nishikomori, Ryuta; Ujiie, Mugen; Takeshita, Nozomi; Hayakawa, Kayoko; Kato, Yasuyuki; Kanagawa, Shuzo

    2016-01-01

    A 26-year-old woman presented with fever and pharyngitis. She previously experienced four periodic febrile episodes at 30- to 40-day intervals. We suspected periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, and prescribed predisolone, thereby her fever rapidly subsided. Her febrile episodes improved after daily cimetidine treatment. Genetic testing results of genomic DNA for periodic fever syndromes were negative, although she was heterozygous for p.Glu148Gln variation in MEFV, supporting the diagnosis of PFAPA syndrome.

  4. Analysis of histamine receptors in the central thermoregulatory mechanism of Mastomys natalensis.

    OpenAIRE

    Dhawan, B. N.; Shukla, R.; Srimal, R. C.

    1982-01-01

    1 The effect of intracerebroventricular (i.c.v.) injection of histamine on the rectal temperature of Mastomys natalensis at ambient temperatures of 10, 24 and 33 degrees C has been studied. 2 Low doses (0.1-1.0 microgram) of histamine produced hypothermia while larger doses (5-20 micrograms) produced dose-dependent hyperthermia. The hypothermic effect was significantly antagonized by mepyramine while the hyperthermia was blocked by cimetidine. 3 Histamine H1-receptor agonists, 2-methyl-histam...

  5. Phentolamine-induced rhythmic contractions in bladder detrusor muscle of guinea-pig.

    OpenAIRE

    Satake, N; Shibata, S.; Ueda, S.

    1984-01-01

    Phentolamine caused a rhythmic contraction concentration-dependently without affecting resting tone in the detrusor muscle. Prazosin, yohimbine, propranolol, noradrenaline, clonidine or isoprenaline failed to cause the rhythmic contraction. These agents did not modify the response to phentolamine suggesting no involvement of alpha- or beta-adrenoceptors in the response to phentolamine. Chlorpheniramine, cimetidine, methysergide, SK&F 83566, atropine, bretylium, hemicholinium or tetrodotoxin f...

  6. In vivo and in vitro analysis of the effect of various acid-secretion blockers on UDP-galactosyltransferase activities in rat gastric mucosa

    OpenAIRE

    2002-01-01

    Gastric mucus glycoprotein is important for the protection of gastric mucosa from acid. UDP-galactosyltransfer-ase (UDP-Gal-T) is a key enzyme for the synthesis of gastric mucus glycoprotein. In this study, we investigted the effects of five acid-secretion blockers, cimetidine, ranitidine, famotidine, roxatidine and omprazole on the UDP-Gal-T activity in rat gastric mucosa to clarify the interaction of the acid-secretion blocker and the gastric mucosal barrier. Intraperitoneal administration ...

  7. Effect(s) of Pharmacologic Intervention on Oxygenation, Lung Water and Protein Leak in the Pseudomonas ARDS Porcine Model

    Science.gov (United States)

    1990-07-01

    We have previously established that treatment with cimetidine, or ranitidine in combination with diphenhydramine, H2 and H, blockers, respectively...extravascular lung water (EVLW). In this technique 10 ml of iced, green dye solution (2 mg indocyanine green dye in 10 ml 5% dextrose) were injected as a...capture pulmonary effluent was attached to the left atrial catheter. All solutions were prepared using aseptic technique. Reagents were obtained from

  8. The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk.

    Science.gov (United States)

    Jonker, Johan W; Merino, Gracia; Musters, Sandra; van Herwaarden, Antonius E; Bolscher, Ellen; Wagenaar, Els; Mesman, Elly; Dale, Trevor C; Schinkel, Alfred H

    2005-02-01

    Contamination of milk with drugs, pesticides and other xenotoxins can pose a major health risk to breast-fed infants and dairy consumers. Here we show that the multidrug transporter BCRP (encoded by ABCG2) is strongly induced in the mammary gland of mice, cows and humans during lactation and that it is responsible for the active secretion of clinically and toxicologically important substrates such as the dietary carcinogen PhIP, the anticancer drug topotecan and the antiulcerative cimetidine into mouse milk.

  9. Effect of Disodium Cromoglycate (DSCG) and Antihistamines on Postirradiation Cerebral Blood Flow and Plasma Levels of Histamine and Neurotensin

    Science.gov (United States)

    1988-01-01

    73 6 SOTI UNCLASIFIE ESCURIIY CLASSIFICATION OF Tm-S siki FUNDAMENTAL AND APPLIED TOXICOLOGY 10, 233-242 (1988) Effect of Disodium Cromoglycate (DSCG...given the mast cell stabilizer disodium cromoglycate and the antihistamines mepyramine and cimetidine before Irradiation did not exhibit an abrupt...occur ment with the mast cell stabilizer, disodium with equal frequency in all species, having cromoglycate (DSCG, cromolyn sodium), in- been reported

  10. Journal of Special Operations Medicine, Volume 3, Edition 3

    Science.gov (United States)

    2003-01-01

    These medications, known by their trade names Tagamet® (cimetidine), Pepcid® (famotidine), Axid® (nizatidine), and Zantac® ( ranitidine ) selectively...Claritin Reditabs®) as the first non-sedat- ing antihistamine available in the United States with- out a prescription. Its formulation and dosing are the...the Special Forces Medic. The Chief Medical Aidman’s Course, formulated by 1st Lt Elliott, was specifically designed for Special Forces Medics. Once

  11. Evaluation of H2 receptor antagonists in chronic idiopathic urticaria

    Directory of Open Access Journals (Sweden)

    Minocha Y

    1995-01-01

    Full Text Available H1-antagonist (hydroxyzine hydrochloride in dosage of 10 mg-25 mg thrice a day failed to elicit satisfactory response in 60 out of 170 patients of chronic idiopathic urticaria. Additional administration of H2-antagonist (cimetidine in dosage of 200 mg four times a day, in patients not responding earlier to H1-antagonist alones exhibited moderate to good improvement of various parameters of urticaria in approximately 85% patients

  12. Relaxant effect of the H2-receptor antagonist oxmetidine on guinea-pig and human airways.

    OpenAIRE

    Advenier, C; Gnassounou, J. P.; Scarpignato, C.

    1987-01-01

    The effects of three different H2-receptor antagonists (cimetidine, ranitidine and oxmetidine) were tested on isolated preparations of guinea-pig trachea and human bronchus against contractions induced by acetylcholine, histamine and potassium chloride (KCl). In addition, their influence on calcium concentration-response curves in guinea-pig tracheal spirals was examined in a potassium-rich solution (30 mM). Finally, their effects were studied in vivo against acetylcholine and histamine-induc...

  13. A review of the animal pharmacology of roxatidine acetate.

    Science.gov (United States)

    Scholtholt, J; Bickel, M; Herling, A W

    1988-01-01

    Roxatidine acetate (TZU 0460/HOE 760) [N-(3-[3-(1-piperidinylmethyl)-phenoxy]-propyl)acetoxyacetamide hydrochloride] is a specific and competitive H2-receptor antagonist with a chemical structure different from those of cimetidine, ranitidine and famotidine. Roxatidine acetate and its main metabolite roxatidine inhibit histamine-induced gastric acid secretion in vitro with a potency greater than that of cimetidine, and in the range of that produced by ranitidine. Gastric acid secretion following stimulation with dibutyryl cyclic adenosine monophosphate remains unaffected by roxatidine acetate. In vivo experiments in rats and dogs confirm these in vitro findings. Thus, in rats roxatidine acetate inhibits gastric acid secretion with similar values following intraduodenal or intraperitoneal injection, indicating excellent absorption of the drug from the gastrointestinal tract. In all studies it was shown that roxatidine acetate was more potent than cimetidine. In rats single or repeated dosing with roxatidine acetate did not influence drug metabolising enzymes in the liver nor did the drug show antiandrogenic activity in long term animal studies. Extensive general pharmacological studies with roxatidine acetate demonstrate the lack of effects on the central nervous system, on gastrointestinal motility, the autonomic nervous system and the cardiovascular and urogenital systems. Studies on the pharmacokinetics and metabolism of roxatidine acetate demonstrate that there is a presystemic deacetylation producing the main metabolite roxatidine, which is responsible for the in vivo effects of the drug.

  14. Review article: prevention of stress-related mucosal bleeding with proton-pump inhibitors.

    Science.gov (United States)

    Maton, P N

    2005-12-01

    Stress-related gastric mucosal bleeding occurs in a substantial number of critically ill patients, with clinically important gastrointestinal bleeding prolonging intensive care stay and increasing mortality. This paper reviews the role of proton-pump inhibitors in the prevention of stress-related mucosal bleeding. Bleeding prophylaxis appears to be warranted in patients in intensive care units on mechanical ventilation or those who have coagulopathy. Intravenous histamine H2 receptor antagonists, particularly cimetidine, have demonstrated efficacy for the prevention of bleeding in critically ill patients. Standard delayed-release proton-pump inhibitors have not been extensively studied in this patient group, but there are some data to support their efficacy in increasing intragastric pH, and in the case of intravenous pantoprazole in preventing gastrointestinal bleeding. In a large, randomized controlled trial, immediate-release omeprazole [(IR-OME) Zegerid powder for oral suspension; Santarus Inc., San Diego, CA, USA] administered via gastric tube, was as effective as intravenous cimetidine in the prevention of clinically significant bleeding, and more effective in increasing gastric pH. Effective antisecretory therapy does not appear to increase the risk of nosocomial pneumonia. In conclusion, immediate-release omeprazole provides a safe and effective alternative to intravenous cimetidine for the prevention of stress-related mucosal bleeding in critically ill patients.

  15. Clinical characteristics of roxatidine acetate: a review.

    Science.gov (United States)

    Dammann, H G; de Looze, S M; Bender, W; Labs, R

    1988-01-01

    Pharmacodynamic studies revealed that 150 mg of roxatidine acetate were optimal in suppressing gastric acid secretion, and that a single bedtime dose of 150 mg was more effective than a dose of 75 mg twice daily in terms of inhibiting nocturnal acid secretion. When administered orally as a capsule containing a granule formulation, the drug displayed modified-release properties, which led to a sustained suppression of gastric acid secretion. Clinical trials revealed that roxatidine acetate, 75 mg twice daily and 150 mg at night, was highly effective in healing duodenal and gastric ulcers and in reducing ulcer pain, over 4, 6, and 8 weeks of therapy. A steady reduction in diameter was observed in those ulcers not completely healed during therapy. The single bedtime dose regimen, while producing the same degree of healing as the divided daily dose during controlled clinical trials, may be of greater value in therapeutic use owing to improved patient compliance. In all efficacy criteria (cure, reduction in ulcer size, and pain relief) there was no significant difference between roxatidine acetate in a total daily dose of 150 mg, ranitidine in a total daily dose of 300 mg, and cimetidine in a total daily dose of 800 mg. Prevention of gastric and duodenal ulcer relapse was achieved by roxatidine acetate, 75 mg at night for 6 months, in about 70% of patients, as determined in open, pilot studies--a rate comparable to those reported for cimetidine and ranitidine. Roxatidine acetate shares with ranitidine an improved safety profile when compared with cimetidine. Human pharmacology studies and short-term and long-term clinical trials have all shown that roxatidine acetate is an exceptionally well tolerated compound, without the antiandrogenic activity and interference with hepatic drug metabolism which have characterized cimetidine treatment. A reason for the improved safety profile of roxatidine acetate may be its greater potency than cimetidine (six times less potent) and

  16. Evaluation of the acute toxicity, phytochemical constituents and anti - ulcer properties of methanolic leaf extract of Annona muricata in mice

    Directory of Open Access Journals (Sweden)

    Valentine Uneojo Omoja

    2014-02-01

    Full Text Available This study investigated the acute toxicity, phytochemical constituents and anti - ulcer properties of methanolic leaf extract of Annona muricata in mice. The anti - ulcer activity was evaluated using absolute ethanol-induced ulcer and aspirin-induced ulcer models in mice. An LD50 of 354.8 +/- 8 mg/kg body weight, bw of the extract was obtained on oral administration. Investigation of the phytochemical constituents of the plant extract revealed the presence of saponins, alkaloids and traces of tannins. All doses of the extract (50, 75 and 100 mg/kg used for the study significantly reduced (p<0.05 the mean number of ulcers in both ulcer models when compared to the untreated group A (10 ml/kg distil water. Optimum antiulcer activity of the extract against absolute ethanol-induced ulcer was noted at 50 mg/kg bw. At this 50 mg/kg, the mean number of ulcers and mean ulcer index of the extract was significantly lower (p<0.05 than that of Cimetidine at 100 mg/kg (3.60 +/- 0.51: 5.00 +/- 0.32; 1.5+/-0.05: 0.98+/-0.03, the treated control group whereas the protective index of the extract was higher than that of cimetidine (50.51 %: 24.24 %. The results obtained from this study strongly suggest that methanolic leaf extract of Annona muricata can be effectively used for the treatment of ulcer in low doses and can provide better therapeutic effect than cimetidine if used in ulcers caused by alcoholism and related agents. [J Intercult Ethnopharmacol 2014; 3(1.000: 37-43

  17. Neuronal histamine and expression of corticotropin-releasing hormone, vasopressin and oxytocin in the hypothalamus: relative importance of H1 and H2 receptors.

    Science.gov (United States)

    Kjaer, A; Larsen, P J; Knigge, U; Jørgensen, H; Warberg, J

    1998-08-01

    Centrally administered histamine (HA) stimulates the secretion of the pro-opiomelanocortin-derived peptides ACTH and beta-endorphin as well as prolactin. The effect of HA on secretion of these adenohypophysial hormones is indirect and may involve activation of hypothalamic neurons containing corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) or oxytocin (OT). We studied the effect of activating central HA receptors by central infusion of HA, HA agonists or antagonists on expression of CRH, AVP and OT mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Intracerebroventricular infusion of HA (270 nmol), the H1-receptor agonist 2-thiazolylethylamine or the H2-receptor agonist 4-methylhistamine increased the level of CRH mRNA in the PVN, and OT mRNA in the SON. In contrast, none of these compounds had any effect on expression of AVP mRNA in the PVN or SON. Administration of the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine had no effect on basal expression of CRH, AVP or OT mRNA in the PVN and/or SON except for a slight inhibitory effect of cimetidine on CRH mRNA expression in the PVN. Pretreatment with mepyramine or cimetidine before HA administration inhibited the HA-induced increase in OT mRNA levels but had no effect on the HA-induced increase in CRH mRNA levels in the PVN. We conclude that HA stimulates hypothalamic CRH and OT neurons by increasing mRNA levels, and this effect seems to be mediated via activation of both HA H1 and H2 receptors.

  18. Renal accumulation of [{sup 111}In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, A.R. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany); Universitaetsklinikum Essen, Department of Radiology, Essen (Germany); Wagner, B.; Heemann, U.; Lutz, J. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nephrology, Munich (Germany); Poethko, T.; Perutka, M.; Wester, H.J.; Essler, M.; Schwaiger, M. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany)

    2007-12-15

    Radiation exposure to the kidney limits therapy with radiometal labelled DOTATOC. This study evaluates the organic anion and cation transport (inhibitors: probenecid and cimetidine/dexamethason) as well as diuresis (furosemide and mannitol) regarding renal uptake of [{sup 111}In]DOTATOC. One hundred eight male Fisher rats were injected with [{sup 111}In]DOTATOC via the tail vein. Prior to activity injection a total of 84 rats underwent injection with probenecid vs. sodium chloride 0.9% (48 rats), cimetidine vs. dexamethasone vs. sodium chloride 0.9% (18 rats), and furosemide vs. mannitol vs. sodium chloride 0.9% (18 rats). Rats were sacrificed at predetermined time points up to 48 h after activity injection. Kidneys, adrenal glands, pancreas, spleen, blood, liver, and muscle were harvested and injected activity per gram tissue was determined. Autoradiographic images of the kidneys were acquired in a total of 24 rats. Probenecid led to a reduction in renal uptake by up to 30% while not significantly changing the activity accumulation in the other organs investigated. This reduction was attributable to the renal cortex (ratio cortex/medulla 1.72 vs. 1.99; p = 0.006). Cimetidine and dexamethasone had no effect in any of the organs. Furosemide led to a 44% increase in renal activity accumulation attributable to enhanced renal medullary uptake (ratio cortex/medulla 1.44 versus 1.69; p = 0.006). Mannitol had no effect on renal activity uptake. Inhibition of the organic anion transport by probenecid may help reduce renal uptake regarding therapy with radiometal labelled DOTATOC. The enhancing effect of furosemide may be unfavourable for therapy. The results must be confirmed by human studies. (orig.)

  19. Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo

    Science.gov (United States)

    2014-01-01

    Background Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. Method The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. Results DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC50 values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the Cmax of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination

  20. Evidence of anti-oxidant role of sucralfate in gastric mucosal protection.

    Science.gov (United States)

    Laudanno, O M; Bedini, O A; Cesolari, J A; San Miguel, P

    1990-02-01

    Six percent hydrogen peroxide (H2O2) was used as a generator of the *OH free radical, and as an aggressor of gastric mucosa, in 100 Wistar rats. The mucosal cytoprotector effect of sucralfate, misoprostol, enprostil, cimetidine, ranitidine, famotidine and 10% aluminum sulphate yielded almost complete macroscopic and histological protection to the gastric mucosa. Misoprostol or enprostil gave partial protection whereas the H2 blockers aggravated the gastric necrotic lesions produced by the H2O2. We conclude that sucralfate is a true anti-oxidant that protects the gastric mucosa through its aluminum and sulphydril components, the increment of gastric mucins and endogenous PGs.

  1. PFAPA with facial swelling- a new association?

    Science.gov (United States)

    Khodaghalian, B; Tewary, K K; Narchi, H

    2013-05-01

    PFAPA (periodic fever, apthous stomatitis, pharyngitis, cervical adenitis) is a rare condition of unknown cause affecting children. Although the exact etiology is unknown, inflammatory, immunological or genetic causes have been suggested. The diagnosis is made by exclusion of other causes of periodic fever. Although management is essentially symptomatic, single corticosteroid dose, tonsillectomy and Cimetidine has been shown to be associated with resolution of symptoms. Although abdominal pain and genital ulcers have been reported in association with PFAPA, unilateral transient facial swelling has not been previously reported. The authors present a hitherto unreported association of PFAPA with recurrent episodes of unilateral facial swelling.

  2. The effect of intravenous omeprazole on the gastric and duodenal potential difference and pH in healthy subjects

    DEFF Research Database (Denmark)

    Rubinstein, E; Højgaard, L

    1993-01-01

    The effect of intravenous omeprazole (40 and 80 mg) on the gastric and duodenal potential difference (PD) and pH was investigated in 9 healthy volunteers. Gastric PD and pH increased significantly (p omeprazole, and the increases were equal following the two doses. No changes were...... found in duodenal PD or pH. It has been claimed that gastric PD changes following acid secretion inhibition with cimetidine and glucagon might be due to changes in the parietal cell surface area. Omeprazole causes no changes in the parietal cell structure, and the changes in gastric PD following...... omeprazole might therefore be ascribed to changes in mucosal electrophysiologic transport or resistance....

  3. Observation Curative and Untoward Effect on Omeprazole Combined With Antibiotics in Treatment of Gastric Ulcer%奥美拉唑联合抗生素治疗胃溃疡的疗效及不良反应观察

    Institute of Scientific and Technical Information of China (English)

    程艳艳

    2016-01-01

    目的:观察奥美拉唑联合抗生素治疗胃溃疡的疗效及不良反应。方法将我院收治的52例胃溃疡患者作为研究对象,随机分组,各26例。西咪替丁组予以甲硝唑片、阿莫西林及西咪替丁片治疗,奥美拉唑组予以甲硝唑片、阿莫西林及奥美拉唑肠溶片治疗。对比两组患者临床效果、不良反应发生率。结果西咪替丁组临床总有效率69.2%,低于奥美拉唑组96.2%,差异有统计学意义(P<0.05);西咪替丁组不良反应发生率46.2%,高于奥美拉唑组15.4%,差异有统计学意义(P<0.05)。结论应用抗生素与奥美拉唑联合治疗胃溃疡可提高其临床效果,有效降低不良反应发生率。%Objective To observe the curative effect and adverse reaction of omeprazole combined with antibiotics in the treatment of gastric ulcer.Methods 52 cases of gastric ulcer patients treated in our hospital were studied, random divided into difference groups, each of 26 cases. The cimetidine group were given metronidazole tablets, amoxicillin and cimetidine tablets treatment, The omeprazole group received metronidazole tablets, amoxicillin and omeprazole enteric-coated tablets treatment. The clinical effect and incidence of adverse reactions in the two groups were analyzed.Results The clinical total effective rate of cimetidine group was 69.2%, lower than the omeprazole group 96.2%, and the difference was signiifcant (P<0.05), The incidence of adverse reactions in cimetidine group was 46.2%, higher than that in omeprazole group 15.4%, the difference was signiifcant (P<0.05).Conclusion The combination of antibiotics and omeprazole in the treatment of gastric ulcer can signiifcantly improve the clinical effect, reduce the incidence of adverse reactions.

  4. Antiulcer properties of Glycyrrhiza glabra L. extract on experimental models of gastric ulcer in mice.

    Science.gov (United States)

    Jalilzadeh-Amin, Ghader; Najarnezhad, Vahid; Anassori, Ehsan; Mostafavi, Mostafa; Keshipour, Hadi

    2015-01-01

    Glycyrrhiza glabra L. is used in folk medicine for treatment of stomach disorders including peptic ulcers. The hydroalcoholic extract of Glycyrrhiza glabra L. (HEGG) was evaluated for antiulcerogenic activity and acute toxicity profile in mice. Various doses of HEGG (50-200 mg/kg) were administered orally to animals of different groups. Omeprazole and cimetidine at doses of 30 and 100 mg/kg were used as positive controls, respectively. Stomach was opened along the greater curvature then ulceration index was determined examining the inner lining of stomach. Oral administration of the extract at 1600 mg/kg did not produce toxic symptoms and mortality in mice. 2950 mg/kg was determined as the oral LD50. The HEGG (50-200 mg/kg) showed a significant reduction in ulcer index in HCl/Ethanol-induced ulcer. G. glabra extract (50-150 mg/kg) showed antiulcer activity against indomethacin-induced gastric lesions dose dependently. The extract effectively inhibited formation of gastric lesions induced by ethanol. The extract (200 mg/kg) was more potent than omeprazole (30 mg/kg). HEGG reduced the ulcer index in hypothermic stress induced gastric ulcers in mice and the antiulcer effect was comparable to that of cimetidine. The results indicated that G. glabra hydroalcoholic extract exerted an antiulcergenic effect that could be associated with increase in gastric mucosal defensive factors.

  5. Drug-drug interaction and doping, part 1: an in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene.

    Science.gov (United States)

    Mazzarino, Monica; de la Torre, Xavier; Fiacco, Ilaria; Palermo, Amelia; Botrè, Francesco

    2014-05-01

    The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results.

  6. Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice.

    Science.gov (United States)

    Mobarakeh, Jalal Izadi; Takahashi, Kazuhiro; Sakurada, Shinobu; Kuramasu, Atsuo; Yanai, Kazuhiko

    2006-09-01

    We have previously shown that antinociceptive effects of morphine are enhanced in histamine H1 receptor gene knockout mice. In the present study, involvement of supraspinal histamine H2 receptor in antinociception by morphine was examined using histamine H2 receptor gene knockout (H2KO) mice and histamine H2 receptor antagonists. Antinociception was evaluated by assays for thermal (hot-plate, tail-flick and paw-withdrawal tests), mechanical (tail-pressure test) and chemical (formalin and capsaicin tests) stimuli. Thresholds for pain perception in H2KO mice were higher than wild-type mice. Antinociceptive effects of intracerebroventricularly administered morphine were enhanced in the H2KO mice compared to wild-type mice. Intracerebroventricular co-administration of morphine and cimetidine produced significant antinociceptive effects in the wild-type mice when compared to morphine or cimetidine alone. Furthermore, zolantidine, a selective and hydrophobic H2 receptor antagonist, enhanced the effects of morphine in all nociceptive assays examined. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H2 receptors at the supraspinal level. Our present and previous studies suggest that H1 and H2 receptors cooperatively function to modulate pain perception in the central nervous system.

  7. Effect of histamine on regional cerebral blood flow of the parietal lobe in rats.

    Science.gov (United States)

    Yang, Peng-Bo; Chen, Xin-Lin; Zhao, Jian-Jun; Zhang, Jian-Shui; Zhang, Jun-Feng; Tian, Yu-Mei; Liu, Yong

    2010-09-01

    Histamine is a powerful modulator that regulates blood vessels and blood flow. The effect of histamine on the extracortical vessels has been well described, while much less is known about the effect of histamine on intracortical vessels. In this study, we investigated the effect of histamine on regional cerebral blood flow in rat parietal lobe with laser Doppler flowmetry. The pharmacological characteristics of distinct ways (intracerebroventricular injection, intraperitoneal injection, and cranial window infusion) in applying histamine to the brain were also obtained and compared. Histamine applied in three ways all produced a decrease of rCBF in parietal lobe in a concentration-dependent manner. Cranial window infusion was the most effective way and intraperitoneal injection of L-histidine was the most ineffective, although it is a simple and applied way. To determine which type of receptor takes part in the vessel contraction induced by histamine, H1 receptor antagonist, diphenhydramine, and H2 receptor antagonist, cimetidine, were applied, respectively, before histamine administration. When the injection of cimetidine was conducted in advance, histamine still resulted in a decrease of infusion amount; while the injection of diphenhydramine was conducted in advance, the infusion of blood amount wasn't changed. These findings indicated that histamine could result in a reduction of rCBF in the rat parietal lobe and this effect of histamine may attribute partly to its combination with H1 receptor.

  8. Effects of histamine and opioid systems on memory retention of passive avoidance learning in rats.

    Science.gov (United States)

    Zarrindast, Mohammad-Reza; Eidi, Maryam; Eidi, Akram; Oryan, Shahrbano

    2002-10-04

    The present study investigated the effect of interactions between histamine receptor agents and the opioid peptidergic system on memory retention of passive avoidance learning in rats. Post-training intracerebroventricular (i.c.v.) injections were carried out in all the experiments. Administration of histamine (20 micro g/rat) reduced, but the histamine H(1) receptor antagonist, pyrilamine (20 and 50 micro g/rat), and the histamine H(2) receptor antagonist, cimetidine (10 and 50 micro g/rat), increased memory retention in rats. The histamine receptor antagonists decreased the response induced by histamine. Morphine (1-10 micro g/rat) reduced, while pentazocine (5 and 10 micro g/rat) or the opioid receptor antagonist, naloxone (5 and 15 micro g/rat), increased memory retention. The combination of histamine with morphine showed potentiation. Effects of pyrilamine and cimetidine were attenuated by morphine. The responses to pentazocine and naloxone also were decreased by histamine. It is concluded that the histaminergic system has an interaction with opioidergic system that is involved in the memory retention process.

  9. Involvement of central histamine in amygdaloid kindled seizures in rats.

    Science.gov (United States)

    Kamei, C

    2001-10-15

    The involvement of central histamine in amygdaloid kindled seizures in rats was investigated using histamine-related compounds. Histamine contents in the amygdala of electrical stimulation site was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H(1)-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H(1)-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine (i.c.v.)-induced inhibition of amygdaloid kindled seizures, however, no significant antagonism was observed with H(2)-antagonists (cimetidine, ranitidine or zolantidine). Intracerebroventricular injection of H(3)-antagonists (thioperamide and AQ 0145) resulted in a dose-related inhibition of amygdaloid kindled seizures. The same findings were observed when thioperamide and clobenpropit were injected i.p. The effects of thioperamide (i.p.) and AQ 0145 (i.p.) were inhibited by an H(3)-agonist [(R)-alpha-methylhistamine] and H(1)-antagonists (diphenhydramine and chlorpheniramine). On the other hand, H(2)-antagonists (cimetidine and ranitidine) showed no antagonistic effects. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H(1)-receptors.

  10. Neural histamine in the tuberomammillary nucleus regulates the onset of neurogenic pulmonary edema in rabbits

    Institute of Scientific and Technical Information of China (English)

    Rong Dong; Xiaohong Zhang; Lijuan Shi

    2009-01-01

    Objective:To explore the effect of neural histamine in the tuberomammillary nucleus(TM) on neurogenic pulmonary edema (NPE) onset in rabbits and the function of the rostral ventrolateral medulla(RVLM) in the neural histamine modulation of NPE.Methods:NPE was produced by the intracisternal injections of fibrinogen and thrombin.The contents of histamine in the TM and RVLM in rabbits were measured with high performance liquid chromatography(HPLC).Rabbits were placed on a stereotaxic frame and microinjection cannulae were inserted into the TM and RVLM using brain atlas coordinates.Animals were pretreated with R-α-methylhistamine(MeHA) in the TM and chlorphenamine Mmaleate/cimetidine in the RVLM prior to establishing the NPE model.Changes in the lung water ratio and mean arterial pressure(MAP) were recorded,and paraffin sections of lung tissue were observed by light microscope.Results:We found that the contents of histamine(HA) in the TM and RVLM increased significantly with the onset of NPE.Pretreatment with MeHA in the TM and chlorphenamine Mmaleate in the RVLM significantly decreased MAP,and the lung water ratio and histological characteristics of the NPE in the rabbit model.Pretreatment with cimetidine in the RVLM had no effect on NPE.Conculsion:The results suggest that neural histamine in the TM is involved in the onset of NPE,and this effect of neural histamine is mediated by H receptor in the RVLM.

  11. Thioperamide treats neonatal hypoxic-ischemic encephalopathy by postsynaptic H1 receptors*

    Institute of Scientific and Technical Information of China (English)

    Feiyong Jia; Lin Du; Yunpeng Hao; Shicheng Liu; Ning Li; Huiyi Jiang

    2013-01-01

    Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic- is-chemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre-vent oxidative damage and attenuate brain edema fol owing neonatal hypoxic-ischemic encepha-lopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci-metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide;however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo-natal hypoxic-ischemic encephalopathy.

  12. Evaluation of domperidone as a modifier of gamma-radiation-induced emesis. Report for January 1984-January 1986

    Energy Technology Data Exchange (ETDEWEB)

    Cordts, R.E.; Yochmowitz, M.G.; Hardy, K.A.

    1987-09-01

    The D2 antidopaminergic drug Domperidone was evaluated singly and in combination with synthetic adrenocorticoid and an H2 antihistamine for its ability to reduce the acute emetic effects of /sup 60/Co whole-body radiation. Random-source adult male dogs were fasted 12 hours, fed a standard meal, injected 44 minutes later and irradiated 47 minutes after that. Four groups of dogs were radiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim+Thi), and dexamethasone + domperidone + cimetidine (Dex+Dom+Cim). Drug quantities for dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 ka, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset times, offset times, and number of episodes were recorded. The ED50 of Dex+Dom+Cim was higher than Con. Dom produced more emetic episodes than Con or Dex+Dom+Cim. This drug in combination with an adrenocorticoid and antihistamine significantly raised the emetic threshold while maintaining episodes at a low incidence.

  13. Substrate-immobilized electrospun TiO2 nanofibers for photocatalytic degradation of pharmaceuticals: The effects of pH and dissolved organic matter characteristics.

    Science.gov (United States)

    Maeng, Sung Kyu; Cho, Kangwoo; Jeong, Boyoung; Lee, Jaesang; Lee, Yunho; Lee, Changha; Choi, Kyoung Jin; Hong, Seok Won

    2015-12-01

    A substrate-immobilized (SI) TiO2 nanofiber (NF) photocatalyst for multiple uses was prepared through electrospinning and hot pressing. The rate of furfuryl alcohol degradation under UV irradiation was found to be the highest when the anatase to rutile ratio was 70:30; the rate did not linearly increase as a function of the NF film thickness, mainly due to diffusion limitation. Even after eight repeated cycles, it showed only a marginal reduction in the photocatalytic activity for the degradation of cimetidine. The effects of pH and different organic matter characteristics on the photodegradation of cimetidine (CMT), propranolol (PRP), and carbamazepine (CBZ) were investigated. The pH-dependence of the photocatalytic degradation rates of PRP was explained by electrostatic interactions between the selected compounds and the surface of TiO2 NFs. The degradation rates of CMT showed the following order: deionized water > l-tyrosine > secondary wastewater effluent (effluent organic matter) > Suwannee River natural organic matter, demonstrating that the characteristics of the dissolved organic matter (DOM) can affect the photodegradation of CMT. Photodegradation of CBZ was affected by the presence of DOM, and no significant change was observed between different DOM characteristics. These findings suggest that the removal of CMT, PRP, and CBZ during photocatalytic oxidation using SI TiO2 NFs is affected by the presence of DOM and/or pH, which should be importantly considered for practical applications.

  14. A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

    Science.gov (United States)

    Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H

    2015-04-01

    Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

  15. Influence of the histaminergic system on opiate-induced neurosecretion and behaviour.

    Science.gov (United States)

    Duka, T; Hoehe, M; Doenicke, A; Stephan, U; Matussek, N

    1987-01-01

    The influence of the histaminergic system on fentanyl (Fe)-induced growth hormone (GH) and prolactin (PRL) release as well as on Fe-induced increase of noradrenaline (NA) plasma levels has been studied in male volunteers. These volunteers received, according to a randomized block design, different pretreatments: the H1-antagonist dimethindene (Di) (0.1 mg/kg i.v.), or the H2-antagonist cimetidine (Ci)(5 mg/kg i.v.), or a combination of dimethindene and cimetidine (Di + Ci), or saline. The PRL increase caused by Fe (0.2 mg/70 kg) was not altered by pretreatment with the H1-antagonist Di, the H2-antagonist Ci, or the combination of both. The increase of NA plasma levels after Fe also was not modified by the histamine antagonists. In contrast, the maximum GH increase after Fe was blunted by the combination of Ci and Di, but not by either Ci or Di alone. These results suggest an involvement of the histaminergic system in opiate-induced GH-release.

  16. Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists.

    Science.gov (United States)

    He, Shao-Heng; Xie, Hua; Fu, Yi-Ling

    2005-03-01

    The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).

  17. Choledochoscope manometry about different drugs on the Sphincter of Oddi

    Institute of Scientific and Technical Information of China (English)

    Jing Kong; Shuo-Dong Wu; Xiao-Bo Zhang; Zhen-Sheng Li; Gang Shi; Wei Wang; Jun-Zhi Chen

    2008-01-01

    AIM: To assess the effects of H2-receptor blocking pharmacon, protease inhibitor, and gastro kinetic agents on the human Sphincter of Oddi (SO) motility by choledochoscope manometry.METHODS: One hundred and seventy-five patients with T tube installed after cholecystectomy and choledochotomy were assessed by choledochoscope manometry. They were randomly assigned into groups of H2-receptor blocking pharmacon, protease inhibitor, and gastro kinetic agents. The Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duodenal pressure (DP), and common bile duct pressure (CBDP) were scored and analyzed.RESULTS: SOBP and SOCA were significantly decreased after Cimetidine administration, and no statistical difference was seen in the Famotidine group. In the Gabexate mesilate group, SOBP had decreased significantly. In the Ulinastatin group, SOCA decreased when Ulinastatin was given at the rate of 2500 U/min; when Ulinastatin administration was raised to 5000 U/ min, SOBP, SOF and SOCA all experienced a fall. SOBP and SOCA for Domperidone and SOCA for Mosapride groups all decreased distinctly after administration.CONCLUSION: The regular dosage of Cimetidine showed an inhibitory effect on the motility of SO, while Pamotidine had no obvious effects otherwise. Gabnexata mesilate, Ulinastatin and gastro kinetic agents also showed inhibitory effects on the SO motility.

  18. Postmarketing drug surveillance by record linkage in Tayside.

    Science.gov (United States)

    Crombie, I K; Brown, S V; Hamley, J G

    1984-09-01

    The feasibility of conducting postmarketing drug surveillance by record linkage in Tayside was assessed. The key feature of the method is that all hospital discharge data are already computerised by the area health board and may be accessed through the unique community health number (CHNo) which has been allocated to all Tayside residents. The 12 861 prescriptions for cimetidine dispensed in Tayside over a nine month period were collected and the CHNo identified for 76%. These corresponded to 3802 individuals and their discharge data, together with those for an equal number of controls matched by age, sex, and general practitioner were retrieved from the computer. The expected excess of those diseases for which cimetidine is prescribed (peptic ulcer and oesophagitis) was observed. Other drug-disease associations were observed but may have been due to confounding and emphasise the inadequacy of community based controls. The major advantages of record linkage are, firstly, the low cost of the method, the present study costing just over pounds 12 000, and, secondly, the duration of patient follow up which may may be extended for as many years as required simply by rerunning the computer programs. To assemble large patient cohorts the study would have to be extended to other area health boards that are currently developing similar computer systems. Record linkage may provide a cost effective method for the follow up of patients to identify serious adverse drug reactions, particularly those that take several years to develop.

  19. Effect of Two Histamine Receptor Antagonists on Hematology of Porcine Reproductive and Respiratory Syndrome%组胺受体拮抗剂对高致病性猪蓝耳病血液学的影响

    Institute of Scientific and Technical Information of China (English)

    刘芳; 高登慧; 欧德渊; 万文华; 向智龙; 禾采红; 黄露

    2011-01-01

    为探索组胺(HA)受体拮抗剂对高致病性蓝耳病(PRRS)病毒感染患猪血液学的影响,揭示内源性组胺在高致病性猪蓝耳病发生发展过程中的部分作用,通过人工使仔猪感染高致病性蓝耳病,并相应注射扑尔敏、西咪替丁后第5天采用RT-PCR方法检测仔猪血液中的PRRSV,第7天采用ETDA抗凝管颈静脉采血,全自动血液分析仪测定血液指标.结果表明,1)攻毒后第5天均扩出1条约1064 bp的特异性目的条带,表明攻毒成功;2)西咪替丁组、阳性组仔猪血液中白细胞总数、淋巴细胞数量、单核细胞数量极显著低于阴性组(P<0.01),而扑尔敏组均显著高于阳性组(P<0.05);3)阳性组仔猪血液中血红蛋白浓度、红细胞压积显著低于阴性组(P<0.05),西咪替丁组红细胞数显著高于阳性组;4)扑尔敏组、西咪替丁组仔猪血液中血小板含量、血小板压积极显著高于阴性组(P<0.0l),阳性组血小板含量极显著高于阴性组(P<0.01),阳性组血小板压积显著高于阴性组(P<0.05).说明,扑尔敏能抑制高致病性蓝耳病患猪血液中白细胞总数、白细胞中淋巴细胞数量和白细胞中单核细胞数量的下降,稳定红细胞相关指标的数量,具有增强机体免疫力的作用,但促进了血小板的升高,西咪替丁能维持高致病性蓝耳病患猪血液中红细胞相关指标的稳定.%The piglets artificially infected with porcine reproductive and respiratory syndrome were injected with two histamine receptor antagonists (Cimetidine and Chlorpheniramine) and then PRRSV in tested piglets was detected by RT-PCR after 5d and the blood indexes were determined by an automatic blood analyzer after 7 d to study the effect of histamine receptor antagonist on hematology of porcine reproductive and respiratory syndrome and to reveal the part effect of endogenous histamine on occurrence and development of porcine reproductive and respiratory syndrome. The

  20. Impact of impurities on IC50 values of P450 inhibitors.

    Science.gov (United States)

    Huang, Zeqi

    2011-08-01

    During early drug discovery, the synthetic pathways for test compounds are not well defined and impurities in the test compounds are inevitable. Compounds undergo serial screening tests at this stage to assess their biological activities and drug-like properties. Impurities in the test compounds can produce false positive results and therefore complicate the interpretation of data. P450 inhibition is one of the screens used in the early drug discovery process to assess the potential of drug-drug interactions caused by the inhibition of P450 enzymes. The impact of impurities on P450 inhibition has not been investigated. In this study, the impact of impurities on CYP2D6 IC(50) values was evaluated using model compounds. Cimetidine was chosen as the test compound. Quinidine, fluoxetine, fluvoxamine, and ibuprofen were chosen to represent impurities as they inhibit CYP2D6 to varying degrees. The IC(50) values of these model impurities for CYP2D6 were 0.11 µM, 0.98 µM, 13.4 µM, and >100 µM, respectively. Impurities with potent CYP2D6 inhibition, such as quinidine, can significantly decrease the apparent IC(50) value for the mixture. With the addition of only 2% quinidine to cimetidine (mol/mol), the apparent IC(50) value of cimetidine decreased from 98 µM to 4.4 µM. With the addition of 10% quinidine, the apparent IC(50) decreased to 1.04 µM. Such a significant decrease in apparent IC(50) values can produce a false alert and cause the inappropriate elimination of good compounds at an early stage. Impur6ities with low inhibitory potential, such as fluvoxamine and ibuprofen, did not cause a significant change in apparent IC(50) values. An impurity can have a similar effect on the IC(50) values for inhibition of other biological activities. The effect of an impurity on apparent IC(50) values can be predicted by using a simulation curve if the potency of the impurity is characterized.

  1. Comparison on the efficacy and safety of different scheme combined with fluid therapy in children with rotavirus diarrhea%不同方案联合液体疗法治疗小儿轮状病毒感染性腹泻的疗效和安全性比较

    Institute of Scientific and Technical Information of China (English)

    梁景林; 杨学群; 李少光

    2014-01-01

    Objective To investigate the efficacy and safety of cimetidine and interferon combined with zinc treatment in children with rotavirus diarrhea. Methods Selecting 108 cases of children with rotavirus enteritis and randomly dividing them into two groups, 54 cases for each group. Patients in the control group using cimetidine and interferon treatment, observation group were based on the control group and increase of zinc treatment, compared two groups of recovery, curative effect and adverse reaction. Results The observation group after treatment in children dehydration correcting time, defecate normal time and the temperature recovery time compared with the control group, the difference was statistically significant(P0.05). Conclusion Clinical effect of cimetidine and interferon combined with zinc treatment in children with rotavirus diarrhea is good, with fast recovery and less adverse reaction.%目的:探讨西咪替丁和干扰素联合补锌治疗小儿轮状病毒感染性腹泻的疗效和安全性。方法选取轮状病毒肠炎患儿108例,随机分为两组,每组54例。对照组患儿使用西咪替丁和干扰素进行治疗,观察组在对照组的基础上增加补锌治疗,对比两组患儿恢复情况、疗效和不良反应。结果观察组脱水纠正时间、大便恢复正常时间和体温恢复正常时间明显短于对照组,差异有统计学意义(P0.05)。结论西咪替丁和干扰素联合补锌治疗小儿轮状病毒感染性腹泻的临床效果好,患儿恢复快,不良反应少。

  2. Equine gastric ulcer syndrome (egus: diagnosis and therapy

    Directory of Open Access Journals (Sweden)

    Mot, T.,

    2008-06-01

    Full Text Available Equine gastric ulcer syndrome is especially reported in racing horses, with a prevalence of 60-90% in adults and 25-50% in foals. The ethiology of equine gastric ulcer is polifactorial, represented by nutritional factors, stress generated by training and captivity, drugs (corticosteroids-prednisolone, dexametasone, nesteroidicanti-inflammatory drugs: flumixin-meglumine, fenilbutazone, duodenal refluence. The diagnosis is established on clinical signs and therapeutic response and it is confirmed by endoscopic exam. Therapeutically it is recommended to administer: antiacide (aluminiu hydroxide, magnesium hydroxide, inhibitors of H2 receptors(cimetidine, ranitidine, famotidine, inhibitors of protons pump (Omeprazol, Sucralphate. Diagnosis and therapeutic aspects in equine gastric ulcer syndrome are presented in this study.

  3. The major impacts of James Black's drug discoveries on medicine and pharmacology.

    Science.gov (United States)

    Walker, Michael J A

    2011-04-01

    James Black has many claims to pharmacological fame as the creator of two new classes of drugs (beta-blockers and H2 antihistamines) and as a tireless innovator in drug discovery strategies and analytical procedures. The latter attributes in particular assisted Black in the invention of the prototypes for the two major classes of drugs for which he is best known, propranolol and cimetidine. The clinical impact of these drugs on both morbidity and mortality has been profound. In addition, the application of his analytical approach to drug discovery and pharmacology led others in the field to create many other new classes of drugs. Shortly before he died in 2010, Black wrote a retrospective review of his research career that provides insight into his innovative thinking and career success. This overview affords readers a very personal picture of the man, his ideas and his contributions.

  4. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...... not on partial flow-volume curves. Pretreatment with either cimetidine and mepyramine or with indomethacin, did not affect the bronchial obstruction after LTD4.(ABSTRACT TRUNCATED AT 250 WORDS)...

  5. PFAPA (Periodic fever, aphtous stomatitis, pharingitis, cervical adenitis or Marshall’s syndrome in children

    Directory of Open Access Journals (Sweden)

    N N Kuzmina

    2005-01-01

    Full Text Available PFAPA (periodic fever, aphtous stomatitis, pharingitis, cervical adenitis or Marshall’s syndrome is one of the rare periodic fever conditions appearing in children. Its cause is unknown. This syndrome may continue for several years. During interictal period the child is quite well, grows and develops normally. The disease should be differentiated from Behcet’s disease, cyclic neutropenia, familial Mediterranean fever, familial Ireland fever, hyperimmunoglobulinemia D syndrome, systemic juvenile idiopathic arthritis, chronic tonsillitis, some infectious diseases. Many drugs are used for the treatment of PFAPA syndrome: antibiotics, non-steroidal anti-inflammatory drugs, chloroquin, antiviral drugs, glucocorticoids, cimetidin. Tonsillectomy is used quite often. Analysis of the literature data shows that best results may be achieved with tonsillectomy (sometimes in combination with ade- notomy. PFAPA in a child of 2 years age diagnosed for the first time in Russian pediatric rheumatology is described.

  6. Intracerebroventricular histamine, but not 48/80, causes posttraining memory facilitation in the rat.

    Science.gov (United States)

    de Almeida, M A; Izquierdo, I

    1988-01-01

    The immediate posttraining intracerebroventricular injection of histamine (1 or 10 ng/rat) facilitated memory both of a stepdown inhibitory avoidance task, and of the habituation of rearing responses to an open field. As previously shown for the avoidance task, the combination of cimetidine (1,000 ng/rat) plus prometazine (1,000 ng/rat), but not each drug on its own, blocked the effect of histamine in the habituation task. The effect of histamine was not shared by the intracerebroventricular administration of the mast cell histamine releaser, 48/80 (0.1 to 100 micrograms/rat). The present findings indicate that the memory facilitatory action of histamine might be general across tasks, and that 48/80-releasable, presumably mast cell, endogenous histamine is probably not involved in memory regulation.

  7. Effects of antidepressants and antihistaminics on catalepsy induced by intracerebroventricular administration of histamine in mice.

    Science.gov (United States)

    Onodera, K

    1991-01-01

    The intracerebroventricular (icv) administration of histamine but not N-telemethylhistamine and 1-methyl-4-imidazole acetic acid induced catalepsy in mice. Histamine H1-receptor blockers such as cyproheptadine, mepyramine and diphenhydramine reduced histamine-induced catalepsy. However, astemizole which is known to be without central effects, did not reduce histamine-induced catalepsy. The icv pretreatment with histamine H2-receptor blockers, such as metiamide and cimetidine, also had no effect. Moreover, various antidepressants, both imipramine- and atypical-type drugs antagonized histamine-induced catalepsy to various degrees in this experiment. Thus, the induction of catalepsy by icv administration of histamine was mediated through histamine H1-receptors, and suggested that antidepressants reduced histamine-induced catalepsy via this mechanism. Histamine-induced catalepsy is a possible new animal model of depression which can also be used for evaluation of atypical antidepressants.

  8. High-frequency oscillation in the hippocampus of the behaving rat and its modulation by the histaminergic system.

    Science.gov (United States)

    Knoche, A; Yokoyama, H; Ponomarenko, A; Frisch, C; Huston, J; Haas, H L

    2003-01-01

    The histaminergic neurons located in the posterior hypothalamus modulate whole brain activity in a manner dependent on behavioral state. We have investigated their influence on high-frequency oscillation (200-Hz ripples) in the hippocampal CA1 region of freely moving rats. The occurrence of these ripples, assumed to be involved in memory trace formation, was markedly enhanced after injection of the H1-antagonists pyrilamine and ketotifen in a lateral ventricle, indicating a tonic activity of the histaminergic system. The H2- and H3-antagonists cimetidine and thioperamide were ineffective. We suggest a mediation of these effects through blocking the known histaminergic excitation of septal neurons. Histamine administered by the intracerebroventricular route had an inhibitory action on ripples. H1-receptor activation, which has been shown to inhibit learning and memory, thus shifts hippocampal activity away from high-frequency oscillation toward theta activity.

  9. Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature in mice.

    Science.gov (United States)

    Chen, Z; Sugimoto, Y; Kamei, C

    1995-12-01

    Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature were studied in mice. Histamine (0.1-1.0 mu g) and histidine (500-1,000 mg/kg) caused a dose-related hypothermia. H1 agonist, 2-methylhistamine and 2-thiazolylethylamine also displayed a dose-dependent hypothermia. In addition, H2 agonists, 4-methylhistamine and dimaprit elicited a decrease in body temperature. Preinjection of not only H1-antagonists (diphenhydramine and chlorpheniramine) but also H2 antagonists (cimetidine and ranitidine) abolished histamine-induced hypothermia. Either intracerebroventricular or intraperitoneal injection of thioperamide, a histamine H3 antagonist, showed hypothermia. The hypothermic effect produced by intracerebroventricular injection of thioperamide was significantly blocked by (R)-alpha-methylhistamine, a selective H3 agonist. In addition, the effect induced by thioperamide was inhibited by H1 and H2 antagonists, indicating that the H3 receptor also participates in histamine-induced hypothermia.

  10. In vitro and in vivo invasiveness of different pulsed-field get electrophoresis types of Listeria monocytogenes

    DEFF Research Database (Denmark)

    Larsen, Charlotte Nexmann; Nørrung, Birgit; Sommer, Helle Mølgaard

    2002-01-01

    The virulence of different pulsed-field gel electrophoresis (PFGE) types of Listeria monocytogenes was examined by monitoring their ability to invade Caco-2 cells. Strains belonging to seven different PFGE types originating from both foods and humans were included. No significant differences...... others is supported by this study showing that certain PFGE types of L. monocytogenes commonly found in food are less invasive than others to Caco-2 cells. In contrast to the differences in invasion, identical intracellular growth rates between the different PFGE types were observed. In vivo studies...... of the actual ability of the strains to invade the liver and spleen of cimetidine-treated rats following an oral dose of 109 L. monocytogenes cells were performed for isolates of PFGE types 1, 2, 5, and 15. After 2 days, equal amounts of bacteria were observed in the liver and spleen of the rats for any...

  11. Cytoprotective action of roxatidine acetate HCl.

    Science.gov (United States)

    Shiratsuchi, K; Fuse, H; Hagiwara, M; Mikami, T; Miyasaka, K; Sakuma, H

    1988-01-01

    The cytoprotective action of roxatidine acetate HCl (roxatidine) was investigated. We also studied the involvement of endogenous prostaglandins (PGs) in the cytoprotective action of roxatidine and the effect of roxatidine on SRS content in pleurisy induced by A23187. Simultaneously, these effects of roxatidine were compared with those of other histamine H2-receptor antagonists at the same anti-secretory activity level. Roxatidine prevented formation of the gastric mucosal lesions induced by abs. ethanol, 0.6 N HCl and 0.2 N NaOH, but it failed to prevent 30% NaCl-induced gastric mucosal lesions. Cimetidine, ranitidine and famotidine failed to prevent formation of the gastric mucosal lesions induced by necrotizing agents. The cytoprotective action of roxatidine was not abolished by pretreatment with indomethacin. Roxatidine did not greatly influence SRS production. Consequently, it appears that roxatidine has a cytoprotective action and that this action is not associated with endogenous PGs and SRS.

  12. Interaction of roxatidine acetate with antacids, food and other drugs.

    Science.gov (United States)

    Labs, R A

    1988-01-01

    The inhibition of hepatic mixed-function oxidase microsomal enzymes by cimetidine can lead to clinically important drug interactions. The metabolism of antipyrine is used as an index of hepatic enzymatic activity. The pharmacokinetic profiles of salivary antipyrine obtained following treatment with roxatidine acetate 75 mg or placebo twice a day for 7 days showed similar characteristics with no difference in the areas under the plasma concentration-time curves. In addition, roxatidine acetate 75 mg daily did not modify the clearance of propranolol, diazepam, desmethyldiazepam or controlled release theophylline preparations. Furthermore, there was no interference in the bioavailability of roxatidine acetate 150 mg daily when administered alone or in combination with a meal or antacids.

  13. Chemical and biologic characteristics of roxatidine acetate.

    Science.gov (United States)

    Bickel, M; Herling, A W; Schoelkens, B; Scholtholt, J

    1988-01-01

    Roxatidine acetate is a specific and competitive H2-receptor antagonist, as shown in isolated rabbit gastric glands or guinea pig atria preparations. The antisecretory effect of roxatidine acetate is mediated by its main metabolite, roxatidine. In the rat, roxatidine acetate was equipotent after intraduodenal and intraperitoneal administration, indicating excellent bioavailability. Roxatidine acetate and roxatidine were equipotent in the rat after intravenous administration. In the Heidenhain-pouch dog stimulated by food ingestion or maximal histamine dosing, roxatidine acetate and roxatidine proved to be 3-6 times more potent than cimetidine in inhibiting gastric acid secretion. From in vitro experiments it can be concluded that roxatidine acetate and ranitidine are equipotent. Roxatidine acetate has no antiandrogenic effects and does not influence drug-metabolizing enzymes in the liver.

  14. Effect of antihistamines, disodium cromoglycate (DSCG) or methysergide on post-irradiation cerebral blood flow and mean systemic arterial blood pressure in primates after 25 Gy, whole-body, gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Forcino, C.D. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)

    1995-06-01

    Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA) and serotonin (5-HT). To investigate the relationship among these responses, rhesus monkeys (Macaca mulatta) received physiological saline (i.v.), disodium cromoglycate (DSCG), antihistamines (AH, mepyramine and cimetidine), or methysergide (METH), then were given 25 Gy whole-body irradiation. Monkeys receiving DSCG, AH or METH had higher post-irradiation mean arterial blood pressure (MBP) than saline-treated controls. Compared to levels in controls, post-irradiation hippocampal blood flow (rCBF) levels were higher in monkeys receiving DSCG, AH or METH. Treatment with the 5-HT{sub 2} receptor antagonist methysergide was the most effective in maintaining both rCBF and MBP after irradiation. Results support the hypothesis that the irradiation-induced cerebral ischemia and, to some extent, the hypotension is mediated by serotonin through 5-HT{sub 2} receptor sites. (author) 72 refs.

  15. Effect of restraint stress on nociceptive responses in rats: role of the histaminergic system.

    Science.gov (United States)

    Ibironke, G F; Mordi, N E

    2011-12-20

    Stress induced analgesia (SIA) is well known, but the reverse phenomenon, hyperalgesia is poorly documented. This study investigated the role of the histaminergic system in restraint stress hyperalgesia in rats, using thermal stimulation method (hot plate and tail flick tests). Paw licking and tail withdrawal latencies were taken before and after restraint for about one hour. Significant decreases (p<0.05) were obtained in these latencies after the restraint in both tests. Administration of H1 and H2 receptor blockers, chlorpheniramine and cimetidine respectively 30 mins before the restraint still resulted in significant reductions (p<0.05) in these latencies, connoting the persistence of hyperalgesia, showing that histamine H1 and H2 receptors did not participate in the mechanism of restraint stress hyperalgesia. We therefore suggest a histaminergic independent mechanism for restraint stress induced hyperalgesia.

  16. Efficacy and safety of herbal medicines in treating gastric ulcer: a review.

    Science.gov (United States)

    Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

    2014-12-01

    Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects.

  17. IS PEPTIC ULCER WITH HELICOBACTER INFEC¬TION THE CAUSE OF CHRONIC URTICARIA?

    Directory of Open Access Journals (Sweden)

    A. Farhoudi

    2000-01-01

    Full Text Available Helicobacter pylori, the most important cause of gastritis and peptic ulcer, has recently been associated with several extradigestive diseases. The aim of this study was to assess the prevalence of Helicobacter pylori infection and effects of bacterium eradication in 50 patients affected by idiopathic chronic urticaria. Helicobacter pylori was assessed by serology or biopsy and urease test or 13C urea breath test. Amoxicillin, bismuth subcitrate (Denol, metronidazole and cimetidine were given to infected patients for 2 weeks. The results of therapy were assessed by urea breath test six weeks after therapy. In response to treatment urticaria clinically regressed in 16 out of 24 patients (66.6%. Thus bacterium eradication was associated with a remission of urticaria symptoms, suggesting a possible role in the pathogenesis of this disorder.

  18. Phytochemical Analysis and Gastroprotective Activity of the Root Bark from Maytenus robusta.

    Science.gov (United States)

    Benvenutti, Danyela Francine; Della Monache, Franco; Cechinel Filho, Valdir; de Andrade, Sérgio Faloni; Niero, Rivaldo

    2016-05-01

    The present work evaluated the chemical composition and antiulcerogenic potential of the crude extract, fractions and pure compounds isolated of roots barks from Maytenus robusta Reiss, using different pharmacological models in mice. 3,12-Dioxofriedelane (1) and 11-hydroxylup-20 (29)-en-3-one (2) were isolated from the n-hexane fraction, and mayteine (3) and 3,7-dioxofriedelane (4) from the dichloromethane fraction. The crude extract (50, 259, 500 mg/kg), all the fractions (250 mg/kg) and cimetidine (100 mg/kg) significantly reduced the lesion index, total lesion area, and percentage of lesions, in comparison with the control group (p < 0.05), by ethanol and NSAID-induced ulcer models. All the isolated compounds also presented significant pharmacological effects at 30 mg/kg. These results show that the root bark of M. robusta may be a promising source of molecules with applicability in the treatment of gastric disorders.

  19. A study on the aetiology of reserpine ulceration and the antiulcer action of solcoseryl in rat stomach.

    Science.gov (United States)

    Cho, C H; Ogle, C W; Dai, S

    1985-11-01

    The aetiology of reserpine-induced gastric ulcer formation and the antiulcer effects of solcoseryl were studied in rats. Intraperitoneal injection of reserpine produced severe ulceration, as well as mast cell and histamine depletion, in the gastric glandular mucosa. Mepyramine and cimetidine markedly antagonized the gastric lesions, but did not influence the reduced mast cell count; atropine pretreatment significantly inhibited both parameters. Intramuscular injection of solcoseryl lessened ulcer severity and prevented the decreased mast cell counts and histamine levels in reserpine-treated rats. However, the same dose of solcoseryl injected intraperitoneally was ineffective. Solcoseryl, irrespective of the route of administration, did not influence the gastric secretory activities of reserpine. It is concluded that reserpine ulceration is both cholinergic- and histamine-mediated, and that the antiulcer effects of solcoseryl appear to be due to prevention of histamine depletion in the gastric mucosa.

  20. Histamine potentiates neuronal excitation by blocking a calcium-dependent potassium conductance.

    Science.gov (United States)

    Haas, H L

    1984-04-01

    Histaminergic neurones send their axons to the whole forebrain. The diffuse projection is consistent with a modulatory role of these pathways. In hippocampal slices from rats a mechanism for this modulation is described, on pyramidal neurones of the CA 1 area: Strong excitations induced by intracellular current injection, ionophoretic administration of glutamate or synaptic stimulation normally restrict themselves by the activation of the calcium-dependent potassium current (gK(Ca) ). This current causes a long lasting afterhyperpolarization and an accommodation of firing. Their block by histamine and impromidine (reversed by metiamide and cimetidine) leads to a profound potentiation of excitatory signals. It is suggested that HA, through H2 receptors, accelerates the removal of intracellular free Ca++ ions.

  1. The evidence for histamine H3 receptor-mediated endothelium-dependent relaxation in isolated rat aorta

    Directory of Open Access Journals (Sweden)

    D. M. Djuric

    1995-01-01

    Full Text Available The presence of histamine H3 receptors was evaluated on the rat aorta endothelium. In the presence of pyrilamine (1 nM, 7 nM, 10 nM or thioperamide (1 nM, 10 nM, 30 nM the concentration–response curve for histamine-induced (0.1 nM − 0.01 mM endothelium-dependent rat aorta relaxation was shifted to the right without significant change of the Emax indicating competitive antagonism by pyrilamine (pA2 = 9.33 ± 0.34, slope = 1.09 ± 0.36 or thioperamide (pA2 =9.31 ± 0.16, slope=0.94 ± 0.10. Cimetidine (1 μM did not influence histamine-induced endothelium-dependent rat aorta relaxation. In the presence of thioperamide (1 nM, 10 nM, 30 nM the concentration–response curve for (Rα-MeHA-induced (0.1 nM − 0.01 mM endothelium-dependent relaxation was shifted to the right without significant change of Emax indicated competitive antagonism by thioperamide (pA2 = 9.21 ± 0.4, slope = 1.03 ± 0.35. Pyrilamine (100 nM or cimetidine (1 μM did not influence (Rα-MeHA-induced endothelium-dependent rat aorta relaxation. These results suggest the presence of a heterogenous population of histamine receptors, H1 and H3, on rat aorta endothelium.

  2. Antiulcerogenic activity of Carica papaya seed in rats.

    Science.gov (United States)

    Pinto, Lorraine Aparecida; Cordeiro, Kátia Wolff; Carrasco, Viviane; Carollo, Carlos Alexandre; Cardoso, Cláudia Andréa Lima; Argadoña, Eliana Janet Sanjinez; Freitas, Karine de Cássia

    2015-03-01

    The purpose of the present study was to evaluate the gastroprotective and healing effects of the methanolic extract of the seed of the papaya Carica papaya L. (MECP) in rats. Models of acute gastric ulcer induction by ethanol and indomethacin and of chronic ulcer by acetic acid were used. The gastric juice and mucus parameters were evaluated using the pylorus ligation model, and the involvement of sulfhydryl compounds (GSH) and nitric oxide in the gastroprotective effect was analyzed using the ethanol model. The toxicity was assessed through toxicity tests. No signs of toxicity were observed when the rats received a single dose of 2000 mg/kg of extract. The MECP in doses of 125, 250, and 500 mg/kg significantly reduced the gastric lesion with 56, 76, and 82 % inhibition, respectively, and a dose of 30 mg/kg lansoprazole showed 79 % inhibition in the ethanol model. MECP (125, 250, 500 mg/kg) and cimetidine (200 mg/kg) reduced the gastric lesion in the indomethacin model, with 62, 67, 81, and 85 % inhibition, respectively. The MECP (500 mg/kg) and cimetidine (200 mg/kg) treatments showed a reduction in ulcerative symptoms induced by acetic acid by 84 and 73 %, respectively. The antiulcerogenic activity seems to involve GSH because the inhibition dropped from 72 to 13 % in the presence of a GSH inhibitor. Moreover, the MECP showed systemic action, increasing the mucus production and decreasing gastric acidity. Treatments with MECP induce gastroprotection without signs of toxicity. This effect seems to involve sulfhydryl compounds, increased mucus, and reduced gastric acidity.

  3. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion.

    Science.gov (United States)

    Knigge, U; Kjaer, A; Kristoffersen, U; Madsen, K; Toftegaard, C; Jørgensen, H; Warberg, J

    2003-10-01

    Prostaglandins and histamine in the hypothalamus are involved in the regulation of oxytocin and vasopressin secretion, and appear to be involved in the mediation of pituitary hormone responses to immunochallenges. Therefore, we investigated in conscious male rats: (i) whether blockade of H1 or H2 receptors affected the oxytocin and vasopressin responses to prostaglandins and (ii) whether blockade of prostaglandin synthesis affected the oxytocin and vasopressin responses to histamine or to Escherichia coli lipopolysaccharide (LPS), in order to determine any interaction between prostaglandins and histamine in the hypothalamus. Oxytocin secretion was dose-dependently stimulated by intracerebroventricular infusion of 1 or 5 microg of PGE1, PGE2 or PGF2alpha, with PGE2 being the most potent of the compounds used. Prior central infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the oxytocin response to all three prostaglandins by approximately 50%. Vasopressin secretion was increased by PGE1 but not by PGE2 or PGF2alpha. The stimulatory effect of PGE1 was almost annihilated by prior administration of mepyramine or cimetidine. Central infusion of histamine or immunochallenge with LPS administered intraperitoneally increased oxytocin and vasopressin secretion four- and two-fold, respectively. Pretreatment with systemic injection of the prostaglandin synthesis inhibitor indomethacin dose-dependently reduced the oxytocin response and prevented the vasopressin response to histamine or LPS. We conclude that histamine and PGE1, PGE2 or PGF2alpha interact in the regulation of oxytocin secretion, whereas histamine and only PGE1 interact in the regulation of vasopressin secretion. Furthermore, histamine as well as LPS may affect oxytocin and vasopressin neurones via activation of prostaglandins, probably in the hypothalamic supraoptic nucleus.

  4. Mechanism of renal effects of intracerebroventricular histamine in rabbits.

    Science.gov (United States)

    Kook, Y J; Kim, K K; Yang, D K; Ahn, D S; Choi, B K

    1988-01-01

    Histamine, when given intracerebroventricularly (i.c.v.), has been reported to produce antidiuresis in the rabbit. In this study it was attempted to elucidate the mechanism involved in the effect. Histamine (H), 100 micrograms/kg i.c.v., produced antidiuresis with decreases in renal plasma flow and glomerular filtration rate in urethane-anesthetized rabbits. With larger doses, a tendency towards increased electrolyte excretion was noted in spite of decreased filtration. In the denervated kidney, marked diuresis and natriuresis were observed following i.c.v. H, whereas the contralateral innervated kidney responded with typical antidiuresis. Reserpinized rabbits also responded with marked natriuresis to i.c.v. H. Diphenhydramine (D), 250 micrograms/kg i.c.v., increased urine flow rate, sodium and potassium excretion, along with increase in renal perfusion. With 750 micrograms/kg i.c.v., marked natriuresis was observed in spite of decreased filtration. When H was given after D (250 micrograms/kg) the antidiuresis was completely abolished, and diuresis became more prominent. Cimetidine, 250 micrograms/kg i.c.v., elicited antidiuresis with decreases in renal hemodynamics, the pretreatment with cimetidine did not influence the antidiuresis by H and no natriuresis was noted. The present study suggests that histamine, given i.c.v., influences renal function in dual ways, i.e., antidiuresis by increasing the sympathetic tone to the kidney and diuresis due to some humoral natriuretic factor, the latter becoming apparent only when the former influence has been removed, and further suggests that H1-receptors might be involved in the nerve-mediated antidiuresis, whereas H2-receptors might mediate the humorally induced natriuresis and diuresis.

  5. Formation of 4'-carboxyl acid metabolite of imrecoxib by rat liver microsomes

    Institute of Scientific and Technical Information of China (English)

    Hai-yan XU; Peng ZHANG; Ai-shen GONG; Yu-ming SUN; Feng-ming CHU; Zong-ru GUO; Da-fang ZHONG

    2006-01-01

    Aim:Imrecoxib is a novel and moderately selective COX-2 inhibitor.The aim of the present in vitro investigation was to study the formation of the major metabolite 4'-carboxylic acid imrecoxib (M2) and identify the enzyrne(s) involved in the reaction.Methods:The formation of M2 was studied in rat liver cytosol in the absence or presence of liver microsomes.The formed metabolite was identified and quantified by LC/MSn.In addition,to characterize the cytochrome P450 (CYP) isozymes involved in M2 formation,the effects of typical CYP inhibitors (such as ketoconazle,quinine,α-naphthoflavone, methylpyrazole,and cimetidine) on the formation rate of M2 were investigated.Results:The formation of M2 from 4'hydroxymethyl imrecoxib (M4) was completely dependent on rat liver microsomes and NADPH.Enzyme kinetic studies demonstrated that the formation rate of M2 conformed to monophasic Michaelis-Menten kinetics.Additional experiments showed that the formation of M2 was induced significantly by dexamethasone and lowered by ketoconazole strongly and concentration-dependently.By comparison.other CYP inhibitors.such as α-naphthoflavone,cimetidine,quinine,and methylpyrazole had no inhibitory effects on this metabolic pathway.Conclusion:These biotransformation studies of M4 and imrecoxib in rat liver at the subcellular level showed that the formation of M2 occurs in rat liver microsomes and is NADPH-dependent.The reaction was mainly catalyzed by CYP 3A in untreated rats and in dexamethasone-induced rats.Other CYP,such as CYP 1A,2C,2D,and 2E,seem unlikely to participate in this metabolic pathway.

  6. Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib

    Institute of Scientific and Technical Information of China (English)

    Hai-yan XU; Zhi-yong XIE; Peng ZHANG; Jin SUN; Feng-ming CHU; Zong-ru GUO; Da-fang ZHONG

    2006-01-01

    Aim: To investigate the in vitro metabolism of imrecoxib in rat liver microsomes and to identify the cytochrome P450 (CYP) forms involved in its metabolism. Methods: Liver microsomes of Wistar rats were prepared using an ultracentrifuge. The in vitro metabolism of imrecoxib was studied by incubation with rat liver microsomes. To characterize the CYP forms involved in the 4'-methyl hydroxylation of imrecoxib, the effects of typical CYP inducers (such as dexamethasone, isoniazid and (3-naphthoflavone) and of CYP inhibitors (such as ketoconazole, quinine, a-naphthoflavone, methylpyrazole, and cimetidine) on the formation rate of 4'-hydroxymethyl imrecoxib were investigated. Results: Imrecoxib wasmetabolized to 3 metabolites by rat liver microsomes: 4'-hydroxymethyl imrecoxib (M4), 4'-hydroxymethyl-5-hydoxyl imrecoxib (M3), and 4'-hydroxymethyl-5-carbonyl imrecoxib (M5). Over the imrecoxib concentration range studied (5-600 umol/L), the rate of 4'-methyl hydroxylation conformed to monophasic Michaelis-Menten kinetics. Dexamethasone significantly induced the formation of M4. Ketoconazole markedly lowered the metabolic rate of imrecoxib in a concentration-dependent manner. Moreover, a significant inhibitory effect of quinine on the formation of M4 was observed in microsomes obtained from control rats, isoniazid-induced rats, and (3-naphthoflavone-induced rats. In contrast, α-naphthoflavone, cimetidine, and methylpyrazole had no inhibitory effects on this metabolic pathway. Conclusion: Imrecoxib is metabolized via 4'-methyl hydroxylation in rat liver microsomes. The reaction is mainly catalyzed by CYP 3A. CYP 2D also played a role in control rats, in isoniazid-induced rats and in β-naphthoflavone-induced rats.

  7. Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae).

    Science.gov (United States)

    Klopell, Fernando Canani; Lemos, Marivane; Sousa, João Paulo Barreto; Comunello, Eros; Maistro, Edson Luis; Bastos, Jairo Kennup; de Andrade, Sérgio Faloni

    2007-01-01

    In this study, the antiulcerogenic effect of essential oil from Baccharis dracunculifolia was evaluated using the model of acute gastric lesions induced by ethanol. The ulcerative lesion index (ULI) was significantly reduced by oral administration of the essential oil of B. dracunculifolia at doses of 50, 250 and 500 mg/kg which reduced the lesions by 42.79, 45.70 and 61.61%, respectively. The analysis of the chemical composition of the essential oil from B. dracunculifolia by GC showed that this was composed mainly of mono- and sesquiterpenes and the majority compound was nerolidol. Therefore, antiulcerogenic activity of nerolidol (50, 250 and 500 mg/kg) was investigated using ethanol-, indomethacin- and stress-induced ulcer models in rat. In the stress-induced ulcer model, a significant reduction of the ULI in animals treated with nerolidol (50, 250 and 500 mg/kg) and cimetidine (100 mg/kg) was observed, compared to the control group (p omeprazol (positive control), respectively. In indomethacin-ulcer the percentage of inhibition of ulcer was 34.69, 40.80, 51.02 and 46.93% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/ kg of cimetidine (positive control), respectively. The results of this study show that nerolidol displays antiulcer activity, as it significantly inhibited the formation of ulcers induced in different animal models. However, further pharmacological and toxicological investigations, to delineate the mechanism(s) of action and the toxic effects, are required to allow the use of nerolidol for the treatment of gastric ulcer.

  8. Bidirectional crosstalk between stress-induced gastric ulcer and depression under chronic stress.

    Directory of Open Access Journals (Sweden)

    Shuang Zhang

    Full Text Available Stress contributes to a variety of diseases and disorders such as depression and peptic ulcer. The present study aimed to investigate the correlation between stress ulcer and depression in pathogenesis and treatment by using chronic stress depression (CSD, chronic psychological stress ulcer (CPSU and water immersion restrain stress models in rats. Our data showed that the ulcer index of the animals after CSD exposure was significantly higher than that of controls. Depression-like behaviors were observed in rat after CPSU exposure. Fluoxetine hydrochloride significantly reduced the ulcer index of rats exposed to CPSU stress, while ranitidine inhibited depression-like behavior of the animals in CSD group. The ulcer index of rats administered with mifepristone after CPSU stress was markedly reduced compared to CPSU group, although there was no significant difference in the depression-like behavior between mifepristone-treated CSD group and naive controls. We also found that the rats exposed to CPSU or CSD stress displayed a lower level of corticosterone than naive controls, however, the acute stress (AS group showed an opposite result. Additionally, in order to study the relevance of H(2 receptors and depression, we treated the CSD group with cimetidine and famotidine respectively. The data showed that cimetidine inhibited depression-like behavior in CSD rats, and famotidine had no impact on depression. Overall our data suggested that the hypothalamic-pituitary-adrenal (HPA axis dysfunction may be the key role in triggering depression and stress ulcer. Acid-suppressing drugs and antidepressants could be used for treatment of depression and stress ulcer respectively. The occurrence of depression might be inhibited by blocking the central H(2 receptors.

  9. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats

    Institute of Scientific and Technical Information of China (English)

    Hussein O B Oloyede; Matthew C Adaja; Taofeek O Ajiboye; Musa O Salawu

    2015-01-01

    OBJECTIVE:Carica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria. This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed against indomethacin-induced peptic ulcer in male rats. METHODS:Thirty male rats were separated into 6 groups (A–F) of ifve rats each. For 14 d before ulcer induction with indomethacin, groups received once daily oral doses of vehicle (distil ed water), cimetidine 200 mg/kg body weight (BW), or aqueous extract of C. papaya seed at doses of 100, 150 or 200 mg/kg BW (groups A, B, C, D, E and F, respectively). Twenty-four hours after the last treatment, groups B, C, D, E and F were treated with 100 mg/kg BW of indomethacin to induce ulcer formation. RESULTS:Carica papaya seed extract signiifcantly (P<0.05) increased gastric pH and percentage of ulcer inhibition relative to indomethacin-induced ulcer rats. The extract signiifcantly (P<0.05) decreased gastric acidity, gastric acid output, gastric pepsin secretion, ulcer index and gastric secretion volume relative to group B. These results were similar to that achieved by pretreatment with cimetidine. Speciifc activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in the extract-treated groups (D, E and F) were increased signiifcantly over the group B (P<0.05). Pretreatment with the seed extract protected rats from the indomethacin-mediated decrease in enzyme function experienced by the group B. Similarly, indomethacin-mediated decrease in reduced glutathione level and indomethacin-mediated increase in malondialdehyde were reversed by Carica papaya extract. CONCLUSION:In this study, pretreatment with aqueous extract of Carica papaya seed exhibited anti-ulcerogenic and antioxidant effects, which may be due to the enhanced antioxidant enzymes.

  10. Role of effluent organic matter in the photochemical degradation of compounds of wastewater origin.

    Science.gov (United States)

    Bodhipaksha, Laleen C; Sharpless, Charles M; Chin, Yu-Ping; MacKay, Allison A

    2017-03-01

    The photoreactivity of treated wastewater effluent organic matter differs from that of natural organic matter, and the indirect phototransformation rates of micropollutants originating in wastewater are expected to depend on the fractional contribution of wastewater to total stream flow. Photodegradation rates of four common compounds of wastewater origin (sulfamethoxazole, sulfadimethoxine, cimetidine and caffeine) were measured in river water, treated municipal wastewater effluent and mixtures of both to simulate various effluent-stream water mixing conditions that could occur in environmental systems. Compounds were chosen for their unique photodegradation pathways with the photochemically produced reactive intermediates, triplet-state excited organic matter ((3)OM*), singlet oxygen ((1)O2), and hydroxyl radicals (OH). For all compounds, higher rates of photodegradation were observed in effluent relative to upstream river water. Sulfamethoxazole degraded primarily via direct photolysis, with some contribution from OH and possibly from carbonate radicals and other unidentified reactive intermediates in effluent-containing samples. Sulfadimethoxine also degraded mainly by direct photolysis, and natural organic matter appeared to inhibit this process to a greater extent than predicted by light screening. In the presence of effluent organic matter, sulfadimethoxine showed additional reactions with OH and (1)O2. In all water samples, cimetidine degraded by reaction with (1)O2 (>95%) and caffeine by reaction with OH (>95%). In river water mixtures, photodegradation rate constants for all compounds increased with increasing fractions of effluent. A conservative mixing model was able to predict reaction rate constants in the case of hydroxyl radical reactions, but it overestimated rate constants in the case of (3)OM* and (1)O2 pathways. Finally, compound degradation rate constants normalized to the rate of light absorption by water correlated with E2/E3 ratios (sample

  11. Misoprostol in peptic ulcer disease.

    Science.gov (United States)

    Watkinson, G; Akbar, F A

    1987-01-01

    Misoprostol, a synthetic prostaglandin E1 (PGE1) methyl ester analog has potent antisecretory and cytoprotective effects on the gastric and duodenal mucosa which should make it an effective drug in the treatment of gastric and duodenal ulcer. In two multicenter, randomised, double-blind, controlled studies involving over 900 patients with endoscopically proven benign gastric ulcer and in six similar studies involving over 2000 patients with active duodenal ulcers, differing doses of misoprostol have been compared with either placebo therapy or with conventional doses of cimetidine. In these studies misoprostol 800 mcg daily given as two or four divided doses has been shown to produce rates of complete ulcer healing and pain relief which were significantly superior to placebo therapy and comparable to those achieved with cimetidine. Drug related adverse effects were infrequent. A dose related diarrhea occurred in a small proportion of patients which seldom necessitated suspension of therapy. Because of the known uterotropic effect of prostaglandins the drug should not be used in pregnant women or women of child bearing age unless they are using adequate contraceptive measures. No clinically significant adverse, hematological or biochemical effects have been reported. Two studies suggested that misoprostol reduced the adverse effect of smoking on the healing of duodenal ulcer. In addition, misoprostol has been shown to protect the gastro-duodenal mucosa from the damaging effects of alcohol and non-steroidal anti-inflammatory drugs. This action may prove of value in the treatment of ulcer patients who are inveterate smokers, alcohol users or who are compelled to consume non-steroidal anti-inflammatory drugs for pain relief from rheumatic and allied diseases.

  12. Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine

    Directory of Open Access Journals (Sweden)

    Holzer Peter

    2009-06-01

    Full Text Available Abstract Background Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. Methods Adult rats were treated with vehicle, lafutidine (10 – 30 mg/kg or cimetidine (10 mg/kg, and 30 min later their stomachs were exposed to exogenous HCl (0.25 M. During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry. Results Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects. Conclusion These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect

  13. PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis).

    Science.gov (United States)

    Lee, W I; Yang, M H; Lee, K F; Chen, L C; Lin, S J; Yeh, K W; Huang, J L

    1999-01-01

    This paper aims to remind paediatric clinicians to suspect and confirm 'PFAPA' syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome). We report two cases of PFAPA syndrome: a 3-year-old healthy boy with atopic rhinitis and a boy aged 8 years 5 months who simultaneously had lymphocytic vasculitis syndrome treated with immunosuppressive drugs. Both met Marshall's criteria. The literature regarding PFAPA syndrome was complied using a Medline search for articles published between 1963 and 1998 and we then reviewed the reference lists of the articles. The Medline search revealed 28 cases with available clinical manifestations, management and prognosis. Our study describes two additional cases. We divided the cases into typical (28 cases) and atypical (two cases) PFAPA syndrome. In typical PFAPA, the age of onset was less than 5 years in most cases and the patients presented 4.9 +/- 1.4 days of fever (100%), pharyngitis (89.3%), cervical adenitis (72.1%), stomatitis (71.4%), malaise (64.3%), headache (60.7%), abdominal pain (53.6%) and nausea/vomiting (17.9%). Afebrile intervals were 3.2 +/- 2.4 months and increased with age. The time from initial onset to final episode was 3 years 7 months +/- 3 years 6 months. The total number of episodes was 8.3 +/- 2.5 (range 6-14). Effective treatment included steroids, tonsillectomy/adenoidectomy and cimetidine. The general outcome was good. In atypical PFAPF, the clinical manifestations were similar to those of typical PFAPA except that the age of onset was more than 5 years, and life-threatening intestinal perforation happened once in a patient with underlying Fanconi's anaemia. It was concluded that typical PFAPA syndrome is benign and can be diagnosed by detailed history-taking and from physical findings during repeated febrile episodes with tests to rule out other periodic fever syndromes. A review of the literatures since the first report in 1987 has shown that typical PFAPA syndrome is

  14. Prevalence of anti-ulcer drug use in a Chinese cohort

    Institute of Scientific and Technical Information of China (English)

    Tzeng-Ji Chen; Li-Fang Chou; Shinn-Jang Hwang

    2003-01-01

    AIM: To estimate the age-specific prevalence of anti-ulcer drug use and to calculate the usage of different anti-ulcer drugs over 5 years within the universal health insurance program in Taiwan area. METHODS: The National Health Insurance Research Database in Taipei supplied the cohort data sets of 200 000people. The ambulatory and inpatient claims of the cohort from 1997 to 2001 were analyzed. The anti-ulcer drugs included all drug items of the group A02B (drugs for treatment of peptic ulcer) in the Anatomical Therapeutic Chemical classification system (version 2000). The amount of drug usage was measured in unit of defined daily dose. RESULTS: Among bhe totally 13 034 393 visits wibh 56 672 631ambulatory prescription items, there were 398 150 (0.7 %)prescribed items of anti-ulcer drugs in 378 855 (2.9 %)visits. Among the 107 649 admissions with 5 762 312inpatient prescription items, there were 24 598 (0.4 %)prescribed items of anti-ulcer drugs in 11 548 (10.7 %)admissions. The annual prevalence of anti-ulcer drug use was 9.6 % in 1997, 11.6 % in 1998, 15.4 % in 1999, 14.5 %in 2000, and 15.9 % in 2001 respectively. The 5-year prevalence was 36.1%. The age-specific prevalence among the people younger than 20 years was 9.2 % in 2001 and 23.7 % during the 5-year period. Cimetidine not only was the most popular ingredient among anti-ulcer drugs (57 634cimetidine users in 70 729 all anti-ulcer drug users during the 5-year period) but also had the largest prescribed amount (42.3 % of DDDs for all anti-ulcer drug users during the 5-year period). The annually prescribed amount of anti-ulcer drugs had grown from 4.9 DDDs/1000 inhabitants/day in 1997 to 7.5 in 2001. This increase was largely attributed to H2-receptor antagonists and the expanding number of users. CONCLUSION: Prescribing of anti-ulcer drugs is indeed popular among the Chinese population in Taiwan area. The disproportionate use of anti-ulcer drugs by children demands further investigation.

  15. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats.

    Science.gov (United States)

    Puebla, L; Rodríguez-Martín, E; Arilla, E

    1996-01-01

    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 micrograms) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity was markedly increased in hippocampal membranes from rats treated with 10 micrograms of histamine (23% +/- 1% vs. 17% +/- 1% and 37% +/- 2% vs. 23% +/- 1%, respectively). In contrast, neither the basal nor the FK-stimulated enzyme activities were affected by histamine administration. The functional activity of the hippocampal guanine-nucleotide binding inhibitory protein (Gi protein), as assessed by the capacity of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity, was not modified by histamine administration. These data suggest that the increased response of the enzyme to SS was not related to an increased functional activity of Gi proteins. In fact, the increased AC response to SS in hippocampal membranes from histamine (10 micrograms)-treated rats was associated with quantitative changes in the SS receptors. Equilibrium binding data obtained with [125I]Tyr11-SS indicate an increase in the number with specific SS receptors (541 +/- 24 vs. 365 +/- 16 fmol/mg protein, P histamine (10 micrograms)-treated rats as compared to control animals. With the aim of determining if these changes were related to histamine binding to its specific receptor sites, the histaminergic H1 and H2 receptor antagonists mepyramine and cimetidine, respectively, were administered 1 h before histamine injection. The pretreatment with mepyramine or cimetidine induced an increase in the

  16. Animal pharmacodynamics of omeprazole. A survey of its pharmacological properties in vivo.

    Science.gov (United States)

    Larsson, H; Mattson, H; Sundell, G; Carlsson, E

    1985-01-01

    In the present paper, a collection of experimental data is presented describing the pharmacological profile of omeprazole mainly in dogs and rats. Omeprazole potently inhibited gastric acid secretion in different experimental models. In the dog, for instance, omeprazole was 2-7 times more potent than cimetidine, depending on the route of administration, and in the rat the difference was even greater. Omeprazole was equally potent against different types of stimulation, whereas cimetidine was not, indicating differences in their mechanisms of action. In the dog, the duration of the antisecretory effect was long and lasted for 3-4 days after a single maximal dose of omeprazole. The inhibitory effect after repeated, daily administration of submaximal doses therefore gradually increased and attained a steady-state level after five doses. Treatment up to one year with very high oral doses did not affect the duration of effect. During long-term treatment with high doses of omeprazole a 10-fold increase in meal-stimulated plasma gastrin levels was recorded. This was probably due to a nearly complete inhibition of acid secretion over 24 hours during the study. The gastrin values returned to control levels within eight days after the end of the treatment. Omeprazole was rapidly absorbed (peak plasma levels were reached within one hour) and the elimination half-life was approximately one hour. In the dog, the gastric antisecretory effect was related to the total dose and the area under the plasma concentration curve, whereas the peak level or the shape of the curve was of minor importance. Omeprazole, given orally to rats, dose-dependently prevented experimentally induced gastric lesions. Neither inhibition of acid secretion, stimulation of gastric bicarbonate secretion nor interference with the synthesis of endogenous prostaglandins seems to be of any great importance for the gastric protective effect of omeprazole. Omeprazole seems to be very specific in its gastric acid

  17. The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

    Science.gov (United States)

    Tsume, Yasuhiro; Amidon, Gordon L

    2010-08-02

    The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns

  18. 组胺H1和H2受体在新生大鼠离体延髓脑片呼吸节律性放电调节中的作用%Role of histamine H1 and H2 receptors in the modulation of respiratory rhythmical discharge in medulla oblongata slice preparation of neonatal rats

    Institute of Scientific and Technical Information of China (English)

    齐莹; 千智斌; 吴中海

    2008-01-01

    本研究探讨组胺H1和H2受体在新生大鼠基本节律性呼吸的发生和调节中的作用.以改良的Kreb's液恒温灌流新生Sprague-Dawley大鼠离体延髓脑片标本,稳定记录与之相连舌下神经根的呼吸节律性放电活动(respiratory-related rhythmical discharge activity, RRDA).实验分为5组:第1、2、3组分别单独给予组胺(histamine, HA)、 H1受体特异阻断剂pyrilamine和H2受体特异阻断剂cimetidine;第4组分别先后给予HA和HA+pyrilamine;第5组分别先后给予HA和HA+cimetidine,观察舌下神经根RRDA的变化.结果显示,单独给予HA后呼吸周期(respiratory cycle, RC)及呼气时程(expiratory time, TE)明显缩短,而吸气时程(inspiratory time, TI)及放电积分幅度(integral amplitude, IA)无明显变化;给予pyrilamine后RC、 TE明显延长,TI、 IA也无明显变化,且HA的作用可以被pyrilamine逆转;给予cimetidine后RC、 TE、 TI、 IA均无明显变化,且HA的作用不能被cimetidine逆转.结果提示,H1受体参与哺乳动物基本呼吸节律的产生和调节,H2受体对哺乳动物基本节律性呼吸的调控无明显影响.

  19. Physicians' perspectives on the diagnosis and management of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.

    Science.gov (United States)

    Manthiram, Kalpana; Li, Suzanne C; Hausmann, Jonathan S; Amarilyo, Gil; Barron, Karyl; Kim, Hanna; Nativ, Simona; Lionetti, Geraldina; Zeft, Andrew; Goldsmith, Donald; Kimberlin, David; Edwards, Kathryn; Dedeoglu, Fatma; Lapidus, Sivia

    2017-03-07

    To assess the practice patterns of pediatric rheumatology and infectious diseases subspecialists in the diagnosis and treatment of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. An online survey assessing diagnostic and treatment approaches was sent to 424 members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and 980 members of the Pediatric Infectious Disease Society (PIDS). 277 physicians (123 from CARRA and 154 from PIDS representing 21% of the total membership) completed the survey. To diagnose PFAPA, most respondents agreed that patients must have the following features of the diagnostic criteria: stereotypical fever episodes (95%), asymptomatic intervals between episodes (93%), and normal growth and development (81%). However, 71% of the respondents did not require age of onset <5 years, 33% did not require regular intervals between episodes, and 79% did not require the concomitant signs of aphthous stomatitis, adenitis, or pharyngitis during episodes as long as episodes were regular. Over half (58%) considered episode resolution with steroids to be diagnostic of PFAPA. Corticosteroids, antipyretics, tonsillectomy, and cimetidine were the most commonly prescribed treatments, while steroids and tonsillectomy were most effective. Subspecialists in pediatric rheumatology and infectious diseases showed limited adherence to the complete published criteria for diagnosing PFAPA suggesting heterogeneity in the characteristics of patients diagnosed with the disorder. These findings emphasize the need to develop consensus diagnostic and treatment guidelines in well-characterized patient populations.

  20. A Sensitive Medium-Throughput Method to Predict Intestinal Absorption in Humans Using Rat Intestinal Tissue Segments.

    Science.gov (United States)

    Da Silva, Laís Cristina; Da Silva, Taynara Lourenço; Antunes, Alisson Henrique; Rezende, Kênnia Rocha

    2015-09-01

    A range of in vitro, ex vivo, and in vivo approaches are currently used for drug development. Highly predictive human intestinal absorption models remain lagging behind the times because of numerous variables concerning permeability through gastrointestinal tract in humans. However, there is a clear need for a drug permeability model early in the drug development process that can balance the requirements for high throughput and effective predictive potential. The present study developed a medium throughput screening Snapwell (MTS-Snapwell) ex vivo model to provide an alternative method to classify drug permeability. Rat small intestine tissue segments were mounted in commercial Snapwell™ inserts. Unidirectional drug transport (A-B) was measured by collecting samples at different time points. Viability of intestinal tissue segments was measured by examining transepithelial electric resistance (TEER) and phenol red and caffeine transport. As a result, the apparent permeability (Papp; ×10(-6) cm/s) was determined for atenolol (10.7 ± 1.2), caffeine (17.6 ± 3.1), cimetidine (6.9 ± 0.1), metoprolol (12.6 ± 0.7), theophylline (15.3 ± 1.6) and, ranitidine (3.8 ± 0.4). All drugs were classified in high/low permeability according to Biopharmaceutics Classification System showing high correlation with human data (r = 0.89). These findings showed a high correlation with human data (r = 0.89), suggesting that this model has potential predictive capacity for paracellular and transcellular passively absorbed molecules.

  1. Comparison of Mass Transfer Models for Determination of the Intestinal Permeability

    Directory of Open Access Journals (Sweden)

    P Zakeri-Milani

    2008-09-01

    Full Text Available Background and the purpose of the study: In determination of the permeability of the intestinal wall by external perfusion techniques, several models have been proposed. In the present study three models were used for experimental results that differ in their convection and diffusion assumptions. Material and Methods: Permeability coefficients for 13 compounds (metoprolol, propranolol, naproxen, ketoprofen, furosemide, hydrochlorothiazide, cimetidine, ranitidine, atenolol, piroxicam, antipyrine, ibuprofen and carbamazepine with known human intestinal permeability values were determined in anaesthetized rats by different mass transfer models and plotted versus the observed human intestinal permeabilities. Results: The calculated dimensionless wall permeability values were in the range of 0.37 - 4.85, 0.38-6.54 and 0.41-16.59 for complete radial mixing, mixing tank and laminar flow models respectively. The results indicated that all of the models work relatively well for our data despite fundamentally different assumptions. The wall permeabilities were in the order laminar flow > mixing tank > complete radial mixing. Conclusion: Although laminar flow model provides the most direct measure of the intrinsic wall permeability, it has limitations for highly permeable drugs such as ibuprofen. The normal physiological hydrodynamics is more complex and more investigation is required to find out the real hydrodynamics.

  2. Proton-Coupled Organic Cation Antiporter Contributes to the Hepatic Uptake of Matrine.

    Science.gov (United States)

    Wu, Chunyong; Sun, Xiaomin; Feng, Chao; Liu, Xiaoying; Wang, Hufang; Feng, Fang; Zhang, Junying

    2016-03-01

    Matrine is the major bioactive alkaloid found in certain Sophora plants and has been used for the treatment of liver diseases and protection of liver function. The aim of this study was to investigate the human liver uptake mechanism of matrine by using HepG2 cells as the in vitro model. Matrine was transported into HepG2 cells in a time- and temperature-dependent manner. The cellular uptake was saturable and was significantly reduced by the metabolic inhibitors, such as sodium azide and rotenone. Furthermore, the uptake of matrine was found to be regulated by a protonophore (carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone) and pH, indicating that this influx transporter may be a proton-coupled antiporter. The uptake of matrine was sensitive to inhibition by the cationic drugs including pyrilamine, quinidine, verapamil, amantadine, diphenhydramine, and cimetidine but insensitive to other typical substrates or inhibitors of well-known organic cation transport systems. The present study reveals that, for the first time, in HepG2 cells, the existence of a proton-coupled organic cation antiporter that contributes substantially to the hepatic uptake of matrine.

  3. Modulation of trichloroethylene in vitro metabolism by different drugs in human.

    Science.gov (United States)

    Cheikh Rouhou, Mouna; Haddad, Sami

    2014-08-01

    Toxicological interactions with drugs have the potential to modulate the toxicity of trichloroethylene (TCE). Our objective is to identify metabolic interactions between TCE and 14 widely used drugs in human suspended hepatocytes and characterize the strongest using microsomal assays. Changes in concentrations of TCE and its metabolites were measured by headspace GC-MS. Results with hepatocytes show that amoxicillin, cimetidine, ibuprofen, mefenamic acid and ranitidine caused no significant interactions. Naproxen and salicylic acid showed to increase both TCE metabolites levels, whereas acetaminophen, carbamazepine and erythromycin rather decreased them. Finally, diclofenac, gliclazide, sulphasalazine and valproic acid had an impact on the levels of only one metabolite. Among the 14 tested drugs, 5 presented the most potent interactions and were selected for confirmation with microsomes, namely naproxen, salicylic acid, acetaminophen, carbamazepine and valproic acid. Characterization in human microsomes confirmed interaction with naproxen by competitively inhibiting trichloroethanol (TCOH) glucuronidation (Ki=2.329 mM). Inhibition of TCOH formation was also confirmed for carbamazepine (partial non-competitive with Ki=70 μM). Interactions with human microsomes were not observed with salicylic acid and acetaminophen, similar to prior results in rat material. For valproic acid, interactions with microsomes were observed in rat but not in human. Inhibition patterns were shown to be similar in human and rat hepatocytes, but some differences in mechanisms were noted in microsomal material between species. Next research efforts will focus on determining the adequacy between in vitro observations and the in vivo situation.

  4. [Diagnosis and management of periodic fever with aphthous pharyngitis and adenitis (PFAPA)].

    Science.gov (United States)

    Murata, Takuji; Okamoto, Nami; Shimizu, Toshio; Tamai, Hiroshi

    2007-04-01

    PFAPA is non-hereditary syndrome characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis and cervical adenitis. It manifests usually in early childhood, especially before 5 years of age, and last for several years. Its etiology is unknown, but some recent reports suggest a dysregulation of the immune response with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response both during and between febrile attacks. The diagnosis is clinical and it is important to exclude other entities of similar presentation with periodic fever and orofacial manifestations. The findings of laboratory are unspecified and show only nonspecific acute inflammatory response. Several treatments have been performed but with various results. Most effective therapy for a fast resolution of the symptoms is one or two doses of oral prednisone, but its efficacy is not permanent. Effectiveness of cimetidine and tonsillectomy in PFAPA is not clear as yet. PFAPA is a benign syndrome and the prognosis is better than other autoinflammatory syndromes, because PFAPA patients grow normally and symptoms diminish within a few years.

  5. Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1990-01-01

    Exposure of rats to 1-15 Gy of gamma radiation induced hyperthermia, whereas exposure to 20-150 Gy produced hypothermia. Since radiation exposure induced the release of prostaglandins (PGs) and histamine, the role of PGs and histamine in radiation-induced temperature changes was examined. Radiation-induced hyper- and hypothermia were antagonized by pretreatment with indomethacin, a cyclooxygenase inhibitor. Intracerebroventricular administration of PGE2 and PGD2 induced hyper- and hypothermia, respectively. Administration of SC-19220, a specific PGE2 antagonist, attenuated PGE2- and radiation-induced hyperthermia, but it did not antagonize PGD2- or radiation-induced hypothermia. Consistent with an apparent role of histamine in hypothermia, administration of disodium cromoglycate (a mast cell stabilizer), mepyramine (H1-receptor antagonist), or cimetidine (H2-receptor antagonist) attenuated PGD2- and radiation-induced hypothermia. These results suggest that radiation-induced hyperthermia is mediated via PGE2 and that radiation-induced hypothermia is mediated by another PG, possibly PGD2, via histamine.

  6. Arterial baroreceptors and brain histamine contribute to bradycardia to peripheral hyperosmolality.

    Science.gov (United States)

    Kenney, M J; Bealer, S L

    1993-10-01

    The purpose of this study was to determine whether the bradycardic response to peripheral hyperosmolality in conscious rats is dependent on afferent baroreceptor mechanisms and whether central histamine H2 receptors play a role in baroreflex-mediated changes in heart rate (HR). Mean arterial pressure (MAP) and HR were recorded continuously during a 30-min infusion of 2.5 M NaCl (10 microliters.100 g-1.min-1) hypertonic saline (HTS). HTS infusion significantly increased MAP (21 +/- 4 mmHg) and reduced HR (-62 +/- 10 beats/min) in rats with intact arterial baroreceptors. In sinoaortic-denervated rats, HR remained unchanged from control despite a significant increase in MAP. After intracerebroventricular (lateral ventricle) administration of cimetidine or ranitidine (H2-receptor antagonists) in intact rats, HTS infusion significantly increased MAP (19 +/- 2 and 17 +/- 2 mmHg, respectively) but the bradycardia was abolished (-12 +/- 10 and -10 +/- 10 beats/min, respectively). In contrast, central H2-receptor blockade did not alter reflex HR responses to the intravenous administration of phenylephrine and nitroprusside or to the central administration of histamine or angiotensin II. These results indicate that the bradycardic response to HTS infusion is mediated through the arterial baroreceptor reflex and involves in part a selective histaminergic pathway.

  7. Evidence for the involvement of histaminergic neurones in the regulation of the rat oxytocinergic system during pregnancy and parturition.

    Science.gov (United States)

    Luckman, S M; Larsen, P J

    1997-06-15

    1. Previous studies have shown that histaminergic neurones of the tuberomammillary nucleus project directly to hypothalamic magnocellular nuclei and that intracerebroventricular administration of histamine increases the synthetic activity of magnocellular oxytocin neurones. 2. Histaminergic neurones of the dorsomedial tuberomammillary nucleus that project to the magnocellular region of the paraventricular nucleus are activated during late pregnancy and lactation, as measured by an increase in mRNA for the synthetic enzyme histidine decarboxylase. 3. There is a concomitant increase in oxytocin mRNA in magnocellular neurones of the paraventricular nucleus. This increase in mRNA contributes to an accumulation of oxytocin before birth and to continued oxytocin synthesis during lactation. 4. Intracerebroventricular administration of mepyramine, a specific antagonist of the H1 histamine receptor, causes a delay in the birth of subsequent pups if given to the mother during parturition. Vehicle or the H2 receptor antagonist cimetidine has no effect. Thus, histamine acts centrally, via H1 receptors, during parturition and may have an excitatory effect on oxytocin release. 5. These results suggest that afferent histaminergic neurones show increased activity during pregnancy and may be responsible for the increase of synthesis in magnocellular oxytocin neurones at this time. If, as previously reported, these histamine neurones can reduce the electrical activity of oxytocin neurones via H2 receptors, then they may have a dual effect, increasing the synthesis of oxytocin while inhibiting its premature release. At term, any inhibitory effects of histamine are overcome to allow oxytocin secretion.

  8. H(1) and H(2) receptors in the locus ceruleus are involved in the intracerebroventricular histamine-induced carotid sinus baroreceptor reflex resetting in rats.

    Science.gov (United States)

    Wang, Guo-Qing; Sun, Wan-Ping; Zhu, Yong-Jin; Zou, Rong; Zhou, Xi-Ping

    2006-07-01

    Objective To investigate the role of H(1) and H(2) receptors in the locus ceruleus (LC) in carotid sinus baroreceptor reflex (CSR) resetting induced by intracerebroventricular (i.c.v.) injection of histamine (HA). Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner in vivo. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H(1) or H(2) receptors selective antagonist, chlorpheniramine (CHL) or cimetidine (CIM) into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA (100 ng in 5 mu l) significantly shifted the ISP-MAP relationship curve upwards (P 0.05). Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H(1) and H(2) receptors activities in the LC, especially by H(1) receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.

  9. Improgan antinociception does not require neuronal histamine or histamine receptors.

    Science.gov (United States)

    Izadi Mobarakeh, Jalal; Nalwalk, Julia W; Watanabe, Takeshi; Sakurada, Shinobu; Hoffman, Marcel; Leurs, Rob; Timmerman, Henk; Silos-Santiago, Immaculada; Yanai, Kazuhiko; Hough, Lindsay B

    2003-06-06

    Improgan, a chemical congener of the H(2) antagonist cimetidine, induces antinociception following intracerebroventricular (i.c.v.) administration in rodents, but the mechanism of action of this compound remains unknown. Because the chemical structure of improgan closely resembles those of histamine and certain histamine blockers, and because neuronal histamine is known to participate in pain-relieving responses, the antinociceptive actions of improgan were evaluated in mice containing null mutations in the genes for three histamine receptors (H(1), H(2), and H(3)) and also in the gene for histidine decarboxylase (the histamine biosynthetic enzyme). Similar to earlier findings in Swiss-Webster mice, improgan induced maximal, reversible, dose-related reductions in thermal nociceptive responses in ICR mice, but neither pre-improgan (baseline) nor post-improgan nociceptive latencies were changed in any of the mutant mice as compared with wild-type controls. Improgan also had weak inhibitory activity in vitro (pK(i)=4.7-4.9) on specific binding to three recently-discovered, recombinant isoforms of the rat H(3) receptor (H(3A), H(3B), and H(3C)). The present findings strongly support the hypothesis that neuronal histamine and its receptors fail to play a role in improgan-induced antinociception.

  10. Effects of histamine and cholinergic systems on memory retention of passive avoidance learning in rats.

    Science.gov (United States)

    Eidi, Maryam; Zarrindast, Mohammad-Reza; Eidi, Akram; Oryan, Shahrbanoo; Parivar, Kazem

    2003-03-28

    In the present study, the effects of the histamine and cholinergic systems on memory retention in adult male rats were investigated. Post-training intracerebroventricular injections were carried out in all the experiments. Cholinoceptor agonist, acetylcholine (1-10 microg/rat) or nicotine (1-10 microg/rat), increased, while a cholinoceptor antagonist, scopolamine (5-20 microg/rat), decreased memory retention. The response to acetylcholine was attenuated by scopolamine. Administration of histamine (5-20 microg/rat) reduced, but the histamine H(1) receptor antagonist, pyrilamine (10-50 microg/rat), and the histamine H(2) receptor antagonist, cimetidine (1-50 microg/rat), increased memory retention in rats. The histamine receptor antagonists attenuated the response to histamine. Histamine reduced the acetylcholine- or nicotine-induced enhancement. The histamine receptor antagonists enhanced the nicotine- or acetylcholine-induced response. Histamine potentiated the inhibitory effect induced by scopolamine. It is concluded that histaminergic and cholinergic systems have opposing effects on memory retention. Also, the histaminergic system elicits an interaction with the cholinergic system in memory retention.

  11. [Roles of histamine receptors in pain perception: a study using receptors gene knockout mice].

    Science.gov (United States)

    Yanai, Kazuhiko; Mobarakeh, Jalal Izadi; Kuramasu, Atsuo; Sakurada, Shinobu

    2003-11-01

    To study the participation of histamine H1- and H2-receptors in pain perception, H1 and H2 receptor knockout (KO) mice were examined for pain threshold by means of three kinds of nociceptive tasks. These included assays for thermal, mechanical, and chemical nociception. H1KO mice showed significantly fewer nociceptive responses to the hot-plate, tail-flick, tail-pressure, paw-withdrawal, formalin, capsaicin, and abdominal constriction tests. Sensitivity to noxious stimuli in H1KO mice was significantly decreased when compared to wild-type mice. The antinociceptive phenotypes of H2KO were relatively less prominent when compared to H1KO mice. We also examined the antinociceptive effects of intrathecally-, intracerebroventricularly-, and subcutaneously-administered morphine in H1KO and H2KO mice. In these nociceptive assays, the antinociceptive effects produced by morphine were more enhanced in both H1KO and H2KO mice. The effects of histamine H1- and H2-receptor antagonists on morphine-induced antinociception were studied in ICR mice. The intrathecal, intracerebroventricular and subcutaneous co-administrations of d-chlorpheniramine enhanced the effects of morphine in all nociceptive assays examined. In addition, intrathecal co-administrations of cimetidine enhanced the antinociception of morphine in the hot plate tests. These results suggest that existing H1 and H2 receptors play an inhibitory role in morphine-induced antinociception in the spinal and supra-spinal levels.

  12. A quantitative HPLC-MS/MS method for studying internal concentrations and toxicokinetics of 34 polar analytes in zebrafish (Danio rerio) embryos.

    Science.gov (United States)

    Brox, Stephan; Ritter, Axel P; Küster, Eberhard; Reemtsma, Thorsten

    2014-08-01

    An analytical method using high-performance liquid chromatography-tandem mass spectrometry was developed to determine internal concentrations of 34 test compounds such as pharmaceuticals and pesticides in zebrafish embryos (ZFE), among them, cimetidine, 2,4-dichlorophenoxyacetic acid, metoprolol, atropine and phenytoin. For qualification and quantification, multiple reaction monitoring mode was used. The linear range extends from 0.075 ng/mL for thiacloprid and metazachlor and 7.5 ng/mL for coniine and clofibrate to 250 ng/mL for many of the test compounds. Matrix effects were strongest for nicotine, but never exceeded ±20 % for any of the developmental stages of the ZFE. Method recoveries ranged from 90 to 110 % from an analysis of nine pooled ZFE. These findings together with the simple sample preparation mean this approach is suitable for the determination of internal concentrations from only nine individual ZFE in all life stages up to 96 h post-fertilization. Exemplarily, the time course of the internal concentrations of clofibric acid, metribuzin and benzocaine in ZFE was studied over 96 h, and three different patterns were distinguished, on the basis of the speed and extent of uptake and whether or not a steady state was reached. Decreasing internal concentrations may be due to metabolism in the ZFE.

  13. Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats

    Institute of Scientific and Technical Information of China (English)

    Li-sha XU; Li-xia YANG; Wei-wei HU; Xiao YU; Li MA; Lu-ying LIU; Er-qing WEI; Zhong CHEN

    2005-01-01

    Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 μg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 μg/site, ih) and the H2 antagonist cimetidine (2.5 μg/site,ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion:The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.

  14. Prokinetic Activity of Prunus persica (L. Batsch Flowers Extract and Its Possible Mechanism of Action in Rats

    Directory of Open Access Journals (Sweden)

    Wei Han

    2015-01-01

    Full Text Available The peach tree, Prunus persica (L. Batsch, is widely cultivated in China, and its flowers have been used for centuries in traditional Chinese medicine to treat gut motility disorders. But few studies have explored the pharmacological effect of Prunus persica (L. Batsch flowers on gastrointestinal motility. In this study, the activities of different extracts from Prunus persica (L. Batsch flowers on the smooth muscle contractions were evaluated using isolated colon model, and the ethyl acetate extract (EAE showed the strongest effects in vitro. EAE (10−8–10−5 g/mL caused a concentration-dependent stimulatory effect in rat colonic tissue. Additionally, ketotifen (100 µM, cimetidine (10 µM, and pyrilamine (1 µM produced a significant inhibition of contractions caused by EAE. Furthermore, immunofluorescence and toluidine blue staining revealed increased numbers of mast cells in the EAE group, and EAE increased histamine release from the colonic tissues. These data indicate that EAE has significant prokinetic activity and acts by a mechanism that mainly involves mast cell degranulation. Our study provides a pharmacological basis for the use of an extract of Prunus persica (L. Batsch flowers in the treatment of gut motility disorders.

  15. Effect of Lanthanum on Acid Secretion from Isolated Mouse Stomach in Vitro

    Institute of Scientific and Technical Information of China (English)

    徐项桂; 夏洪涛; 芮光; 胡翠英; 袁福根

    2004-01-01

    To explore the effect and the mechanism of La3+ on gastric acid secretion (GAS) of isolated mouse stomach with perfused lumen, 12 cm H2O column intragastric pressure-provided, whole stomach preparations from mice were incubated in buffer at 37 ℃ in vitro, and perfusate was measured for pH with a pHS-3 type pH meter. The results show that La3+ (0.41~820×10-6 mol*L-1) significantly promotes GAS in a concentration-dependant manner. Proglutamine, a blocker of gastrin receptor, potently inhibits GAS, and it may block the promotive effect of La3+ on GAS, and this effect increases with the increase of proglutamin concentration. Cimetidine, a blocker of histamine H2 receptor, also potently inhibits GAS, and blocks the promotive effect of La3+ on GAS in the same manner with proglutamine. These results suggest that La3+ promotes GAS in isolated stomach possibly by stimulating the releases of gastrin from G cell and Histamine from ECL cell or by activating the gastrin receptors and Histamine H2 receptors on the parietal cell, thereby accelerating the acid secretion of parietal cells in stomach.

  16. Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze in SD rats%组胺对地佐环平诱发的SD大鼠八臂迷宫空间记忆障碍的改善作用

    Institute of Scientific and Technical Information of China (English)

    黄育文; 陈忠; 胡薇薇; 张力三; 吴炜; 应力阳; 魏尔清

    2003-01-01

    AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK 801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by αfluoromethylhistidine (α-FMH, 5 μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H1-antagonist pyrilamine (1 μg/site, ih), but not by H2-antagonist cimetidine, even at a high dose (2.5 μg/site, ih).CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits, and its action is mediated through postsynaptic H1-receptor.

  17. Vasoactive intestinal polypeptide provokes acetylcholine release from the myenteric plexus

    Energy Technology Data Exchange (ETDEWEB)

    Kusunoki, M.; Tsai, L.H.; Taniyama, K.; Tanaka, C.

    1986-07-01

    Effects of vasoactive intestinal polypeptide (VIP) on the release of acetylcholine (ACh) from longitudinal muscle strips with myenteric plexus (LM) preparations were examined in the guinea pig small intestine. VIP (10 to 10 W M) induced a concentration-dependent contraction of LM preparation. The VIP-induced contractions seem to be related to three components, the scopolamine-sensitive, the scopolamine-insensitive, the tetrodotoxin-sensitive, and the tetrodotoxin-insensitive contractions. VIP (10 to 10 W M) induced a concentration-dependent increase in the release of (TH)ACh from LM preparations preloaded with (TH)choline. The VIP-evoked (TH)ACh release was inhibited by removal of CaS from the perfusion medium and by treatment with tetrodotoxin but not by scopolamine and hexamethonium. The spontaneous and VIP-evoked (TH)ACh release was not affected by phentolamine, propranolol, methysergide, diphenhydramine, cimetidine, bicuculline, or (D-ProS, D-Trp/sup 7,9/)substance P. The result demonstrates that VIP induces contractions of longitudinal smooth muscle directly and indirectly by the stimulation of both cholinergic neurons and noncholinergic excitatory neurons.

  18. Investigating Photosensitized Properties of Natural Organic Matter and Effluent Organic Matter

    KAUST Repository

    Niu, Xi-Zhi

    2013-05-01

    The photosensitized processes significantly enhance photolysis of various chemicals in the aqueous system with dissolved organic matter (DOM) as sensitizer. The excitation of chromophores on the DOM molecule further generates reactive species as triplet states DOM, singlet oxygen, hydroxyl radical, carbonate radical etc. We investigated the photosensitization properties of Beaufort Fulvic Acid, Suwannee River Fulvic Acid, South Platte River Fulvic Acid, and Jeddah wastewater treatment plant effluent organic matter with a sunlight simulator. DOM photochemical properties were characterized by observing their performances in 3DOM*, singlet oxygen, hydroxyl radical production with indirect probing protocols. Sensitized degradation of 0.1 μM and 0.02 μM 2, 4, 6- Trimethylphenol exhibited higher pseudo-first-order rate constant than that of 10 μM. Pre-irradiated DOMs were found to be depressed in photochemical properties. Photolysis of 5 different contaminants: ibuprofen, bisphenol A, acetaminophen, cimetidine, and caffeine were found to be enhanced in the presence of sensitizers. The possible reaction pathways were revealed. Long time irradiance induced change in contaminants degradation kinetics in some DOM solutions, which was proposed to be due to the irradiation initiated indirect transformation of DOMs. Key Words: Photolysis Dissolved Organic Matter, Triplet State DOM, Singlet Oxygen, Hydroxyl Radical, Contaminants Degradation.

  19. The ABCG2 efflux transporter from rabbit placenta: Cloning and functional characterization.

    Science.gov (United States)

    Halwachs, Sandra; Kneuer, Carsten; Gohlsch, Katrin; Müller, Marian; Ritz, Vera; Honscha, Walther

    2016-02-01

    In human placenta, the ATP-binding cassette efflux transporter ABCG2 is highly expressed in syncytiotrophoblast cells and mediates cellular excretion of various drugs and toxins. Hence, physiological ABCG2 activity substantially contributes to the fetoprotective placenta barrier function during gestation. Developmental toxicity studies are often performed in rabbit. However, despite its toxicological relevance, there is no data so far on functional ABCG2 expression in this species. Therefore, we cloned ABCG2 from placenta tissues of chinchilla rabbit. Sequencing showed 84-86% amino acid sequence identity to the orthologues from man, rat and mouse. We transduced the rabbit ABCG2 clone (rbABCG2) in MDCKII cells and stable rbABCG2 gene and protein expression was shown by RT-PCR and Western blot analysis. The rbABCG2 efflux activity was demonstrated with the Hoechst H33342 assay using the specific ABCG2 inhibitor Ko143. We further tested the effect of established human ABCG2 (hABCG2) drug substrates including the antibiotic danofloxacin or the histamine H2-receptor antagonist cimetidine on H33342 accumulation in MDCKII-rbABCG2 or -hABCG2 cells. Human therapeutic plasma concentrations of all tested drugs caused a comparable competitive inhibition of H33342 excretion in both ABCG2 clones. Altogether, we first showed functional expression of the ABCG2 efflux transporter in rabbit placenta. Moreover, our data suggest a similar drug substrate spectrum of the rabbit and the human ABCG2 efflux transporter.

  20. Prevention of radiation emesis in dogs by combinations of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Mattsson, J.L.; Cordts, R.E.; Yochmowitz, M.G.; Hardy, K.A.

    1984-07-01

    Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis. Cim was chosen as an H/sub 2/ antihistamine, Pro as an H/sub 1/ antihistamine, and Thi as a phenothiazine derivative dopamine blocker. Doses were calculated to approximate doses for an average human. Exposure was to /sup 60/Co at 60 rad (midline) per min. The dogs were fed 0.4 kg canned dog food 1 hour before exposure, and injected with the appropriate drugs 30 minutes prior to exposure. Emesis onset times, number of episodes, and time to last episode were recorded. The radiation dose (midline tissue rad) to cause a 50% incidence of emesis (ED/sub 50/) was calculated using an up-and-down procedure. The ED/sub 50/ were: 258 (212-315) for controls; 240 (151-380) for Cim; 313 (256-384) for Pro; 405 (319-514) for Thi; 334 (284-394) for Cim + Pro; 446 (365-546) for Cim + Thi; 347 (306-399) for Pro + Thi; and 478 (428-539) for Cim + Pro + Thi.

  1. Effects of changing the type of H2-blocker in the treatment of H2-blocker-resistant ulcers: comparison of roxatidine acetate hydrochloride and other H2-blockers.

    Science.gov (United States)

    Yasutake, K; Amano, M; Mizokami, Y; Kubota, S; Fukumoto, H; Imamura, Y; Yokoya, H; Irie, K

    1998-01-01

    The efficacy of switching from one type of H2-receptor antagonist (H2-blocker) to another, in the treatment of H2-blocker-resistant ulcers was investigated using H2-blockers with five-membered rings (five-membered-ring agents)--such as cimetidine, ranitidine and famotidine--and an H2-blocker with a six-membered ring, roxatidine. By switching from a five-membered-ring agent to roxatidine in the treatment of five-membered-ring resistant ulcers (study I), gastric ulcers were healed in nine of 19 patients (47%) and duodenal ulcers were healed in eight of nine patients (89%). By switching from roxatidine to one of the five-membered-ring agents in the treatment of roxatidine-resistant ulcers (study II), gastric ulcer was healed in six of 15 patients (40%), and duodenal ulcer was healed in 4 of 10 patients (40%). Particularly in the case of duodenal ulcers, the switch to treatment with roxatidine, which has a different chemical structure from the five-membered-ring agents, may be useful in the treatment of five-membered-ring-resistant ulcers.

  2. A histamine H2 receptor antagonist, roxatidine, stimulates mucus secretion and synthesis by cultured rabbit gastric mucosal cells.

    Science.gov (United States)

    Takahashi, S; Okabe, S

    1995-12-01

    We examined the effects of the known antisecretory and mucosal protective drug, roxatidine, on the secretion and synthesis of mucus by cultured rabbit gastric mucosal cells. The amounts of secreted and synthesized mucus were determined by the [3H] glucosamine labelling method. Exposure of the cells to roxatidine for 8 hr caused increases in the secretion and synthesis of mucus in a dose-related manner. The increase in mucus synthesis was maximally induced 4 hr after the addition of roxatidine, while mucus secretion was maximally enhanced a further 4 hr later. However, other H2 antagonists such as cimetidine, rantidine and famotidine failed to stimulate the secretion and synthesis of gastric mucus. In addition, neither indomethacin nor NG-nitro-L-arginine methyl ester affected the roxatidine-induced increases in mucus secretion and synthesis. We conclude that roxatidine directly acts on gastric mucosal cells, inducing increases in both the secretion and synthesis of mucus, and that an unknown regulatory pathway might be involved in these stimulatory actions of roxatidine.

  3. Roxatidine acetate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic potential in peptic ulcer disease and related disorders.

    Science.gov (United States)

    Murdoch, D; McTavish, D

    1991-08-01

    Roxatidine acetate is a histamine H2-receptor antagonist which, after almost complete oral absorption (greater than 95%), is rapidly converted to its active metabolite, roxatidine, by esterases in the small intestine, plasma and liver. Roxatidine is a potent inhibitor of basal and stimulated gastric acid secretion in animals and humans and, like most other H2-receptor antagonists, has no anti-androgenic effects and does not interfere with the hepatic metabolism of other drugs. Large-scale trials have shown that roxatidine acetate 150mg per day is as effective as standard doses of cimetidine and ranitidine in the treatment of patients with duodenal or gastric ulcer, and that roxatidine acetate 75mg in the evening is likely to become a 'standard' regimen for the prevention of peptic ulcer recurrence. Preliminary data also suggest that roxatidine acetate may be useful in the treatment of reflux oesophagitis and stomal ulcer, and in the prevention of pulmonary acid aspiration. Roxatidine acetate is an H2-receptor antagonist which has been well tolerated in clinical trials. However, broader experience is required before definitive statements about tolerability relative to other H2-receptor antagonists can be made, and before the role of roxatidine acetate in the treatment of reflux oesophagitis and stomal ulcer, and the prophylaxis of acid aspiration pneumonitis, can be clearly defined.

  4. Kavalactone metabolism in rat liver microsomes.

    Science.gov (United States)

    Fu, Shuang; Rowe, Anthony; Ramzan, Iqbal

    2012-07-01

    The specific CYP enzymes involved in kavalactone (KLT) metabolism and their kinetics have not been fully examined. This study used rat liver microsomes (RLM) to determine kavain (KA), methysticin (MTS) and desmethoxyyangonin (DMY) enzyme kinetic parameters, to elucidate the major CYP450 isoforms involved in KLT metabolism and to examine gender differences in KLT metabolism. Formation of the major KLT metabolites was first-order, consistent with classic enzyme kinetics. In both male and female RLM, clotrimazole (CLO) was the most potent inhibitor of KA and MTS metabolism. This suggests CYP3A1/3A23 (females) and CYP3A2 (males) are the main isoenzymes involved in the metabolism of these KLTs in rats, while the roles of CYP1A2, -2 C6, -2 C9, -2E1 and -3A4 are limited. Desmethoxyyangonin metabolism was equally inhibited by cimetidine (CIM) and CLO in females, and CIM and nortriptyline in males. This implies that DMY metabolism involves CYP2C6 and CYP2C11 in males, and CPY2C12 in females. CYP3A1/3A23 may also be involved in females.

  5. Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs

    Science.gov (United States)

    Kandasamy, S. B.; Williams, B. A.

    1984-01-01

    Intracerebroventricular administration of adrenocorticotropin (ACTH 1-24) and alpha-melanotropin (alpha-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21 C) and also produced greater hypothermia at low (10 C) ambient temperature. However, when the experiments were repeated in a warm (30 C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and alpha-MSH was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E2, norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.

  6. Validation of phenol red versus gravimetric method for water reabsorption correction and study of gender differences in Doluisio's absorption technique.

    Science.gov (United States)

    Tuğcu-Demiröz, Fatmanur; Gonzalez-Alvarez, Isabel; Gonzalez-Alvarez, Marta; Bermejo, Marival

    2014-10-01

    The aim of the present study was to develop a method for water flux reabsorption measurement in Doluisio's Perfusion Technique based on the use of phenol red as a non-absorbable marker and to validate it by comparison with gravimetric procedure. The compounds selected for the study were metoprolol, atenolol, cimetidine and cefadroxil in order to include low, intermediate and high permeability drugs absorbed by passive diffusion and by carrier mediated mechanism. The intestinal permeabilities (Peff) of the drugs were obtained in male and female Wistar rats and calculated using both methods of water flux correction. The absorption rate coefficients of all the assayed compounds did not show statistically significant differences between male and female rats consequently all the individual values were combined to compare between reabsorption methods. The absorption rate coefficients and permeability values did not show statistically significant differences between the two strategies of concentration correction. The apparent zero order water absorption coefficients were also similar in both correction procedures. In conclusion gravimetric and phenol red method for water reabsorption correction are accurate and interchangeable for permeability estimation in closed loop perfusion method.

  7. A new sensitive flow-injection chemiluminescence method for the determination of H(2)-receptor antagonists.

    Science.gov (United States)

    Tang, Yu-Hai; Wang, Nan-Nan; Xiong, Xun-Yu; Xiong, Feng-Mei; Sun, Si-Juan

    2007-01-01

    Based on the chemiluminescence (CL) intensity generated from the potassium ferricyanide [K(3)Fe(CN)(6)]-rhodamine 6G system in sodium hydroxide (NaOH) medium, a new sensitive flow-injection chemiluminescence (FI-CL) method has been developed, validated and applied for the determination of three kinds of H(2)-receptor antagonists: cimetidine (CIMT), ranitidine (RANT) hydrochloride and famotidine (FAMT). Under the optimum conditions, the linear range for the determination was 1.0 x 10(-9)-7.0 x 10(-5) g/ml for CIMT, 1.0 x 10(-9)-5.0 x 10(-5) g/mL for RANT hydrochloride and 5.0 x 10(-9)-7.0 x 10(-5) g/mL for FAMT. During 11 repeated measurements of 1.0 x 10(-6) g/mL sample solutions, the relative standard deviations (RSDs) were all <5%. The detection limit was 8.56 x 10(-10) g/mL for CIMT, 8.69 x 10(-10) g/mL for RANT hydrochloride and 2.35 x 10(-9) g/mL for FAMT (S:N = 3). This method has been successfully implemented for the analysis of H(2)-receptor antagonists in pharmaceuticals.

  8. Spectrophotometric determination of H(2)-receptor antagonists via their oxidation with cerium(IV).

    Science.gov (United States)

    Darwish, Ibrahim A; Hussein, Samiha A; Mahmoud, Ashraf M; Hassan, Ahmed I

    2008-01-01

    A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H(2)-receptor antagonists: cimetidine, famotidine, nizatidine and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium(IV) in presence of perchloric acid and subsequent measurement of the excess Ce(IV) by its reaction with p-dimethylaminobenzaldehyde to give a red colored product (lambda(max) at 464nm). The decrease in the absorption intensity of the colored product (DeltaA), due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990-0.9994) were found between DeltaA values and the concentrations of the drugs in a concentration range of 1-20microgml(-1). The assay limits of detection and quantitation were 0.18-0.60 and 0.54-1.53microgml(-1), respectively. The method was validated, in terms of accuracy, precision, ruggedness and robustness; the results were satisfactory. The proposed method was successfully applied to the determination of the investigated drugs in pure and pharmaceutical dosage forms (recovery was 98.3-102.6+/-0.57-1.90%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.

  9. Influence of patient medication on diagnostic accuracy in nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Sampson, C.B. [Addenbrooke`s Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine

    1997-12-31

    Full text. In recently years many reports have published of unusual or unexpected changes in the biodistribution of radiopharmaceuticals which do not correlate with normality or disease. Whilst many extraneous factors can alter tracer kinetics it has become apparent that concomitant patient medication can be such a factor. If the clinician is unaware that patient is on drug therapy difficulties arise in making a accurate diagnosis. Most drug/radio pharmaceutical effects are those in which the functional status of the organ is altered as a result of the pharmacological action of the drug. Examples here are narcotic analgesics such as methadone, pethidine and morphine which cause spasm of the biliary tract due to contraction of the sphincter of Oddi and an altered transit time of the technetium labelled tracer. Cytotoxic drugs such as cyclophosphamide and vincristine can markedly affect tumour uptake of 67-gallium so that litter or no activity is taken up by the tumour. Nifedipine, because of its powerful calcium channel blocking activity is known to affect the radiolabelling of white cells and red cells and to affect uptake of Tc-99 m MDP into bones. Other important and confusing effects are caused by phenothiazines, cimetidine and oral contraceptives. In recent years it has been reported that drugs such as cyclosporin, azathioprine and heparin and derivatives of heparin can markedly interfere with cell labelling procedures. This review will consider some of the clinical effects of drugs and will also address the reporting of instances of drug/radio pharmaceutical interactions

  10. Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats

    Directory of Open Access Journals (Sweden)

    Gaofeng Liu

    2011-01-01

    Full Text Available Flos carthami is a traditional Chinese herbal medicine. Clinically, the Flos carthami Injection has been used concomitantly with other Western drugs and may be used concomitantly with β-blockers, such as metoprolol, to treat cerebrovascular and coronary heart diseases, in China. Metoprolol is a CYP2D6 substrate and is predominantly metabolized by this isozyme. However, we do not know whether there is an effect of Flos carthami on CYP2D6 and the consequences of such an effect. Concern is raised regarding the possible herb-drug interaction. In this report, the effects of Flos carthami on the activity of CYP2D6 in vivo and in vitro and on the pharmacokinetics of metoprolol, in rats, are investigated. To assess the inhibitory potency of Flos carthami, the concentration associated with 50% inhibition (IC50 of dextromethorphan metabolism was determined based on the concentration-inhibition curves. The inhibitory effect of Flos carthami on CYP2D6 was also compared with cimetidine in vitro. Flos carthami could significantly inhibit CYP2D6 in rats both in vitro and in vivo (P<.05 and could slow down the metabolic rate of metoprolol as suggested by prolonged t1/2 (67.45%, by increased Cmax (74.51% and AUC0−∞ (76.89%. These results suggest that CYP2D6 is a risk factor when Flos carthami is administered concomitantly with metoprolol or other CYP2D6 substrates.

  11. FACTORS AFFECTING PHARMACOKINETIC DISPOSITION OF DRUGS

    Directory of Open Access Journals (Sweden)

    Mehta Hiren R

    2011-05-01

    Full Text Available Absorption of drugs from the gastrointestinal tract is a complex process the variability of which is influenced by many physicochemical and physiologic factors. The two most important physicochemical factors that affect both the extent and the rate of absorption are lipophilicity and solubility. The rate and extent of absorption are governed by the solubility, permeability and stability of the drug, with solubility being a pH-dependent parameter for weak acids and bases. The gastrointestinal tract can be viewed as discrete sections with a variety of differential local pH environments ranging from the acidic stomach to the more basic small intestine. The multiple peaking, double peaking or secondary peaking phenomena can occur in the disposition of a variety of xenobiotics during drug development (the pre-clinical phase and in subsequent clinical studies and use. The physicochemical and physiological mechanisms underlying the occurrence of this phenomenon are often multi factorial and include but are not limited to solubility-limited absorption, modified-release formulations, complexation, enterohepatic recirculation, gastric emptying and the intestinal transit time, site-specific absorption, gastric secretion-enteral reabsorption. Double peak absorption has been described with several orally administered drugs such as cimetidine furosemide, piroxicam, ranitidine, talinolol, alprazolam and phenazopyridine.

  12. Immunomodulators in warts: Unexplored or ineffective?

    Science.gov (United States)

    Sinha, Surabhi; Relhan, Vineet; Garg, Vijay K

    2015-01-01

    Cutaneous warts are known to be recurrent and often resistant to therapy. Resistant warts may reflect a localized or systemic cell mediated immune (CMI) deficiency to HPV. Many modalities of treatment are in use; most of the provider-administered therapies are destructive and cause scarring, such as cryotherapy, chemical cauterisation, curettage, electrodessication and laser removal. Most patient-applied agents like podophyllotoxin have the risk of application-site reactions and recurrence. Thus immunotherapy is a promising modality which could lead to resolution of warts without any physical changes or scarring and in addition would augment the host response against the causative agent, thereby leading to complete resolution and decreased recurrences. Immunomodulators can be administered systemically, intralesionally or intradermally, and topically. A few agents have been tried and studied extensively such as cimetidine and interferons; others are new on the horizon, such as Echinacea, green tea catechins and quadrivalent HPV vaccine, and their efficacy is yet to be completely established. Though some like levamisole have shown no efficacy as monotherapy and are now used only in combination, other more recent agents require large and long term randomized placebo-controlled trials to clearly establish their efficacy or lack of it. In this review, we focus on the immunomodulators that have been used for the treatment of warts and the studies that have been conducted on them. PMID:25814698

  13. Effect of disodium cromoglycate (DSCG) and antihistamines on post-irradiation cerebral blood flow and plasma levels of histamine and neurotensin

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Pautler, E.L.; Carraway, R.E.; Cochrane, D.E.; Hampton, J.D.

    1988-01-01

    In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and visual cortical blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100-Gy, whole-body, gamma irradiation. Systemic blood pressures were monitored simultaneously. Systemic arterial plasma histamine and neurotensin levels were determined preirradiation and postirradiation. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 23% of the preirradiation level within 10-min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10-min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The cortical blood flow for the same animals showed a steady decrease to 29% of the preirradiation levels by 60-min postirradiation. Animals given the mast-cell stabilizer disodium cromoglycate and the antihistamines mepyramine and cimetidine before irradiation did not exhibit an abrupt decline in blood pressure but displayed a gradual decrease to a level 33% below preirradiation levels by 60 min postirradiation. Also, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. The plasma neurotensin levels in the irradiated animals, treated and untreated, indicated a nonsignificant postirradiation increase above control levels.

  14. Amrinone effects on electromechanical coupling and depolarization-induced automaticity in ventricular muscle of guinea pigs and ferrets.

    Science.gov (United States)

    Malécot, C O; Arlock, P; Katzung, B G

    1985-01-01

    The effects of the cardiotonic agent, amrinone (0.05-4 mM), on electrical and mechanical activities of ferret and guinea-pig papillary muscles were studied using current and voltage clamp (single sucrose gap) techniques. In current clamp studies, amrinone increased, in a dose-dependent manner, contractile force elicited by action potential in both species. Depolarization-induced automaticity was facilitated in ferret muscles at all maximum diastolic potentials between -70 and -15 mV. Facilitation of automaticity in guinea-pig muscles occurred only at potentials more negative than -35 mV and was suppressed at more positive potentials. Cimetidine (10 microM) partially reversed the effects of amrinone on automaticity in both species. In voltage clamp studies, amrinone increased the slow inward current. Steady-state outward current was increased in guinea-pig but not in ferret muscles. A dual effect of amrinone on tension was observed. Amrinone was found to increase phasic tension of ferret papillary muscles only for depolarizations lasting less than 250 to 300 msec. For longer depolarizations, amrinone decreased the phasic tension (in a dose-dependent manner), whereas the tonic tension was not modified. The decrease as well as the increase in tension was associated with an increase of the slow inward current. The results suggest that amrinone may be arrhythmogenic and may have an intracellular action at the sarcoplasmic reticulum level (partial inhibition) in addition to its action on the calcium current.

  15. Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

    Science.gov (United States)

    Kimura, Louise F; Prezotto-Neto, José Pedro; Távora, Bianca C L F; Faquim-Mauro, Eliana L; Pereira, Nicole A; Antoniazzi, Marta M; Jared, Simone G S; Teixeira, Catarina F P; Santoro, Marcelo L; Barbaro, Katia C

    2015-09-01

    This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.

  16. Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis.

    Science.gov (United States)

    Deng, Long; Hong, Tao; Lin, Jinyi; Ding, Suling; Huang, Zheyong; Chen, Jinmiao; Jia, Jianguo; Zou, Yunzeng; Wang, Timothy C; Yang, Xiangdong; Ge, Junbo

    2015-08-17

    Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b(+)Gr-1(+) immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC(-/-)) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b(+)Gr-1(+) IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration.

  17. Prejunctional inhibition of sympathetically evoked pupillary dilation in cats by activation of histamine H3 receptors.

    Science.gov (United States)

    Koss, M C; Hey, J A

    1993-08-01

    Frequency-dependent pupillary dilations were evoked by electrical stimulation of the pre- or post-ganglionic cervical sympathetic nerve (sympatho-excitation) or the hypothalamus (parasympatho-inhibition) in sympathectomized anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist (R)-alpha-methylhistamine (R alpha MeHA) produced a dose-dependent depression of mydriasis due to direct neural sympathetic activation but had no effect on responses elicited by parasympathetic withdrawal. The histamine H2 receptor agonist, dimaprit, was inactive. R alpha MeHA was much more effective in depressing sympathetic responses obtained at lower frequencies when compared to higher frequencies of stimulation. Responses evoked both pre- and postganglionically were inhibited by R alpha MeHA. This peripheral sympatho-inhibitory action of R alpha MeHA was antagonized by the histamine H3 receptor blocker thioperamide but not by intravenous pretreatment with the histamine H1 receptor antagonist chlorpheniramine. Histamine H2 receptor blockers cimetidine and ranitidine were also without effect. R alpha MeHA did not depress pupillary responses elicited by i.v. (-)-adrenaline. The results demonstrate that histamine H3 receptors modulate sympathetic activation of the iris at a site proximal to the iris dilator muscle. The predominant mechanism of action appears to the prejunctional inhibition of noradrenaline release from postganglionic sympathetic nerve endings. However, a concomitant ganglionic inhibitory action cannot be excluded.

  18. Dehydration-induced vasopressin secretion in humans: involvement of the histaminergic system.

    Science.gov (United States)

    Kjaer, A; Knigge, U; Jørgensen, H; Warberg, J

    2000-12-01

    In rats, the hypothalamic neurotransmitter histamine participates in regulation of vasopressin secretion and seems to be of physiological importance, because blockade of the histaminergic system reduces dehydration-induced vasopressin secretion. We investigated whether histamine is also involved in regulation of vasopressin secretion during dehydration in humans. We found that 40 h of dehydration gradually increased plasma osmolality by 10 mosmol/kg and induced a fourfold increase in vasopressin levels. Pretreatment with the H(2)-receptor antagonists cimetidine or ranitidine significantly reduced the dehydration-induced increase in vasopressin levels approximately 40% after 34 and 37 h of dehydration, whereas this was not the case with the H(1)-receptor antagonist mepyramine. Dehydration reduced aldosterone secretion by approximately 50%. This effect of dehydration was reduced by both H(1)- and H(2)-receptor blockade after 16 and/or 34 h of dehydration. We conclude that vasopressin secretion in response to dehydration in humans is under the regulatory influence of histamine and that the effect seems to be mediated via H(2)-receptors. In addition, the regulation of aldosterone secretion during dehydration also seems to involve the histaminergic system via H(1) and H(2) receptors.

  19. Histaminergic system in co-cultures of hippocampus and posterior hypothalamus: a morphological and electrophysiological study in the rat.

    Science.gov (United States)

    Diewald, L; Heimrich, B; Büsselberg, D; Watanabe, T; Haas, H L

    1997-11-01

    Neurons of the tuberomammillary nucleus in the posterior hypothalamus diffusely project to most parts of the central nervous system, where their main transmitter, histamine, modulates the excitability of the target neurons. The development of a histaminergic hypothalamo-hippocampal pathway and its function were studied in organotypic co-cultures. Immunocytochemistry for histidine decarboxylase, the specific synthesizing enzyme, stained clusters of neurons in the hypothalamic tuberomammillary area. Immunolabelled varicose processes innervated the co-cultured hippocampus and established a few synaptic contacts on dendrites. Cultured tuberomammillary neurons displayed their typical membrane properties and were spontaneously active. In hippocampal pyramidal cells of the CA3 region the long-lasting afterhyperpolarization was reduced by histamine or impromidine and increased by the H2 antagonist cimetidine, but not by the H1 antagonist mepyramine. The membrane potential was depolarized in presence of an H2 agonist and hyperpolarized by an H2 antagonist. In single hippocampal cultures histamine antagonists did not affect afterhyperpolarization and membrane potential. Histaminergic neurons retain their main morphological and physiological characteristics in slice cultures and establish a functional connection with co-cultured target cells.

  20. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice.

    Science.gov (United States)

    Li, Weifeng; Huang, Huimin; Niu, Xiaofeng; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5ml/100g) were pre-treated with THC (10 or 20mg/kg, ip), cimetidine (100mg/kg, ip) or saline in different experimental sets for a period of 3days, and animals were euthanized 4h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression.

  1. Protective effect of δ-amyrone against ethanol-induced gastric ulcer in mice.

    Science.gov (United States)

    Li, Weifeng; Yao, Huan; Niu, Xiaofeng; Wang, Yu; Zhang, Hailin; Li, Huani; Mu, Qingli

    2015-06-01

    The purpose of this study is to examine the protective effect of δ-amyrone on ethanol-induced gastric ulcer in mice. The mice intragastric administration 75% (0.5 mL/100g) ethanol was pretreated with δ-amyrone (4 and 8 mg/kg) and cimetidine (100 mg/kg) or vehicles in different experimental groups for a continuous three-day, and animals were euthanized 3h after ethanol ingestion. The gastric lesions were significantly attenuated by δ-amyrone (4 and 8 mg/kg) as compared to the ulcer control group. Pre-treatment with δ-amyrone prevented the myeloperoxidase (MPO) activity, production of nitric oxide (NO) in serum, expression of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) p65 protein expression. Analysis of cytokines in gastric tissue and serum of ethanol-induced mice showed the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased by δ-amyrone in response to NF-κB p65. These results suggested that δ-amyrone exerts its protective effect on experimental gastric ulcer by inhibiting NF-κB signaling pathways, which subsequently reduces overproduction of the inducible enzymes iNOS and suppresses the release of the inflammatory factors TNF-α, IL-6 and NO. Thus, δ-amyrone shows promise as a therapeutic agent in experimental gastric ulcer.

  2. Theoretical and experimental study of aparisthman: A natural product with anti-ulcer activity

    Science.gov (United States)

    Brasil, D. S. B.; Moreira, R. Y. O.; Müller, A. H.; Alves, C. N.

    Aparisthman is a furan diterpenoid with a clerodane skeleton isolated from Aparisthmium cordatum (Juss.) Bail. (Euphorbiaceae). This natural product presents significant anti-ulcer activity to the level of cimetidine (Tagamet®), a compound used for the treatment of ulcers provoked by stress. The structure of X-ray diffraction of the aparisthman was compared with theoretical calculations and the results showed that the theory is in accordance with the experimental data. The infrared (IR) and nuclear magnetic resonance (NMR) spectra also were obtained and compared with theoretical calculations. The B3LYP theory level, with the 6-31G(d,p) basis set, leads the value to the IR absorption close to the value experimentally observed. NMR theoretical obtained with HF/6-311+G(2d,p) shows little deviation of experimental results. Calculations of molecular electrostatic potential and stabilization energies suggest that the protonation of aparisthman will be able to occur on carbonyl oxygen atom (O4).

  3. Enhancement of famotidine dissolution rate through liquisolid tablets formulation: in vitro and in vivo evaluation.

    Science.gov (United States)

    Fahmy, Rania H; Kassem, Mohammed A

    2008-08-01

    Although famotidine was reported to be 7.5 and 20 times more potent than ranitidine and cimetidine, respectively, its oral bioavailability is low and variable; due mainly to its poor aqueous solubility. The purpose of this study was to improve famotidine dissolution through its formulation into liquisolid systems and then to investigate the in vitro and in vivo performance of the prepared liquisolid tablets. The new mathematical model was utilized to formulate various liquisolid powder systems. Both DSC and XRD suggested loss of famotidine crystallinity upon liquisolid formulation which was further confirmed by SEM indicating that even though the drug existed in a solid dosage form, it is held within the powder substrate in a solubilized, almost molecularly dispersed state, which contributed to the enhanced drug dissolution properties. All the tested liquisolid tablet formulations showed higher drug dissolution rates (DR) than the conventional, directly compressed tables. In addition, the selected optimal formula released 78.36% of its content during the first 10 min which is 39% higher than that of the directly compressed tablets. Further, the bioavailability study indicated that the prepared optimal liquisolid formula did not differ significantly from the marketed famotidine tablets concerning Cmax, tmax, and AUC(0-8) at P<0.05.

  4. Simultaneous determination of moxifloxacin and H2 receptor antagonist in pharmaceutical dosage formulations by RP-HPLC: application to in vitro drug interactions

    Directory of Open Access Journals (Sweden)

    Najma Sultana

    2011-01-01

    Full Text Available Simultaneous determination of moxifloxacin (MOX and H2-antagonists was first time developed in bulk and formulations. Purospher STAR C18 (250 x 4.6 mm, 5 μm column was used. The mobile phase (methanol: water: ACN, 60:45:5 v/v/v, pH 2.7 was delivered at a flow rate of 1.0 mL min-1, eluent was monitored at 236, 270 and 310 nm for cimetidine, famotidine and ranitidine, respectively. The proposed method is specific, accurate (98-103%, precise (intra-day and inter-day variation 0.098-1.970% and linear (r>0.998. The LOD and LOQ were 0.006-0.018 and 0.019-0.005 μg mL-1, respectively. The statistical parameters were applied to verify the results. The method is applicable to routine analysis of formulations and interaction of MOX with H2-antagonist.

  5. Update and future of systemic acne treatment.

    Science.gov (United States)

    Zouboulis, Christos C; Piquero-Martin, Jaime

    2003-01-01

    Systemic treatment is required in patients with moderate-to-severe acne, especially when acne scars start to occur. Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline and limecycline) and macrolide antibiotics (erythromycin and azithromycin) are the agents of choice for papulopustular acne, even though the emerging resistant bacterial strains are minimizing their effect, especially regarding erythromycin. Systemic antibiotics should be administered during a period of 8-12 weeks. In severe papulopustular and in nodulocystic/conglobate acne, oral isotretinoin is the treatment of choice. Hormonal treatment represents an alternative regimen in female acne, whereas it is mandatory in resistant, severe pubertal or post-adolescent forms of the disease. Compounds with anti-androgenic properties include estrogens combined with progestins, such as ethinyl estradiol with cyproterone acetate, chlormadinone acetate, desogestrel, drospirenone, levonogestrel, norethindrone acetate, norgestimate, and other anti-androgens directly blocking the androgen receptor (flutamide) or inhibiting androgen activity at various levels, corticosteroids, spironolactone, cimetidine, and ketoconazole. After 3 months of treatment control of seborrhea and acne can be obtained. Low-dose corticosteroids (prednisone, prednisolone, or dexamethasone) are indicated in patients with adrenal hyperandrogenism or acne fulminans. New developments and future trends represent low-dose long-term isotretinoin regimens, new isotretinoin formulations (micronized isotretinoin), isotretinoin metabolites, combination treatments to reduce toxicity, insulin-sensitizing agents, 5alpha-reductase type 1 inhibitors, antisense oligonucleotide molecules, and, especially, new anti-inflammatory agents, such as lipoxygenase inhibitors.

  6. Review of therapeutic agents for burns pruritus and protocols for management in adult and paediatric patients using the GRADE classification

    Directory of Open Access Journals (Sweden)

    Goutos Ioannis

    2010-10-01

    Full Text Available To review the current evidence on therapeutic agents for burns pruritus and use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE classification to propose therapeutic protocols for adult and paediatric patients. All published interventions for burns pruritus were analysed by a multidisciplinary panel of burns specialists following the GRADE classification to rate individual agents. Following the collation of results and panel discussion, consensus protocols are presented. Twenty-three studies appraising therapeutic agents in the burns literature were identified. The majority of these studies (16 out of 23 are of an observational nature, making an evidence-based approach to defining optimal therapy not feasible. Our multidisciplinary approach employing the GRADE classification recommends the use of antihistamines (cetirizine and cimetidine and gabapentin as the first-line pharmacological agents for both adult and paediatric patients. Ondansetron and loratadine are the second-line medications in our protocols. We additionally recommend a variety of non-pharmacological adjuncts for the perusal of clinicians in order to maximise symptomatic relief in patients troubled with postburn itch. Most studies in the subject area lack sufficient statistical power to dictate a ′gold standard′ treatment agent for burns itch. We encourage clinicians to employ the GRADE system in order to delineate the most appropriate therapeutic approach for burns pruritus until further research elucidates the most efficacious interventions. This widely adopted classification empowers burns clinicians to tailor therapeutic regimens according to current evidence, patient values, risks and resource considerations in different medical environments.

  7. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

  8. Vitamin D: Pharmacokinetics and Safety When Used in Conjunction with the Pharmaceutical Drugs Used in Cancer Patients: A Systematic Review

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, Deborah A.; Cooley, Kieran; Skidmore, Becky; Fritz, Heidi; Campbell, Tara [Canadian College of Naturopathic Medicine, 1255 Sheppard Avenue East, Toronto, Ontario, M2K 1E2 (Canada); Seely, Dugald, E-mail: dseely@ccnm.edu [Canadian College of Naturopathic Medicine, 1255 Sheppard Avenue East, Toronto, Ontario, M2K 1E2 (Canada); Ottawa Integrative Cancer Centre, 29 Bayswater Avenue, Ottawa, Ontario, K1Y 2E5 (Canada)

    2013-03-11

    Vitamin D has reported anti-cancer and anti-inflammatory properties modulated through gene transcription and non-genomic signaling cascades. The purpose of this review was to summarize the available research on interactions and pharmacokinetics between vitamin D and the pharmaceutical drugs used in patients with cancer. Hypercalcemia was the most frequently reported side effect that occurred in high dose calcitriol. The half-life of 25(OH)D{sub 3} and/or 1,25(OH){sub 2}D{sub 3} was found to be impacted by cimetidine; rosuvastatin; prednisone and possibly some chemotherapy drugs. No unusual adverse effects in cancer patients; beyond what is expected from high dose 1,25(OH){sub 2}D{sub 3} supplementation, were revealed through this review. While sufficient evidence is lacking, supplementation with 1,25(OH){sub 2}D{sub 3} during chemotherapy appears to have a low risk of interaction. Further interactions with vitamin D{sub 3} have not been studied.

  9. Renal transepithelial transport of nucleosides.

    Science.gov (United States)

    Nelson, J A; Vidale, E; Enigbokan, M

    1988-01-01

    Previous work from this and other laboratories has suggested that the mammalian kidney has unique mechanisms for handling purine nucleosides. For example, in humans and in mice, adenosine undergoes net renal reabsorption whereas deoxyadenosine is secreted [Kuttesch and Nelson: Cancer Chemother. Pharmacol. 8, 221 (1982)]. The relationships between these renal transport systems and classical renal organic cation and anion, carbohydrate, and cell membrane nucleoside transport carriers are not established. To investigate possible relationships between such carriers, we have tested effects of selected classical transport inhibitors on the renal clearances of adenosine, deoxyadenosine, 5'-deoxy-5-fluorouridine (5'-dFUR), and 5-fluorouracil in mice. The secretion of deoxyadenosine and 5'-dFUR, but not the reabsorption of adenosine or 5-fluorouracil, was prevented by the classical nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine. Cimetidine, an inhibitor of the organic cation secretory system, also inhibited the secretion of 5'-dFUR, although it did not inhibit deoxyadenosine secretion in earlier studies [Nelson et al.: Biochem. Pharmacol. 32, 2323 (1983)]. The specific inhibitor of glucose renal reabsorption, phloridzin, failed to inhibit the reabsorption of adenosine or the secretion of deoxyadenosine. Failure of the nucleoside transport inhibitors and phloridzin to prevent adenosine reabsorption suggests that adenosine reabsorption may occur via a unique process. On the other hand, inhibition of the net secretion of deoxyadenosine and 5'-dFUR by dipyridamole and nitrobenzylthioinosine implies a role for the carrier that is sensitive to these compounds in the renal secretion (active transport) of these nucleosides.

  10. Oral dosing with papaya latex is an effective anthelmintic treatment for sheep infected with Haemonchus contortus

    Directory of Open Access Journals (Sweden)

    Donnan Alison A

    2011-03-01

    Full Text Available Abstract Background The cysteine proteinases in papaya latex have been shown to have potent anthelmintic properties in monogastric hosts such as rodents, pigs and humans, but this has not been demonstrated in ruminants. Methods In two experiments, sheep were infected concurrently with 5,000 infective larvae of Haemonchus contortus and 10,000 infective larvae of Trichostrongylus colubriformis and were then treated with the supernatant from a suspension of papaya latex from day 28 to day 32 post-infection. Faecal egg counts were monitored from a week before treatment until the end of the experiment and worm burdens were assessed on day 35 post-infection. Results We found that the soluble fraction of papaya latex had a potent in vivo effect on the abomasal nematode H. contortus, but not on the small intestinal nematode T. colubriformis. This effect was dose-dependent and at tolerated levels of gavage with papaya latex (117 μmol of active papaya latex supernatant for 4 days, the H. contortus worm burdens were reduced by 98%. Repeated treatment, daily for 4 days, was more effective than a single dose, but efficacy was not enhanced by concurrent treatment with the antacid cimetidine. Conclusions Our results provide support for the idea that cysteine proteinases derived from papaya latex may be developed into novel anthelmintics for the treatment of lumenal stages of gastro-intestinal nematode infections in sheep, particularly those parasitizing the abomasum.

  11. Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse.

    Science.gov (United States)

    Yong, T; Zheng, M Q; Linthicum, D S

    1997-10-01

    Histamine-mediated induction of leukocyte rolling and adhesion in the cerebral microcirculation was examined in two inbred strains of mice (SJL/J and BALB/c). A cranial window was surgically prepared for the visualization of the cerebral microcirculation using intra-vital microscopy. Leukocyte rolling and adhesion to pial venular walls were assessed during off-line video playback analyses. The surgical preparation of the cranial windows was found to trigger 'spontaneous' leukocyte rolling, and this was attributed to disruption of dural mast cells and localized release of vasoactive histamine. This spontaneous leukocyte rolling was observed only in the SJL/J strain of mice, and could be prevented by presurgical treatment with the mast cell stabilizer sodium cromoglycate. BALB/c mice did not show 'spontaneous' leukocyte rolling or adhesion; this strain is known to have low numbers of CNS-associated mast cells. Exogenous histamine, applied topically to the cerebral microcirculation via the cranial window in mice pretreated with sodium cromoglycate, produced significant dose-dependent increases in leukocyte rolling and adhesion to pial venules in SJL/J mice, but not in BALB/c mice. Diphenhydramine (H1 receptor antagonist), but not cimetidine (H2 receptor antagonist), abolished both 'spontaneous' and histamine-induced leukocyte rolling. Anti-P-selectin antibody was found efficiently to block both spontaneous and histamine-induced increases in leukocyte rolling, but not leukocyte adhesion.

  12. Pharmacology of Casimiroa edulis; II. Cardiovascular effects in the anesthesized dog.

    Science.gov (United States)

    Vidrio, H; Magos, G A

    1991-06-01

    The cardiovascular effects of an aqueous extract of seeds of Casimiroa edulis were assessed in pentobarbital-anesthetized dogs. The extract produced marked hypotension which lasted more than two hours; it was accompanied by moderate and less persistent bradycardia. The histaminergic nature of these effects was investigated in animals pretreated with the specific antagonists diphenhydramine, cimetidine, or a combination of both agents. These experiments showed that both H1- and H2-receptors were involved in the hypotensive response, while the bradycardia was mediated solely through an H1-mechanism. In open-chest dogs instrumented for recording cardiac output (ascending aortic flow), left ventricular contractility (dp/dt), central venous pressure (superior vena cava), systemic blood pressure, heart rate, total peripheral resistance and stroke volume, the extract decreased blood pressure and peripheral resistance and increased cardiac output and stroke volume, without modifying the other parameters. It was concluded that the cardiovascular pattern of Casimiroa edulis in the dog is that of a peripheral arterial vasodilator and that it increases cardiac output by reducing left ventricular afterload.

  13. Effects of histamine on atrial and ventricular contractility in the canine isovolumic heart.

    Science.gov (United States)

    Vidrio, H; Priola, D V

    1990-03-01

    The effects of intracoronary administration of histamine on atrial and ventricular contractility were determined in a paced canine isovolumic heart preparation. Contractility was assessed by recording the pressure developed in saline-filled balloons placed in each of the four cardiac chambers. At doses above 0.1 mg and up to 100 mg histamine produced dose-related positive inotropic responses in all chambers. These were preceded by transient negative effects. The positive responses were not affected by a combination of H1 and H2 receptor antagonists antazoline and cimetidine but were almost completely abolished by the beta adrenoceptor blocker timolol. The negative responses were uninfluenced by either treatment. It was concluded that, in the canine isovolumic heart not subjected to complicating chronotropic and extracardiac factors, moderate doses of histamine are devoid of inotropic effects. Higher doses do produce myocardial stimulation, not mediated by histamine receptors, but probably due to norepinephrine release. These responses are preceded by transient non-specific depressant effects.

  14. H2S cytotoxicity mechanism involves reactive oxygen species formation and mitochondrial depolarisation.

    Science.gov (United States)

    Eghbal, Mohammad A; Pennefather, Peter S; O'Brien, Peter J

    2004-10-15

    A number of scavengers of reactive oxygen species (ROS) were found to be protective against cell death induced by hydrogen sulfide (H2S) in isolated hepatocytes. The H2O2 scavengers alpha-ketoglutarate and pyruvate, which also act as energy substrate metabolites, were more protective against H2S toxicity than lactate which is only an energy substrate metabolite. All of these results suggest that H2S toxicity is dependent on ROS production. We measured ROS formation directly in hepatocytes using the fluorogenic dichlorofluorescin method. H2S-induced ROS formation was dose dependent and pyruvate inhibited this ROS production. Non-toxic concentrations of H2S enhanced the cytotoxicity of H2O2 generated by glucose/glucose oxidase, which was inhibited by CYP450 inibitors. Furthermore, hepatocyte ROS formation induced by H2S was decreased by CYP450 inhibitors cimetidine and benzylimidazole. These results suggest that CYP450-dependant metabolism of H2S is responsible for inducing ROS production. H2S-induced cytotoxicity was preceded by mitochondrial depolarization as measured by rhodamine 123 fluorescence. Mitochondrial depolarization induced by H2S was prevented by zinc, methionine and pyruvate all of which decreased H2S-induced cell death. Treatment of H2S poisoning may benefit from interventions aimed at minimizing ROS-induced damage and reducing mitochondrial damage.

  15. Fluorescence imaging for a noninvasive in vivo toxicity-test using a transgenic silkworm expressing green fluorescent protein.

    Science.gov (United States)

    Inagaki, Yoshinori; Matsumoto, Yasuhiko; Ishii, Masaki; Uchino, Keiro; Sezutsu, Hideki; Sekimizu, Kazuhisa

    2015-06-10

    In drug development, the toxicity of candidate chemicals must be carefully examined in an animal model. Here we developed a live imaging technique using silkworms for a noninvasive toxicity test applicable for drug screening. Injection of carbon tetrachloride, a tissue-injuring chemical, into transgenic silkworms expressing green fluorescent protein (GFP) induced leakage of GFP from the tissues into the hemolymph. The leakage of GFP was suppressed by pre-administration of either cimetidine, a cytochrome P450 inhibitor, or N-acetyl cysteine, a free-radical scavenger. The transgenic silkworm was made transparent by feeding a diet containing chemicals that inhibit uric acid deposition in the epithelial cells. In the transparent silkworms, GFP fluorescence in the fat body could be observed from outside the body. Injection of salicylic acid or iron sulfate, tissue-injuring chemicals, into the transparent silkworms decreased the fluorescence intensity of the GFP in the fat body. These findings suggest that the transparent GFP-expressing silkworm model is useful for evaluating the toxicity of chemicals that induce tissue injury.

  16. Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part II: extension to describe performance of solid dosage forms.

    Science.gov (United States)

    Thelen, Kirstin; Coboeken, Katrin; Willmann, Stefan; Dressman, Jennifer B; Lippert, Jörg

    2012-03-01

    The physiological absorption model presented in part I of this work is now extended to account for dosage-form-dependent gastrointestinal (GI) transit as well as disintegration and dissolution processes of various immediate-release and modified-release dosage forms. Empirical functions of the Weibull type were fitted to experimental in vitro dissolution profiles of solid dosage forms for eight test compounds (aciclovir, caffeine, cimetidine, diclofenac, furosemide, paracetamol, phenobarbital, and theophylline). The Weibull functions were then implemented into the model to predict mean plasma concentration-time profiles of the various dosage forms. On the basis of these dissolution functions, pharmacokinetics (PK) of six model drugs was predicted well. In the case of diclofenac, deviations between predicted and observed plasma concentrations were attributable to the large variability in gastric emptying time of the enteric-coated tablets. Likewise, oral PK of furosemide was found to be predominantly governed by the gastric emptying patterns. It is concluded that the revised model for GI transit and absorption was successfully integrated with dissolution functions of the Weibull type, enabling prediction of in vivo PK profiles from in vitro dissolution data. It facilitates a comparative analysis of the parameters contributing to oral drug absorption and is thus a powerful tool for formulation design.

  17. Spectrophotometric determination of H 2-receptor antagonists via their oxidation with cerium(IV)

    Science.gov (United States)

    Darwish, Ibrahim A.; Hussein, Samiha A.; Mahmoud, Ashraf M.; Hassan, Ahmed I.

    2008-01-01

    A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H 2-receptor antagonists: cimetidine, famotidine, nizatidine and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium(IV) in presence of perchloric acid and subsequent measurement of the excess Ce(IV) by its reaction with p-dimethylaminobenzaldehyde to give a red colored product ( λmax at 464 nm). The decrease in the absorption intensity of the colored product (Δ A), due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990-0.9994) were found between Δ A values and the concentrations of the drugs in a concentration range of 1-20 μg ml -1. The assay limits of detection and quantitation were 0.18-0.60 and 0.54-1.53 μg ml -1, respectively. The method was validated, in terms of accuracy, precision, ruggedness and robustness; the results were satisfactory. The proposed method was successfully applied to the determination of the investigated drugs in pure and pharmaceutical dosage forms (recovery was 98.3-102.6 ± 0.57-1.90%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.

  18. The effect of betahistine on vestibular habituation: comparison of rotatory and sway habituation training.

    Science.gov (United States)

    Mierzwinski, J; Kazmierczak, H; Pawlak-Osinska, K; Piziewicz, A

    2001-07-01

    This study was designed to investigate the effect of histaminergic agonists and antagonists on the acquisition of vestibular habituation. The experimental animals, pigeons, were subjected to unilateral rotatory and sway habituation training sessions. The habituation of postural reflexes and post-rotatory head nystagmus was assessed. Vestibular habituation in the control group was achieved by adopting the kinetic reflex posture after approximately 9 training sessions, and after 10 and 14 training sessions, respectively for 50% reduction of the total number of beats (TNB) and the duration of post-rotatory head nystagmus. In the sway adaptation test control pigeons needed nearly 15 training sessions while pigeons receiving betahistine adapted after approximately 8 sessions. Administration of histamine and, most notably, betahistine accelerated the process, while both H1 and H2 antagonists (clemastine, cimetidine) tended to retard it, indicating a less significant contribution of H2 receptors. The cholinergic agent physostigmine strongly retarded habituation while the anticholinergic agent scopolamine markedly accelerated it. In addition the adrenomimetic agent ephedrine also accelerated habituation while the adrenolytic agent droperidol retarded reduction of nystagmus beats. The results indicate that histaminergic receptors play a significant role in the vestibular habituation mechanism but are intricately involved with other types of receptors. Betahistine is clearly the agent of choice for attenuating vestibular effects.

  19. Photocatalytic applications of paper-like poly(vinylidene fluoride)-titanium dioxide hybrids fabricated using a combination of electrospinning and electrospraying.

    Science.gov (United States)

    Ramasundaram, Subramaniyan; Son, Aseom; Seid, Mingizem Gashaw; Shim, Sujin; Lee, Sang Hyup; Chung, Yun Chul; Lee, Changha; Lee, Jaesang; Hong, Seok Won

    2015-03-21

    A paper-like photocatalyst was fabricated by electrospraying an N,N'-dimethylformamide (DMF) dispersion of titanium dioxide (TiO2) nanoparticles (NPs) on a poly(vinylidene fluoride) nanofiber (PVDF NF) mat prepared by electrospinning. Morphological studies revealed that the TiO2 NPs uniformly deposited as clusters on the surface of the PVDF NF mat. The immobilized amount of TiO2 was found to be 2.08, 2.44, 3.80, and 4.73 mg per 45 cm(2) of PVDF-TiO2 hybrids for the electrospraying of 10, 20, 40, and 60 ml of TiO2-DMF, respectively. The hybrid photocatalysts were effective in degrading bisphenol A (BPA), 4-chlorophenol (4-CP), and cimetidine (CMT), which dissolved in both deionized water and secondary wastewater effluents, with activity being proportional to the quantity of TiO2 NPs immobilized. For the highest loading amount of TiO2, BPA, 4-CP, and CMT degraded completely within 100, 100, and 40 min of UV irradiation, respectively. Stable photo-oxidation of CMT was maintained through 10 repeated cycles. During these cycles, it was confirmed that there was no loss of TiO2 NPs by inductively coupled plasma optical emission spectrometry. Our results suggest that effective and stable PVDF-TiO2 hybrid photocatalysts can be fabricated on a large scale by combining electrospinning and electrospraying techniques.

  20. Immunomodulators in warts: Unexplored or ineffective?

    Directory of Open Access Journals (Sweden)

    Surabhi Sinha

    2015-01-01

    Full Text Available Cutaneous warts are known to be recurrent and often resistant to therapy. Resistant warts may reflect a localized or systemic cell mediated immune (CMI deficiency to HPV. Many modalities of treatment are in use; most of the provider-administered therapies are destructive and cause scarring, such as cryotherapy, chemical cauterisation, curettage, electrodessication and laser removal. Most patient-applied agents like podophyllotoxin have the risk of application-site reactions and recurrence. Thus immunotherapy is a promising modality which could lead to resolution of warts without any physical changes or scarring and in addition would augment the host response against the causative agent, thereby leading to complete resolution and decreased recurrences. Immunomodulators can be administered systemically, intralesionally or intradermally, and topically. A few agents have been tried and studied extensively such as cimetidine and interferons; others are new on the horizon, such as Echinacea, green tea catechins and quadrivalent HPV vaccine, and their efficacy is yet to be completely established. Though some like levamisole have shown no efficacy as monotherapy and are now used only in combination, other more recent agents require large and long term randomized placebo-controlled trials to clearly establish their efficacy or lack of it. In this review, we focus on the immunomodulators that have been used for the treatment of warts and the studies that have been conducted on them.

  1. The role of environmental estrogens and autoimmunity.

    Science.gov (United States)

    Chighizola, Cecilia; Meroni, Pier Luigi

    2012-05-01

    The prevalence of autoimmune diseases has significantly increased over the recent years. It has been proposed that this epidemiological evidence could be in part attributable to environmental estrogens, compounds that display estrogen-like activity and are ubiquitously present in the environment. Environmental estrogens can be found in a wide variety of foods: phytoestrogens occur in plants such as clover and soy, while mycoestrogens are food contaminants produced by fungi. Meat, eggs and dairy products from animals given exogenous hormones contain relatively high concentration of estrogens. Among xenoestrogens, industrial estrogens are synthetic chemicals produced for specific purposes (pesticides, plastics, surfactants and detergents) while metalloestrogens are found in heavy metals. Estrogens can be also administered through medications (contraceptive pill, hormone replacement therapy, genistein, cimetidine, creams). There is a considerable burden of evidence in vitro and in animal models that these compounds may exert immunotoxic effects. However, to date there is no convincing data that exposure to environmental estrogens can be regarded as a risk for human health. In particular, there is no consensus whether prolonged exposure to relatively low concentrations of different estrogenic chemicals can affect the human immune system and induce clinically evident diseases in real-life scenario. Moreover, the effects on human health of the synergistic interactions between natural, medical, dietary and environmental estrogens have not been fully elucidated yet. Here we provide an extensive review of the in vivo and in vitro effects of environmental estrogens on the immune system, focusing on the evidences of association between exposure and autoimmune disorders.

  2. Histamine releases PGI2 from human pulmonary artery.

    Science.gov (United States)

    Schellenberg, R R; Duff, M J; Foster, A; Paddon, H B

    1986-08-01

    Histamine caused a triphasic response of human pulmonary artery strips in vitro, consisting of a small initial contraction followed by pronounced relaxation preceding a second contractile response. These characteristics were not seen with other contractile stimuli including 5-hydroxytryptamine, leukotriene D4, and KCl. The relaxant component of this response was ablated by removal of endothelium from the vascular strips or by pretreatment of the tissue with 1 microM indomethacin. Measurement of the PGI2 degradation product 6-keto-PGF1 alpha in supernatants from histamine-challenged tissues confirmed the synthesis of PGI2. Supernatants from unstimulated or leukotriene-challenged tissues contained no detectable amounts of 6-keto-PGF1 alpha. The histamine H1 antagonist diphenydramine inhibited both the contractile and relaxant responses to histamine whereas the H2 antagonist cimetidine affected neither component. The released PGI2 significantly altered the dose-response curve to histamine without inhibiting the maximal contractile responses. We conclude that histamine induces PGI2 formation from pulmonary arterial endothelium via an H1 receptor.

  3. Role of histamine H1-and H2-receptors in the cardiovascular system of the rabbit.

    Science.gov (United States)

    Sakai, K

    1980-01-01

    The effects of histamine were examined on the circulation of the blood-perfused heart, kidney, intestine, and hindlimb of rabbits. Single intrarterial injections of drugs were made into the perfusion system of the coronary, renal, mesenteric, or femoral vascular bed. In the hearts, histamine caused dose-dependent positive inotropic and chronotropic responses and vaso-constriction. 2-Methylhistamine, a relatively selective histamine H1-receptor agonist, produced vascular effects very similar to those of histamine, but had no cardiac actions at low and negative inotropic responses at high doses. 4-Methylhistamine, a relatively selective histamine H2-receptor agonist, induced slight vasodilatation and positive inotropic and chronotropic responses. In the renal, mesenteric, and femoral vascular beds, histamine and 2-methylhistamine caused vasoconstriction, while 4-methylhistamine induced slight vasodilatation. Mepyramine, a selective H1-receptor antagonist, blocked the vasoconstriction in response to histamine and 2-methylhistamine, but not the positive inotropic and chronotropic responses to histamine. The combined action of mepyramine and cimetidine (a selective H2-receptor antagonist) eliminated all cardiac and vascular effects of histamine. These results strongly support the view that in the cardiovascular system of the rabbit, H1-receptors mediate negative inotropic effects and vasoconstriction, whereas H2-receptors are responsible for positive inotropic and chronotropic effects and vasodilatation.

  4. Therapeutic Options for Controlling Fluids in the Visual System

    Science.gov (United States)

    Curry, Kristina M.; Wotring, Virginia E.

    2014-01-01

    Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

  5. Posterior hypothalamic receptors involved in the cardiovascular changes elicited by electrical stimulation of the rostral ventrolateral medulla.

    Science.gov (United States)

    Bachelard, H; Rivest, R; Marsden, C A

    1991-07-01

    The posterior hypothalamic receptors involved in the cardiovascular responses to electrical stimulation of the rostral ventrolateral medulla were investigated in urethane-anaesthetized rats. Electrical stimulation of the rostral ventrolateral medulla produced a significant increase in systolic blood pressure. This response was significantly attenuated by the prior administration of d,l-propranolol (20 micrograms), clonidine (8 micrograms), atropine (8 micrograms) or methysergide (10 micrograms) into the posterior hypothalamus, but not by cimetidine (11 micrograms), chlorpheniramine (12 micrograms), naloxone (10 micrograms) or a vasopressin V1 antagonist (100 ng). The effect of clonidine (8 micrograms) on the pressor response to stimulation of the rostral ventrolateral medulla was antagonized by idazoxan (66 micrograms). These results confirm that the cardiovascular changes elicited by stimulation of the rostral ventrolateral medulla area are, in part, centrally modulated by alpha 2 and beta-adrenoceptors in the posterior hypothalamus which exert respectively, inhibitory and stimulatory effect. Furthermore the results indicate the involvement of posterior hypothalamic cholinergic and serotonergic receptors in the pressor response produced by stimulation of the rostral ventrolateral medulla.

  6. Histamine receptors in isolated bovine oviductal arteries.

    Science.gov (United States)

    Martínez, A C; Novella, S; Raposo, R; Recio, P; Labadía, A; Costa, G; Garcia-Sacristán, A; Benedito, S

    1997-05-20

    The present in vitro study was designed to evaluate the effect of histamine on isolated rings of bovine oviductal artery and to characterize the histamine receptors involved in the histamine-induced response. Endothelial dependence of the response was also investigated. Cumulative addition of histamine and 2-pyridylethylamine (histamine H receptor agonist) induced a concentration-dependent relaxation in intact arterial segments precontracted with noradrenaline. The histamine H1 receptor antagonist mepyramine showed non-competitive antagonism in the histamine-induced concentration-response curve. However, when the response to histamine was evaluated in the presence of mepyramine and histamine H1 and H3 receptors were blocked, Schild analysis yielded a line with a slope of 1.10 and a pA2 value of 8.91, indicating simple competitive antagonism of mepyramine at histamine H1 receptor sites. The histamine H2 receptor agonist, dimaprit, caused marked dilatation only at high doses. Cimetidine, propranolol and mepyramine failed to inhibit this relaxant effect. In precontracted oviductal arteries, cimetidine did not modify the histamine-induced concentration-response curves. Combined treatment with histamine H1 and H2 receptor antagonists did not induce an additional displacement with respect to the isolated effect of mepyramine thus excluding activation of histamine H2 receptors. Histamine and (R)-alpha-methylhistamine, a selective histamine H3 receptor agonist, produced a moderate contractile effect on the resting tone of preparations. Pretreatment with the selective histamine H1 receptor antagonist decreased the (R)-alpha-methylhistamine response but increased the maximal relaxant effect and abolished the contractile effect of histamine, suggesting the presence of a limited population of contractile histamine H3 receptors. Removal of the endothelium or pretreatment with methylene blue produced a significant inhibition of the relaxant response to histamine. Remaining

  7. An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations.

    Science.gov (United States)

    Kindberg, Abigail A; Bendriem, Raphael M; Spivak, Charles E; Chen, Jia; Handreck, Annelie; Lupica, Carl R; Liu, Jinny; Freed, William J; Lee, Chun-Ting

    2014-12-01

    Neocortical development involves ordered specification of forebrain cortical progenitors to various neuronal subtypes, ultimately forming the layered cortical structure. Modeling of this process using human pluripotent stem cells (hPSCs) would enable mechanistic studies of human neocortical development, while providing new avenues for exploration of developmental neocortical abnormalities. Here, we show that preserving hPSCs aggregates - allowing embryoid body formation - while adding basic fibroblast growth factor (bFGF) during neuroepithelial development generates neural rosettes showing dorsal forebrain identity, including Mash1(+) dorsal telencephalic GABAergic progenitors. Structures that mirrored the organization of the cerebral cortex formed after rosettes were seeded and cultured for 3 weeks in the presence of FGF18, BDNF and NT3. Neurons migrated along radial glia scaffolding, with deep-layer CTIP2(+) cortical neurons appearing after 1 week and upper-layer SATB2(+) cortical neurons forming during the second and third weeks. At the end of differentiation, these structures contained both glutamatergic and GABAergic neurons, with glutamatergic neurons being most abundant. Thus, this differentiation protocol generated an hPSC-based model that exhibits temporal patterning and a neuronal subtype ratio similar to that of the developing human neocortex. This model was used to examine the effects of cocaine during neocorticogenesis. Cocaine caused premature neuronal differentiation and enhanced neurogenesis of various cortical neuronal subtypes. These cocaine-induced changes were inhibited by the cytochrome P450 inhibitor cimetidine. This in vitro model enables mechanistic studies of neocorticogenesis, and can be used to examine the mechanisms through which cocaine alters the development of the human neocortex.

  8. Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

    Science.gov (United States)

    Lee, N-Y; Choi, H-M; Kang, Y-S

    2009-04-01

    Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

  9. Exacerbation of nonsteroidal anti-inflammatory drug-induced small intestinal lesions by antisecretory drugs in rats: the role of intestinal motility.

    Science.gov (United States)

    Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

    2012-11-01

    Antisecretory drugs such as histamine H2-receptor antagonists (H2-RAs) and proton pump inhibitors (PPIs) are commonly used for the treatment of gastric and duodenal ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, the effects of these drugs on NSAID-induced small intestinal ulcers are not fully understood. The effects of H2-RAs and PPIs on NSAID-induced gastrointestinal lesions and small intestinal motility were examined in rats. Male Wistar rats (180-220 g) were used. Indomethacin (10 mg/kg) was administered orally in fasted or fed rats, and gastrointestinal lesions were examined 24 h after indomethacin administration. Intestinal motility was measured by using a balloon method under urethane anesthesia. Indomethacin produced multiple lesions in the gastric corpus in fasted rats and in the small intestine in fed rats: 1) H2-RAs (cimetidine, ranitidine, and famotidine) and PPIs (omeprazole, lansoprazole, and rabeprazole) markedly inhibited the formation of gastric lesions. 2) The drugs, except for lansoprazole, increased intestinal lesions. 3) H2-RAs augmented the increase in intestinal motility caused by indomethacin, and the effects of H2-RAs on motility and intestinal lesions were markedly inhibited by atropine. 4) Lansoprazole inhibited the formation of intestinal lesions, and the effect was prevented by both pharmacological ablation of capsaicin-sensitive sensory neurons and pretreatment with N-nitro-l-arginine methyl ester, a selective inhibitor of nitric-oxide synthesis. The results suggest that: 1) inhibition of acid secretion by antisecretory drugs may exacerbate NSAID-induced intestinal lesions, 2) H2-RAs further aggravate lesions by increasing intestinal motility via the activation of cholinergic pathways, and 3) lansoprazole protects the intestinal mucosa against NSAID-related ulcerative stimuli.

  10. Changes in plasma adrenocorticotropic hormone and cortisol levels induced by intracerebroventricular injection of histamine and its related compounds in dogs.

    Science.gov (United States)

    Tsujimoto, S; Kamei, C; Yoshida, T; Tasaka, K

    1993-08-01

    Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H(i)) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 micrograms/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2-10 micrograms/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 micrograms/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 micrograms/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with H(i) resulted in the significant inhibition of H(i)-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after H(i) injection at a dose of 5 micrograms/kg. Intravenous infusion of hexamethonium continued before and after H(i) injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by H(i). From these findings, it can be concluded that intracerebroventricular injection of H(i) caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by H(i) is certainly produced without participation of ACTH.

  11. Feeding, drinking, and temperature responses of chickens to intracerebroventricular histamine.

    Science.gov (United States)

    Meade, S; Denbow, D M

    2001-05-01

    The present study examines the effects of intracerebroventricular injections of histamine (HA) and two HA antagonists, the H(1) receptor antagonist chloropheneramine maleate (CM) and the H(2) receptor antagonist cimetidine (CIM), on food and water consumption and body temperature in chickens. Single-Comb White Leghorns (SCWL) and broiler cockerels were utilized for these experiments. The first pair of experiments consisted of intracerebroventricular injections of HA and its effects on food and water consumption. HA was infused at dosages of 0, 25, 50, and 100 microg/10 microl of artificial cerebrospinal fluid (aCSF). HA significantly decreased food and water intake in a dose-dependent manner. The second pair of experiments examined the effects of HA on water intake while birds had no access to feed. Water intake was not significantly affected by intracerebroventricular injections of HA. The next pair of experiments examined the effects of HA on body temperature. In SCWL, body temperature was not affected by HA until 165 min postinjection when HA decreased temperature in a quadratic dose-response with maximum hypothermia being achieved at a dose of 25 microg. In contrast, HA increased body temperature in broilers beginning at 75 min postinjection. In the final series of experiments, the anorexia induced by HA was attenuated in SCWL and broilers with pretreatment of either CM or CIM. These results suggest that HA has an anorexigenic effect in SCWL and broiler cockerels, and this effect is mediated by both H(1) and H(2) receptors. Water intake is not directly affected by the intracerebroventricular injection of HA. Whereas HA increased body temperature in broilers, the response in SCWL is equivocal.

  12. Effects of intracerebroventricular injection of histamine and related compounds on corticosterone release in rats.

    Science.gov (United States)

    Tsujimoto, S; Okumura, Y; Kamei, C; Tasaka, K

    1993-07-01

    1. The effects of intracerebroventricular (i.c.v.) injection of histamine and related compounds on plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations were studied in conscious rats. 2. Histamine at doses of 5-20 micrograms kg-1 rapidly increased plasma ACTH and corticosterone concentrations almost simultaneously, and subsequent courses were also similar to each other. However, in the case of CRF-41 (i.v.), the plasma ACTH concentration first increased followed by an increase in plasma corticosterone concentration. Even in hypophysectomized rats, a significant increase in plasma corticosterone concentration was induced by histamine at doses of 20 and 50 micrograms kg-1. 3. Histamine at doses of 10 and 20 micrograms kg-1 elicited an increase in the amplitude of adrenal nerve activity, and electrical stimulation to the adrenal nerves resulted in an increase in plasma corticosterone concentration. 4. Both H1-agonist (2-methylhistamine) and H2-agonists (4-methylhistamine and impromidine) also induced similar effects to those of histamine. Pretreatment with pyrilamine caused an inhibition of histamine-induced increase in plasma ACTH and corticosterone concentrations, while both cimetidine and ranitidine failed to inhibit this effect. However, both H2-blockers were effective in inhibiting the 4-methylhistamine-induced elevation of plasma ACTH and corticosterone concentrations. 5. Neither (R)-alpha-methylhistamine nor thioperamide had a significant effect, indicating that the H3-receptor is not involved in the histamine-induced increase in plasma ACTH and corticosterone concentrations. 6. From these findings, it was concluded that (1) electrical signals transmitted from the brain to the adrenal gland through the neurones may be involved in the rapid corticosterone release induced by histamine, and (2) not only H1- but also H2-receptors are implicated in histamine-induced hormone secretions in rats, though the contribution of the H2-receptor is

  13. Comparison of airway responses in sheep of different age in precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Verena A Lambermont

    Full Text Available Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages.Lambs were delivered spontaneously at term (147d and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM and mast cells staining were evaluated.PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages.PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.

  14. One-step extraction of polar drugs from plasma by parallel artificial liquid membrane extraction.

    Science.gov (United States)

    Pilařová, Veronika; Sultani, Mumtaz; Ask, Kristine Skoglund; Nováková, Lucie; Pedersen-Bjergaard, Stig; Gjelstad, Astrid

    2017-02-01

    The new microextraction technique named parallel artificial liquid membrane extraction (PALME) was introduced as an alternative approach to liquid-liquid extraction of charged analytes from aqueous samples. The concept is based on extraction of analytes across a supported liquid membrane sustained in the pores of a thin polymeric membrane, a well-known extraction principle also used in hollow fiber liquid-phase microextraction (HF-LPME). However, the new PALME technique offers a more user-friendly setup in which the supported liquid membrane is incorporated in a 96 well plate system. Thus, high-throughput is achievable, in addition to the green chemistry offered by using PALME. The consumption of organic solvent is minimized to 3-5μL per sample. With a sample volume of 250μL and acceptor solution volume of 50μL, a maximal enrichment factor of five is achievable. Based on these parameters, a new method for extraction of polar basic drugs was developed in the present work. The basic drugs hydralazine, ephedrine, metaraminol, salbutamol, and cimetidine were used as model analytes, and were extracted from alkalized human plasma into an aqueous solution via the supported liquid membrane. The extraction was promoted by a carrier dissolved in the membrane, creating a temporary ion-pair complex between the hydrophilic drug and the carrier. As the model analytes were extracted directly into an aqueous solution, there was no need for evaporation of the extract before injection into LC-MS. Hence, the sample preparation is performed in one step. With optimized conditions, the extraction recoveries were in the range 50-89% from human plasma after 45min extraction. The data from the method evaluation were satisfactory and in line with current guidelines, and revealed an extraction method with substantial potential for high throughput bioanalysis of polar basic drugs.

  15. Biliary excretion of acetaminophen-glutathione as an index of toxic activation of acetaminophen: effect of chemicals that alter acetaminophen hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Madhu, C.; Gregus, Z.; Klaassen, C.D.

    1989-03-01

    Acetaminophen (AA) is converted, presumably by cytochrome P-450, to an electrophile which is conjugated with glutathione (GS). AA-GS is excreted into bile, therefore the biliary excretion rate of AA-GS may reflect the rate of activation of AA in vivo. In order to test this hypothesis, the effect of agents capable of altering the activation of AA including cytochrome P-450 inducers and inhibitors, cobaltous chloride which decreases the amount of P-450, prostaglandin synthetase inhibitors (indomethacin and naproxen), antioxidants (butylated hydroxyanisole, alpha-tocopherol, ascorbic acid and ascorbic acid palmitate) and other chemicals known to decrease AA hepatotoxicity (dimethylsulfoxide and cysteamine), on the biliary excretion of AA-GS was studied in hamsters, the species most sensitive to AA-induced hepatotoxicity. The biliary excretion of AA-GS increased linearly up to 1 mmol/kg of AA i.v., but at higher dosages exhibited saturation kinetics. Dosages above 0.5 mmol/kg lowered hepatic GS concentration. Of the cytochrome P-450 inducers, 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin, increased the biliary excretion of AA-GS (2.9- and 3.2-fold, respectively) whereas ethanol and isoniazid did not affect it, and pregnenolone-16 alpha-carbonitrile tended to decrease it (43%). Phenobarbital tended to increase the biliary excretion of AA-GS, but not in a statistically significant manner. Several cytochrome P-450 inhibitors (metyrapone, 8-methoxypsoralen, 2-(4,6-dichloro-biphenyloxy) ethylamine, alpha-naphthoflavone and cimetidine) decreased the biliary excretion of AA-GS, although SKF 525-A and piperonyl butoxide did not. Cobaltous chloride decreased dramatically the biliary excretion of AA-GS.

  16. [Duodenal complications of rheumatoid purpura. Endoscopic aspects].

    Science.gov (United States)

    Chapoy, P; Guidon, M J; Louchet, E

    1984-01-01

    The aim of this work was to describe the endoscopic features and clinical outcome of the duodenal complications in anaphylactoid purpura. Over a 3-year period, 20 patients were hospitalized in our unit because of purpura rheumatica. Duodenal complications occurred in 5 cases warranting endoscopic assessment. All patients had bilious vomiting and epigastric pain, constantly associated with low-grade purpuric rash. Plasma factor XIII concentrations were always decreased. The duodenal complication was suspected radiologically in 2 cases when "thumbprint" impressions were seen. Petechiae, oedema and intramural hematoma with superficial erosions were present endoscopically in 3 cases. The lesions were severe and extensive, involving the entire duodenum in 3 cases and the jejunum in one case. In one patient, there was a stricture of the upper part of the second duodenum. Treatment consisted of parenteral nutrition (using a central catheter: 3 cases, or a peripheral vein: 2 cases) and cimetidine (30 mg/kg.bw). The clinical outcome was favorable in 4 patients; the symptoms vanished and the endoscopic lesions were reversible (including the stricture) with restitutio ad integrum after 10 days. The last patient died the 8th day of treatment, 3 days after digestive improvement; the cause of death was probably iatrogenic and related to accidental migration of the central catheter. These results suggest that endoscopic examination should be performed in all patients with anaphylactoid purpura presenting with bilious vomiting. Endoscopy seems to be of great value in deciding if parenteral nutrition is indicated--or not--and perhaps in order to contraindicate the use of steroid therapy in the case of ulcerated hematomas.

  17. 腹型荨麻疹80例治疗分析%Treatment Analysis of 80 Cases with Abdominal Urticaria

    Institute of Scientific and Technical Information of China (English)

    楼芳; 冯小清; 齐焕英

    2014-01-01

    目的:探讨不同方法治疗腹型荨麻疹的疗效及预后。方法:80例腹型荨麻疹患者分为A、B两组,每组40例,A组给予口服地氯雷他定片、盐酸左西替利嗪片联合静滴西咪替丁治疗,B组在给予A组口服药的同时联合静滴地塞米松,3 d为一疗程。结果:A、B两组有效率分别为22.5%、67.5%,两组有效率比较,差异有统计学意义(P<0.01)。结论:腹型荨麻疹大多症状较重,抗组织胺药物联合肾上腺皮质激素疗效显著。%Objective:To explore the efficacy and prognosis of different methods in the treatment of abdominal urticaria.Method:80 cases with abdominal urticaria were divided into group A and group B,40 cases in each group,group A was given Desloratadine,Levocetirizine Hydrochloride oral combined with Cimetidine intravenous drip,group B received Dexamethasone intravenously on the basis of group A oral drug,3 days for a course of the treatment.Result:The efficiency of group A and group B were 22.5%,67.5%,the difference of efficiency between two groups was statistically significant(P<0.01).Conclusion:The symptoms of most abdominal urticaria are severe,the method of antihistamines and adrenal cortex hormone has a very significant effect on this disease.

  18. Modulatory effects of taurine on jejunal contractility

    Directory of Open Access Journals (Sweden)

    Q.Y. Yao

    2014-12-01

    Full Text Available Taurine (2-aminoethanesulfonic acid is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  19. Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, SAN 05.

    Science.gov (United States)

    2004-01-01

    Santarus Inc. is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitreltrade mark [SAN 05] and also as Rapinex powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers. Acitreltrade mark is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for gastrointestinal (GI) diseases. Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders. Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20 mg outside the US, to one or more well established pharmaceutical companies. The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA. Santarus announced positive results in August 2003 from a phase III trial comparing oral Acitrel (Rapinex 40 mg) with intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of this omeprazole 40 mg powder suspension for an 8-week period. In connection with the NDA for omeprazole powder suspension 40 mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that omeprazole powder suspension 40 mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

  20. Omeprazole/antacid-powder suspension--Santarus: Acitrel, Rapinex Powder for oral suspension, SAN 05.

    Science.gov (United States)

    2004-01-01

    Santarus Inc., is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitrel [SAN 05], and also as Rapinex powder for oral suspension. Acitrel is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for GI diseases. Santarus have licensed exclusive, worldwide rights to patent applications covering specific combination-formulations of proton pump inhibitors and antacids for treating various upper GI diseases and disorders. Santarus plans to license development, distribution and marketing rights of Rapinex Powder for oral suspension 20mg outside the US, to one or more well established pharmaceutical companies. The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA. Santarus announced positive results, in August 2003, from a phase III trial comparing oral Acitrel (Rapinex 40mg) to intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of Rapinex 40mg for an 8-week period. In connection with the NDA for Rapinex 40mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that Rapinex 40mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

  1. Contrasting cardiovascular properties of the µ-opioid agonists morphine and methadone in the rat.

    Science.gov (United States)

    Tung, Kenneth H; Angus, James A; Wright, Christine E

    2015-09-05

    Morphine and methadone share the property of μ-opioid receptor agonism yet have markedly different cardiovascular actions suggesting additional properties are at play. We investigated the i.v. dose-response relationships of the opioids on cardiovascular metameters in anaesthetised rats in the absence or presence of H1- and H2-receptor antagonism and the μ-opioid antagonist naloxone. In vitro tissue assays were employed to define more clearly cardiac and vascular mechanisms of action. Morphine (9, 30, 90mg/kg i.v.) decreased heart rate (HR) and mean arterial pressure (MAP) - responses that were blocked by naloxone pretreatment (10mg/kg i.v.). In contrast, methadone (3, 10, 30mg/kg i.v.) caused dramatic short-lived (1-3min) bradycardia, hypotension and lengthening of the QT interval before stabilising 5min after i.v. dosing. Only the steady-state responses of HR and MAP were blocked by naloxone. Mepyramine (10mg/kg i.v.) and cimetidine (100mg/kg i.v.) also blocked the naloxone-sensitive components. In isolated small mesenteric arteries precontracted by K(+) 62mM or endothelin-1, methadone (1-30μM) relaxed vessels while morphine (1-100μM) had no effect. Pretreatment with naloxone (10μM), indomethacin (30μM) or nitro-l-arginine (100μM) did not affect the relaxation to methadone. In rat isolated left atria, morphine and methadone inhibited inotropic responses at high concentrations (100μM). In rat papillary muscle and right atria, methadone was more than 30 times more potent at lengthening the refractory period and slowing the atrial rate than morphine. We conclude that methadone is a potent vasodilator agent, possibly through blocking L-type calcium channels.

  2. Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae).

    Science.gov (United States)

    Zanatta, Francielle; Gandolfi, Renan Becker; Lemos, Marivane; Ticona, Juan Carlos; Gimenez, Alberto; Clasen, Bruna Kurz; Cechinel Filho, Valdir; de Andrade, Sérgio Faloni

    2009-07-15

    As part of our continuing search for bioactive natural products from plants, the present study was carried out in order to evaluate the gastroprotective properties of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora (Rutaceae). Anti-ulcer assays were performed using the following protocols in mice: nonsteroidal anti-inflammatory drug (NSAID)/bethanecol-induced ulcer, ethanol/HCl-induced ulcer, and stress-induced ulcer. The effects of the extract on gastric content volume, pH and total acidity were also evaluated, using the pylorus ligated model. Treatment using doses of 50, 125 and 250 mg/kg of G. longiflora alkaloid extract and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, total lesion area, and percentage of lesion, in comparison with the negative control groups in all the models evaluated. Regarding the model of gastric secretion, a reduction in volume of gastric juice and total acidity was observed, as well as an increase in gastric pH. The main alkaloid of the plant, 2-phenylquinoline, was also evaluated in the ethanol-induced ulcer model. The results showed that at a dose of 50 mg/kg, it significantly inhibited ulcerative lesions. However, this effect was less than that of the alkaloid extract. All these results taken together show that G. longiflora displays gastroprotective activity, as evidenced by its significant inhibition of the formation of ulcers induced by different models. There are indications that mechanisms involved in anti-ulcer activity are related to a decrease in gastric secretion and an increase in gastric mucus content. Also, there is evidence of involvement of NO in the gastroprotector mechanisms. These effects may be attributed, at least in part, to the presence of some alkaloids, particularly 2-phenylquinoline.

  3. Impairment by 5-fluorouracil of the healing of gastric lesions in rats: effect of lafutidine, a histamine H2 receptor antagonist, mediated by capsaicin-sensitive afferent neurons.

    Science.gov (United States)

    Murashima, Yukiko; Kotani, Tohru; Hayashi, Shusaku; Komatsu, Yoshino; Nakagiri, Akari; Amagase, Kikuko; Takeuchi, Koji

    2009-01-01

    We investigated the influence of 5-fluorouracil (5-FU), an anti-tumor agent, on the healing of gastric lesions generated by 0.6 M HCl in rats and the effect of lafutidine, a histamine H(2) receptor antagonist, on the impaired healing. Animals fasted for 18 h were given 1 ml of 0.6 M HCl p.o., fed normally from 1 h later, and killed 1-96 h thereafter. 5-FU was given i.v. twice, 1 h and 24 h after the HCl. The gastric lesions healed spontaneously within 96 h. Although it decreased acid secretion, 5-FU markedly delayed the healing. Lafutidine, but not cimetidine, given p.o. immediately after each dosing of 5-FU significantly reversed the delay in healing by 5-FU, and this effect was attenuated by the chemical ablation of capsaicin-sensitive afferent neurons. Capsaicin also significantly reversed the delay in healing. The mucosal application of 50 mM HCl did not affect gastric mucosal blood flow (GMBF) in the normal stomach, but significantly increased it in the stomach damaged by 0.6 M HCl. The increases in GMBF were attenuated by 5-FU; however, the co-administration of lafutidine significantly restored the response. In addition, 5-FU inhibited both cell proliferation and migration in rat gastric epithelial cells (RGM1) in vitro. These results suggest that 5-FU delayed the healing of gastric lesions generated by 0.6 M HCl, probably through the inhibition of cell migration and proliferation, as well as the impairment of GMBF, and lafutidine reversed the delay in healing, mainly through the amelioration of the GMBF response mediated by capsaicin-sensitive afferent neurons.

  4. Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats.

    Science.gov (United States)

    Melo, Júnio Rios; de Araújo, Gnana Keith Marques; da Luz, Magda Maria Profeta; da Conceição, Sérgio Alexandre; Lisboa, Felipe Assis; Moraes-Santos, Tasso; Cunha-Melo, José Renan

    2006-10-01

    Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18-20 h (n=122) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg (n=10) or TX 375 microg/kg (n=32). Test groups (n=10, each) received atropine 5 mg/kg, cimetidine 10mg/kg, ranitidine 2.5mg/kg, ranitidine 5mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 microg/kg 10 min before the TX was injected. After 1h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML (p<0.05). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication.

  5. Effect of disodium cromoglycate (DSCG) and antihistamines on postirradiation cerebral blood flow and plasma levels of histamine and neurotensin

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Pautler, E.L.; Carraway, R.E.; Cochrane, D.E.; Hampton, J.D.

    1988-02-01

    In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and visual cortical blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100 Gy, whole-body, gamma irradiation. Systemic blood pressures were monitored simultaneously. Systemic arterial plasma histamine and neurotensin levels were determined preirradiation and postirradiation. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 23% of the preirradiation level within 10 min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10 min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The cortical blood flow for the same animals showed a steady decrease to 29% of the preirradiation levels by 60 min postirradiation. Animals given the mast cell stabilizer disodium cromoglycate and the antihistamines mepyramine and cimetidine before irradiation did not exhibit an abrupt decline in blood pressure but displayed a gradual decrease to a level 33% below preirradiation levels by 60 min postirradiation. Also, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. The plasma neurotensin levels in the irradiated animals, treated and untreated, indicated a nonsignificant postirradiation increase above control levels. However, the postirradiation plasma histamine levels in both irradiated groups showed an increase of approximately 1600% above the preirradiation levels and the postirradiation control levels.

  6. Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum.

    Science.gov (United States)

    Zira, Athina; Mikros, Emmanuel; Giannioti, Konstantina; Galanopoulou, Panagiota; Papalois, Apostolos; Liapi, Charis; Theocharis, Stamatios

    2009-07-01

    The metabonomic approach has been widely used in toxicology to investigate mechanisms of toxicity. In the present study alterations in the metabolic profiles, monitored by (1)H-NMR spectroscopy, on serum samples in acetaminophen (APAP)-induced liver injury in rabbits were examined. Furthermore, the effect of the established antidote N-acetylcysteine (NAC) and the proposed antidotes silybinin (SIL), cimetidine (CIM) and SIL/CIM was also investigated. A single dose of APAP (2 g kg(-1) b.w., i.g.) was administered to rabbits and APAP combined with the antidotes SIL, CIM and NAC. Animals were sacrificed at 24 h post-APAP treatment. Healthy untreated animals served as controls. (1)H-NMR spectra of serum samples were acquired and underwent principal component analysis (PCA). Acute liver injury was verified by histopathological examination and the alterations of serum biochemical enzymes AST and ALT. (1)H-NMR spectroscopy revealed variations in the serum metabolic profile of APAP-intoxicated rabbits compared with controls. Co-administration of APAP with NAC, CIM and SIL + CIM seems to ameliorate the metabolic profile of animals compared with simply APAP-treated ones. In this study, the model of APAPinduced liver injury was successfully described using the (1)H-NMR based metabonomic approach in serum. Furthermore, the use of antidotes that reduced the toxic insult was also recorded using this technique. The combination of NMR spectroscopy and PCA is a rapid methodology, capable of detecting alterations in the metabolic profile, and produces adequate models that could be used for the characterization of unknown samples, both experimental and clinical, reinforcing its future use in clinical settings.

  7. Activation of histamine H3 receptors produces presynaptic inhibition of neurally evoked cat nictitating membrane responses in vivo.

    Science.gov (United States)

    Koss, M C; Hey, J A

    1992-08-01

    This study was undertaken in order to determine the potential role of prejunctional histamine H3 receptors in an in vivo adrenergic model system. Frequency-dependent nictitating membrane responses were elicited by sympathetic nerve stimulation in anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist, (R)-alpha-methylhistamine (R alpha MeHA) produced a dose-related depression of amplitude of the evoked nictitating membrane responses with a threshold of about 10 micrograms/kg and maximal effect (50% depression at the lowest frequency; 0.5 Hz) seen at 100-300 micrograms/kg. Responses obtained with low frequency stimulation were more sensitive to depression by R alpha MeHA than were responses evoked with higher frequencies of stimulation. Larger doses of R alpha MeHA given to the same animals, failed to produce additional inhibition. R alpha MeHA depressed the amplitude of nictitating membrane responses evoked by either pre- or postganglionic nerve stimulation to an equivalent degree. This depressant action of R alpha MeHA was antagonized by pretreatment with the specific histamine H3 antagonist, thioperamide (3 mg/kg), but not by combined pretreatment with histamine H1 and H2 blockers chlorpheniramine (300 micrograms/kg) and cimetidine (5 mg/kg). Intravenous administration of adrenaline (1-30 micrograms/kg) also produced graded nictitating membrane responses that were not altered by subsequent administration of R alpha MeHA. These results suggest that histamine H3 receptors are involved in the modulation of neurally evoked noradrenaline release in the cat nictitating membrane by an inhibitory presynaptic action.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Modulation of noradrenaline release in rat isolated stomach by prostanoids, but not by histaminergic mechanisms.

    Science.gov (United States)

    Racké, K; Berrino, L; Möhlig, A; Jäger, R; Griepenkerl, I; Bräutigam, M; Reimann, A

    1995-12-01

    Several gastric functions are modulated by the sympathetic nervous system, but local mechanisms involved in the control of noradrenaline release are largely unknown. Overflow of endogenous noradrenaline was studied from isolated rat stomach incubated in Ussing chambers allowing the separate determination of mucosal and serosal overflow. Spontaneous noradrenaline overflow was similar at the mucosal and serosal side, but electrical field stimulation caused a frequency-dependent increase in noradrenaline overflow selectively at the serosal side. Evoked noradrenaline overflow was blocked by tetrodotoxin, not affected by indometacin and markedly enhanced (by about 250%) by yohimbine. In the presence of indometacin and yohimbine, sulprostone (an agonist at EP1/EP3 receptors) and misoprostol (an agonist at EP2/EP3 receptors) reduced the noradrenaline overflow evoked by stimulation at 3 Hz maximally by about 80% (EC50: 6 nmol/l and 11 nmol/l, respectively). The EP1 receptor selective antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) did not antagonize the inhibition by sulprostone. Noradrenaline overflow evoked by stimulation at 1 Hz and 3 Hz was increased by scopolamine by about 50% and almost completely inhibited by oxotremorine. Neither, histamine nor the H3 receptor selective agonist (R)-alpha-methyl-histamine, nor the H1, H2 and H3 selective receptor antagonists mepyramine, cimetidine and thioperamide significantly affected noradrenaline overflow evoked by stimulation at 1 Hz or 3 Hz. In conclusion, impulse-induced noradrenaline release in the rat stomach is controlled by multiple presynaptic mechanisms involving alpha 2-adrenergic autoreceptors, EP3 prostanoid and muscarine heteroreceptors, whereas histaminergic mechanisms do not appear to be significant.

  9. Study of Total Alkaloids from Rhizoma Coptis Chinensis on Experimental Gastric Ulcers

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To study the effects of total alkaloids (TA) extracted from Rhizoma Coptis Chinensis on experimental gastric ulcer models. Methods: Four kinds of experimental ulcer models were established respectively by water-immersion stress, intragastric ethanol, acetic acid erosion, and pylorus ligation. The anti-ulcer effects of TA were evaluated, and compared with that of berberine (Ber) and cimetidine(Cim). Results: TA showed significant inhibitory effects on ulcerative formation induced by water-immersion stress, intragastric ethanol, and pylorus l igation in dose-dependent manner, and showed therapeutic effect on acetic acid erosion-inducing ulcer, in comparison with the control group. The anti-ulcer activity of Ber was less than TA containing equal content of Ber. TA significantly reduced the free acidity, total acidity and total acid output, but didn't affect the gastric juice volume, gastric pepsin activity, adherent mucus quantity of stomach wall and free mucus dissolving in gastric juice. The suppressive activities of TA on gastric acid secretion didn't occur when it was administered into dodecadactylon at a dose of 360 mg/kg wt. Moreover,when compared with Cim, the inhibitory effect of TA on gastric acid secretion isn't proportional to the inhibitory effects on the formation of the 4 kinds of experimental ulcers. Conclusion: TA is a potent candidate in therapeutic drugs for treating gastric ulcer. Its anti-ulcer effective components and mechanism is not only related to Ber and inhibition of gastric acid, but also to other ingredients of TA and mechanism so far unknown.

  10. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori.

    Science.gov (United States)

    Ziebarth, D; Spiegelhalder, B; Bartsch, H

    1997-02-01

    Micro-organisms commonly present in human saliva and three DSM strains (Helicobacter pylori, Campylobacter jejuni and Neisseria cinerea), which can be isolated from the human gastro-intestinal tract, were assayed in vitro for their capacity to catalyse N-nitrosation of a series of medicinal drugs and other compounds. Following incubation at pH 7.2 in the presence of nitrate (or nitrite) for up to 24 (48) h, the yield of N-nitroso compounds (NOC) was quantified by HPLC equipped with a post-column derivatization device, allowing the sensitive detection of acid-labile and acid-stable NOC. Eleven out of the 23 test compounds underwent bacteria-catalysed nitrosation by salivary bacteria, the yield of the respective nitrosation products varying 800-fold. 4-(Methylamino)antipyrine exhibited the highest rate of nitrosation, followed by dichlofenac > metamizole > piperazine > five other drugs, whilst L-proline and L-thioproline had the lowest nitrosation rate. Ten drugs including aminophenazone, cimetidine and nicotine, did not inhibit bacterial growth, allowing transitory nitrite to be formed, but no N-nitroso derivatives were detected. Three drugs inhibited the proliferation of bacteria and neither nitrite nor any NOC were formed. Using metamizole as an easily nitrosatable precursor, two strains, Campylobacter jejuni and Helicobacter pylori, were shown to catalyse nitrosation in the presence of nitrite at pH 7.2. As compared to Neisseria cinerea used as a nitrosation-proficient control strain, H. pylori was 30-100 times less effective, whilst C. jejuni had intermediary activity. The results of our sensitive nitrosation assay further confirm that bacteria isolated from human sources, possessing nitrate reductase and/or nitrosating enzymes such as cytochrome cd1-nitrite reductase (Calmels et al., Carcinogenesis, 17, 533-536, 1996), can contribute to intragastric nitrosamine formation in the anacidic stomach when nitrosatable precursors from exogenous and endogenous sources

  11. Comparison of the kinetic characteristics of inhibitory effects exerted by biguanides and H2-blockers on human and rat organic cation transporter-mediated transport: Insight into the development of drug candidates.

    Science.gov (United States)

    Umehara, K-I; Iwatsubo, T; Noguchi, K; Kamimura, H

    2007-06-01

    In this study, the comparison of the transport of substrates (1-methyl-4-phenylpydinium (MPP) and tetraethyl ammonium (TEA)) and the inhibition potency of the inhibitors (biguanides and H(2)-blockers) for human and rat organic cation transporters (hOCTs and rOcts), and the inhibition type of inhibitors for these transporters were investigated using HEK293 cells that stably express hOCT/rOct. The concentration-dependent uptake of [(3)H]-MPP and [(14)C]-TEA by hOCT1-3/rOct1-3 had K(m) values similar to those in the literature. It was also deduced that MPP and TEA are competitive inhibitors for hOCT1-2/rOct1-2. The K(i) values for phenformin inhibition of [(3)H]-MPP and [(14)C]-TEA uptake by hOCT1-3/rOct1-3 were lower than that for metformin. The [(3)H]-MPP uptake by hOCT1/rOct1 and hOCT3/rOct3 was inhibited by famotidine and ranitidine whereas that by hOCT2/rOct2 was not. The inhibitory potency of cimetidine for hOCT1-2 was very weak. In most cases, the differences in the V(max)/K(m) values of substrates and the K(i) values of inhibitors between hOCT and rOct were minor. The acquisition of information on OCT/Oct mediated-transport and/or inhibition such as that presented in this report is very useful for further understanding of certain aspects of uptake, distribution, and excretion for drug candidates.

  12. Intestinal Oxidative State Can Alter Nutrient and Drug Bioavailability

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    Faria Ana

    2009-01-01

    Full Text Available Organic cations (OCs are substances of endogenous (e.g., dopamine, choline or exogenous (e.g., drugs like cimetidine origin that are positively charged at physiological ph. since many of these compounds can not pass the cell membrane freely, their transport in or out of cells must be mediated by specific transport systems. Transport by organic cation transporters (OCTs can be regulated rapidly by altering their trafficking and/or affinities in response to stimuli. However, for example, a specific disease could lead to modifications in the expression of OCTs. Chronic exposure to oxidative stress has been suggested to alter regulation and functional activity of proteins through several pathways. According to results from a previous work, oxidation-reduction pathways were thought to be involved in intestinal organic cation uptake modulation. The present work was performed in order to evaluate the influence of oxidative stressors, especially glutathione, on the intestinal organic cation absorption. For this purpose, the effect of compounds with different redox potential (glutathione, an endogenous antioxidant, and procyanidins, diet antioxidants was assessed on MPP+ (1-methyl-4-phenylpyridinium iodide uptake in an enterocyte cell line (Caco-2. Caco-2 cells were subcultured with two different media conditions (physiological: 5 mM glucose, referred as control cells; and high-glucose: 25 mM glucose, referred as HG cells. In HG cells, the uptake was significantly lower than in control cells. Redox changing interventions affected Mpp+ uptake, both in control and in high-glucose Caco-2 cells. Cellular glutathione levels could have an important impact on membrane transporter activity. The results indicate that modifications in the cellular oxidative state modulate MPP+ uptake by Caco-2 cells. Such modifications may reflect in changes of nutrient and drug bioavailability.

  13. Importance of the dentist in early diagnosis of pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Thiago de Santana Santos

    2009-10-01

    Full Text Available The vulgar pemphigus is a chronic, rare, vesicle-bubble disease of autoimmune origin and with a possibility of following a dangerous clinical course when it is not diagnosed and treated in its initial stage. It usually affects people from 40 to 60 years old, being rare in children. In the majority of cases, oral manifestations are the first signs of the disease, so that dentists play an important rol in its early diagnosis. The authors present a case report of vulgar pemphigus in a 17 year-old patient, attended by the Bucco-Maxillo-Facial Surgery Service of the “Fundação de Beneficência Hospital de Cirurgia” in Aracaju-SE, Brazil. The patient was admitted with a complaint of the presence of numerous scattered painful ulcers in the mouth that had developed in approximately two months, and reported that at first, blisters that broke quickly appeared, leading to extremely painful ulcerations. Incisional biopsies were performed in the jugal mucosa and retromolar regions, and also a complete hemogram to discard the hypothesis of leukemia. In view of the clinical and histopathological findings, the final diagnosis of pemphigus vulgaris was made. Before receiving specialized treatment, the patient presented marked worsening of the clinical condition, with exacerbation of intraoral signs and symptoms and development of skin lesions around the body surface. The patient was hospitalized in the “Hospital Universitário da Universidade Federal de Sergipe” and treated with prednisone, cimetidine and nystatin, showing significant improvement of symptoms in approximately two weeks. At present, the patient is under the care of an interdisciplinary team that includes dermatologists and dentists.

  14. Crucial role of cytochrome P450 in hepatotoxicity induced by 2,3-dimethoxy-1,4-naphthoquinone in rats.

    Science.gov (United States)

    Ishihara, Yasuhiro; Ishii, Satomi; Sakai, Yufu; Yamamura, Nobue; Onishi, Yukiko; Shimamoto, Norio

    2011-03-01

    Quinone toxicity is induced by two principal mechanisms: arylation/alkylation and a redox cycle. We have previously shown that increases in intracellular levels of superoxide anion and cell death induced by 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a redox cycling quinone, are enhanced by pretreatment of rat primary hepatocytes with cytochrome P450 inhibitors. This indicates a novel interaction of quinones with cytochrome P450, and is thus worthy of further investigation using an in vivo model. The aim of this study was to examine the effects of cytochrome P450 inhibitors on DMNQ-induced hepatotoxicity in rats. When DMNQ was administered intraperitoneally, the activities of serum alanine aminotransferase and aspartate aminotransferase were found to increase in a dose-dependent manner, indicating that hepatotoxicity was induced by treatment with DMNQ. Pretreatment with the cytochrome P450 inhibitors SKF-525A (SKF), cimetidine and ketoconazole potentiated the DMNQ-induced hepatotoxicity. The blood concentration of DMNQ was not affected by administration of SKF. Pretreatment with the antioxidant α-tocopherol almost completely attenuated the hepatotoxicity induced by DMNQ and by the combination of DMNQ with SKF. Levels of reduced glutathione in the liver were decreased and levels of oxidized glutathione were increased by treatment with DMNQ. These effects were potentiated by pretreatment with SKF. DMNQ-induced lipid peroxidation in the liver was also enhanced by pretreatment with SKF. Taken together, these results indicate that DMNQ-induced hepatotoxicity is augmented by inhibition of cytochrome P450 and that this augmentation is due to the enhancement of oxidative stress.

  15. 龙血竭胶囊治疗带状疱疹后遗神经痛42例疗效观察%Clinical Observation of 42 Cases of Longxuejie Capsule in the Treatment of Postherpetic Neuralgia

    Institute of Scientific and Technical Information of China (English)

    金广连

    2016-01-01

    目的:观察龙血竭胶囊治疗带状疱疹后遗神经痛的临床疗效。方法选择2012年1月~2014年1月的82例具有典型带状疱疹后遗神经痛表现的患者随机分为两组,对照组40例服西咪替丁;治疗组42例服龙血竭胶囊,并都给予维生素B1、维生素B12。均为15d为一疗程。结果治疗组总有效率83.3豫,对照组总有效率62.5豫,两组总有效率比较,差异有显著性意义(<0.05)。结论龙血竭胶囊治疗带状疱疹后遗神经痛,疗效显著,值得临床推广作用。%Objective To observe the clinical efficacy of Longxuejie capsule in the treatment of postherpetic neuralgia. Methods Select January 2012~2014 years 1 month of 82 cases with typical postherpetic neuralgia performance patients were randomly divided into two groups, control group (n=40) service cimetidine; treatment group (n=42)service Longxuejie capsule and vitamin B1, vitamin B12. For 15 days for a course. Results The total effective rate of treatment group 83.3%, control group total effective rate was 62.5%, the total efficiency of two groups, there were significant differences ( <0.05). Conclusion Longxuejie capsule in the treatment of postherpetic neuralgia, significant effect, worthy of clinical effect.

  16. Postadulticide pulmonary hypertension of canine heartworm disease: successful treatment with oxygen and failure of antihistamines.

    Science.gov (United States)

    Rawlings, C A; Tackett, R L

    1990-10-01

    Postadulticide pulmonary hypertension mechanisms and treatment with antihistamines and supplemental oxygen were studied in eight dogs with heartworm disease. To ensure severe postadulticide thromboembolism, additional heartworms (either 20 or 40 into 4 dogs each) were transplanted into naturally infected dogs before thiacetarsamide treatment. During pentobarbital anesthesia, 2 pulmonary hemodynamic studies were conducted on each dog with a sequence of baseline, hypoxia with FlO2 = 10%, hyperoxia with FlO2 = 100%, a second baseline, treatment with either diphenhydramine (D) or cimetidine (C), and another hypoxia. All dogs were pulmonary hypertensive, with each dog having a mean pulmonary arterial pressure (PPA) greater than 20 mm of Hg. Mean PPA increased from baseline conditions (25.0 +/- 4.5 SD for D and 24.3 +/- 4.4 for C) to hypoxia (28.5 +/- 4.7 for D and 28.4 +/- 3.7 for C), and decreased during hyperoxia (16.9 +/- 3.0 for D and 17.4 +/- 3.0 for C), respectively. Neither antihistamine reduced PPA at normoxia. The degree of pulmonary hypertension when breathing room air increased even more during hypoxia, and this increase was not attenuated by either antihistamine. Histamine did not appear to mediate pulmonary hypertension during postadulticide thromboembolism, nor to modify the hypoxia-mediated pulmonary hypertension at this disease stage. Because baseline PO2 was low (66.6 +/- 11.7 mm of Hg for D and 69.4 +/- 14.2 for C) and because PPA decreased during administration of oxygen, the pulmonary hypertension was mostly hypoxia-induced. In addition to the arterial lesions, much of the pulmonary hypertensive mechanism was an active and reversible vasoconstriction in response to hypoxia caused by the secondary lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy

    Science.gov (United States)

    Fussell, A. L.; Garbacik, E. T.; Löbmann, K.; Offerhaus, H. L.; Kleinebudde, P.; Strachan, C. J.

    2014-02-01

    A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn't appear to crystallize during dissolution. We observed solid-state conversions on the compact's surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compact's surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.

  18. Microscopic colitis

    Institute of Scientific and Technical Information of China (English)

    Gianluca Ianiro; Giovanni Cammarota; Luca Valerio; Brigida Eleonora Annicchiarico; Alessandro Milani; Massimo Siciliano; Antonio Gasbarrini

    2012-01-01

    Microscopic colitis may be defined as a clinical syndrome,of unknown etiology,consisting of chronic watery diarrhea,with no alterations in the large bowel at the endoscopic and radiologic evaluation.Therefore,a definitive diagnosis is only possible by histological analysis.The epidemiological impact of this disease has become increasingly clear in the last years,with most data coming from Western countries.Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management.Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC.The main feature of LC is an increase of the density of intra-epitll lial lymphocytes in the surface epithelium.A number of pathogenetic theories have been proposed over the years,involving the role of luminal agents,autoimmunity,eosinophils,genetics (human leukocyte antigen),biliary acids,infections,alterations of pericryptal fibroblasts,and drug intake; drugs like ticlopidine,carbamazepine or ranitidine are especially associated with the development of LC,while CC is more frequently linked to cimetidine,non-steroidal antiinflammatory drugs and lansoprazole.Microscopic colitis typically presents as chronic or intermittent watery diarrhea,that may be accompanied by symptoms such as abdominal pain,weight loss and incontinence.Recent evidence has added new pharmacological options for the treatment of microscopic colitis:the role of steroidal therapy,especially oral budesonide,has gained relevance,as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine.The use of anti-tumor necrosis factor-α agents,infliximab and adalimumab,constitutes a new,interesting tool for the treatment of microscopic colitis,but larger,adequately designed studies are needed to confirm existing data.

  19. Photocatalytic applications of paper-like poly(vinylidene fluoride)–titanium dioxide hybrids fabricated using a combination of electrospinning and electrospraying

    Energy Technology Data Exchange (ETDEWEB)

    Ramasundaram, Subramaniyan; Son, Aseom; Seid, Mingizem Gashaw; Shim, Sujin; Lee, Sang Hyup; Chung, Yun Chul [Center for Water Resource Cycle Research, Korea Institute of Science and Technology, Hwarangno 14 gil,Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Lee, Changha [Urban and Environmental Engineering, and KIST-UNIST-Ulsan Center for Convergent Materials (KUUC), Ulsan National Institute of Science and Technology, Ulsan 698-805 (Korea, Republic of); Lee, Jaesang [School of Civil, Environmental, and Architectural Engineering, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul 136-701 (Korea, Republic of); Hong, Seok Won, E-mail: swhong@kist.re.kr [Center for Water Resource Cycle Research, Korea Institute of Science and Technology, Hwarangno 14 gil,Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Energy and Environmental Engineering, Korea University of Science and Technology, Hwarangno 14 gil,Seongbuk-gu, Seoul 136-791 (Korea, Republic of)

    2015-03-21

    Highlights: • A PVDF–TiO{sub 2} photocatalyst was fabricated by electrospinning and electrospraying. • The TiO{sub 2} nanoparticles mainly formed clusters on the PVDF nanofiber mat surface. • The photo-degradation of aqueous organic pollutants was efficiently achieved. • The hybrid photocatalysts were robust, reusable, and stable in aqueous solution. - Abstract: A paper-like photocatalyst was fabricated by electrospraying an N,N′-dimethylformamide (DMF) dispersion of titanium dioxide (TiO{sub 2}) nanoparticles (NPs) on a poly(vinylidene fluoride) nanofiber (PVDF NF) mat prepared by electrospinning. Morphological studies revealed that the TiO{sub 2} NPs uniformly deposited as clusters on the surface of the PVDF NF mat. The immobilized amount of TiO{sub 2} was found to be 2.08, 2.44, 3.80, and 4.73 mg per 45 cm{sup 2} of PVDF–TiO{sub 2} hybrids for the electrospraying of 10, 20, 40, and 60 ml of TiO{sub 2}–DMF, respectively. The hybrid photocatalysts were effective in degrading bisphenol A (BPA), 4-chlorophenol (4-CP), and cimetidine (CMT), which dissolved in both deionized water and secondary wastewater effluents, with activity being proportional to the quantity of TiO{sub 2} NPs immobilized. For the highest loading amount of TiO{sub 2}, BPA, 4-CP, and CMT degraded completely within 100, 100, and 40 min of UV irradiation, respectively. Stable photo-oxidation of CMT was maintained through 10 repeated cycles. During these cycles, it was confirmed that there was no loss of TiO{sub 2} NPs by inductively coupled plasma optical emission spectrometry. Our results suggest that effective and stable PVDF–TiO{sub 2} hybrid photocatalysts can be fabricated on a large scale by combining electrospinning and electrospraying techniques.

  20. Human-health pharmaceutical compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

    Science.gov (United States)

    Boyd, Robert A.; Furlong, Edward T.

    2002-01-01

    The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake Mead on the Colorado River and Las Vegas Wash, a waterway used to transport treated wastewater from the Las Vegas metropolitan area to Lake Mead. Current research indicates many of these compounds can bioaccumulate and may adversely affect aquatic organisms by disrupting physiological processes, impairing reproductive functions, increasing cancer rates, contributing to the development of antibiotic-resistant strains of bacteria, and acting in undesirable ways when mixed with other substances. These compounds may be present in effluent because a high percentage of prescription and non-prescription drugs used for human-health purposes are excreted from the body as a mixture of parent compounds and degraded metabolite compounds; also, they can be released to the environment when unused products are discarded by way of toilets, sinks, and trash in landfills. Thirteen of 33 targeted compounds were detected in at least one water sample collected between October 2000 and August 2001. All concentrations were less than or equal to 0.20 micrograms per liter. The most frequently detected compounds in samples from Las Vegas Wash were caffeine, carbamazepine (used to treat epilepsy), cotinine (a metabolite of nicotine), and dehydronifedipine (a metabolite of the antianginal Procardia). Less frequently detected compounds in samples collected from Las Vegas Wash were antibiotics (clarithromycin, erythromycin, sulfamethoxazole, and trimethoprim), acetaminophen (an analgesic and anti-inflammatory), cimetidine (used to treat ulcers), codeine (a narcotic and analgesic), diltiazem (an antihypertensive), and 1,7-dimethylxanthine (a metabolite of caffeine). Fewer compounds were detected in samples collected from Lake Mead than from Las Vegas Wash. Caffeine was detected in all samples

  1. Olfactory interference during inhibitory backward pairing in honey bees.

    Directory of Open Access Journals (Sweden)

    Matthieu Dacher

    Full Text Available BACKGROUND: Restrained worker honey bees are a valuable model for studying the behavioral and neural bases of olfactory plasticity. The proboscis extension response (PER; the proboscis is the mouthpart of honey bees is released in response to sucrose stimulation. If sucrose stimulation is preceded one or a few times by an odor (forward pairing, the bee will form a memory for this association, and subsequent presentations of the odor alone are sufficient to elicit the PER. However, backward pairing between the two stimuli (sucrose, then odor has not been studied to any great extent in bees, although the vertebrate literature indicates that it elicits a form of inhibitory plasticity. METHODOLOGY/PRINCIPAL FINDINGS: If hungry bees are fed with sucrose, they will release a long lasting PER; however, this PER can be interrupted if an odor is presented 15 seconds (but not 7 or 30 seconds after the sucrose (backward pairing. We refer to this previously unreported process as olfactory interference. Bees receiving this 15 second backward pairing show reduced performance after a subsequent single forward pairing (excitatory conditioning trial. Analysis of the results supported a relationship between olfactory interference and a form of backward pairing-induced inhibitory learning/memory. Injecting the drug cimetidine into the deutocerebrum impaired olfactory interference. CONCLUSIONS/SIGNIFICANCE: Olfactory interference depends on the associative link between odor and PER, rather than between odor and sucrose. Furthermore, pairing an odor with sucrose can lead either to association of this odor to PER or to the inhibition of PER by this odor. Olfactory interference may provide insight into processes that gate how excitatory and inhibitory memories for odor-PER associations are formed.

  2. Effects of pirarubicin, an antitumor antibiotic, on the cardiovascular system.

    Science.gov (United States)

    Hirano, S; Agata, N; Hara, Y; Iguchi, H; Shirai, M; Tone, H; Urakawa, N

    1991-01-01

    In the present study we examined the effects of pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39-3.13 mg/kg, i.v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5 x 10(-6)-1.5 x 10(-5) M, THP markedly relaxed a contraction induced by 10(-7) M norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02-0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5 x 10(-5)-1.5 x 10(-4) M), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10(-6)-5 x 10(-5) M), chlorpheniramine (3 x 10(-7)-3 x 10(-5) M), and tripelennamine (3 x 10(-7)-3 x 10(-5) M) but not by propranolol (10(-6) M), cimetidine (10(-5) M), diltiazem (10(-6) M), or ryanodine (10(-8) M). THP given i.v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.

  3. Evaluation of Gastroprotective Potential of the Ethanol Extract From Murdannia loriformis in rats

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    Phraepakaporn Kunnaja

    2015-01-01

    Full Text Available Summary. Murdannia loriformis (ML has been used in traditional medicine for the treatment of various diseases. The objective of this study was to examine gastroprotective activity of ethanol extract of ML. For the gastroprotective study, rats received ML extract (100-400 mg/kg via oral route before induction of gastric ulcer using three different inducer models; EtOH/HCl, indomethacin, and restraint water immersion stress. ML extract significantly inhibited gastric ulcer formation induced by EtOH/HCl (p<0.001, indomethacin (p<0.01 and stress (p<0.001. Like misoprostol, ML extract, increased the amount of mucus content in gastric wall mucus assay (p<0.001. Moreover, the extract was equivalent to cimetidine for reducing gastric acid secretion in pylorus ligation model (p<0.05. Therefore, all of these results indicated that ML extract possessed an effective gastroprotective effect via promoting mucus production and inhibiting gastric acid secretion.Industrial relevance. In recent years, Thai government has had a policy for medicinal plant research and development in order to support the alternative health care. M. loriformis has long been used to treat a broad spectrum of disorders. The ethanol extract of this plant has already been proved to possess anti-inflammatory, analgesic, and antipyretic activities in rats without ulcerogenic effect. This research aims to investigate the gastroprotective activity of the ethanol extract of ML. The results from this study might give useful information in supporting one of its folklore uses.Keywords. Murdannia loriformis; ethanol extract; gastroprotective activity; gastric ulcer; rat models

  4. Modulatory effects of taurine on jejunal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y. [Dalian Medical University, Dalian, Liaoning (China)

    2014-10-14

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca{sup 2+} dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  5. Anti-ulcer activity of Ipomoea batatas tubers (sweet potato

    Directory of Open Access Journals (Sweden)

    Vandana Panda

    2012-04-01

    Full Text Available Background: Peptic ulcers occur in that part of the gastrointestinal tract which is exposed to gastric acid and pepsin, i.e., the stomach and duodenum. Gastric and duodenal ulcers are common pathologies that may be induced by a variety of factors such as stress, smoking and noxious agents including non-steroidal anti-inflammatory drugs. Ipomoea batatas tubers (sweet potato contain ample amounts of antioxidants. It has been proven already by many scientific studies that antioxidants have ulcer healing properties. In reference to this, we tried assessing the ulcer healing effect of Ipomoea batatas tubers. Methods: The anti-ulcer activity of the tubers of Ipomoea batatas (sweet potato was studied in cold stress and aspirin-induced gastric ulcers in Wistar rats. Methanolic extracts of Ipomoea batatas tubers (TE at two doses, viz., 400 and 800 mg /kg were evaluated in cold stress and aspirin-induced gastric ulcer models using cimetidine and omeprazole respectively as standards. The standard drugs and the test drugs were administered orally for 7 days in the cold stressmodel and for 1 day in the aspirin-induced gastric ulcer model. Gastroprotective potential, status of the antioxidant enzymes {superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and glutathione reductase(GR} along with GSH, and lipid peroxidation were studied in both models. Results: The results of the present study showed that TE possessed gastroprotective activity as evidenced by its significant inhibition of mean ulcer score and ulcer index and a marked increase in GSH, SOD, CAT, GPx, and GR levels and reduction in lipid peroxidation in a dose dependant manner.Conclusion: The present experimental findings suggest that tubers of Ipomoea batatas may be useful for treating peptic ulcers.

  6. Clinical analysis on 114 neonates with gastrointestinal hemorrhage%114例新生儿消化道出血临床分析

    Institute of Scientific and Technical Information of China (English)

    李彤; 林若玲; 李丹

    2011-01-01

    Objective: To explore the related clinical factors, prevention and treatment of neonatal gastrointestinal hemorrhage.Methods: The clinical data of 114 neonates with gastrointestinal hemorrhage were analyzed retrospectively.Results: The incidence rate of gastrointestinal hemorrhage in premature infants, , low birth weight infants and the infants with the history of perinatal asphyxia were significantly higher than that in full - term infants, normal birth weight infants and the infants without the history of perinatal asphyxia (P < 0.05).The most of neonatal gastrointestinal hemorrhage occurred within the first three days after birth, the main causes of neonatal gastrointestinal hemorrhage included neonatal hypoxic ischemic encephalopathy, hyaline membrane disease and severe pneumonia.Conclusion: Stress ulcer is a common cause of neonatal gastrointestinal hemorrhage.Good perinatal health care and active treatment of the original diseases can reduce the incidence of neonatal gastrointestinal hemorrhage obviously.Vitamin K1 combined with thrombin,cimetidine and reptilase is effective in treatment of neonatal gastrointestinal hemorrhage.%目的:探讨新生儿消化道出血的临床相关因素、预防和治疗.方法:对114例新生儿消化道出血临床资料进行回顾性分析.结果:早产儿、低出生体重儿及有围生期窒息史儿消化道出血发生率明显高于足月儿、正常出生体重儿及无围生期窒息史儿(P<0.05).大部分新生儿消化道出血在生后3天内发病,它的主要病因为新生儿缺氧缺血性脑病、肺透明膜病及重症肺炎.结论:应激性溃疡是新生儿消化道出血的最常见原因.做好围产期保健、积极治疗原发病可明显减少新生儿消化道出血的发牛率.联合使用维生素K1、凝血酶、西米替丁及立止血治疗新生儿消化道出血效果好.

  7. A mechanism for the inhibition of neural progenitor cell proliferation by cocaine.

    Directory of Open Access Journals (Sweden)

    Chun-Ting Lee

    2008-06-01

    Full Text Available BACKGROUND: Prenatal exposure of the developing brain to cocaine causes morphological and behavioral abnormalities. Recent studies indicate that cocaine-induced proliferation inhibition and/or apoptosis in neural progenitor cells may play a pivotal role in causing these abnormalities. To understand the molecular mechanism through which cocaine inhibits cell proliferation in neural progenitors, we sought to identify the molecules that are responsible for mediating the effect of cocaine on cell cycle regulation. METHODS AND FINDINGS: Microarray analysis followed by quantitative real-time reverse transcription PCR was used to screen cocaine-responsive and cell cycle-related genes in a neural progenitor cell line where cocaine exposure caused a robust anti-proliferative effect by interfering with the G1-to-S transition. Cyclin A2, among genes related to the G1-to-S cell cycle transition, was most strongly down-regulated by cocaine. Down-regulation of cyclin A was also found in cocaine-treated human primary neural and A2B5+ progenitor cells, as well as in rat fetal brains exposed to cocaine in utero. Reversing cyclin A down-regulation by gene transfer counteracted the proliferation inhibition caused by cocaine. Further, we found that cocaine-induced accumulation of reactive oxygen species, which involves N-oxidation of cocaine via cytochrome P450, promotes cyclin A down-regulation by causing an endoplasmic reticulum (ER stress response, as indicated by increased phosphorylation of eIF2alpha and expression of ATF4. In the developing rat brain, the P450 inhibitor cimetidine counteracted cocaine-induced inhibition of neural progenitor cell proliferation as well as down-regulation of cyclin A. CONCLUSIONS: Our results demonstrate that down-regulation of cyclin A underlies cocaine-induced proliferation inhibition in neural progenitors. The down-regulation of cyclin A is initiated by N-oxidative metabolism of cocaine and consequent ER stress. Inhibition of

  8. Interactions of histaminergic and serotonergic neurons in the hypothalamic regulation of prolactin and ACTH secretion.

    Science.gov (United States)

    Jørgensen, H; Knigge, U; Kjaer, A; Warberg, J

    1996-11-01

    Serotonergic and histaminergic neuronal systems are both involved in mediation of the stress-induced release of the pituitary hormones prolactin (PRL) and ACTH. We investigated the possibility of an interaction between serotonin (5-HT) and histamine (HA) in regulation of PRL and ACTH secretion in conscious male rats. Animals were pretreated systemically with antagonists to 5-HT1, 5-HT2 or 5-HT3 receptors prior to intracerebroventricular (icv) administration of HA. The 5-HT1 + 2 receptor antagonist methysergide prevented and the 5-HT2 receptor antagonist LY 53857 attenuated the HA-induced PRL release while the 5-HT3 receptor antagonist ondansetron had no effect on this response. None of the three 5-HT receptor antagonists affected the ACTH response to HA. Specific blockade of HA synthesis by alpha-fluoromethylhistidine or blockade of postsynaptic HA receptors by icv infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine inhibited the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytryptophan (5- HTP) given in combination with the 5-HT reuptake inhibitor fluoxetine (Flx). Blockade of the histaminergic system had no effect on the ACTH response to serotonergic stimulation. The H3 receptors are inhibitory HA receptors. Systemic pretreatment with the H3 receptor agonist R(alpha)methylhistamine, or the H3 receptor antagonist thioperamide had no effect on the hormone response to activation of the serotonergic system by 5-HTP plus Flx. We conclude that the serotonergic and histaminergic neuronal systems interact in their stimulation of PRL secretion, but not in their stimulation of ACTH secretion. This interaction involves serotonergic 5-HT1 and 5-HT2 receptors and histaminergic H1 and H2 receptors. Furthermore, the previously observed inhibitory effect of the H3 receptor agonist R(alpha)methylhistamine on stress-induced PRL and ACTH release seems not to be exerted by activation of presynaptic H3 receptors located on serotonergic

  9. Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes.

    Science.gov (United States)

    Chi, Yu-Chou; Lee, Shou-Lun; Lai, Ching-Long; Lee, Yung-Pin; Lee, Shiao-Pieng; Chiang, Chien-Ping; Yin, Shih-Jiun

    2016-10-25

    Alcohol dehydrogenase (ADH) is the principal enzyme responsible for metabolism of ethanol. Human ADH constitutes a complex isozyme family with striking variations in kinetic function and tissue distribution. Liver and gastrointestinal tract are the major sites for first-pass metabolism (FPM). Their relative contributions to alcohol FPM and degrees of the inhibitions by aspirin and its metabolite salicylate, acetaminophen and cimetidine remain controversial. To address this issue, mathematical organ modeling of ethanol-oxidizing activities in target tissues and that of the ethanol-drug interactions were constructed by linear combination of the corresponding numerical rate equations of tissue constituent ADH isozymes with the documented isozyme protein contents, kinetic parameters for ethanol oxidation and the drug inhibitions of ADH isozymes/allozymes that were determined in 0.1 M sodium phosphate at pH 7.5 and 25 °C containing 0.5 mM NAD(+). The organ simulations reveal that the ADH activities in mucosae of the stomach, duodenum and jejunum with ADH1C*1/*1 genotype are less than 1%, respectively, that of the ADH1B*1/*1-ADH1C*1/*1 liver at 1-200 mM ethanol, indicating that liver is major site of the FPM. The apparent hepatic KM and Vmax for ethanol oxidation are simulated to be 0.093 ± 0.019 mM and 4.0 ± 0.1 mmol/min, respectively. At 95% clearance in liver, the logarithmic average sinusoidal ethanol concentration is determined to be 0.80 mM in accordance with the flow-limited gradient perfusion model. The organ simulations indicate that higher therapeutic acetaminophen (0.5 mM) inhibits 16% of ADH1B*1/*1 hepatic ADH activity at 2-20 mM ethanol and that therapeutic salicylate (1.5 mM) inhibits 30-31% of the ADH1B*2/*2 activity, suggesting potential significant inhibitions of ethanol FPM in these allelotypes. The result provides systematic evaluations and predictions by computer simulation on potential ethanol FPM in target tissues and hepatic

  10. [Effect of intracerebroventricular injection of histamine on carotid sinus baroreceptor reflex in anesthetized rats and its mechanism].

    Science.gov (United States)

    Wang, Guo-Qing; Zhou, Xi-Ping; Huang, Wei-Qiu

    2002-12-25

    The changes in carotid sinus baroreceptor reflex (CSR) performance induced by intracerebroventricular injection (i.c.v.) of histamine (HA) were investigated. The effects of pretreatment with HA receptors antagonists into the cerebroventricle or nucleus of solitary tract (NTS) on the responses of CSR to HA were also examined. Intracarotid sinus pressure (ISP)-mean arterial pressure (MAP) relationship curve was constructed by fitting to the logistic function with five parameters in 50 Wistar rats anesthetized with pentobarbital sodium. The left and right carotid sinus regions were isolated from the systemic circulation and the ISP was altered in a stepwise manner. The main results obtained are as follows. (1) i.c.v. injection of HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and moved the middle part of ISP-Gain relationship curve downwards, and reduced the MAP range and maximum gain (G(max)), but increased the threshold pressure (TP), saturation pressure (SP) and ISP at G(max) (ISP (Gmax)). (2) The pretreatment with H(1) or H(2) receptors antagonist, chlorpheniramine (CHL, 5 microg) or cimetidine (CIM, 15 microg), could obviously diminish the above-mentioned changes in CSR performance induced by HA, but the effect of CIM was less remarkable than that of CHL. (3) The pretreatment with both CHL and CIM (5 microg and 15 microg) at the same time abolished the responses of CSR performance to HA completely. (4) After microinjection of CHL (0.5 microg) or CIM (1.5 microg) into the NTS, the responses of CSR to HA were similar to those after i.c.v. CHL or CIM, but the change in TP was significantly decreased. These findings suggest that the intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity. The response of CSR to HA might be mediated by both central H(1) and H(2) receptors, especially by H(1) receptors. The effects of the central HA on CSR might be related to a histaminergic

  11. H1 and H2 receptors in the locus ceruleus are involved in the intracerebroventricular histamine-induced carotid sinus baroreceptor reflex resetting in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-Qing WANG; Wan-Ping SUN; Yong-Jin ZHU; Rong ZOU; Xi-Ping ZHOU

    2006-01-01

    Objective To investigate the role of H1 and H2 receptors in the locus ceruleus (LC) in carotid sinus baroreceptor reflex (CSR) resetting induced by intracerebroventricular (i.c.v.) injection of histamine (HA). Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner in vivo. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine (CHL) or cimetidine (CIM) into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA (100 ng in 5 μl) significantly shifted the ISP-MAP relationship curve upwards (P < 0.05) and obviously decreased the value of the reflex parameters such as MAP range and maximum gain (P < 0.05), but increased the threshold pressure, saturation pressure and ISP at maximum gain (P < 0.05). The pretreatment with CHL (0.5 μg in 1 μl) or CIM (1.5 μg in 1 μl) into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that ofCHL (P < 0.05). Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly (P > 0.05). Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.

  12. Different effects of H1 and H2 blockers on the tone and the contractile activity of guinea pig stomach fundus.

    Science.gov (United States)

    Milenov, K; Todorov, S; Vassileva, M; Zamfirova, R; Shahbazian, A

    1995-11-01

    The action of H1 and H2 blockers on the spontaneous and evoked contractile activity of gastric fundus smooth muscles as well as the effects of H2 antagonists on the release of acetylcholine (ACh) from gastric myenteric neurons were studied. The experiments were performed on smooth muscle strips (25 x 3 mm) cut out in circular direction from guinea pig fundus region. In concentrations of 1 x 10(-7) M to 1 x 10(-4) M, the H1 blockers diphenhydramine (DPH), mepyramine (MEP) and dimethpyrindene (DMPD), but not the H2 blockers ranitidine (RAN), cimetidine (CIM) and roxatidine (ROX), increased in a concentration-dependent manner the smooth muscle tone, the maximum contractions being about 50% of the contractile effects of 1 x 10(-5) M ACH and 5 x 10(-5) M histamine (HA). The concentration-dependent contractions of the stomach fundus strips in response to electrical field stimulation (EFS) were enhanced by RAN, CIM and ROX (but not by MEP and DPH), all in concentrations of 1 x 10(-7) M to 1 x 10(-4) M. EFS increased the resting [3H]-ACh release by 67.8%, the S2/S1 ratio being 0.85 +/- 0.04. ROX in a concentration of 1 x 10(-5) M significantly increased (by 16.1%) the EFS-induced release with a S2/S1 ratio of 1.22 +/- 0.04. The ROX effect on the [3H]-ACh release was reduced or even abolished by 1 x 10(-6) M tetrodotoxin (TTX) and 1 x 10(-6) M scopolamine or in Ca(2+)-free medium, while 1 x 10(-6) M hexamethonium did not change it. It might be concluded that H2 blockers have no direct myogenic effect and do not interfere with muscarinic receptors in guinea pig stomach fundus. The H2 antagonists enhance the EFS-evoked contractions of the gastric smooth muscle most probably by increasing the release of ACH.

  13. 紫杉醇脂质体治疗肿瘤的护理体会%The nursing of paclitaxel liposome formula on tumour

    Institute of Scientific and Technical Information of China (English)

    刘玉芳; 梁英梅; 李倩; 何会娜; 王红茜; 张晓静

    2011-01-01

    Objectives To investigate the side effects and the nursing of paclitaxel liposome (lipusu) formula on advanced lung cancer and breast cancer. Methods 100 cancer patients diagnosed by pathology were given paclitaxel liposome (lipusu) in the first day of chemotherapy 135 mg/m2 plus 5% GS 500 mL intravenous drip for 3 hours. Firstly 5% GS injection 10 mL was injected into paclitaxel liposome bottle, rocked for 10~20 minutes with a special oscillator, until dissolved completely, then injected into 5 % GS 500 mL for intravenous drip. 30 minutes prior to the administration of paclitaxel liposome pre-treatment was carried out with dexamethasone 5 ~ 10 mg intravenous injection, diphenhydramine 40 mg intramuscular injection, and cimetidine 400 mg in-travenous drip. Result Based on the observation of side effects to medicines and nursing of patients, none of serious life-threatening adverse reactions arose. Conclusion Through pre-treatment, in and after treatment observation and care, the occurrence rate and extent of adverse drug reactions can be reduced.%目的 研究应用紫杉醇脂质体(力朴素)治疗晚期肺癌和乳腺癌出现的不良反应和护理.方法 100例经病理学确诊的癌症患者,采用力朴素在化疗第1天用135 mg/m2加入5% 葡萄糖(GS) 500 mL静脉滴入3 h, 先用5% G.S 10 mL注入紫杉醇脂质体瓶内,用专用振荡器振摇10~20 min, 待完全溶解后注入5% GS 500 mL静脉滴注,用药前30 min行预处理,地塞米松5~10 mg静脉入壶,苯海拉明40 mg肌肉注射,西咪替丁400 mg静脉滴注.结果通过对药物不良反应的观察和护理,患者无1例发生严重不良反应而危及生命.结论 经过用药前、用药中及用药后的观察和护理,可减轻药物不良反应的发生程度和发生机率.

  14. Endothelium-dependent relaxation of rat aorta to a histamine H3 agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na+,K+-ATPase

    Directory of Open Access Journals (Sweden)

    D. M. Djuric

    1996-01-01

    Full Text Available The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, β-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na+,K+-ATPase was evaluated in a histamine H3 receptor agonist-induced ((Rα-methylhistamine, (Rα-MeHA endothelium-dependent rat aorta relaxation assay. (Rα-MeHA (0.1 nM – 0.01 mM relaxed endothelium-dependent rat aorta, with a pD2 value of 8.22 ± 0.06, compared with a pD2 value of 7.98 ± 0.02 caused by histamine (50% and 70% relaxation, respectively. The effect of (Rα-MeHA (0.1 nM – 0.01 mM was competitively antagonized by thioperamide (1, 10 and 30 nM (pA2 = 9.21 ± 0.40; slope = 1.03 ± 0.35 but it was unaffected by pyrilamine (100 nM, cimetidine (1 μM, atropine (10 μM, propranolol (1 μM, indomethacin (10 μM or nordthydroguaiaretic acid (0.1 mM. Inhibitors of nitric oxide synthase, L-NG-monomethylarginine (L-NMMA, 10 μM and NG-nitro-L-arginine methylester (L-NOARG, 10 μM inhibited the relaxation effect of (Rα-MeHA, by approximately 52% and 70%, respectively. This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 μM. Methylene blue (10 μM and ouabain (10 μM inhibited relaxation (Rα-MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (Rα-MeHA-induced endothelium-dependent rat aorta relaxation nor are the muscarinic cholinergic and β-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na+,K+-ATPase in (Rα-MeHA-induced endothelium-dependent rat aorta relaxation.

  15. The pharmacodynamics and pharmacokinetics of multiple doses of the new H2-receptor antagonist, roxatidine acetate, in healthy men.

    Science.gov (United States)

    Lassman, H B; Ho, I; Puri, S K; Sabo, R; Scheffler, M R

    1988-01-01

    Roxatidine acetate (HOE 760, TZU 0460) is a new H2-receptor antagonist which is more potent than cimetidine and ranitidine. A randomised, double-blind, placebo-controlled study was conducted in healthy men to determine the effects of multiple oral doses of roxatidine acetate on unstimulated gastric acid secretion, and to assess the preliminary multiple-dose pharmacokinetics of its active desacetyl metabolite. The subjects were randomised to receive either roxatidine acetate 150 mg or placebo daily at 9 pm for 14 days. Gastric secretions were collected by aspiration using a nasogastric tube placed in the distal part of the stomach. Gastric fluid volume, pH, and acid concentrations were determined for 2 hours before drug administration and over 24 hours after administration on days 1, 7, 14 (the last day of dosing), and 17 (3 days after the last dose). Plasma and urine samples were collected throughout the study for the pharmacokinetic assessment. All subjects completed the study without side effects or clinically significant changes in any of the safety variables. Subjects receiving roxatidine acetate had substantial increases in gastric pH and decreases in acid secretion compared to baseline and to placebo-treated subjects. The duration of effect was approximately 12 hours. Nocturnal pH was greater than or equal to 6.0 in 80% of the roxatidine acetate-treated subjects. When sampled 3 days after the last dose (day 17) no differences in pH, acid secretion, or gastric volume were observed between the roxatidine acetate- and placebo-treated groups. The gastric pH increased with the mean plasma concentrations of the desacetyl metabolite. Mean plasma levels at steady state were attained between the 4th and 7th days after which there was no evidence of appreciable accumulation of the desacetyl metabolite. Roxatidine acetate 150 mg administered orally at 9 pm for 14 days to healthy men was safe, well tolerated, and produced clinically relevant increases in gastric pH, and

  16. Effects of steric bulk and conformational rigidity on fatty acid omega hydroxylation by a cytochrome P450 4A1 fusion protein.

    Science.gov (United States)

    Bambal, R B; Hanzlik, R P

    1996-10-01

    The action of cytochrome P450 4A1 (CYP4A1) on fatty acid substrates is characterized by a pronounced regioselectivity for omega-hydroxylation. To elucidate the chemical basis of this specificity we probed the active site of a CYP4A1 fusion protein (f4A1) with bulky and/ or rigid analogs of lauric acid, the optimum natural substrate for f4A1 and CYP4A1. f4A1 efficiently omega-hydroxylates lauric acid, epoxidizes 11-dodecenoic acid, and oxidizes 11-dodecynoic acid to 1,12-dodecanedioic acid. Medium length fatty acids having omega-terminal groups as large as t-butyl or m-tolyloxy bind tightly to f4A1 as Type I ligands and are efficiently hydroxylated on their methyl termini. omega-Phenylnonanoic acid also induces a Type I binding spectrum (Ks = 0.77 microM) but fails to undergo hydroxylation and strongly inhibits lauric acid hydroxylation by f4A1. Slightly shorter acids such as omega-phenyloctanoic acid, naproxen, and ibuprofen also strongly inhibit lauric acid hydroxylation but do not induce a Type I spectrum and do not undergo hydroxylation. Like 10-methoxydecanoic acid, the rigid and rod-like 4'-methoxy-4-biphenylcarboxylic acid is O-demethylated by f4A1, which also omega-hydroxylates m- and p-heptyloxybenzoic acids but not m- or p-amyloxyhydrocinnamic acids. The histamine antagonist cimetidine and the peroxisome proliferator perfluorodecanoic acid are both potent inhibitors of f4A1. Thus the active site of f4A1 is quite tolerant of steric bulk and rigidity around the heme region and the polar group recognition site, but perhaps less so in the midchain region. Although CYP4A enzymes are not usually regarded as "drug metabolizing P450s," the fact that commonly used therapeutic agents strongly inhibit lauric acid omega-hydroxylation by f4A1 as well as liver microsomes from clofibrate-induced rats suggests these and related agents could potentially interfere with the contribution of CYP4A enzymes to the metabolism of endogenous lipids.

  17. Resistance to Qian soup ZhuSheKa interface sp6 joint foot acupoint treatment of chronic urticaria nucleic acid bacteria polysaccharide 30 cases curative effects%抗荨湯联合足三里穴位注射卡介菌多糖核酸治疗慢性荨麻疹30例疗效观察

    Institute of Scientific and Technical Information of China (English)

    胡建农

    2011-01-01

    Objective: To observe Qian soup (bachelor since resistance points to ZhuSheKa sp6 joint foot fungus polysaccharide nucleic acid injection interface. Brand name: ji Sue, zhejiang million horses pharmaceutcal Co. Production. The curative effect of treating chronic urticaria. Methods Selected 60 cases were randomly divided into two groups: treatment group of 30 cases Qian soup to fight ZhuSheKa interface sp6 joint foot fungus polysaccharide acupuncture treatment of nucleic acid injection, four weeks. 30 cases in oral chlorobenzene that sensitivity to 4mg, three times/d, cimetidine 0. 2 g, 2 times a/d; Two groups of course are for 1 month, 2 months after the completion of course judge curative effect, and were followed up for half a year. Results The treatment group and control group 70% , 90% efficiency was statistically significant difference (P<0. OS ) -Conclusion Qian resistance points ZhuSheKa sp6 joint foot soup of nucleic acid injection dielectric bacteria polysaccharide treatment of chronic nettle has good curative effect, and clinical application.%目的:观察抗荨汤联合足三里穴位注射卡介菌多糖核酸注射液治疗慢性荨麻疹的疗效.方法:将入选的60例患者随机分为两组,各30例,治疗组予抗荨汤联合足三里穴位注射卡介菌多糖核酸注射液治疗,隔日1次;对照组予口服氯苯那敏4mg,3次/d,西咪替丁0.2g,2次/d;两组疗程均为1个月,疗程结束后2个月时判定疗效,并随访半年.结果:治疗组有效率90%,对照组70%,差异有统计学意义(P<0.05).结论:抗荨汤联合足三里穴位注射卡介菌多糖核酸注射液治疗慢性荨麻疗效好,值得临床选用.

  18. Effects of histamine and its antagonists on murine T-cells and bone marrow-derived dendritic cells.

    Science.gov (United States)

    Hu, Xiufen; Zafar, Mohammad Ishraq; Gao, Feng

    2015-01-01

    We determined the effects of histamine and its antagonists on the surface marker expression of dendritic cells (DCs) and the influence of lipopolysaccharide (LPS), histamine, and histamine receptor antagonists on DCs and T-cells. The bone marrow was extracted from the femurs and tibiae of 6- to 8-week-old female Balb/c mice and cultured in medium containing penicillin, streptomycin, L-glutamine, fetal calf serum, or granulocyte macrophage colony-stimulating factor (GM-CSF) alone or with interleukin (IL)-4. The cells received three different doses of LPS and histamine, plus three different doses of descarboethoxyloratadine (DCL). We assayed the supernatant for various cytokines. The spleen cells of DO11.10 mice were examined by flow cytometry, which included labeling and sorting CD4+ T-cells, as well as coculture of DCs and T-cells with ovalbumin (OVA)323-339 peptide. Histamine or histamine plus DCL did not affect the expression of major histocompatibility complex class II, CD11c, CD11b, CD86, and CD80. However, GM-CSF increased the expression of all markers except CD80. Histamine increased interferon-γ production in GM-CSF + IL-4-cultured cells; it also enhanced IL-10 production, but suppressed IL-12 production in LPS-stimulated DCs with no DCL. Cimetidine inhibited IL-10 production and restored IL-12 secretion in LPS-treated DCs. LPS increased IL-10 and decreased IL-12 levels. GM-CSF + IL-4-generated DCs had a stronger stimulatory effect on DO11.10 T-cell proliferation than GM-CSF-generated DCs. Inducible costimulator ligand expression was higher in GM-CSF + IL-4- than in GM-CSF-generated DC groups after 2 days of coculture, but decreased 4 days later. IL-13 production was higher in bone marrow DCs generated with GM-CSF than in those generated with GM-CSF + IL-4. OVA-pulsed DCs and OVA-plus-DCL DCs showed increased IL-12 levels. OVA plus LPS increased both IL-10 and interferon-α. Although histamine or histamine receptor-1 antagonists did not influence DC LPS

  19. Production by R-alpha-methylhistamine of a histamine H3 receptor-mediated decrease in basal vascular resistance in guinea-pigs.

    Science.gov (United States)

    McLeod, R L; Gertner, S B; Hey, J A

    1993-10-01

    1. The effect of the selective histamine H3 receptor agonist, R-alpha-methylhistamine given intravenously (10-100 micrograms kg-1) was examined on baseline total peripheral resistance (TPR), and cardiovascular haemodynamics in bilaterally vagotomized, anaesthetized guinea-pigs. 2. R-alpha-methylhistamine produced a dose-dependent hypotension and fall in TPR at 30 and 100 micrograms kg-1. A decrease in heart rate (HR) was observed at a dose of 100 micrograms kg-1. R-alpha-methylhistamine (10-100 micrograms kg-1) also produced a dose-dependent fall in rate pressure product (RPP). There was no effect on cardiac output (CO) or stroke volume (SV) at these doses. 3. Histamine H1 and H2 blockade in animals pretreated with a combination of chlorpheniramine (0.3 mg kg-1) and cimetidine (3.0 mg kg-1) did not alter the haemodynamic actions of R-alpha-methyl-histamine (100 micrograms kg-1, i.v.). Pretreatment with the selective H3 antagonist, thioperamide (1 mg kg-1), completely blocked the action of R-alpha-methylhistamine on haemodynamic parameters. 4. To study the mechanism of action of R-alpha-methylhistamine, the vasodilator hydralazine (1 mg kg-1, i.v.) was used. Hydralazine lowered BP, TRP and RPP in guinea-pigs pretreated with ipratropium (50 micrograms kg-1, i.v.). Hydralazine had no effect on HR, SV or CO. 5. R-alpha-methylhistamine (100 micrograms kg-1) did not affect the vasopressor action and increases in TPR produced by adrenaline (1 and 3 micrograms kg-1). On the other hand, the vasodilator hydralazine (1 mg kg-1, i.v.) inhibited the effects of adrenaline (3 micrograms kg-1) on TPR and RPP. The effect of both doses of adrenaline on BP were attenuated by hydralazine. Therefore, the inhibitory effects of R-alpha-methylhistamine are not mediated through a direct action on vascular smooth muscle.6. In adrenalectomized guinea-pigs, R-alpha-methylhistamine (100 microg kg-1) produced a drop in BP and HR.There was no difference between the effects of R

  20. In vivo electrophysiological investigations into the role of histamine in the dentate gyrus of the rat.

    Science.gov (United States)

    Manahan-Vaughan, D; Reymann, K G; Brown, R E

    1998-06-01

    Drugs acting at the three known classes of histamine receptors were injected intracerebroventricularly into the rat. The effects of these drugs upon synaptic potentials recorded from the dentate gyrus of the freely-moving rat were determined. Population spikes and field excitatory postsynaptic potentials were recorded from the granule cell layer of the dentate gyrus following stimulation of the perforant path. Drugs, dissolved in 0.9% NaCl were applied into the lateral cerebral ventricle in a volume of 5 microl over a period of 6 min. The histamine H1 receptor antagonist mepyramine (0.4 or 0.8 microg) had no significant effect on population spikes or field excitatory postsynaptic potentials. In contrast the H2 receptor antagonist cimetidine (3.25, 6.5 or 13 microg) showed a biphasic effect. At the lower doses (3.25 or 6.5 microg) a small (15%) depression of the field excitatory postsynaptic potentials and population spikes was observed beginning about 1 h following the infusion. At the highest dose tested (13 microg) a marked increase of the population spike was observed beginning immediately following the infusion and lasting for 90 min. Application of the H3 receptor agonist R-alpha-methylhistamine (0.2 microg) depressed the field excitatory postsynaptic potentials (15% at 4 h post-injection) and even more strongly the population spike (50%). Surprisingly, at higher doses (0.4 and 0.8 microg) no effect was seen. The H3 receptor antagonist thioperamide (0.41 and 0.82 microg) did not cause an increase in synaptic potentials but rather at the highest dose a small depression occurred at later time points (2-4 h following the infusion). At the lower dose (0.41 microg) thioperamide blocked the effect of R-alpha-methylhistamine (0.2 microg). These results show that the histaminergic system modulates information flow through the dentate gyrus in a complex manner involving both histamine H2 and H1 receptors.

  1. Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis.

    Science.gov (United States)

    Bro, S; Rasmussen, R A; Handberg, J; Olgaard, K; Feldt-Rasmussen, B

    1998-02-01

    The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium

  2. Scintigraphic assessment of Barrett's esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Kotler, J.A.; Sampliner, R.E.; Kogan, F.J.; Henry, R.E.; Mason, B.F.

    1984-01-01

    Barrett's (B) esophagus is defined by the presence of columnar epithelium above the gastroesophageal junction. Patients with 5cm histologically proven B were evaluated for mucosal labeling (ML), esophageal motility (EM), gastroesophageal reflux (GER), and gastric emptying (GE) of solids and liquids with and without iv metaclopramide (MCP). ML, after premedication with cimetidine, was evaluated 20 and 40 min after injection of Tc-99m04 with ANT and RAO views. Eight of 11 B and 0 of 2 controls (C) labeled esophageal mucosa. EM was assessed in the supine position over one min after a 15 ml swallow Tc-99mSc-H2O. The normal pattern shows sequential, aboral, discreet peaks with no retrograde movement over one min in three computer derived regions over the esophagus. Five of 16 B and 1 of 6 C demonstrated abnormal pattern. GER was assessed in the supine position by serially increasing extrinsic binder pressures from 0 to 100 Torr after ingestion of 300 ml of Tc-99mSc-orange juice (OJ). GER was present in 13 of 15 B and 0 of 11 C. Reflux ranged from 5.1% to 30% at 100 Torr. Hiatal hernia (HH) was identified in 14 of 16 B by endoscopy and in 10 of 16 by scintigraphy. GE was evaluated after a liquid meal of 300 ml Tc-99mSc-OJ and a solid meal of Tc-99mSc-egg salad sandwich. The supine subject was imaged anteriorly for 30 min (liquid) or 60 min (solid). GE was assessed an additional 10 min after MCP. Clearance time (50%) for solid Ge was calculated from extrapolated linear fits of decay corrected data. There was no significant difference in liquid or solid GE between B and C. The authors conclude the following: 1) ML detects B with lower sensitivity than previously reported; 2) EM disorders are frequently found in B; 3) GER is frequently identified in B; 4) HH can be identified by nuclear technique; and 5) B shows normal GE and responds to MCP.

  3. Evaluation and management of patients with recurrent peptic ulcer disease after acid-reducing operations: a systematic review.

    Science.gov (United States)

    Turnage, Richard H; Sarosi, George; Cryer, Byron; Spechler, Stuart; Peterson, Walter; Feldman, Mark

    2003-01-01

    This systematic review examines the evidence for commonly employed strategies of managing patients with recurrent ulcer disease after acid-reducing operations. Particular attention is given to recent evidence relating Helicobacter pylori (H. pylori ) and nonsteroidal anti-inflammatory drugs (NSAIDs) to ulcer recurrence after operative therapy. MEDLINE word searches of the literature from 1966 to 2001 identified 895 articles that cross-reference the terms "peptic ulcer disease (PUD)," "surgery," and "recurrence." Articles were selected for systematic review of evidence relating incomplete vagotomy, NSAIDs, and H. pylori to postoperative ulcer recurrence and evidence supporting common medical and surgical strategies. The relationship between incomplete vagotomy and recurrent ulcer disease is suggested by randomized controlled trials and well-designed prospective case series. The evidence that NSAID use is an important pathogenic factor in recurrent ulcer disease includes the relationship between NSAIDs and primary PUD, the occurrence of NSAID-induced ulcers in patients taking proton pump inhibitors, and case series demonstrating virulent ulcer disease in patients taking aspirin despite prior acid-reducing operations. The relationship between H. pylori infection and postoperative ulcer recurrence remains uncertain despite multiple controlled trials and well-designed case series that have documented high rates of H. pylori infection in postoperative patients. The initial management of patients with recurrent ulcer disease after acid-reducing operations consists of a protein pump inhibitor or a histamine-2 receptor antagonist and antibiotics directed at H. pylori, if present. Evidence for this regimen includes prospective randomized trials demonstrating the efficacy of cimetidine in healing ulcers after acid-reducing operations and prospective, randomized studies documenting the efficacy of histamine-2 receptor antagonists and protein pump inhibitors in the management

  4. 小剂量红霉素治疗新生儿胃食管反流病的Meta分析%Meta-analysis of Low-dose Erythromycin in the Treatment of Neonate Gastroesophageal Reflux

    Institute of Scientific and Technical Information of China (English)

    茅旭; 李奇玉; 李海朋

    2013-01-01

    Objective To evaluate the curative effect and safety of low-dose erythromycin in the neonate gastroesphageal reflux with Meta-analysis methods. Methods The documents of randomized controlled clinical trials of neonate gastroesophageal reflux disease, which had been published in domestic and foreign journals from the year 2000 to 2010, have been retrieved and screened by the study inclusion criteria. According to the Jadad evaluation questionaire,the documents’ quality had been evaluated. The meta-analysis of comparing with different control methods have been done for evaluating the therapeutic agent of low-dose erythromycin. In addition, the adverse events occurred during treatment were analyzed. Result There are 20 documents iftting inclusion criteria. 1201 cases of children(604 cases in treatment groups and 597 cases in control groups)have been included in these randomized controlled clinical trials, and adopted in three kinds of controls. The results of meta-analysis show that the OR(OR95%CI) are 0.12(0.06~0.25) compared with posture therapy;0.17(0.07~0.39) compared with supportive therapy;0.41(0.24~0.70) compared with the cimetidine treatment. These results show that low-dose erythromycin is more effective than other therapeutic agents. Furthermore, their adverse events reported in these documents are drug eruption (3.3‰), increased stool frequency (3.3‰), diarrhea (1.7‰), metabolic acidosis (3.3‰), all of them were less than 5‰. Therefore, low-dose erythromycin is safe for neonates. Conlusion Low-dose erythromycin therapy is better than postural therapy, supportive therapy and Cimetidine for neonate gastroesphageal relfux,and there are a few of adverse events.%目的评价小剂量红霉素治疗新生儿胃食管反流病的疗效及安全性。方法检索并选取2000~2010年国内外公开发表的小剂量红霉素治疗新生儿胃食管反流病的随机对照临床试验文献,筛选符合纳入标准的文献进行研究。按照Jadad

  5. Histamine H3 receptors regulate ACTH release by AtT-20 cel ls%组胺H3受体对垂体瘤AtT-20细胞分泌ACTH的调节作用

    Institute of Scientific and Technical Information of China (English)

    谢建军; 罗晓星; 赵德化

    2001-01-01

    AIM To investigate the signal transduction mechanism of histamine H3 r eceptor. METHODS The adrenocorticotropic hormone (ACTH) levels of supernatants on AtT- 20 cells from the pituitary gland tumor were measured by radioimmunoassa y at the given time after histamine agonists were administrated and the effects o f R-(α)-methylhistamine on the cells proliferation were observed. RES ULTS The H3 receptor specific agonist, R-(α)-methylhistamine incre ased the release of A CT H in time-dependent manner. It increased significantly after administrated r e agents 8 h which reached 1920 μg*L-1 compared to the control group 7 80 μg*L-1 . while the H1 receptor agonist 2-methylhistamine and the H2 agonist impro midine were significantly less potent. Furthermore, this response was blocked by thiop eramide, an H3 receptor specific antagonist, but not by the H1 and H2 anta gonist chlorpheniramine and cimetidine. R-(α)- methylhistamine had no significant i nf luence on cell proliferation within 24 h. Pretreatment with N-ethylmaleimide (N EM ) could abolish the effects of R-(α)-methylhistamine on the release of ACTH. CO NCLUSION Specific activation of H3 receptor could evoke the excitatio n-secreti on coupling process, and G protein might be involved in the signal transdu ction.%目的 观察组胺受体激动剂对AtT-20细胞分泌ACTH的影响,并探讨G蛋 白在组胺H3 受体信号转导机制中的作用. 方法 选用文献报道的高表达组胺H3受体 的垂体细胞瘤AtT-20 作为观察系统,用放免分析法测定给予组胺受体激动剂后各时间点细胞上清液中ACTH分泌量 的变化,并观察药物对细胞增殖的影响. 结果 组胺H3受体激动剂R- (α)- MeHA(0.1 μmol*L-1)作用8 h能明显促进ACTH的释放,释放量为1920 μg * L-1,与同时间对照组(780 μg*L-1)相比,明显增高(P<0.01);H 1和H2激动剂则无此作用. 且R-(α)-MeHA引起ACTH分泌 的效应能被H3受体特异

  6. 静电喷射技术制备可酸致突释给药的壳聚糖微颗粒%Preparation of chitosan microparticles with acid-induced burst release property via electrospraying

    Institute of Scientific and Technical Information of China (English)

    王小雪; 巨晓洁; 褚良银; 谢锐; 汪伟; 刘壮

    2015-01-01

    Drug-loaded chitosan microparticles with acid-induced burst release property are successfully prepared by electrospraying technology. Chitosan aqueous solution containing cimetidine is used as the spray liquid and a mixture of toluene andn-hexanol is used as the collection solution. The effects of cross-linking degree on the drug entrapment efficiency and drug loading are systematically investigated. The results show that,when the cross-linker concentration is up to 2%,the highest drug entrapment efficiency and drug loading are obtained. Due to the use of terephthalaldehyde as cross-linker via forming Schiff base bonds,the prepared chitosan microparticles display rapid acid-triggered decomposition. As a result,the drug-loaded chitosan microparticles show acid-induced burst drug release in simulated gastric acid solution with pH of 2 and 37℃ within 1min. The prepared chitosan microparticles with acid-induced burst release property are promising as gastric drug delivery systems.%利用静电喷射技术,以西咪替丁作为模型药物,混有药物的壳聚糖水溶液作为喷射液,甲苯/正己醇的混合溶液作为接收液,成功制备得到可在酸性条件下溶解并突释给药的壳聚糖载药微颗粒。系统考察了交联剂含量对壳聚糖微颗粒的药物包封率以及载药量的影响,并研究了壳聚糖微颗粒在酸性条件下的溶解特性以及在体外的突释给药效果。结果表明,当交联剂质量分数为2%时,壳聚糖微颗粒的包封率及载药量最大,分别为80%和3.8%。由于对苯二甲醛与壳聚糖交联形成的Schiff-base结构,使得壳聚糖微颗粒能够在中性条件下保持结构完整,而在酸性条件下由于 Schiff-base 结构的不稳定性致使微颗粒迅速溶解。因此,体外释药实验结果显示,在pH =2、37℃的模拟胃酸溶液中,1min内壳聚糖微颗粒即可达到最大释药效果,而在pH =6.4、37℃的水溶液中,壳聚糖微颗粒

  7. H2 receptor-mediated facilitation and H3 receptor-mediated inhibition of noradrenaline release in the guinea-pig brain.

    Science.gov (United States)

    Timm, J; Marr, I; Werthwein, S; Elz, S; Schunack, W; Schlicker, E

    1998-03-01

    The effect of histamine and related drugs on the tritium overflow evoked electrically (0.3 Hz) or by introduction of Ca2+ ions into Ca2+-free K+-rich (25 mmol/l) medium containing tetrodotoxin was studied in superfused guinea-pig brain cortex, cerebellum, hippocampus or hypothalamus slices and in mouse brain cortex slices preincubated with 3H-noradrenaline. The electrically evoked tritium overflow in guinea-pig cortex slices was inhibited by histamine; the H3 receptor antagonist clobenpropit reversed the effect of histamine to a slight facilitation. The facilitatory effect of histamine (obtained in the presence of clobenpropit) was not affected by the H1 receptor antagonist mepyramine but abolished by the H2 receptor antagonist ranitidine. In the absence of clobenpropit, ranitidine augmented the inhibitory effect of histamine. In slices superfused in the presence of ranitidine, the evoked overflow was inhibited by histamine and, more potently, by the H3 receptor agonist R-alpha-methylhistamine in a concentration-dependent manner (maximum inhibitory effect obtained for both agonists 30-35%). The concentration-response curve of histamine was shifted to the right by the H3 receptor antagonist thioperamide. R-alpha-methylhistamine inhibited the electrically evoked tritium overflow also in guinea-pig cerebellar, hippocampal and hypothalamic slices. In cortex slices superfused in the presence of clobenpropit, the H2 receptor agonists impromidine and, less potently, R-sopromidine facilitated the evoked overflow in a concentration-dependent manner. S-Sopromidine only tended to increase the evoked overflow. The effect of impromidine was counteracted by the H2 receptor antagonists ranitidine and cimetidine. The extent of the maximum facilitatory effect of impromidine (by 15-20%) was about the same when (i) the Ca2+ concentration in the medium was reduced from 1.3 to 0.98 mmol/l, (ii) the time of exposure to impromidine was reduced from 28 to 8 min or (iii) cerebellar

  8. 输液性静脉炎发生的原因及药物治疗进展%Causes of infusion phlebitis and advances in drug treatment

    Institute of Scientific and Technical Information of China (English)

    张峥; 朱全刚; 毛燕君

    2012-01-01

    Infusion phlebitis (IP) is the most common complication in the treatment of intravenous infusion, which not only increases the suffering of patients and health care costs, prolongs hospitalization, but also is a common cause of medical dispute. The occurrence of IP is related to drug factors, such as antineoplastic agents, antibiotics, sedative-hypnotics,etc, as well as infusion osmotic pressure and infusion pH value. Non-drug factors include paniculate pollution, catheter material and indwelling needle, etc. The mechanism involved may be associated with the E-selectin and intercellular adhesion molecule-1. Main emphasis should be paid to the prevention of IP. Prior intravenous administration of 200 mg cimetidine is effective in preventing vinorelbine-induced IP. Local applications of 25 % magnesium sulfate solution and anisodamine solution can also reduce the occurrence of IP. Partial hermetization, local application and physical therapy are the main treatment of IP. Drugs commonly used for the treatment of IP include nitroglycerin patch, heparin sodium ointment, multi-sulfonic acid mucopolysac-charide cream, piroxicam gel, Sanqi cream, diclofenac gel, tablets, etc.%输液性静脉炎(infusion phlebitis,IP)是静脉输液治疗中最常见的并发症,不仅增加病人的痛苦及医疗费用,延长住院时间,同时也是医患纠纷的常见原因.该病症的发生有药物因素,如抗肿瘤药、抗生素、镇静催眠药等可能诱发IP,输液渗透压以及输液pH值也与IP的发生有关.非药物因素有微粒污染、导管材质和静脉留置针等.IP的发生机制可能与E-选择素和细胞间黏附分子-1有关.IP应以预防为主,事先静脉注射西咪替丁200mg可有效预防长春瑞滨引起的IP.局部外敷25%硫酸镁溶液和山莨菪碱溶液也可减少IP的发生率.IP的治疗可采用局部封闭、局部外敷及物理疗法,常用药物包括硝酸甘油贴膜、肝素钠软膏、多磺酸黏多糖软膏、吡罗昔

  9. A role for inositol 1,4,5-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle.

    Science.gov (United States)

    Hashimoto, T; Hirata, M; Ito, Y

    1985-09-01

    cimetidine (10-5M), nor prostaglandin F2 alpha. (PGF2 alpha. 1O-7 M) showed any effect on the contents of PI-P2 or PA in the lipid fraction of the smooth muscle cells. 8 These results indicate that in muscle cells of the dog trachea, Ins-P3 may play the role ofintracellular second messenger in the initiation of ACh or 5-HT-induced contraction, but not in the case of histamine or PGF2 alpha-induced contraction.

  10. 补锌疗法佐治婴幼儿轮状病毒肠炎的临床效果观察%Clinical efficacy of zinc in the adjunctive treatment of infantile rotavirus enteritis

    Institute of Scientific and Technical Information of China (English)

    杨敏

    2013-01-01

    目的 观察补锌疗法对轮状病毒肠炎治疗的效果.方法 将2010年8月至2012年10月间收治的140例轮状病毒肠炎患儿随机分为观察组(n=76)与对照组(n=64),对照组患儿给予病毒唑、蒙脱石散、西咪替丁及补液纠酸等综合疗法,观察组在此基础上加服葡萄糖酸锌片或甘草锌颗粒,治疗72 h后观察两组临床疗效,治疗14 d后对比两组血锌含量与免疫球蛋白水平.结果 ①治疗后2周,患儿血锌与IgG、IgA、IgM含量均有所上升,观察组血锌、IgG、IgA水平明显高于对照组(P<0.05).②治疗后观察组腹泻持续天数为(6.21±1.52)d,明显少于对照组的(7.14±1.82)d (P<0.05).③治疗72h后,两组患儿临床疗效构成不同,观察组总体有效率与显效率均高于对照组(P<0.05).结论 婴幼儿轮状病毒肠炎在常规基础上佐以补锌疗法能提高患儿免疫功能,缩短病程,提高治疗有效率.%Objective To observe the clinical efficacy of zinc in the treatment of infantile rotavirus enteritis.Methods One hundred and forty patients admitted from Aug.2010 to Oct.2012 were randomly divided into the treatment group (n=76) and the control group (n=64).The control group was given ribavirin+cimetidine+smectite therapeutic regimen and symptomatic treatment,based on which the treatment group was added with zinc gluconate or zinc glycyrrhetate granules orally.After treatment for 72 h,the clinical efficacy of the two groups was compared,and serum zinc level,immunoglobulin level were checked and compared after treatment for 14 d.Results ① After treatment for 14 d,serum zinc and IgG,IgA,IgM all increased,and zinc,IgG,IgA levels of the treatment group were significantly higher than those of the control group (P<0.05).② After treatment,diarrhea duration of the treatment group [(6.21±1.5) d] was significantly lower than that of the control group [(7.14±1.8) d],P<0.05.③ After treatment for 72 h,the overall effective rare and markedly

  11. 以奥美拉唑为主的三联疗法治疗小儿消化性溃疡%Omeprazole-based Triple Therapy for Treatment of Children with Peptic Ulcer

    Institute of Scientific and Technical Information of China (English)

    詹璐

    2015-01-01

    目的:讨论研究应用以奥美拉唑为主的三联疗法治疗小儿消化性溃疡的临床疗效与意义。方法随机选取该院儿科消化性溃疡患者60例。随机分为A、B两组。 A组患者使用奥美拉唑、克拉霉素片及阿莫西林进行治疗;B组患者使用西咪替丁、克拉霉素片、阿莫西林治疗。比较两组患者治疗后总有效率以及幽门螺杆菌根除率等指标。结果A组以奥美拉唑为主使用三联疗法治疗后其幽门螺杆菌清除率86.7%显著优于其他药物组73.3%(P<0.05);A组以奥美拉唑为主三联疗法治疗后总有效率100%显著优于常规治疗B组93.3%(P<0.01)。结论应用以奥美拉唑为主的三联疗法治疗小儿消化性溃疡可有效提高幽门螺杆菌根除率。可缩短疾,病治疗时间并促进恢复,更能够显著降低疾病复发率,快速改善胃黏膜糜烂并抑制细菌闭合成。%Objective To discuss the clinical effect and significance of omeprazole-based triple therapy in children with peptic ulcer. Methods 60 children with peptic ulcer in our hospital. were randomly divided into A, B two groups. Patients in the group A was given triple therapy of omeprazole, clarithromycin tablets and amoxicillin; while those in the group B received treatment of cimetidine, clarithromycin tablets and amoxicillin. Indexes including the total efficiency and Helicobacter pylori eradication rate of the two group was compared. Results Clearance rate of 86% is significantly better than other drugs group 72% the Helicobacter pylori A group with omeprazole based triple therapy using after treatment (P<0.05);A group with omeprazole-based triple therapy after treatment, the total efficiency of 100%was significantly higher than that of conventional treatment and 96%in B group (P<0.05). Conclusion The application of omeprazole-based triple therapy for treatment of children with peptic ulcer can effectively improve the eradication of helicobacter pylori and

  12. 孟鲁司特钠治疗小儿过敏性紫癜疗效观察%Clinical Effect of Montelukast Soudium in Treating Children with Henoch-Sch(o)nlein Purpura

    Institute of Scientific and Technical Information of China (English)

    赵素香

    2013-01-01

    目的:探讨孟鲁司特钠治疗小儿过敏性紫癜(HSP)的临床疗效.方法:96例HsP患儿随机分为治疗组和对照组各48例.两组患儿均予抗组胺药物、钙剂、维生素C治疗,并停止服用可能引起过敏的食物、药物,避免接触可疑过敏物,有感染征象的给予抗生素治疗,消化道出血者卧床休息,暂禁食,给予西咪替丁及胃粘膜保护剂,腹痛、关节肿痛者加用激素,治疗组在此基础上给予孟鲁司特钠咀嚼片口服,<10岁患儿每次5 mg,≥10岁患儿每次10 mg,每晓睡前服1次,疗程1个月.观察比较两组疗效.结果:治疗组总有效率95.8%(46/48),对照组总有效率85.4% (41/48),治疗组高于对照组,但两组总有效率比较差异无统计学意义(x2=3.065,P>0.05);治疗组皮肤紫癜、消化道病变、关节肿痛、肾脏病变消失时间等方面均比对照组明显缩短,两组比较差异均有统计学意义(P<0.05).结论:孟鲁司特钠治疗小儿HSP,疗效确切,能较快缓解症状、缩短病程,未发现明显不良反应,值得临床推广使用.%Objective: To explore the clinical effect of montelukast soudium in treating children with Henoch-Schonlein Puipura ( HSP). Methods: Ninety six cases of children with HSP were randomly divided into a treatment group and a control group equally. Patients in the two groups were given anlihistamine drugs, calcium, vitamin C, and antibiotic treatment to those with signs of infection. All patients stopped taking food and medications that may cause allergy, and avoided contacting with suspicious allergens. Patients with gastrointestinal bleeding received cimetidine and mucosa protective agent, and had bed rest and fasting. Patients with abdominal pain, joint swelling and pain were given glucocorticoids. Based on the comprehensive therapy, the treatment group was given montelukast soudium chewing tablets, 5 mg/day for 0. 05). The durations of cutaneous purpura, gastrointestinal lesions, joint

  13. [Involvement of cross interaction between central cholinergic and histaminergic systems in the nucleus tractus solitarius in regulating carotid sinus baroreceptor reflex].

    Science.gov (United States)

    Hu, Li-Xun; Zhang, Guo-Xing; Zhang, Yu-Ying; Zhao, Hong-Fen; Yu, Kang-Ying; Wang, Guo-Qing

    2013-12-25

    possible modulatory mechanism of preceding microinjection with different histaminergic receptor antagonists, the selective histaminergic H1 receptor antagonist, i.e., chlorpheniramine (CHL) or the H2 receptor antagonist, i.e., cimetidine (CIM) into the NTS on the changes in function of CSR resulted from the i.c.v. cholinesterase inhibitor, physostigmine (PHY) were also examined in order to confirm and to analyze effects of cross interaction between central histaminergic and cholinergic systems on CSR. The main results obtained are as follows. (1) Standalone microinjection of different selective cholinergic receptor antagonists (PRZ, MTR or HEX) or different selective histaminergic receptor antagonists (CHL or CIM) into the NTS with each given dose had no effects on the CSR function and on the basic levels of the artery blood pressure, respectively (P > 0.05). (2) The pretreatment of PRZ or MTR into the NTS with each corresponding dose could attenuate CSR resetting resulted from i.c.v. HA in some degrees, which remarkably moved the posterior half range of ISP-MAP relationship curve downwards (P 0.05). (3) The effects of pretreatment of CHL or CIM into the NTS with each corresponding dose on CSR resetting made by i.c.v. PHY were similar to those of pretreatment of PRZ or MTR into the NTS on CSR resetting resulted from i.c.v. HA, and the decreasing effects of pretreatment with CHL into the NTS on CSR resetting induced by i.c.v. PHY were more remarkable than those with CIM (P < 0.05). These findings suggest that CSR resetting resulted from either HA or PHY into the lateral ventricle may partly involve the descending histaminergic or cholinergic pathway from the hypothalamus to NTS, which might evoke a cross activation of the cholinergic system in the NTS, via cholinergic M1 and M2 receptors mediation, especially the M2 receptors showing actions, or trigger another cross activation of the histaminergic system in the NTS, by histaminergic H1 and H2 receptors mediation

  14. 孤束核胆碱能与组胺能系统对颈动脉窦压力感受器反射调节的交互作用%Involvement of cross interaction between central cholinergic and histaminergic systems in the nucleus tractus solitarius in regulating carotid sinus baroreceptor reflex

    Institute of Scientific and Technical Information of China (English)

    胡力旬; 张国兴; 张玉英; 赵红芬; 于康英; 王国卿

    2013-01-01

    脑胆碱能系统与组胺能系统影响颈动脉窦压力感受器反射(carotid sinus baroreceptor reflex,CSR)活动,然而二者是否在孤束核(nucleus tractus solitarius,NTS)水平相互作用,跨转调节CSR,尚不清楚.本文在麻醉Sprague-Dawley (SD)大鼠孤离的一侧颈动脉窦区,通过窦内逐级加压引发CSR和动脉血压变化,经Logistic五参数曲线拟合,求得窦内压(intracarotid sinus pressure,ISP)-平均动脉压(mean arterial pressure,MAP)关系曲线及其特征参数,观察预先在NTS微量注射各选择性胆碱能受体拮抗剂[M1受体拮抗剂哌仑西平(pirenzepine,PRZ)、M2受体拮抗剂美索曲明(methoctramine,MTR)或N1受体拮抗剂六烃季胺(hexamethonium,HEX)]对侧脑室微量注射(intracerebroventricular injection,i.c.v.)组胺(histamine,HA)所致CSR变化的影响,以及预先在NTS微量注射组胺能H1受体拮抗剂氯苯吡胺(chlorpheniramine,CHL)或H2受体拮抗剂西咪替丁(cimetidine,CIM)对i.c.v.拟胆碱药毒扁豆碱(physostigmine,PHY)所致CSR变化的影响,以期解析中枢两大系统对CSR是否具有跨转调节机制.结果显示:(1)单独NTS内注射所给剂量的各选择性胆碱能受体拮抗剂或组胺能受体拮抗剂对CSR均无明显作用(P>0.05),也不引起动脉血压水平明显变动;(2)预先NTS内注射PRZ或MTR可部分翻转i.c.v.HA所致的CSR重调定,表现为ISP-MAP关系曲线在高窦压区明显左下移位(P<0.05),ISP-Gain关系曲线在中窦压区显著上移(P<0.05),反射参数平均动脉压变动范围和最大增益加大(P<0.05),最大增益时的窦内压值与饱和压减少(P<0.05),上述效应中PRZ的作用不如MTR的显著(P<0.05),但HEX对i.c.v.HA所致的CSR变化无明显作用(P>0.05);(3)预先NTS内注射CHL或CIM对i.c.v.PHY所致CSR变化的影响,类似于NTS内注射PRZ或MTR对i.c.v.HA所致CSR变化的作用,且CHL的效应强于CIM (P< 0.05).上述结果表明:侧脑室注射HA所致的CSR重调定机制

  15. Tranexamic acid for upper gastrointestinal bleeding.

    Science.gov (United States)

    Bennett, Cathy; Klingenberg, Sarah Louise; Langholz, Ebbe; Gluud, Lise Lotte

    2014-11-21

    Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. This review includes updated searches and new trials.Objectives To assess the effects of tranexamic acid versus no intervention, placebo or other antiulcer drugs for upper gastrointestinal bleeding.Search methods We updated the review by performing electronic database searches (Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, Science Citation Index) and manual searches in July 2014.Selection criteriaRandomised controlled trials, irrespective of language or publication status.Data collection and analysis We used the standard methodological procedures of the The Cochrane Collaboration. All-cause mortality, bleeding and adverse events were the primary outcome measures. We performed fixed-effect and random-effects model meta-analyses and presented results as risk ratios (RRs) with 95% confidence intervals (CIs) and used I² as a measure of between-trial heterogeneity. We analysed tranexamic acid versus placebo or no intervention and tranexamic acid versus antiulcer drugs separately. To analyse sources of heterogeneity and robustness of the overall results, we performed subgroup, sensitivity and sequential analyses.Main results We included eight randomised controlled trials on tranexamic acid for upper gastrointestinal bleeding. Additionally, we identified one large ongoing pragmatic randomised controlled trial from which data are not yet available. Control groups were randomly assigned to placebo (seven trials) or no intervention (one trial). Two trials also included a control group randomly assigned to antiulcer drugs(lansoprazole or cimetidine). The included studies were published from 1973 to 2011. The number of participants randomly assigned ranged from 47 to 216 (median 204). All trials reported mortality. In total, 42 of 851 participants randomly assigned to

  16. Anestesia para correção intra-útero de mielomeningocele: relato de caso Anestesia para corrección intra-útero de mielomeningocele: relato de caso Anesthesia for intrauterine myelomeningocele correction: case report

    Directory of Open Access Journals (Sweden)

    Angélica de Fátima de Assunção Braga

    2005-06-01

    mantenida arriba de 100 mmHg, con efedrina en bolus (5 mg, coloides y cristalóides. El líquido amniótico perdido fue sustituido por solución fisiológica entibiada. Después de la corrección del defecto fetal, se procedió al encerramiento uterino y de la membrana amniótica en dos planos, con hilo de vicryl y cola de fibrina. Se siguió la disminución gradativa de la concentración del isoflurano, y para el mantenimiento del relajamiento uterino se utilizó sulfato de magnesio (4 g/20minutos, seguido de infusión continuada (2 g/hora. Al final de la cirugía se inyectó morfina (2 mg por el catéter peridural para la analgesia postoperatoria. CONCLUSIONES: La anestesia para cirugía fetal envuelve dos seres, madre y feto, y el manoseo anestésico requiere: seguridad materno-fetal, anestesia e inmovilidad fetal, relajamiento uterino, prevención del trabajo de alumbramiento prematuro y analgesia postoperatoria.BACKGROUND AND OBJECTIVES: Fetal surgery is the treatment of choices for prenatal malformations that are not adequately corrected after birth and aims at treating or preventing the progression of the abnormalities. This report describes a case of anesthesia for intrauterine correction of a myelomeningocele. CASE REPORT: Pregnant patient, 19 years old, 23 weeks of gestational age, without previous anesthetic history, physical status ASA I, submitted to intrauterine fetal surgery under general anesthesia associated to continuous epidural continuous anesthesia. The patient was premedicated with rectal indomethacin (50 mg, intravenous metoclopramide (10 mg and cimetidine (50 mg, in addition to intravenous midazolam (2 mg. The patient received 0.25% bupivacaine with epinephrine (25 mg associated to fentanyl (100 µg epidurally, followed by cephalic catheter insertion for postoperative analgesia. The uterus was left-displace with a Crawford's wedge. Rapid sequence anesthesia was induced with fentanyl, propofol and rocuronium, and was maintained with 2.5% - 3

  17. Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus.

    Science.gov (United States)

    Plosker, Greg L; Figgitt, David P

    2004-01-01

    . Good glycaemic control has also been achieved with preprandial administration of repaglinide in flexible meal schedules. This was demonstrated in a placebo-controlled trial and in a large, prospective survey of patients receiving repaglinide in a clinical setting. The tolerability profile of repaglinide is characterised by adverse events of mild-to-moderate intensity similar to those associated with sulphonylureas. The most frequently reported adverse events with repaglinide include hypoglycaemia, upper respiratory infection, headache, other respiratory events, musculoskeletal events and gastrointestinal events. Severe episodes of hypoglycaemia are rare with repaglinide and occur approximately 2-2.5 times less frequently than with sulphonylureas. In addition, available data indicate that repaglinide may be less likely to increase bodyweight than various commonly used sulphonylurea agents. In general, repaglinide is also well tolerated when used as part of combination therapy. Repaglinide is metabolised by the cytochrome P450 (CYP) 3A4 enzyme system and therefore has the potential to interact with other CYP3A4 substrates when administered concurrently. A number of studies in healthy volunteers have shown no clinically significant pharmacokinetic drug interactions when repaglinide was administered concomitantly with digoxin, theophylline, warfarin, cimetidine, ketoconazole, rifampicin (rifampin), ethinylestradiol, simvastatin or nifedipine. However, a clinically significant increase in systemic exposure to repaglinide occurs when clarithromycin and repaglinide are administered concurrently, which may necessitate a reduction in repaglinide dosage. Moreover, a potentially hazardous interaction occurs when gemfibrozil (alone or with itraconazole) is used concomitantly with repaglinide. In view of the marked increase in systemic exposure to repaglinide, the combination of repaglinide and gemfibrozil should be avoided if possible. Pharmacoeconomic Analyses of Repaglinide