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Sample records for cimetidine

  1. Cimetidine

    Science.gov (United States)

    Cimetidine is also used sometimes to treat stress ulcers, hives and itching, and viral warts, and to prevent aspiration pneumonia during anesthesia. Talk to your doctor about the possible risks of using ...

  2. Cimetidin og kreatininclearance

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Ladefoged, S D; Feldt-Rasmussen, B F; Fogh-Andersen, N; Munck, O

    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 an...... 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....

  3. 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/i...n_vitro/cimetidine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/cimetidine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/cimetidine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates

  4. Interaction between succinylcholine and cimetidine in rats.

    Science.gov (United States)

    Mishra, Y; Ramzan, I

    1992-04-01

    The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg.kg-1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (+/- 2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (+/- 0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (+/- 4.6) micrograms.ml-1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine. PMID:1314141

  5. Effect of cimetidine on the absorption of orally administered tetracycline.

    OpenAIRE

    Fisher, P; House, F; Inns, P; Morrison, P. J.; Rogers, H. J.; Bradbrook, I D

    1980-01-01

    1 Six healthy female subjects received orally two 250 mg tetracycline tablets either with 400 mg cimetidine or placebo. In a separate experiment six healthy female volunteers received 500 mg tetracycline as a suspension on the fifth day of a 6 day regime of 400 mg cimetidine or placebo, 8 hourly and at bedtime. 500 mg tetracycline as tablets was also given with cimetidine only. 2 Following a single dose of cimetidine the mean peak tetracycline plasma concentration was significantly reduced by...

  6. Cortisol and dexamethasone elimination during treatment with cimetidine.

    OpenAIRE

    Peden, N R; Rewhorn, I; Champion, M C; Mussani, R; Ooi, T C

    1984-01-01

    In a randomised cross-over study of treatment for 7 days with cimetidine 600 mg twice daily and placebo, cimetidine had no effect on the pharmacokinetics of a single intravenous dose of dexamethasone sodium phosphate. Likewise the elimination characteristics of endogenous cortisol in the dexamethasone suppressed state were not affected by cimetidine.

  7. 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

  8. Treatment of ulcerative reflux oesophagitis with colloidal bismuth subcitrate in combination with cimetidine.

    OpenAIRE

    Borkent, M V; Beker, J A

    1988-01-01

    Twenty patients took part in a controlled double blind study comparing the efficacy of colloidal bismuth and cimetidine (800 mg at night) with cimetidine alone in the treatment of ulcerative reflux oesophagitis. Colloidal bismuth 120 mg was administered through an intraoesophageal tube four times a day. Cimetidine with colloidal bismuth gives significantly (p less than 0.001) better results than cimetidine alone. Of 10 patients treated with cimetidine and bismuth, seven had no endoscopic sign...

  9. Treatment of gastroduodenal ulcers with cimetidine in combination with low-dose propantheline

    DEFF Research Database (Denmark)

    Paerregaard, A; Hendel, L; Schultz-Larsen, K; Tobiasen, K; Mosbech, J

    1983-01-01

    painfree. We were thus not able to show any advantage in combining cimetidine treatment for ulcer healing with low-dose propantheline. In a small open trial the patients with healed ulcers received prophylactic treatment for 12 months with 1) cimetidine 800 mg daily, 2) cimetidine 400 mg at bedtime plus...

  10. 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...

  11. Cimetidine transport in isolated brush border membrane vesicles from bovine choroid plexus

    International Nuclear Information System (INIS)

    The purpose of this study was to elucidate the mechanisms involved in the transport of cimetidine across the brush border membrane of choroid plexus epithelium. Brush border membrane vesicles were prepared from bovine choroid plexus and the uptake of [3H]cimetidine was studied using the methods of rapid vacuum filtration and scintillation counting. Cimetidine accumulated in the vesicles with time reaching equilibrium within 2 hr. The amount of cimetidine taken up by the vesicles at equilibrium decreased with increasing extravesicular media osmolarity suggesting that cimetidine accumulates in an osmotically reactive intravesicular space. Binding of cimetidine to the membrane was estimated to be less than 18%. Michaelis-Menten studies demonstrated that cimetidine transport involved both a saturable and a nonsaturable component. The Vmax and Km (mean +/- S.E.) were 16.7 +/- 5.9 pmol/sec/mg protein and 58.1 +/- 3.1 microM, respectively, suggesting that cimetidine is transported across the choroid plexus brush border membrane with a lower affinity and a higher capacity than across the renal brush border membrane. The organic cation, quinidine (0.1 mM), and the amino acid, histidine (20 mM), both significantly reduced the initial, but not the equilibrium, uptake of cimetidine. However, high concentrations (5 mM) of more polar organic cations including tetraethylammonium, as well as of several organic anions including salicylate did not inhibit cimetidine transport. Studies with unlabeled cimetidine revealed a countertransport phenomenon. Attempts to drive the concentrative uptake of cimetidine with various ion gradients were unsuccessful. Of note was the fact that an outwardly directed proton gradient could significantly accelerate the uptake of cimetidine

  12. Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment.

    OpenAIRE

    Stockbrugger, R W; Cotton, P B; Eugenides, N; Bartholomew, B. A.; Hill, M.J.; Walters, C L

    1982-01-01

    A six week course of cimetidine (1 g/day) healed peptic ulcers in 20 of 23 patients (14 with duodenal ulcer, nine with gastric ulcer). Reduction of basal acid output by 73% and peak acid output by 36% led to a rise in concentrations of intragastric aerobic bacteria and nitrate-reducing bacteria. While the mean intragastric concentration of nitrate was unchanged by treatment, there were statistically significant rises in nitrite and N-nitrosamine concentrations. The conversion from nitrates to...

  13. Radionuclide imaging of Meckel's diverticulum in children: Cimetidine versus pentagastrin plus glucagon

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the effects of prior administration of cimetidine in radionuclide imaging of Meckel's diverticulum. In three groups of seven rats with artificial Meckel's diverticulum, containing ectopic gastric mucosa, the effects of pentagastrin+glucagon plus sup(99m)Tc-pertechnetate, as well as cimetidine premedication plus sup(99m)Tc-pertechnetate, and sup(99m)Tc-pertechnetate alone were compared to attain improve radionuclide imaging of Meckel's diverticulum. This experimental model suggests that the use of cimetidine seemed to have some advantages: (a) nontarget (intestinal) radioactivity was diminished by cimetidine, (b) the target to nontarget (Meckel's diverticulum to intestinal activity) ratio increased with cimetidine pretreatment. This resulted in an enhanced accumulation of pertechnetate in the ectopic gastric mucosa, and reduced excretion of the radionuclide into the lumen. Consequently, better scintiphotograms and a low rate of false results added to the validity of this method. (orig.)

  14. Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug-drug interactions.

    Science.gov (United States)

    Burt, H J; Neuhoff, S; Almond, L; Gaohua, L; Harwood, M D; Jamei, M; Rostami-Hodjegan, A; Tucker, G T; Rowland-Yeo, K

    2016-06-10

    Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney and liver sub-models for metformin (OCT and MATE substrate) and a mechanistic kidney sub-model for cimetidine. The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine. Assuming competitive inhibition and using cimetidine Ki values determined in vitro, the predicted metformin AUC ratio was 1.0 compared to an observed value of 1.46. The observed AUC ratio could only be recovered with this model when the cimetidine Ki for OCT2 was decreased 1000-fold or the Ki's for both OCT1 and OCT2 were decreased 500-fold. An alternative description of metformin renal transport by OCT1 and OCT2, incorporating electrochemical modulation of the rate of metformin uptake together with 8-18-fold decreases in cimetidine Ki's for OCTs and MATEs, allowed recovery of the extent of the observed effect of cimetidine on metformin AUC. While the final PBPK model has limitations, it demonstrates the benefit of allowing for the complexities of passive permeability combined with active cellular uptake modulated by an electrochemical gradient and active efflux. PMID:27019345

  15. Mitigation of cimetidine induced testicular toxicity in mice by Kaempferia parviflora Wall. Ex Baker rhizome extract

    Directory of Open Access Journals (Sweden)

    Ampa Luangpirom

    2011-06-01

    Full Text Available Kaempferia parviflora Wall. Ex Baker is a herb belonging to the family Zingiberaceae, its rhizomes were used as tea or wine and well known as Thai ginseng. This present study is to evaluate the mitigative effect of aqueous rhizome extract of K. parviflora (KPE against testicular toxicity induced by subcutaneous injection of cimetidine 2 mg / 100 gBW for 14 days in male mice. The extracts at oral doses of 5, 10 and 20 mg / 100 gBW were pretreated for 7 days and co-treated with cimetidine for 14 days exhibited the significant results of mitigation by elevating seminal quality, higher than the cimetidine treated group (P K. parviflora rhizome extract as mitigative agent against testicular toxicity induced by cimetidine.

  16. Effect of Immunomodulator Pyrimethamine and Cimetidine on Immunosuppression Induced by Burn Blister Fluid

    Directory of Open Access Journals (Sweden)

    Behnaz Gharegozloo

    2004-09-01

    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.

  17. Efficacy of cimetidin in the prevention of ulcer formation in the stomach during immobilization stress

    Science.gov (United States)

    Dorofeyev, G. I.; Litovskiy, I. A.; Gavrovskaya, L. K.; Ivashkin, V. T.

    1982-01-01

    The effect of stress on the formation of ulcers in the mucous membrane of the stomach, the increase in cyclic adenosine monophosphate level in the gastric tissues, and parietal cell structure alteration. Use of cimetidin prevents these effects

  18. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study.

    OpenAIRE

    Thorens, J; Froehlich, F.; Schwizer, W; Saraga, E.; Bille, J; Gyr, K; Duroux, P; Nicolet, M; Pignatelli, B.; Blum, A L; Gonvers, J J; Fried, M

    1996-01-01

    BACKGROUND: Gastric and duodenal bacterial overgrowth frequently occurs in conditions where diminished acid secretion is present. Omeprazole inhibits acid secretion more effectively than cimetidine and might therefore more frequently cause bacterial overgrowth. AIM: This controlled prospective study compared the incidence of gastric and duodenal bacterial overgrowth in patients treated with omeprazole or cimetidine. METHODS: 47 outpatients with peptic disease were randomly assigned to a four ...

  19. Effect of cimetidine and ranitidine on drug induced damage to gastric epithelial cell monolayers in vitro.

    OpenAIRE

    Romano, M.; Razandi, M; Ivey, K J

    1989-01-01

    The effect of the H2 blockers cimetidine and ranitidine on drug induced damage to gastric cell monolayers has been evaluated in conditions independent of systemic factors and their anti-acid properties. Monolayers of mucous cells from a human cell line MKN 28, obtained from a human gastric adenocarcinoma, have been studied. Cell damage has been assessed qualitatively by trypan blue dye exclusion test and quantitatively by 51Cr release assay. Cimetidine and ranitidine significantly protected c...

  20. Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth.

    OpenAIRE

    Adams, W J; Lawson, J. A.; Morris, D. L.

    1994-01-01

    The effect of histamine and cimetidine on the growth of four human colon cancer cell lines was studied. Histamine significantly stimulated the uptake of tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and 116% of controls for C170 and LIM2412, respectively. This effect was antagonised by cimetidine, but not diphenhydramine. Histamine also stimulated a dose dependent increase in cyclic adenosine monophosphate accumulation in C170 cells, antagonised by cimetidine. ...

  1. Cimetidine-associated patent ductus arteriosus is mediated via a cytochrome P450 mechanism independent of H2 receptor antagonism

    OpenAIRE

    Cotton, Robert B.; Shah, Lisa P.; Poole, Stanley D.; Ehinger, Noah J.; Brown, Naoko; Shelton, Elaine L.; Slaughter, James C.; Baldwin, H. Scott; Paria, Bibhash C.; Reese, Jeff

    2013-01-01

    Persistent patency of the ductus arteriosus (PDA) is a common problem in preterm infants. The antacid cimetidine is a potent antagonist of the H2 histamine receptor but also inhibits certain cytochrome P450 enzymes (CYPs), which may affect DA patency. We examined whether cimetidine contributes to PDA and is mediated by CYP inhibition rather than H2 blockade. Analysis of a clinical trial to prevent lung injury in premature infants revealed a significant association between cimetidine treatment...

  2. 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.

  3. Tubular transport and metabolism of cimetidine in chicken kidneys

    International Nuclear Information System (INIS)

    Renal tubular transport and renal metabolism of [14C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [14C]CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of [14C]CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of [14C]thiamine, [14C]amiloride and [14C]tetraethylammonium. During CIM infusion, two renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did ot inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion

  4. Cimetidine-associated patent ductus arteriosus is mediated via a cytochrome P450 mechanism independent of H2 receptor antagonism.

    Science.gov (United States)

    Cotton, Robert B; Shah, Lisa P; Poole, Stanley D; Ehinger, Noah J; Brown, Naoko; Shelton, Elaine L; Slaughter, James C; Baldwin, H Scott; Paria, Bibhash C; Reese, Jeff

    2013-06-01

    Persistent patency of the ductus arteriosus (PDA) is a common problem in preterm infants. The antacid cimetidine is a potent antagonist of the H2 histamine receptor but it also inhibits certain cytochrome P450 enzymes (CYPs), which may affect DA patency. We examined whether cimetidine contributes to PDA and is mediated by CYP inhibition rather than H2 blockade. Analysis of a clinical trial to prevent lung injury in premature infants revealed a significant association between cimetidine treatment and PDA. Cimetidine and ranitidine, both CYP inhibitors as well as H2 blockers, caused relaxation of the term and preterm mouse DA. CYP enzymes that are inhibited by cimetidine were expressed in DA subendothelial smooth muscle. The selective CYP3A inhibitor ketoconazole induced greater DA relaxation than cimetidine, whereas famotidine and other H2 antagonists with less CYP inhibitory effects caused less dilation. Histamine receptors were developmentally regulated and localized in DA smooth muscle. However, cimetidine caused DA relaxation in histamine-deficient mice, consistent with CYP inhibition, not H2 antagonism, as the mechanism for PDA. Oxygen-induced DA constriction was inhibited by both cimetidine and famotidine. These studies show that antacids and other compounds with CYP inhibitory properties pose a significant and previously unrecognized risk for PDA in critically ill newborn infants. PMID:23454087

  5. 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

  6. 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

    blind study with an eight week parallel group phase and a subsequent eight week crossover or continuation phase. SETTING--Outpatient clinic. SUBJECTS--60 patients (51 women) aged 18-60. MAIN OUTCOME MEASURE--Weight loss. RESULTS--After eight weeks of treatment the mean weight loss in the cimetidine...

  7. Inhibition of adhesion breast cancer cells by anticoagulant drugs and cimetidine

    Czech Academy of Sciences Publication Activity Database

    Bobek, V.; Boubelík, Michael; Kovařík, J.; Taltynov, O.

    2003-01-01

    Roč. 50, č. 2 (2003), s. 148-151. ISSN 0028-2685 Institutional research plan: CEZ:AV0Z5052915 Keywords : cimetidine * breast cancer * anticoagulants Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.782, year: 2003

  8. 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.

  9. Cimetidine treatment of protein-losing gastropathy (Ménétrier's disease). A clinical and pathophysiological study

    DEFF Research Database (Denmark)

    Krag, E; Frederiksen, H J; Olsen, N; Henriksen, Jens Henrik Sahl

    1978-01-01

    In a 47-year-old male with Ménétrier's disease (protein-losing gastropathy) the histamine-H2-receptor antagonist Cimetidine stops the protein loss and improves the clinical condition. Gastric perfusion studies on net and bidirectional ionic fluxes, protein secretion rates, and permeability, with...... simultaneous recording of the transmural electrical potential difference indicate that Cimetidine decreases a paracellular protein secretion by 'tightening' the tight junctions of the gastric epithelium....

  10. Effects of histamine and the histamine antagonists mepyramine and cimetidine on human coronary arteries in vitro.

    OpenAIRE

    Godfraind, Theophile; Miller, R C

    1983-01-01

    The effects of histamine have been studied on human isolated coronary artery preparations taken from hearts ranging in age from 9 to 73 years. Histamine in large concentrations (100 microM) contracted arteries which were without tone or spontaneous activity and sometimes induced rhythmic contractile activity. If spontaneous rhythmic activity was present it was enhanced by histamine. The contractile effects of histamine were inhibited by mepyramine but not by cimetidine. Arteries which were co...

  11. Mechanically-induced solvent-less synthesis of cobalt and nickel complexes of cimetidine

    Directory of Open Access Journals (Sweden)

    Adedibu Clement Tella

    2011-09-01

    Full Text Available Solvent-less synthesis of [Co(CIM2](SO4 and [Ni(CIM2](OAC2 by grinding of CoSO4 and Ni(CH3COO2.4H2O with cimetidine without any solvent is described. The complexes have been characterized by elemental analysis, melting point, AAS, conductivity measurements, TLC, infrared and UV-Vis spectroscopies as well as X-ray powder diffraction. Cimetidine was found to be bidentate or tridentate ligand. Cobalt ion coordinate with cimetidine through the sulphur atom in the thiol group, nitrogen atom of imidazole ring and the nitrogen atom of the secondary amine to give an octahedral geometry with ligand acting as tridentate whereas nickel ion coordinates through the sulphur atom in the thiol group, nitrogen atom of imidazole ring to give tetrahedral structure with ligand acting as bidentate. X-Ray diffraction patterns of the complex were different from that of the ligand suggesting formation of coordination compounds. The method is quick and gives a quantatively yield, without the need for solvents or external heating. Clearly, it can present higher efficiency in terms of materials, energy and time compared to classical solution phase synthesis.

  12. [Therapy of duodenal ulcer and pyloric ulcer with 800 mg cimetidine nightly].

    Science.gov (United States)

    Schütze, K; Hentschel, E; Weiss, W; Kratochvil, P; Brandstätter, G; Menthe, W; Okulski, G

    1986-04-18

    The efficacy of cimetidine 400 mg b.i.d. as compared with a single evening dose 800 mg was evaluated in a single-blind multicentre trial involving 86 patients with endoscopically proven duodenal or pyloric ulcer. After four weeks of treatment the healing rates were 64.4% (29/45) with 400 mg cimetidine twice daily and 78% (32/41) with 800 mg nocte; after eight weeks the corresponding rates were 77.7% (35/45) and 85.3% (35/41). Administration of 800 mg cimetidine every evening is, consequently, at least as effective as a twice-daily regimen. In the second half of the treatment period it was significantly more effective in reducing pain and antacid consumption. The single noctural dose takes the pathogenetic importance of overnight gastric acidity into consideration, entails a simplification of therapy and may improve patient compliance. It should, therefore, take preference over the conventional twice-daily regimen. PMID:3521103

  13. Metabolic changes in cimetidine treatment for scald injury on the peritoneo-serosal surface in far-advanced gastric cancer patients treated by intraperitoneal hyperthermic perfusion.

    Science.gov (United States)

    Fujimoto, S; Takahashi, M; Kobayashi, K; Kokubun, M; Shrestha, R D; Kiuchi, S; Konno, C

    1993-01-01

    Since pretreatment with cimetidine results in the prevention of scald injury on the peritoneo-serosal surface caused by intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, the diverse influence of IPHP on patients who were either given or not given cimetidine was studied both during and after IPHP treatment. Cimetidine 50 mg/kg was injected intravenously into 12 patients immediately prior to IPHP. There were no statistical background differences between the cimetidine and control groups (those not given cimetidine). The inflow and outflow temperatures of the hyperthermic perfusate in the control and cimetidine groups were 46.1 +/- 0.1 degree C and 44.1 +/- 0.1 degree C and 46.3 +/- 0.1 degree C and 44.2 +/- 0.04 degree C, respectively. Either the pre-IPHP hypothermia or IPHP in the control group resulted in a considerable increase in serum noradrenaline and adrenaline. The intravenous administration of cimetidine led to a stransient but moderate drop in the mean blood pressure as well as a delayed appearance of high concentrations of noradrenaline and adrenaline, induced by high concentrations of circulating histamine released with cimetidine. These results suggest that the sympathetic nervous responses were activated either by hypothermia or hyperthermia. The transient hypotension and delayed increases of both serum catecholamines were attributed to a marked increase in circulating histamine, released with the intravenous cimetidine. PMID:8324332

  14. 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 to...

  15. 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; Fogh-Andersen, N; Jordening, H; Munck, O

    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...

  16. Very-low dose antacid in treatment of duodenal ulcer. Comparison with cimetidine.

    Science.gov (United States)

    Zaterka, S; Cordeiro, F; Lyra, L G; Toletino, M M; Miszputen, S J; Jorge, J L; Silva, E P; Vieira, F E; Modena, J L; Massuda, H K

    1991-10-01

    Antacid (AA) in a very low dose (88 mmol/day) was compared to the standard 800-mg dose of cimetidine in healing duodenal ulcers. The influence of sex, age, symptom duration at entry, night pain, smoking, coffee consumption, and alcohol on ulcer healing was studied. The antacid was given in two different schedules: group I--20 ml 1 hr after breakfast and at bedtime; group II--10 ml 1 hr after breakfast and lunch and 20 ml at bedtime. Cimetidine (group III) was given in two divided doses: 400 mg 1 hr after breakfast and 400 mg at bedtime. Endoscopic control was performed after four weeks and, if necessary, after eight weeks of treatment. The healing rate after four weeks of treatment was, respectively, for groups I, II, and III, 45.5%, 55.8%, and 69.4% (group I = group II, and group III different from groups I and II). After eight weeks of treatment the healing rate was 61.5%, 80.8%, and 88.0% for groups I, II, and III, respectively (group II = group III, and group I different from groups II and III). Except for group I, smoking did not influence healing rate. Age, sex, symptoms at entry, night pain, and coffee consumption did not influence the treatment results. The authors concluded that the very low dose of magaldrate (88 mmol/day), when administered in three divided doses (10 ml after breakfast and lunch and 20 ml at bedtime) for eight weeks was as effective as 800 mg of cimetidine (400 mg twice a day) in healing duodenal ulcer. PMID:1914758

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

    OpenAIRE

    Bhargav D. Jayswal; Varun T. Yadav; Kunal N. Patel; Bhavana A. Patel; Poras A. Patel

    2012-01-01

    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 io...

  18. Synthesis of [14C]imidazole ring labeled metiamide, cimetidine and impromidine

    International Nuclear Information System (INIS)

    The radiosynthesis of imidazole ring labeled [14C]metiamide, [14C]cimetidine and [14C]impromidine are described involving the reaction of the key common intermediate 2-[[(4-methyl-1H-[2-14C]imidazol-5-yl)methyl]thio]ethanamine with methyl isothiocyanate, dimethyldithiocyanoiminocarbonate/methylamine and the novel dihydroimidazodiazepine, respectively. The ring labeled precursor was prepared in five steps from potassium [14C]cyanide in an overall radiochemical yield of 63%, and having a specific activity of 9.3 mCi/mmol. (author)

  19. Mitigation of cimetidine induced testicular toxicity in mice by Kaempferia parviflora Wall. Ex Baker rhizome extract

    OpenAIRE

    Ampa Luangpirom; Narumon Komnon

    2011-01-01

    Kaempferia parviflora Wall. Ex Baker is a herb belonging to the family Zingiberaceae, its rhizomes were used as tea or wine and well known as Thai ginseng. This present study is to evaluate the mitigative effect of aqueous rhizome extract of K. parviflora (KPE) against testicular toxicity induced by subcutaneous injection of cimetidine 2 mg / 100 gBW for 14 days in male mice. The extracts at oral doses of 5, 10 and 20 mg / 100 gBW were pretreated for 7 days and co-treated with cimetidine for...

  20. Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2016-02-01

    Full Text Available Histamine and histamine receptors (Hrhs have been identified as critical molecules during inflammation and carcinogenesis. This study was conducted to determine the effects of Hrh1-Hrh3 antagonists on inflammation-associated colorectal carcinogenesis. Male ICR mice were treated with azoxymethane (AOM, 10 mg/kg bw, i.p. and 1.5% dextran sodium sulfate (DSS, drinking water for 7 days to induce colorectal carcinogenesis. The mice were then fed diets containing test chemical (500 ppm terfenadine, 500 ppm cimetidine or 10 ppm clobenpropit for 15 weeks. At week 18, feeding with the diets containing cimetidine (Hrh2 antagonist and clobenpropit (Hrh3 antagonist/inverse agonist significantly lowered the multiplicity of colonic adenocarcinoma. Terfenadine (Hrh1 antagonist did not affect AOM-DSS-induced colorectal carcinogenesis. Adenocarcinoma cells immunohistochemically expressed Hrh1, Hrh2, Hrh3 and Hrh4 with varied intensities. Because clobenpropit is also known to be a Hrh4 receptor agonist, Hrh2, Hrh3 and Hrh4 may be involved in inflammation-related colorectal carcinogenesis. Additional data, including the mRNA expression of pro-inflammatory cytokines and inducible inflammatory enzymes in the colonic mucosa, are also presented.

  1. 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.

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

    OpenAIRE

    Ali Akbar Sial; Azhar Hussain; Arif Zubair; Huma Naseem; Nawab Sher; Farhan Ahmed Siddiqui; Mirza Tasawer Baig; Nighat Shafi

    2013-01-01

    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 fluid...

  3. Cimetidine Injection

    Science.gov (United States)

    ... is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.Your health care provider (doctor, nurse, or pharmacist) may measure the effectiveness and side effects of ...

  4. Control of radiation-induced emesis with promethazine, cimetidine, thiethylperazine, or naloxone

    International Nuclear Information System (INIS)

    Promethazine (2 mg/kg), cimetidine (4 mg;kg), thiethylperazine (0.86 mg/kg), and naloxone (0.08 mg/kg) were each evaluated for their ability to increase the threshold of radiation-induced emesis in the dog. Each dog was fed a can of dog food (ca 0.4 kg) and then injected IM with the appropriate drug 1 hour before being irradiated by a 60Co teletherapy unit. Dogs were then observed continuously for 10 hours while the number, time of onset, and duration of each emetic episode were monitored. The dose of radiation causing emesis in 50% control dogs was 170 rad. The ED50 was increased to 402 rad by promethazine, to 331 rad by cimetidiene, and to 320 rad by thiethylperazine. The ED50 for naloxone was 262.5 rad, which was not a statistically significant increase in threshold

  5. Hepatic glutathione after ethanol administration in rat: effects of cimetidine and omeprazole.

    Science.gov (United States)

    Battiston, L; Tulissi, P; Moretti, M; Mazzoran, L; Marchi, P; Pussini, E; Pozzato, G

    1995-05-01

    As a fraction of ingested ethanol (EtOH) is metabolized by gastric mucosa, different amounts of alcohol reach the liver, when the same dose is administered by oral or intravenous route. In previous experiments, we demonstrated that the decrease of hepatic reduced glutathione (GSH) is less pronounced and is followed by a quicker recovery after oral than after intraperitoneal administration of the same amount of EtOH. Therefore, the time-course of hepatic GSH concentration seems to be an indirect assay of EtOH metabolism by the liver. On the basis of these findings, any condition causing a reduced function of gastric alcohol dehydrogenase (ADH) should show up as a more severe depletion of hepatic GSH. In the same rat experimental model we determined the effects of cimetidine and omeprazole administration on gastric ADH activity and on the time-course of hepatic GSH after EtOH load. Cimetidine was shown to inhibit gastric ADH with a Ki of 0.167 +/- 0.009 mmol l-1; accordingly, the pretreatment with this drug (20 mg kg-1 b.w. per day for 1 week) determined, after oral EtOH load, a marked reduction of hepatic GSH, likewise after intraperitoneal administration. Omeprazole exerted only a marginal inhibition on gastric ADH and this drug (0.3 mg kg-1 b.w. per day for 1 week) did not modify the time-course of hepatic GSH concentrations after EtOH load. This study indicates that the inhibition of gastric ADH, when associated with EtOH intake, induces depletion of the hepatic GSH concentration and, therefore, possible liver damage. PMID:7479528

  6. Effects of dietary fruits, vegetables and a herbal tea on the in vitro transport of cimetidine: comparing the Caco-2 model with porcine jejunum tissue

    OpenAIRE

    Tarirai, Clemence; Hamman, Josias H.; Alvaro M. Viljoen

    2012-01-01

    Context: Dietary botanicals are often consumed together with allopathic medicines, which may give rise to pharmacokinetic interactions. In vitro intestinal models are useful to identify botanical-drug interactions, but they may exhibit different expressions of transporters or enzymes. Objective: To compare the effects of selected dietary botanical extracts on cimetidine transport across two in vitro intestinal models. Materials and Methods: Bi-directional transport of cimetidine was m...

  7. Selective inhibition of acetaminophen oxidation and toxicity by cimetidine and other histamine H2-receptor antagonists in vivo and in vitro in the rat and in man.

    OpenAIRE

    Mitchell, M C; Schenker, S.; Speeg, K V

    1984-01-01

    Acetaminophen-induced hepatotoxicity results from hepatic enzymatic oxidation of acetaminophen to a toxic, electrophilic intermediate. Acetaminophen is ordinarily eliminated after conjugation with glucuronic acid and sulfate to nontoxic derivatives. Cimetidine has been shown to inhibit the hepatic oxidation of a number of drugs and to protect rats from acetaminophen-induced hepatic necrosis. The aim of this study was to define the mechanism by which cimetidine reduced acetaminophen-induced he...

  8. Value of the 14C-aminophenazone respiratory test: Inhibition of the demethylation function of the liver by cimetidine

    International Nuclear Information System (INIS)

    In 15 patients with healthy liver and peptic ulcer the demethylation capacity of the liver was determined by the 14C-aminophenazone breathing test before and during treatment with the H2 antagonist cimetidine (daily dose 1.0 g) measuring the expired 14CO2 (DPM/mmol CO2/70 kg body weight) before and 1 hour after intake. Influenced by cimetidine the mean 14CO2 value of 724.7 DPM (S.D. 127.7) decreased to 404.1 DPM (S.D. 153.1). The enzyme activities (ALAT, ASAT, AP, AAP, GGT, CHE) and the concentrations of serum bilirubin and serum albumin remained unchanged and did not correlate mutually and with the 14CO2 data. The aminophenazone test proved to be suitable technique for the recognition of disturbances of the MFO system. (author)

  9. Pharmacokinetic study of praziquantel administered alone and in combination with cimetidine in a single-day therapeutic regimen.

    OpenAIRE

    H. Jung; Medina, R; Castro, N.; Corona, T; Sotelo, J.

    1997-01-01

    A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weight given at 2-h intervals, alone and with the simultaneous administration of cimetidine. Each volunteer received both regimens in a randomized crossover design. Blood samples wer...

  10. Effect of cimetidine on the amounts of histamine in the gastric mucosa of patients with gastric or duodenal ulcers.

    OpenAIRE

    Man, W K; Saunders, J H; Ingoldby, C; Spencer, J

    1981-01-01

    Measurements were made of the amounts of histamine extracted from patients with peptic ulcer disease and control subjects suffering from various gastrointestinal diseases. Patients with duodenal ulcer, gastric ulcer, or recurrent duodenal ulcer after proximal gastric vagotomy often had less gastric mucosal histamine than did normal controls. Cimetidine therapy increased the amounts of the histamine to above control levels, presumably by suppression of output. It is concluded that endogenous a...

  11. Treatment of metastatic renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine.

    Science.gov (United States)

    Kotake, T; Kinouchi, T; Saiki, S; Kuroda, M; Miki, T; Kiyohara, H; Usami, M

    1991-02-01

    Human lymphoblastoid interferon-alpha was administered intramuscularly at a dose of 5 x 10(6) units/day to 20 metastatic renal cell carcinoma patients. For potentiating the antitumor effect of interferon, cimetidine was also given to them orally at a dose of 800 mg/day. The combination therapy obtained a complete response in three patients (15%) and a partial response in three (15%). Nine patients (45%) had stable disease and five (25%), progressive disease. All six patients who responded to the combination therapy had been nephrectomized and had pulmonary metastases. Two of them also had metastases to other sites (mediastinal lymph nodes and bone). The pulmonary metastases were significantly more receptive to interferon therapy than those at the other sites. The average times before a response was obtained were 2.2 months for a minor response, 2.7 months for a partial response and 3.0 months for a complete response, and the average duration of response was 26 months. The six patients who responded survived for a significantly longer period than the 14 non-responding patients treated with interferon in combination with cimetidine. The major toxicities encountered were fever, fatigue and anorexia due to interferon, and the combination therapy was well tolerated except in three patients. The results suggest that interferon-alpha and cimetidine combination therapy may be of use in the management of patients with metastatic renal cell carcinoma. PMID:2067120

  12. 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.

  13. High Affinity Binding of 3[H]-Cimetidine to a Heme-Containing Protein in Rat Brain

    OpenAIRE

    Stadel, Rebecca; Yang, Jun; Nalwalk, Julia W.; Phillips, James G.; Hough, Lindsay B.

    2007-01-01

    [3H]-Cimetidine (3HCIM) specifically binds to an unidentified site in the rat brain. Because recently-described ligands for this site have pharmacological activity, 3HCIM binding was presently characterized. 3HCIM binding was saturable, heat-labile, and distinct from the histamine H2 receptor. To test the hypothesis that 3HCIM binds to a cytochrome P450 (CYP), the effects of non-selective and isoform-selective CYP inhibitors were studied. The heme inhibitor KCN and the non-selective CYP inhib...

  14. Changes in the response of guinea-pig airways in vivo and in vitro to cimetidine and propranolol during development.

    OpenAIRE

    Brink, C.; Douglas, J S; Duncan, P G

    1982-01-01

    1 Airway responses were examined in isolated tissues and in whole animal preparation of female albino guinea-pigs of known age. 2 Tone induced with acetylcholine in tracheal and bronchial tissues from young and old female guinea-pigs was not reduced by dimaprit or 4-methyl histamine even in tissues pretreated with mepyramine maleate. 3 Antagonism of H2-receptors with cimetidine did not affect the potency or efficacy of histamine in tracheal tissues from animals of either age group. 4 After ci...

  15. The effects of cimetidine, ranitidine and famotidine on the single-dose pharmacokinetics of naproxen and its metabolites in humans.

    Science.gov (United States)

    Vree, T B; van den Biggelaar-Martea, M; Verwey-van Wissen, C P; Vree, M L; Guelen, P J

    1993-12-01

    We studied the effects of cimetidine, ranitidine and famotidine on the kinetics of naproxen. The mean t1/2 beta of naproxen in 6 subjects was 25.7 +/- 5.4 h (range 16 to 36). Naproxen acyl glucuronide accounts for 50.9 +/- 6.9% of the dose, its isomerized isoglucuronide for 6.8 +/- 2.6%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 4.1% and its isoglucuronide for 5.5 +/- 1.5% (n = 6). Naproxen (1.3 +/- 1.1%) and O-desmethylnaproxen (0.6 +/- 0.4%) are excreted in negligible amounts. Cimetidine, ranitidine and famotidine all reduced significantly the t1/2 beta of naproxen by 50% from 25 h to 13 h and the t1/2 alpha from 4.0 h to 1.1 h. No effect of the H2 antagonists was observed on the absorption of naproxen. They also reduced the Vss of naproxen by 50%. The amount of naproxen acyl glucuronide, naproxen isoglucuronide and O-desmethylnaproxen acyl glucuronide excreted in the urine, remained unchanged, 60%, 7%, and 14% respectively. PMID:8314361

  16. Decreased duration of pentobarbital-induced narcosis in immature and adult female rats prenatally exposed to cimetidine

    International Nuclear Information System (INIS)

    The effect of prenatal cimetidine exposure (PreCM) on the duration of pentobarbital-induced narcosis (DPN) was assessed in immature (14- and 28-day old) and adult (50-60-day old) male and female rats. PreCM exposure was accomplished by treating mothers with cimetidine (CM) (20 mg/kg, ip) daily for the last two days of gestation and then (0.01% in drinking water) throughout lactation. Pregnant mothers of untreated offspring (Con) received saline. PreCM decreased DPN to 505 +/- 33 min (from 611 +/- 23 min in Con) and 393 +/- 190 min (from 686 +/- 44 min in Con) in 14-day old male and female rats, respectively. Similarly, PreCM decreased DPN to 88 +/- 15 min (from 134 +/- 3 min in Con) and 102 +/- 19 min (from 171 +/- 44 min in Con) in 28-day old male and female rats, respectively. At 21 days, PreCM did not alter DPN in either sex. At 50-60 days, however, it decreased DPN to 144 +/- 41 min (from 238 +/- 7 min in Con) in females but had no effect in males; PreCM also increased the plasma clearance of administered 14C-pentobarbital more in females than in males. The effects of PreCM, particularly the long-term effects, were most prominent in female rats and were the opposite of those of postnatal treatment with CM. The results together with those of studies with hepatic microsomes suggest that PreCM may have resulted in the induction of hepatic drug-metabolizing enzymes during the perinatal period

  17. Comparative gastroprotective effects of natural honey, nigella sativa and cimetidine against acetylsalicylic acid Induced gastric ulcer in albino rats

    International Nuclear Information System (INIS)

    Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD). The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such. No gastric lesions were seen in control group A while all the animals in group E revealed gastric ulcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively). NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines. (author)

  18. 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. PMID:23298196

  19. NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferens

    Science.gov (United States)

    2013-01-01

    Background Cimetidine, histamine H2 receptors antagonist, has caused adverse effects on the male hormones and reproductive tract due to its antiandrogenic effect. In the testes, peritubular myoid cells and muscle vascular cells death has been associated to seminiferous tubules and testicular microvascularization damages, respectively. Either androgen or histamine H2 receptors have been detected in the mucosa and smooth muscular layer of vas deferens. Thus, the effect of cimetidine on this androgen and histamine-dependent muscular duct was morphologically evaluated. Methods The animals from cimetidine group (CMTG; n=5) received intraperitoneal injections of 100 mg/kg b.w. of cimetidine for 50 days; the control group (CG) received saline solution. The distal portions of vas deferens were fixed in formaldehyde and embedded in paraffin. Masson´s trichrome-stained sections were subjected to morphological and the following morphometrical analyzes: epithelial perimeter and area of the smooth muscular layer. TUNEL (Terminal deoxynucleotidyl-transferase mediated dUTP Nick End Labeling) method, NF-kB (nuclear factor kappa B) and AR (androgen receptors) immunohistochemical detection were also carried out. The birefringent collagen of the muscular layer was quantified in picrosirius red-stained sections under polarized light. The muscular layer was also evaluated under Transmission Electron Microscopy (TEM). Results In CMTG, the mucosa of vas deferens was intensely folded; the epithelial cells showed numerous pyknotic nuclei and the epithelial perimeter and the area of the muscular layer decreased significantly. Numerous TUNEL-labeled nuclei were found either in the epithelial cells, mainly basal cells, or in the smooth muscle cells which also showed typical features of apoptosis under TEM. While an enhanced NF-kB immunoexpression was found in the cytoplasm of muscle cells, a weak AR immunolabeling was detected in these cells. In CMTG, no significant difference was observed

  20. Effects of transdermal scopolamine, alone or in combination with cimetidine, on total 24 hour gastric acid secretion in patients with duodenal ulcer.

    OpenAIRE

    Richardson, C T; M. Feldman

    1986-01-01

    Transdermal scopolamine is an antimuscarinic preparation approved for use in the United States for prevention of motion sickness. A recent study using this drug (0.5 mg/patch) suggested that enough scopolamine was absorbed through the skin to reduce basal gastric acid secretion in patients with duodenal ulcer. We have compared the effect of transdermal scopolamine and oral cimetidine (400 mg twice daily) in seven men with chronic duodenal ulcer, both alone and in combination, on acid secretio...

  1. The pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans. Effect of cimetidine.

    Science.gov (United States)

    Vree, T B; Van Den Biggelaar-Martea, M; Verwey-Van Wissen, C P; Vree, M L; Guelen, P J

    1993-05-01

    1. The pharmacokinetics of 500 mg naproxen given orally were described in 10 subjects using a direct h.p.l.c. analysis of the acyl glucuronide conjugates of naproxen and its metabolite O-desmethylnaproxen. 2. The mean elimination half-life of naproxen was 24.7 +/- 6.4 h (range 7 to 36 h). 3. Naproxen acyl glucuronide accounted for 50.8 +/- 7.3% of the dose recovered in the urine, its isomerised conjugate isoglucuronide for 6.5 +/- 2.0%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 3.4%, and its isoglucuronide for 5.5 +/- 1.3%. Naproxen and O-desmethylnaproxen were excreted in negligible amounts (< 1%). 4. Even though the urine pH of the subjects was kept acid in order to stabilize the acyl glucuronides, isomerisation took place in blood. 5. The extents of plasma binding of the unconjugated compounds were 98% (naproxen) and 100% (O-desmethylnaproxen), while naproxen acyl glucuronide binding was 92%; that of its isomer isoglucuronide 66%. O-desmethylnaproxen acyl glucuronide was 72% bound and its isoglucuronide was 42% bound. 6. Cimetidine (400 mg twice daily) decreased the t1/2 of naproxen by 39-60% (mean 47.3 +/- 11.5%; P = 0.0014) from 24.7 +/- 6.4 h to 13.2 +/- 1.0 h. It increased (10%) the urinary recovery of naproxen acyl glucuronide (P = 0.0492). The urinary recoveries of naproxen isoglucuronide and O-desmethylnaproxen acyl glucuronide remained unchanged. PMID:8512758

  2. Detection method of improvement the Cimetidine Capsule dissolution rate%改进西咪替丁胶囊溶出度的测定方法

    Institute of Scientific and Technical Information of China (English)

    秦松; 张蓓

    2016-01-01

    目的:探讨改进西咪替丁胶囊溶出度的测定方法。方法采用HPLC法测定西咪替丁胶囊的溶出度,同时将改进方法的测定结果与《中国药典》的方法进行比较。结果在0.02~0.2 mg/ml浓度范围内峰面积与浓度呈良好的线性关系(r=0.9998),回收率为99.82%,RSD为0.33%(n=6)。结论改进后的方法准确、精密、科学,且专属性强。%Objective To explore the detection method of improvement the Cimetidine Capsule dissolution rate. Meth-ods HPLC was used to determine the dissolutionrate of Cimetidine Capsule.The measurement results of improved method were compared with Chinese Pharmacopeia. Results On the concentrationscale from 0.02 to 0.2 mg/ml,the peak area had nice linear relationship with concentration,and r,recovery rate and RSD were respectively 0.9998,99.82% and 0.33% (n=6). Conclusion The improved method has advantages of more accurate,more exact,more scientific and strong specificity.

  3. Phase II study of recombinant leukocyte A interferon (IFN-rA) plus cimetidine in disseminated malignant melanoma.

    Science.gov (United States)

    Creagan, E T; Ahmann, D L; Green, S J; Long, H J; Frytak, S; Itri, L M

    1985-07-01

    Thirty-five eligible patients with disseminated malignant melanoma received intramuscular recombinant leukocyte interferon (IFN-rA), 50 X 10(6) U/m2 three times weekly (TIW) for an intended duration of 12 weeks concomitant with daily oral cimetidine, 1,200 mg/d in four divided doses. For all study participants, the median survival time was six months. Among 21 "good risk" patients (performance score [PS] 0, 1 and no prior chemotherapy), we observed seven partial regressions (33%). Six patients had stability of disease (29%), seven had immediate disease progression, and one discontinued treatment after two doses without tumor evaluation due to side effects. Times to disease progression of five patients with regressions of soft-tissue disease were 2.1, 3.3, 3.5, 3.7, and 4.3 months. Two patients had partial regressions of lung nodules for 2.0 and 3.8 months. We observed one regression among 14 "poor risk" patients (PS 2, 3, or prior chemotherapy). A 46-year-old woman with prior treatment had a partial regression of soft-tissue disease for 4.1 months. Four "poor risk" patients achieved disease stability, and nine progressed immediately. Leukopenia (WBC count less than 4,100/microL) affected 21 (66%) of 32 patients with WBC count data. The median count was 3,100/microL; range, 1,300 to 8,400/microL. We detected two cases of mild thrombocytopenia (100,000 and 120,000/microL). Other noteworthy toxicities included moderate-to-severe nausea (34%), anorexia (63%), and fatigue (80%). All patients experienced myalgias. Twenty patients had dosage decreases during the first cycle, and 14 of the 16 patients remaining on study after the first cycle required dosage reductions. The overall response rate is similar to our prior studies with IFN-rA as a single agent using TIW doses of 50 X 10(6) U/m2 and 12 X 10(6) U/m2 among 31 and 30 patients, respectively. PMID:4020408

  4. Analyze the Effect of Cetirizine and Cimetidine in Treatment of Eczema of Vulva%西替利嗪与西咪替丁治疗外阴湿疹临床效果分析

    Institute of Scientific and Technical Information of China (English)

    罗振增

    2015-01-01

    Objective To explore the effect of cetirizine and cimetidine in treating eczema of vulva.Methods62 cases of patients with eczema of vulva were chosen from March 2014 to June 2015 for treatment, and randomly divided into two groups. 38 patients in study group are given comprehensive treatment of cetirizine and cimetidine,24 patients in control group are given cetirizine treatment only, and then observe and compare treatment effects between two groups.ResultsThe total effective rate was in study group was 94.74%, which is higher than 79.17% in control group; there was a differential between two groups and such a differential has statistic value (P<0.05).Conclusion Comprehensive treatment of cetirizine and cimetidine is effective for eczema of vulva, and it is conducive to relieving patients’ symptoms and promoting treatment efficacy, thus, such a treatment method is quite worthwhile to be promoted widespread.%目的:探究外阴湿疹患者采用患西替利嗪和西咪替丁治疗的方法和效果。方法选取2014年3月~2015年6月收治的62例外阴湿疹患者进行治疗,随机分成两组,实验组38例患者选择西替利嗪和西咪替丁的综合治疗,对照组24例患者选择西替利嗪的治疗,对比两组治疗效果。结果实验组治疗的总有效率为94.74%,对照组治疗的总有效率为79.17%。实验组治疗效果更好,差异比较具有统计学意义(P<0.05)。结论外阴湿疹患者采用患西替利嗪和西咪替丁综合治疗,可及时缓解患者的身体不适,提高治疗效果。

  5. Clinical efficacy of cimetidine combined with Bifico prevention of necrotizing enterocolitis in preterm children%西咪替丁联合培菲康防治早产儿坏死性小肠结肠炎的临床疗效

    Institute of Scientific and Technical Information of China (English)

    鲁玉湘

    2015-01-01

    目的:观察西咪替丁联合培菲康(双歧杆菌三联活菌散)防治早产儿坏死性小肠结肠炎的临床疗效。方法:选取100例早产儿坏死性小肠结肠炎患儿,随机分为两组,每组50例。对照组单纯服用培菲康治疗,试验组给予西咪替丁与培菲康联合治疗,对比两组临床疗效及不良反应。结果:试验组总有效率为96%,明显优于对照组的78%,差异具有统计学意义( P﹤0.05)。两组均未见明显不良反应。结论:西咪替丁联合培菲康方案治疗早产儿坏死性小肠结肠炎具有较好的防治效果,安全性高,值得推广应用。%Objective To observe the clinical efficacy of cimetidine combined with Bifico( triple viable Bifidobacterium bulk)prevention of necrotizing enterocolitis in preterm children. Method 100 cases of patients with preterm children necrotizing enterocolitis were randomly divided into two groups,50 cases of each group. The control group received Bifico treatment,the experimental group received cimetidine and Bifico combination therapy. Treatment effects of the two groups were observed and statistically analyzed. Results Total efficiency rate of exper-imental group was 96%,which was significantly higher than 78% of the control group,there was statistical significance(P﹤0. 05). The two groups had no significant adverse reactions. Conclusion The effect of cimetidine combined with Bifico in the treatment of necrotizing enteroco-litis in preterm children is better,high safety,it is worthy of popularization and application.

  6. 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

    humans, the hemodynamic effects of atracurium and cisatracurium as well as the hemodynamic protection of diphenhydramine and cimetidine were investigated in rats. METHODS: 1 Wistar rats were anesthetized with sodium pentobarbital and prepared according to Brown et al. to evaluate different doses of atracurium and cisatracurium in the reduction of T4/T1 equal or greater than 95%. 2 Assessment of the hemodynamic changes caused by the intravenous administration of atracurium and cisatracurium by monitoring the blood pressure in the carotid artery and the electrocardiogram of rats. 3 Observation of the hemodynamic protection of prior treatment with the intravenous administration of diphenhydramine (2 mg.kg-1 and/or cimetidine (4 mg.kg-1. Statistical analysis: Student t test and ANOVA. RESULTS: Doses of 1 mg.kg-1 and 0.25 mg.kg-1 of atracurium and cisatracurium respectively did not change the mean arterial pressure (MAP. Doses of 4 mg.kg-1 of atracurium and cisatracurium decreased MAP to 62.8 ± 4.5% and 82.5 ± 2.3% respectively when compared to control levels. When the rats were pre-treated with diphenhydramine and cimetidine, diastolic pressure was reduced to 95.4% ± 2.5%. With cimetidine, diastolic pressure was reduced to 82.7 ± 8.4% when compared to the control group. The effects on systolic and diastolic blood pressure were reflected in the levels of MAP. CONCLUSIONS: The isolated administration of diphenhydramine and cimetidine did not prevent the reduction in mean arterial pressure induced by atracurium. However, the association of both drugs was able to prevent the hemodynamic effects of atracurium. The doses of cisatracurium used in this study did not cause a reduction in blood pressure significant enough to justify the use of the preventive measures used in the atracurium groups.

  7. 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…

  8. 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

    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 of...... hippuric acid in biological monitoring of persons occupationally exposed to toluene, the consumption of ethanol should be considered....

  9. Effect of histamine on the growth of human gastrointestinal tumours: reversal by cimetidine.

    OpenAIRE

    Watson, S A; Wilkinson, L J; Robertson, J F; Hardcastle, J D

    1993-01-01

    The proliferative effects of histamine were examined on the human gastric tumour cell lines; MKN45, the gastrin producing subline, MKN45G, and the colorectal lines; LoVo and C170. The proliferation of MKN45 as assessed by 75[Se] selenomethionine uptake and cell counts was increased by histamine concentrations of 10(-7) and 10(-9) M. Histamine concentrations between 10(-6) and 10(-7) M maximally stimulated MKN45G proliferation which titrated out at lower histamine concentrations. The accumulat...

  10. The pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans. Effect of cimetidine.

    OpenAIRE

    Vree, T.B.; van den Biggelaar-Martea, M; Verwey-Van Wissen, C P; Vree, M L; Guelen, P J

    1993-01-01

    1. The pharmacokinetics of 500 mg naproxen given orally were described in 10 subjects using a direct h.p.l.c. analysis of the acyl glucuronide conjugates of naproxen and its metabolite O-desmethylnaproxen. 2. The mean elimination half-life of naproxen was 24.7 +/- 6.4 h (range 7 to 36 h). 3. Naproxen acyl glucuronide accounted for 50.8 +/- 7.3% of the dose recovered in the urine, its isomerised conjugate isoglucuronide for 6.5 +/- 2.0%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 3.4%, ...

  11. Histologic evaluation of preventive measures for scald injury on the peritoneo-serosal surface due to intraoperative hyperthermic chemoperfusion for patients with gastric cancer and peritoneal metastasis.

    Science.gov (United States)

    Fujimoto, S; Takahashi, M; Kobayashi, K; Mutou, T; Toyosawa, T; Izawa, E; Numai, T; Kondoh, F; Ohkubo, H

    1998-01-01

    To histologically assess the preventive efficacy of cimetidine against scald injury on the peritoneo-serosal surface during intraperitoneal hyperthermic chemoperfusion (IHCP) for advanced gastric cancer, a randomized histologic study using cimetidine, a histamine H2-receptor antagonist, was performed for 20 patients with advanced or recurrent gastric cancer and peritoneal metastasis. Cimetidine 50 mg/kg was administered intravenously to 10 patients just prior to the IHCP (cimetidine group), and the remaining 10 patients underwent the IHCP without cimetidine (control group). The background factors and IHCP treatments of these two groups were nearly the same. Although the antitumour efficacy of the IHCP was not histologically different between the two groups, the histological analysis revealed that the peritoneo-serosal surface in the cimetidine group was protected against scald injury, compared with the control group. This finding suggests that pre-IHCP cimetidine is of great benefit for protecting the peritoneo-serosal surface from scald injury due to IHCP. PMID:9483448

  12. 甲氰咪胍加阿昔洛韦治疗水痘患者16例报告%Report on the results of treatment of 16 chickenpox patients with cimetidine and aciclovir

    Institute of Scientific and Technical Information of China (English)

    周建南; 麦世萍

    2004-01-01

    水痘是儿科、皮肤科等常见的疾病,易在群体中传播,以往采取传统方法治疗,疗效不明显,病程绵长,易出现感染等合并症以致遗留瘢痕。我们采用甲氰咪胍加阿昔洛韦软膏治疗16例患者,临床疗效明显,现报道如下。

  13. 聚肌胞、西咪替丁联合治疗小儿水痘34例疗效观察%Observation for Unite Treatment with Polyinosinic and Cimetidine for 34 Children with Chickenpox

    Institute of Scientific and Technical Information of China (English)

    郑丽英; 董彩琴

    2003-01-01

    目的:观察聚肌胞、西咪替丁联合治疗小儿水痘的疗效.方法:观察组34例每次应用聚肌胞0.07~0.1mg/kg,隔日1次肌注,西咪替丁每日15 mg/kg,分3次口服,疗程5~7 d.对照组30例应用病毒唑每日10~15 mg/kg,分2次肌注,维生素B12每次250μg,隔日1次肌注,疗程5~7 d.结果:观察组退热、皮疹隐退、疱疹结痂、痂皮脱落,所需平均天数分别为1.65,3.13,4.50,9.58.对照组退热、皮疹隐退、疱疹结痂、痂皮脱落,所需平均天数分别为4.33,4.83,6.28,12.05.两组比较,观察组疗效明显优于对照组,各项指标比较均有显著差异,均为P<0.01.结论:聚肌胞、西咪替丁联合治疗小儿水痘疗效满意,可起到减轻症状,缩短病程,预防并发症的作用;并且见效较快,无严重不良反应.

  14. Evaluation of Cytoprotection Against Ethanol-induced Injury in Gastric Mocosa Pretreated with Honey Alone, Honey in Combination with Ocimum bacilicum Oil or Honey in Combination with Cimetidine in Rats

    Directory of Open Access Journals (Sweden)

    K.A.R.Suzainur

    2005-01-01

    Full Text Available Honey alone or, honey in combination with O. bacilicum oil or with cimitidine was found to posse`s significant anti-ulcer activity against ethanol-induced ulceration in experimental animal models macroscopically and microscopically. Significant inhibition was observed against ethanol-induced ulceration. Macroscopically, oral administration of absolute ethanol (5 ml kg-1 body weight to fasted rats produced extensive hemorrhagic lesions of gastric mucosa. Pretreatment with honey alone (5 ml kg-1 body weight or honey in combination with O. bacilicum oil extracts (5 ml kg-1 body weight or honey in combination with cimitidine (5 ml kg-1 body weight orally 30 minutes before administration of absolute alcohol significantly prevent or reduced the formation of such lesion. Microscopically, pretreatment rats showed significantly marked inhibition or reduction of gastric damage and no submucosal edema or leucocytes infiltration.

  15. Treatment of acne vulgaris with anti androgens

    OpenAIRE

    Vaswani Neena; Pandhi R

    1990-01-01

    This study was conducted to compare the relative efficacy of spironolactone and cimetidine in moderately severe acne vulgaris. Fifteen women were treated with spironolactone (100 mg daily) given cyclically, while 14 women were given cimetidine (1400 mg daily) cyclically. The response was evaluated at 12 weeks. Spironolactone produced a good to excellent response in 11 (73. 3%) acne patients while with cimetidine 6 (42.8%) patients showed a good to excellent response. The mean re...

  16. Flecainide

    Science.gov (United States)

    ... Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); carbamazepine (Carbatrol, Tegretol); cimetidine (Tagamet); clozapine (Clozaril); dichlorphenamide; digoxin (Lanoxin); diltiazem (Cardizem, Tiazac); disopyramide ( ...

  17. Oral ulceration and bleeding associated with pancreatic enzyme supplementation in a German shepherd with pancreatic acinar atrophy

    OpenAIRE

    Snead, Elisabeth

    2006-01-01

    A 20-month-old German shepherd with primary pancreatic acinar atrophy and exocrine pancreatic insufficiency that was treated with pancreatic enzyme supplementation, vitamin B12, and cimetidine developed oral bleeding. Following discontinuation of the cimetidine, increased preincubation of the enzymes with the food, and symptomatic therapy for the ulceration, the dog’s condition improved.

  18. Treatment of acne vulgaris with anti androgens

    Directory of Open Access Journals (Sweden)

    Vaswani Neena

    1990-01-01

    Full Text Available This study was conducted to compare the relative efficacy of spironolactone and cimetidine in moderately severe acne vulgaris. Fifteen women were treated with spironolactone (100 mg daily given cyclically, while 14 women were given cimetidine (1400 mg daily cyclically. The response was evaluated at 12 weeks. Spironolactone produced a good to excellent response in 11 (73. 3% acne patients while with cimetidine 6 (42.8% patients showed a good to excellent response. The mean reduction of the non-inflammatory and inflammatory lesion count was 29. 3 + 3. 6 and 9. 7 + 1. 3 respectively with spironolactone and 18.6 + 5.8 and 6.4 + 2.1 respectively with cimetidine. The response of acne vulgaris to spironolactone was superior to that of cimetidine and this difference was statistically significant (p< .05. The side effects were minimal and did not necessitate withdrawal of treatment.

  19. 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...

  20. Measurements of intestinal villi non-specific and ulcer-associated duodenitis-correlation between area of microdissected villus and villus epithelial cell count.

    OpenAIRE

    M. Hasan; Ferguson, A.

    1981-01-01

    Measurements of villus height, villus area, together with counts of epithelial cells in individual villi, were performed on endoscopic duodenal biopsies from five groups of patients: controls, ulcer-associated duodenitis, mild and severe non-specific (non-ulcerative) duodenitis, cimetidine healed ulcer-associated duodenitis and cimetidine healed non-specific duodenitis. The objectives of the study were two-fold: to establish if epithelial cell count correlated with simpler measurements of vil...

  1. H2-receptor blockade and exercise-induced asthma.

    OpenAIRE

    Nogrady, S G; Hahn, A G

    1984-01-01

    While in vitro studies suggest that H2-receptor blockade enhances mediator release from bronchial mast cells and leads to bronchoconstriction, in vivo studies have given conflicting results. Eight asthmatic subjects were given cimetidine 800 mg and placebo double-blind on different days. Baseline values of forced expiratory volume in one second (FEV1) were obtained before an 8 min standardized exercise test using a bicycle ergometer. Subjects inhaled cold, dry air and exercise on cimetidine a...

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

    Science.gov (United States)

    Ramasundaram, Subramaniyan; Yoo, Ha Na; Song, Kyung Guen; Lee, Jaesang; Choi, Kyoung Jin; Hong, Seok Won

    2013-08-15

    A photocatalytically active stainless steel filter (P-SSF) was prepared by integrating electrospun TiO2 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 TiO2 nanofibers integrated on the P-SSF against sonication, the optimum thickness of the TiO2 and PVDF layer was found to be 29 and 42 μm, respectively. At 10L/m(2)h flux, 40-90% of cimetidine was oxidized when the thickness of TiO2 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(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 TiO2 layer. Further, the degradation efficacy of cimetidine was stably maintained for 72 h at a flux of 10 L/m(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. PMID:23721729

  3. Mechanism for high PCO2 in gastric juice: roles of bicarbonate secretion and CO2 diffusion.

    Science.gov (United States)

    Stevens, M H; Thirlby, R C; Feldman, M

    1987-10-01

    The partial pressure of CO2 (PCO2) in gastric juice often exceeds the PCO2 of blood. CO2 in gastric juice may originate from blood and enter luminal fluid by diffusion, or CO2 may be produced in the lumen of the stomach from the reaction of HCO3- and H+. Because CO2 production from HCO3- is dependent on acid (low pH), we suppressed acid secretion with intravenous cimetidine to estimate to what extent appearance of CO2 in luminal fluid is due to production from HCO3-. When denervated fundic pouches of dogs were distended with saline, the PCO2 of the solution increased to the PCO2 of blood in approximately 20 min, with the initial rate of appearance of CO2 in the pouch solution only minimally affected by cimetidine. Thereafter, PCO2 of luminal fluid continued to increase to 50-60 mmHg in the absence of cimetidine, whereas PCO2 of luminal fluid remained approximately equal to that of blood when cimetidine was infused (P less than 0.001, cimetidine vs. control). The mean pH in the pouch solution remained between 6.3 and 6.9 during cimetidine infusion but decreased to 4.75 without cimetidine (P less than 0.001). In additional experiments, an acidic solution with high PCO2 (242 +/- 3 mmHg) was infused into the fundic pouches. PCO2 in luminal fluid decreased rather slowly toward plasma PCO2, requiring 240 min for luminal fluid PCO2 to decrease to 56 +/- 2 mmHg. Thus the permeability of the gastric mucosa to luminal CO2 was relatively low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3116857

  4. Modulation of drug efflux by aloe materials: An In Vitro investigation across rat intestinal tissue

    Directory of Open Access Journals (Sweden)

    Beneke Carien

    2013-01-01

    Full Text Available Background: Clinically, significant herb-drug interactions have been previously documented and can be pharmacodynamic and/or pharmacokinetic in nature. Pharmacokinetic interactions have been attributed to induction or inhibition of either metabolic enzymes or efflux transporters. Objective: The effect of gel and whole leaf materials from 3 different aloe species namely Aloe ferox, Aloe marlothii, and Aloe vera as well as polysaccharides precipitated from the A. vera materials on the bi-directional transport of cimetidine across rat intestinal tissue was investigated. Materials and Methods: Cimetidine transport studies were performed across excised rat intestinal tissue mounted in Sweetana-Grass diffusion chambers in both the apical-to-basolateral and basolateral-to-apical directions. Results: While A. vera gel and whole leaf materials did not inhibit the efflux of cimetidine, the polysaccharides precipitated from them did show a reduction of cimetidine efflux. On the other hand, both A. ferox and A. marlothii gel and whole leaf materials exhibited an inhibition effect on cimetidine efflux. Conclusions: This study identified a modulation effect of efflux transporters by certain aloe materials. This may cause herb-drug pharmacokinetic interactions when drugs that are substrates for these efflux transporters are taken simultaneously with aloe materials. On the other hand, these aloe materials may be used for drug absorption enhancement for drugs with low bioavailability due to extensive efflux.

  5. 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.

  6. 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...

  7. Potentiation of the hypoglycaemic response to glipizide in diabetic patients by histamine H2-receptor antagonists.

    OpenAIRE

    Feely, J; Collins, W C; Cullen, M; el Debani, A H; MacWalter, R S; Peden, N R; Stevenson, I H

    1993-01-01

    In a randomised placebo controlled study, two groups of six maturity onset diabetic patients stabilised on glipizide were given cimetidine (400 mg) or ranitidine (150 mg) 3 h before a standardised meal. In comparison with placebo, both cimetidine and ranitidine significantly reduced the post-prandial rise in blood glucose by a mean of 40% and 25% respectively producing glucose levels of less than 3 mmol l-1 (lowest 1.5 mmol l-1) in four patients. Both drugs also significantly increased plasma...

  8. Histamine delays gastric emptying of solid food in man through histamine, receptors

    International Nuclear Information System (INIS)

    The authors have shown that histamine (H) contracts the cat pylorus and duodenum through H/sub 1/ receptor mechanisms. The authors investigated the effect of H infusion on gastric emptying (GE) and the role of H/sub 1/ and H/sub 2/ receptor blockade in healthy volunteers. Radionuclide GE studies were performed using chicken liver labeled in vivo with /sup 99m/Technetium-sulfur colloid as a marker of solid food. Study days were as follows: a baseline GE study (Day 1); H infused continuously IV at a rate of 40 μg/kg/hr during the GE study (Day 2); an IV bolus of 50 mg of diphenhydramine (Day 3), or 300 mg cimetidine (Day 4) given just prior to the continuous infusion of H; a final day when cimetidine was given alone (Day 5). GE was monitored for 2 hours on each day. The results of days 1, 2 and 3 are summarized below (+p<0.05 vs baseline or Day 1). Pretreatment with cimetidine (Day 4) augmented the delay in GE induced by H infusion, while cimetidine without H (Day 5) had no effect on GE. The authors conclude that: 1) H given at a dose which elicits maximal acid secretory response in man significantly delays GE; and 2) H/sub 1/ receptor blockade but not H/sub 2/ blockade prevented this effect. Histamine may play a modulatory role in human gastric emptying through an H/sub 1/ receptor mechanism

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

    DEFF Research Database (Denmark)

    Bro, S; Rasmussen, R A; Handberg, J;

    1998-01-01

    , 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...

  10. 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....

  11. Evaluation of the Anti-ulcer Properties of the Aqueous Methanolic Leaf Extract of Palisota hirsuta and its Fractions in mice

    Directory of Open Access Journals (Sweden)

    Aruh O Anaga

    2013-06-01

    Full Text Available Objective: This study evaluated the effects of aqueous methanolic leaf extract of Palisota hirsuta (MLEPH, against experimentally induced gastric ulceration in mice. Materials and methods: The plant material was extracted with 70% methanol for 48h and concentrated in vacuo with rotary evaporator, yielding 8.77%w/w MLEPH. MLEPH (50, 100, 150 mg/kg and MLEPH fractions (MLEPHfr (50 mg/kg were studied in various ulcer models: acetyl salicylic acid (ASA, HCl-ethanol and cold restraint stress-induced ulcer models. Results: MLEPH at all doses used significantly reduced (P0.05 and gave a UPI of 33%. In cold restraint stress, MLEPH (50 and 100 mg/kg decreased both MNU and MUI. However this was not significant (P>0.05 compared with the control. Both doses produced UPI of 57% compared with cimetidine (95%. The MLEPHfr7 (50 mg/kg, significantly decreased (P<0.05 MNU compared with both distilled water and cimetidine and MUI compared with cimetidine in HCl-ethanol-induced gastric ulceration. The UPI for MLEPHfr7 was 58% compared with cimetidine. The phytochemical constituents of MLEPHfr7 include tannins and reducing sugars. Conclusion: Our study shows that MLEPH and MLEPHfr exhibited promising antiulcer properties, mediated by tannins and reducing sugars through cytoprotective mechanisms. [J Intercult Ethnopharmacol 2013; 2(3.000: 141-146

  12. 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 a...

  13. 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.

  14. Characterization of histamine receptors in isolated pig basilar artery by functional and radioligand binding studies

    International Nuclear Information System (INIS)

    Histamine receptors in pig basilar arteries were investigated in vitro by radioligand binding assays and by measuring the contractile and relaxant responses to histamine. Histamine and 2-pyridyethylamine (H1-agonist) induced concentration-dependent contractions, whereas impromidine (H2-agonist) induced concentration-dependent relaxations. These responses were independent of the presence of endothelial cells. Diphenhydramine (H1-antagonist) partially reversed the histamine-induced contractions to relaxations. Cimetidine (Hα2-antagonist) potentiated the contraction in a concentration-dependent manner. In the presence of cimetidine, the pEC50 value of histamine for the contraction was 6.30, and diphenhydramine competitively antagonized the histamine-induced contractions (pA2, 7.77). In the presence of diphenhydramine, the pEC50 value of histamine for the relaxation was 5.93, and cimetidine competitively antagonized the histamine-induced relaxations (pA2, 6.62). In the binding studies, the Kd value of [3H]mepyramine was 2.1 nM and the Bmax value was 95.6 fmol/mg protein. A competition experiment with diphenhydramine showed that the pKi value (7.51) was similar to the pA2 value. The Kd value for [3H]cimetidine was 126.0 nM and the Bmax value was 459.8 fmol/mg protein. The pKd (6.90) for [3H]cimetidine was similar to the pA2 for cimetidine. The Hill coefficients for these experiments were not significantly different from unity. The present findings indicate that the number of H1-receptors, in terms of the Bmax value for [3H]mepyramine, is smaller than that of H2-receptors, in terms of the Bmax value for [3H]cimetidine. However, the contractile response to histamine is predominantly mediated through stimulation of H1-receptors on vascular smooth muscle cells in pig basilar artery

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

    International Nuclear Information System (INIS)

    Highlights: • A photocatalytic metal filter was fabricated with electrospun nanofibrous TiO2. • PVDF layer effectively acted as a binder between TiO2 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/m2 h and 0.1–0.2 kPa TMP. -- Abstract: A photocatalytically active stainless steel filter (P-SSF) was prepared by integrating electrospun TiO2 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 TiO2 nanofibers integrated on the P-SSF against sonication, the optimum thickness of the TiO2 and PVDF layer was found to be 29 and 42 μm, respectively. At 10 L/m2 h flux, 40–90% of cimetidine was oxidized when the thickness of TiO2 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/m2 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 TiO2 layer. Further, the degradation efficacy of cimetidine was stably maintained for 72 h at a flux of 10 L/m2 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

  16. Murine tumor necrosis factor-alpha sensitizes plasma corticosterone activity and the manifestation of shock: modulation by histamine.

    Science.gov (United States)

    Hayley, Shawn; Kelly, O; Anisman, H

    2002-10-01

    Murine tumor necrosis factor-alpha (mTNF-alpha) results in the sensitization of mechanisms underlying plasma corticosterone activity and sickness behavior, the latter being reminiscent of septic or anaphylactic shock. The mTNF-alpha induced a sensitization of sickness and corticosterone in mice that was attenuated by pretreatment with the combinations of histamine H(1) (diphenhydramine, mepyramine) and H(2) (cimetidine) antagonists. Likewise, coadministration of diphenhydramine and cimetidine prevented the mTNF-alpha-provoked rise of monoamine activity within the posterior hypothalamus. Although dexamethasone ameliorated the mTNF-alpha-induced sensitization of corticosterone, illness behavior was unaffected. It is suggested that mTNF-alpha-induced illness and the neuroendocrine sensitization are mediated by endogenous histamine. PMID:12458037

  17. Histamine-2 Receptor Antagonists and Semen Quality.

    Science.gov (United States)

    Banihani, Saleem A

    2016-01-01

    Histamine-2 receptor antagonists are a class of drugs used to treat the acid-related gastrointestinal diseases such as ulcer and gastro-oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine-2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine-2 receptor-independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine-2 receptor antagonists. PMID:26176290

  18. A new method for evaluating gastric ulcer healing by endoscopic ultrasonography

    International Nuclear Information System (INIS)

    The authors observed the quantitative estimation of the transmural changes associated with gastric ulcer healing by using endoscopic ultrasonography (EUS). It was possible to diagnose the depth of ulcer by EUS. 48 patients were divided into three treatment groups. Group A (n=16) was treated with 800 mg cimetidine daily, group B (n=22) with 20 mg omeprazole daily, and group C (n=10) with 400 mg cimetidine + 300 mg gefarnate daily. EUS was performed before and after 2, 4 and 8 weeks of treatment. The groups were compared from the viewpoints of endoscopic findings and contraction rate of the length and the cross-sectional area of the ulcer in EUS pictures. The best healing of both the endoscopic and EUS findings was seen in group B. By estimating the changes inside the ulcer, EUS may provide useful information for choice of anti-ulcer agents. 21 refs., 5 figs., 3 tabs

  19. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    International Nuclear Information System (INIS)

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration of disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia. 34 references, 5 figures, 2 tables

  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...... 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...... 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...

  1. Prophylaxis of anaphylactoid reactions to a polypeptidal plasma substitute by H1- plus H2-receptor antagonists: synopsis of three randomized controlled trials

    OpenAIRE

    Schöning, B.; Lorenz, Wilfried; Doenicke, A.

    1982-01-01

    To demonstrate the efficacy of a premedication with H1- + H2-receptor antagonists against histamine-release responses in anaesthesia and surgery 3 randomized controlled trials were conducted in patients, volunteers and experimental animals (dogs). Cutaneous anaphylactoid reactions following infusion of polygeline (Haemaccel) in orthopedic patients were successfully abolished by premedication with 0.1 mg/kg dimethpyrindene (Fenistil) and 5 mg/kg cimetidine (Tagamet). Chlorpheniramine (Piriton)...

  2. Anti-Ulcerogenic Activity of the Methanol Root Bark Extract of Cochlospermum Planchonii (Hook f)

    OpenAIRE

    Maxwell I. Ezeja; Aruh O Anaga

    2013-01-01

    Cochlospermum planchonii (Hook f) is a common medicinal plant used in Nigeria traditional medicine for treatment of different ailments including ulcers. The anti ulcer activity of the root bark methanol extract of Cochlospermum planchonii was evaluated using different [ethanol, acetylsalicylic acid (aspirin), cold/restraint stress and pyloric ligation/histamine - induced ulcers and acid production] ulcerogenic models in rats at the doses of 250, 500, and 1000 mg/kg body weight using cimetidin...

  3. Effects of anti-allergic drugs on intestinal mastocytosis and worm expulsion of rats infected with Neodiplostomum seoulense

    OpenAIRE

    Shin, Eun-Hee; Kim, Tae-Heung; Hong, Sung-Jong; Park, Jae-Hwan; Guk, Sang-Mee; Chai, Jong-Yil

    2003-01-01

    The effects of anti-allergic drugs on intestinal mastocytosis and the expulsion of Neodiplostomum seoulense were observed in Sprague-Dawley rats, after oral infection with 500 metacercariae. The drugs used were hydroxyzine (a histamine receptor H1 blocker), cimetidine (a H2 blocker), cyclosporin-A (a helper T-cell suppressant), and prednisolone (a T- and B-cell suppressant). Infected, but untreated controls, and uninfected controls, were prepared. Worm recovery rate and intestinal mastocytosi...

  4. Duodenal mucosal architecture in non-specific and ulcer-associated duodenitis.

    OpenAIRE

    M. Hasan; Sircus, W; Ferguson, A.

    1981-01-01

    This study was done to determine the severity and extent of abnormalities of duodenal mucosal architecture in non-specific (non-ulcerative) and ulcer-associated duodenitis. The effect of successful treatment with cimetidine on these changes has also been assessed. A method of microdissection and measurement of villus height, crypt depth, and mitotic figure count per crypt was applied to endoscopic biopsies from the duodenum. Five groups of patients were studied: untreated ulcer-associated duo...

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

    OpenAIRE

    B N Dhawan; 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...

  6. H2 receptor blockade and bronchial hyperreactivity to histamine in asthma.

    OpenAIRE

    Nogrady, S G; Bevan, C

    1981-01-01

    The role of histamine H1 and H2 receptors in the lung is not clear. H1 receptor blockade results in bronchodilatation and inhibition of histamine induced bronchoconstriction. H2 receptor blockade in vitro prevents the normal negative feedback of histamine on further mediator release in antigen challenge. Bronchospasm in guinea pigs given antigen challenge is enhanced by previous administration of metiamide or burimamide but not of cimetidine. These findings suggest the possible deleterious ef...

  7. Impromidine is a partial histamine H2-receptor agonist on human ventricular myocardium.

    OpenAIRE

    English, T A; Gristwood, R. W.; Owen, D A; Wallwork, J

    1986-01-01

    The inotropic effects of impromidine have been studied and compared with those of histamine on human isolated left ventricular preparations stimulated at 1 Hz. Both drugs caused concentration-related increases in force of contraction and were of similar potency, although the maximum response to impromidine was markedly and significantly less than that to histamine. The positive inotropic responses of impromidine were inhibited by cimetidine 1 X 10(-5) M, consistent with histamine H2-receptor ...

  8. Characterization of histamine receptors mediating the stimulation of cyclic AMP accumulation in rabbit cerebral cortical slices.

    OpenAIRE

    Al-Gadi, M.; Hill, S. J.

    1985-01-01

    The characteristics of histamine-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in slices of rabbit cerebral cortex have been investigated. The selective H2-receptor antagonists, cimetidine, tiotidine, metiamide and ranitidine appeared to antagonize the stimulation of cyclic AMP accumulation elicited by histamine in a competitive manner consistent with an interaction with histamine H2-receptors. The H1-receptor antagonist mepyramine (0.8 microM) produced only a weak...

  9. Successful treatment of florid cutaneous warts with intravenous cidofovir in an 11-year-old girl.

    OpenAIRE

    IRVINE, ALAN

    2008-01-01

    Cutaneous warts, commonly seen in children and the immunosuppressed are socially distressing and are often resistant to traditional treatments. Here, we report an 11-year-old girl with bilateral florid verrucous lesions on her hands, feet and chin, which were refractory to a number of standard treatments including cryotherapy, cantharidin preparations, topical salicylic acid, surgical debulking techniques, oral Cimetidine, and topical and intralesional Cidofovir. As the disfiguring lesions ha...

  10. Gastric emptying abnormal in duodenal ulcer

    International Nuclear Information System (INIS)

    To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease

  11. 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

  12. 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.)

  13. Nizatidine, a small molecular compound, enhances killed H5N1 vaccine cell-mediated responses and protects mice from lethal viral challenge

    OpenAIRE

    Wang, Shuang; Wu, Bing; Xue, Jia; Wang, Ming; Chen, Ruiai; Wang, Bin

    2013-01-01

    Nizatidine (NIZ), closely related to Cimetidine, is a histamine H2 receptor inverse agonist used primarily as an anti-acid drug. Recent studies showed that this class of compounds may also modulate immune responses. To evaluate adjuvant effects of NIZ on vaccine immune modulation, we formulated NIZ with a H5N1 killed viral antigen and tested in vitro and in vivo. NIZ activated DC maturation and stimulated Th1 and Th2 immune responses to H5N1 vaccine. As a result, it enhanced both antibody and...

  14. In vitro histamine H2-antagonist activity of the novel compound HUK 978

    International Nuclear Information System (INIS)

    Histamine stimulated adenylate cyclase from guinea-pig fundic mucosa and 3H-tiotidine binding in guinea-pig cerebral cortex were used to assess the in-vitro histamine H2-activity of the novel H2-antagonist HUK 978. The results showed that HUK 978 was a more potent H2-antagonist than either cimetidine or ranitidine. HUK 978 was also shown to be devoid of activity at the histamine H-1-receptor, the muscarinic receptor and the α and β-adrenergic receptors

  15. 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

    Seventy-four patients with duodenal ulcer were followed up longitudinally for 2 years after initial ulcer healing. Endoscopy including biopsy of the antral mucosa was performed every 3rd month and whenever clinical symptoms of relapse occurred. The presence of Helicobacter pylori in the biopsy...... 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 a...... substantial note in the precipitation of active duodenal ulcer....

  16. Pharmacological characterization of histamine receptors in the human temporal artery.

    OpenAIRE

    Ottosson, A; Jansen, I.; Edvinsson, L.

    1989-01-01

    1. The subtypes of histamine-receptors which mediate dilatation of small human temporal arteries have been characterized in vitro using 'selective' agonists and antagonists. 2. Dilatory responses were studied after preconstriction with prostaglandin F2 alpha since contraction was not seen at histamine concentrations up to 10(-4) M. Histamine caused a concentration-related relaxation of cerebral vessels with an IC50 value of 2.8 +/- 0.6 X 10(-7) M. 3. Cimetidine caused a parallel shift to the ...

  17. Nizatidine, a small molecular compound, enhances killed H5N1 vaccine cell-mediated responses and protects mice from lethal viral challenge.

    Science.gov (United States)

    Wang, Shuang; Wu, Bing; Xue, Jia; Wang, Ming; Chen, Ruiai; Wang, Bin

    2014-01-01

    Nizatidine (NIZ), closely related to Cimetidine, is a histamine H2 receptor inverse agonist used primarily as an anti-acid drug. Recent studies showed that this class of compounds may also modulate immune responses. To evaluate adjuvant effects of NIZ on vaccine immune modulation, we formulated NIZ with a H5N1 killed viral antigen and tested in vitro and in vivo. NIZ activated DC maturation and stimulated Th1 and Th2 immune responses to H5N1 vaccine. As a result, it enhanced both antibody and T cell-mediated immune responses. We also observed that a single immunization into C57BL/6 mice blocked IL-10 upregulation and potentiated Th1/Th2 dual polarization. Importantly, the inoculation of H5N1 vaccine with NIZ significantly improved protection of animals from death after challenge and reduced virus loads in the lung tissues. Considering its water-soluble nature, compared with Cimetidine, Nizatidine may be a better choice to use as a vaccine adjuvant. PMID:24253609

  18. Histamine receptors coupled to [3H]cAMP accumulation in brain: pharmacological characterization in a vesicular preparation of guinea pig cortex

    International Nuclear Information System (INIS)

    The histamine-stimulated accumulation of [3H]cAMP (formed by prelabeling with [3H]adenine) was characterized pharmacologically in a vesicular preparation of guinea pig cortex. The H2 antagonist cimetidine maximally blocked 80% of the response, whereas only 45% of the response could be inhibited by H1 antagonists. A combination of H1 and H2 antagonists completely abolished the response. These and other findings show that both H1 and H2 receptors mediate the response, but 25% of the response may require simultaneous activation of both receptors. A role for adenosine as a mediator of the histamine response was investigated. Adenosine deaminase (EC 3.5.4.4., 2.5 units/ml) decreased basal [3H]cAMP levels, abolished the cimetidine-resistant component of the histamine response, and reduced maximal H1 antagonism of the histamine response to 30%. Treatment with a combination of adenosine deaminase and the calcium chelator EGTA (2 mM) appeared to eliminate the H1 component completely. Under these latter conditions only H2 receptors appeared to mediate the histamine response. Thus, both H1 and H2 receptors stimulate [3H]cAMP accumulation in the vesicular preparation, but the H1 response seems to require either concomitant adenosine or H2 receptor stimulation and may be calcium dependent. These findings differ from those found in broken cell membrane preparations, where only H2 receptors appear to be coupled to adenylate cyclase activation

  19. Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.

    Science.gov (United States)

    Duplancic, Bozidar; Stambolija, Vasilije; Holjevac, Jadranka; Zemba, Mladen; Balenovic, Igor; Drmic, Domagoj; Suran, Jelena; Radic, Bozo; Filipovic, Marinko; Blagaic, Alenka Boban; Brcic, Luka; Kolenc, Danijela; Grabarevic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

    2014-03-15

    Anesthetized mice or rats received intravenously 6%, 10%, 20%, 40%, 60%, 80%, and 90% dextran and/or white egg (1ml/rat or 0.15ml/mouse) into their tails. Medication (/kg b.w., 5ml/kg) was given intraperitoneally (BPC 157 10µg, 1µg, 10ng, and 10pg/kg, chloropyramine 20mg/kg, and cimetidine 10mg/kg intraperitoneally, alone or in combination while controls received an equivolume of saline), immediately after challenge or, alternatively, at 5min after or 24 or 48h before challenge. The effect was assessed at 5, 10, 20 and 30min after dextran and/or white egg challenge. We commonly noted prominent edema involving the face, upper and lower lip, snout, paws and scrotum (presented with extreme cyanosis), poor respiration and the number of fatalities after dextran and/or white egg application. Contrary, BPC 157 regimens (10µg, 1µg, 10ng, and 10pg/kg) effectively, may both prevent anaphylactoid reactions that may arise from dextran and/or white egg application and furthermore, rescue already advanced reactions when given after the challenge. Chloropyramine and cimetidine given alone were only moderately effective. When given together with BPC 157, the observed effect correlates with the strong effect of BPC 157 given alone. PMID:24486708

  20. Bar-code technology applied to drug-use evaluation.

    Science.gov (United States)

    Zarowitz, B J; Petitta, A; Mlynarek, M; Touchette, M; Peters, M; Long, P; Patel, R

    1993-05-01

    Bar-code technology was used to determine: (1) patterns in histamine H2-receptor antagonist use and (2) the occurrence of adverse drug effects and drug interactions associated with the use of these agents in critically ill patients. Patients at Henry Ford Hospital (Detroit) receiving histamine H2-receptor antagonists over a two-month period were evaluated. Clinical information was collected in the intensive care units by using a bar-code system. The data-capture menu was based on drug-use-evaluation criteria for H2-receptor antagonists. Data collected in the scanning wands were uploaded into a computer database and were analyzed at the end of the study. Data were collected for 207 patients. Cimetidine was the predominant H2-receptor antagonist used, and the predominant indication was stress-ulcer prophylaxis. Dosing trends followed accepted guidelines for cimetidine dosage adjustment in renal and hepatic failure. Two drug interactions and six adverse drug reactions occurred. Pharmacists made 92 recommendations to the medical staff regarding modification in therapy, involving 32% of the patients. Data collection required an average of 10 minutes per day each for three pharmacists. H2-receptor antagonist use patterns were evaluated in intensive care units through the application of bar-code technology. The speed and efficiency of this automated tool facilitated collection of a large amount of data. PMID:8099468

  1. 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.

  2. Delayed phase of hematoporphyrin-induced phototoxicity: modulation by complement, leukocytes, and antihistamines

    Energy Technology Data Exchange (ETDEWEB)

    Lim, H.W.; Young, L.; Hagan, M.; Gigli, I.

    1985-02-01

    The role of complement, leukocytes, and histamine was investigated in the delayed phase of hematoporphyrin-induced phototoxicity in guinea pigs. The phototoxic response was quantified by the accumulation of intravenously injected (/sup 125/I)bovine serum albumin in the skin. There was a greater than 6-fold increase in the vascular response at the completion of irradiation, which subsided partially to reach a plateau of twice the preirradiation level between 0.5 h and 12 h. At 18 h, the vascular responsiveness returned to the baseline value. The 7 h timepoint was selected in this study to evaluate the modulation of the delayed phase. In complement-depleted guinea pigs, as well as in leukopenic animals, the enhancement in the vascular response was significantly suppressed (p vs control, less than 0.0001 and 0.0022, respectively). Cimetidine, when administered prior to irradiation, significantly suppressed the phototoxic response (p vs control, 0.0365). The combination of diphenhydramine and cimetidine, administered 6 h after the induction of phototoxicity, also suppressed the vascular response (p vs control, less than 0.0001). These data indicate that the expression of the delayed phase of hematoporphyrin-induced phototoxicity, similar to the early phase, requires the presence of an intact complement system, leukocytes, and histamine.

  3. Effects of histamine and some related compounds on conditioned avoidance response in rats

    International Nuclear Information System (INIS)

    When histamine (Hi) and other agonists were applied intraventricularly, Hi caused a dose-dependent inhibition of the avoidance response in rats; its ED50 was 3.60 μg. l-methylHi, l-methylimidazole acetic acid and imidazole acetic acid which are major metabolites of Hi produced no inhibitory effect even at 50 μg. H1-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi. The depressant effects of H2-agonists (4-methylHi and dimaprit) were relatively weak; their dose-response lines were not parallel to that of Hi. When antagonists were pretreated intravenously, Hi action was clearly antagonized by diphehydramine and pyrilamine, but not by cimetidine or ranitidine. Intraventricular injection of Hi mixed with cimetidine or ranitidine did not change the effect induced by Hi alone. The avoidance response was not affected by noradrenaline, dopamine or 5-hydroxytryptamine. Although acetylcholine (ACh) suppressed the avoidance response dose-dependently, its effect was much weaker than that of Hi. Pretreatment with cholinergic blocking drugs (atropine and scopolamine) antagonized ACh action but not Hi action. From these results, it is assumed that the inhibitory effect of Hi on the avoidance response is preferentially linked to the H1-receptor. After intraventricular application of 3H-Hi, the highest radioactivity was determined in the hypothalamus. 21 references, 4 figures, 4 tables

  4. Brain histamine H1- and H2-receptors and histamine-sensitive adenylate cyclase: effects of antipsychotics and antidepressants

    International Nuclear Information System (INIS)

    Several classes of psychoactive compounds have been investigated for their effects on histamine-sensitive adenylate cyclase in cell-free preparations from the guinea-pig cerebral cortex. Their inhibitory actions on this enzyme system have been compared with their abilities to displace [3H]pyrilamine and [3H]cimetidine from histamine H1- and H2-receptor sites, respectively. The results of these studies show that compounds which inhibited the histamine-sensitive cyclase were also displacers of either [3H]pyrilamine or [3H]cimetidine or both 3H-ligands from their binding sites. In spite of the lack of a correlation between binding and cyclase antagonism it was observed that compounds that displace both ligands showed greater inhibition of the cyclase than those that have affinities for sites labeled by one or the other ligand. It was concluded that antihistamines, the antipsychotics and the antidepressants share a common property through their antagonism of H1-receptors and that may be responsible for their sedative side effect. (Auth.)

  5. 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. PMID:26664383

  6. Use of 5-[76Br]bromo-2'-fluoro-2'-deoxyuridine as a ligand for tumour proliferation: validation in an animal tumour model

    International Nuclear Information System (INIS)

    Uncontrolled cell proliferation is one of the prominent features in cancer development. Precise tools are needed for determination of the proliferation rate before, during and after treatment, thereby permitting assessment of treatment efficacy. The purpose of this study was to validate the use of 5-[76Br]bromo-2'-fluoro-2'-deoxyuridine (76Br-BFU) as a proliferation marker in an animal tumour model. Comparison was made with 2-[14C]thymidine (14C-TdR) incorporation and the labelling index assessed by bromodeoxyuridine (BrdUrd-LI). Fibrosarcoma (NFSA)-bearing mice were used for all experiments. Gemcitabine (dFdC), a potent inhibitor of DNA synthesis, was used to modulate cell proliferation. dFdC was injected intraperitoneally at a dose of 0.5 mg/kg or 40 mg/kg to induce partial (∼50%) or complete inhibition of DNA synthesis, respectively. 76Br-BFU (0.5-3 MBq per animal), 14C-TdR (37-74 kBq per animal) and cold BrdUrd (60 mg/kg) were injected intraperitoneally in combination or alone. Animals were sacrificed at various times after tracer administration, and tumour and small intestine were removed for determination of radioactivity in whole tissue and the DNA fraction, as well as for LI assessment by flow cytometry. Cimetidine (6 mg/kg) was used to decrease 76Br-BFU elimination and increase its bioavailability. The fraction of radioactivity associated with DNA increased with the time interval between tracer injection and tissue removal. At 6 h after injection, for both tracers, more than 95% of the radioactivity in the tumours was associated with the DNA fraction and an excellent correlation was observed with the LI. Similar findings were observed in the small intestine. Under all experimental conditions, 76Br-BFU uptake was 4-10 times lower than 14C-TdR uptake. Co-injection of cimetidine resulted in a three- to fourfold increase in 76Br-BFU incorporation without affecting the effect of dFdC on DNA synthesis. 76Br-BFU is a potentially good tracer for the assessment

  7. H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs.

    Science.gov (United States)

    Lorenz, W; Doenicke, A; Schöning, B; Mamorski, J; Weber, D; Hinterlang, E; Schwarz, B; Neugebauer, E

    1980-04-01

    Histamine release by drugs used in anaesthesia and surgery has been often demonstrated in human volunteers, but only occassionally in patients. Three questions arose from these studies. (1) Is the incidence of histamine release high in patients during routine anaesthesia and surgery? (2) Can the clinical effects of histamine release in man be prevented by H1 + H2-receptor antagonists? (3) Are there any side-effects of such a premedication? These problems were investigated in patients and volunteers by randomized controlled clinical trials using only one of the histamine-liberating drugs in man, the plasma substitute Haemaccel. This drug was chosen because it causes a reproducible histamine release in man and because its mechanism of action in man is largely known. (1) Out of 600 orthopaedic patients 30 (5%) showed anaphylactoid reactions following Haemaccel infusion. 26 of these had a histamine release of more than 1 ng histamine/ml plasma. Using predictive values this gives an efficiency of the test by nearly 98%. (2) In volunteers the combination of an H1-plus H2-receptor antagonist (dimethypyrindene and cimetidine) completely prevented the clinical effects of histamine release by Haemaccel (9 allergoid and anaphylactoid reactions in the control group, none in the H1 + H2-group). The incidence of histamine release, however, remained unchanged. (3) The premedication was found to release histamine itself. Cimetidine was effective when given alone but especially in combination with chlorpheniramine (4 events out of 7 applications). The clinical side-effects of these premedication were mild since apparently the free histamine was largely blocked at the receptor sites. It is concluded that premedication with a combination of H1- and H2-receptor antagonists is indicated due to the high incidence of histamine release during anaesthesia and surgery induced by various drugs and treatments. Such premedication is effective but associated with mild side-effects. For this

  8. 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.

  9. 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 in...... virulent than 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...

  10. 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.

  11. Characterization of epidermal growth factor receptors on plasma membranes isolated from rat gastric mucosa

    International Nuclear Information System (INIS)

    The binding of human epidermal growth factor (hEGF), beta-urogastrone, to plasma membranes isolated from rat gastric mucosa was studied to characterize gastric EGF receptors. The binding of [125I]hEGF was temperature dependent, reversible, and saturable. A single class of binding sites for EGF with a dissociation constant of 0.42 nM and maximal binding capacity of 42 fmol/mg protein was suggested. There was little change in the binding of [125I]hEGF upon addition of peptide hormones (secretin, insulin), antiulcer drugs (cimetidine), or an ulcer-inducing reagent (aspirin). Cross-linking of [125I]hEGF to gastric plasma membranes with the use of disuccinimidyl suberate resulted in the labeling of a protein of 150 kDa. These results indicate the presence of EGF receptors on plasma membranes of rat gastric mucosa

  12. Modeling and analysis of transport in the mammary glands

    International Nuclear Information System (INIS)

    The transport of three toxins moving from the blood stream into the ducts of the mammary glands is analyzed in this work. The model predictions are compared with experimental data from the literature. The utility of the model lies in its potential to improve our understanding of toxin transport as a pre-disposing factor to breast cancer. This work is based on a multi-layer transport model to analyze the toxins present in the breast milk. The breast milk in comparison with other sampling strategies allows us to understand the mass transport of toxins once inside the bloodstream of breastfeeding women. The multi-layer model presented describes the transport of caffeine, DDT and cimetidine. The analysis performed takes into account the unique transport mechanisms for each of the toxins. Our model predicts the movement of toxins and/or drugs within the mammary glands as well as their bioaccumulation in the tissues. (paper)

  13. Modeling and analysis of transport in the mammary glands

    Science.gov (United States)

    Quezada, Ana; Vafai, Kambiz

    2014-08-01

    The transport of three toxins moving from the blood stream into the ducts of the mammary glands is analyzed in this work. The model predictions are compared with experimental data from the literature. The utility of the model lies in its potential to improve our understanding of toxin transport as a pre-disposing factor to breast cancer. This work is based on a multi-layer transport model to analyze the toxins present in the breast milk. The breast milk in comparison with other sampling strategies allows us to understand the mass transport of toxins once inside the bloodstream of breastfeeding women. The multi-layer model presented describes the transport of caffeine, DDT and cimetidine. The analysis performed takes into account the unique transport mechanisms for each of the toxins. Our model predicts the movement of toxins and/or drugs within the mammary glands as well as their bioaccumulation in the tissues.

  14. Semitransparent peroral small bowel imaging

    Energy Technology Data Exchange (ETDEWEB)

    Emons, D.

    1981-10-01

    171 follow-through examinations of the small bowel performed in children and adolescents with a large contrast medium meal and the high voltage-low density barium technique (10 to 25 g BaSO/sub 4//100 ml, depending on age), are described. A ready made suspension, diluted with water, proved unsatisfactory. Coating properties and stability of the diluted, weak suspension were then greatly improved by hydroxyethylcellulose as a thickening agent and in addition by premedication of the patient with cimetidine. Pure cellulose solution instead of the last portion of barium prevented thickening in the ileum. The procedure has the well known advantages of a large contrast medium meal without the problem of overly dense superpositions.

  15. Signs of sympathetic denervation associated with a thoracic melanoma in a horse.

    Science.gov (United States)

    Murray, M J; Cavey, D M; Feldman, B F; Trostle, S S; White, N A

    1997-01-01

    Sympathetic denervation in a 20-year-old, gray, Thoroughbred-Percheron gelding was manifested by cutaneous hyperthermia and sweating over the right side of the body, demarcated by a line from the withers to the elbow and extending cranially. There was cutaneous hyperthermia over the right side of the head, but other signs of Horner's syndrome (sweating, ptosis, miosis, enophthalmos) were not present. The pattern of cutaneous hyperthermia and sweating was consistent with sympathetic denervation localized to the cervicothoracic ganglion, and thoracic radiographs revealed increased density in the craniodorsal thorax. Cytologic evaluation of a sample of pleural effusion revealed mesothelial cells containing melanin and cells suggestive of melanocytes or melanoblasts. Treatment with oral cimetidine and intrapleural cisplatin was not successful. A necropsy was not performed, but the clinical findings supported a diagnosis of thoracic melanoma involving the cervicothoracic ganglion. PMID:9298473

  16. Specific cerebral heat shock proteins and histamine receptor cross-talking mechanisms promote distinct lead-dependent neurotoxic responses in teleosts

    International Nuclear Information System (INIS)

    Recent interests are beginning to be directed towards toxic neurobiological dysfunctions caused by lead (Pb) in aquatic vertebrates. In the present work, treatment with a maximum acceptable toxic concentration of this heavy metal was responsible for highly significant (p 2R) antagonist cimetidine (Cim), as shown by the very robust (p 3R) thioperamide (Thio), instead, blocked Pb-dependent up-regulatory trends of both chaperones in mostly hypothalamic areas. Moreover, intense neuronal damages of the above brain regions coincided with altered expressions of HSP70 and HSP90 when treated only with Cim. Overall these first results show that distinct HnR are able to exert a net neuroprotective role arising from their interaction with chaperones in fish exposed to Pb-dependent stressful conditions making this a potentially key interaction especially for T. pavo, aquatic species which plays an important ecological role towards the survival of other commercially vital fishes

  17. Anti-ulcerogenic activity of the methanol root bark extract of Cochlospermum planchonii (Hook f).

    Science.gov (United States)

    Ezeja, Maxwell I; Anaga, Aruh O

    2013-01-01

    Cochlospermum planchonii (Hook f) is a common medicinal plant used in Nigeria traditional medicine for treatment of different ailments including ulcers. The anti ulcer activity of the root bark methanol extract of Cochlospermum planchonii was evaluated using different [ethanol, acetylsalicylic acid (aspirin), cold/restraint stress and pyloric ligation/histamine - induced ulcers and acid production] ulcerogenic models in rats at the doses of 250, 500, and 1000 mg/kg body weight using cimetidine (100 mg/kg) as a standard reference drug. The different doses of the extract and the reference drug significantly (p Cochlospermum planchonii methanolic root bark extract showed significant antiulcer activity in this study which may be as a result of its cytoprotective, antioxidant or antisecretory properties. PMID:24311856

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

    International Nuclear Information System (INIS)

    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)D3 and/or 1,25(OH)2D3 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)2D3 supplementation, were revealed through this review. While sufficient evidence is lacking, supplementation with 1,25(OH)2D3 during chemotherapy appears to have a low risk of interaction. Further interactions with vitamin D3 have not been studied

  19. 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

    International Nuclear Information System (INIS)

    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-HT2 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-HT2 receptor sites. (author) 72 refs

  20. Snake oil for the 21st century.

    Science.gov (United States)

    Bigby, M

    1998-12-01

    Dermatology has been associated with quackery for at least a century. The dictionary defines a quack as "a pretender to medical knowledge or skill; ignorantly or falsely pretending to cure." The term quack is derived from quacksalver, or one who quacks like a duck in promoting his salves. Quacksalvers hacked many potions, including snake oil, with claims that it cured everything from dermatitis to rheumatism. With the current promulgation of skin "products" and their promotion and even sale by dermatologists, and the use of treatments of no proven efficacy, this association between dermatology and quackery is set to continue well into the 21st century. The list of offending treatments includes silicone gel sheets and onion extract cream (Mederma) for keloids, alpha-hydroxy acid creams and peels, topical ascorbic acid and phytonadione, "laser resurfacing," and cimetidine for warts, to name only a few. PMID:9875187

  1. 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.

  2. Complete inhibition of food-stimulated gastric acid secretion by combined application of pirenzepine and ranitidine.

    Science.gov (United States)

    Londong, W; Londong, V; Ruthe, C; Weizert, P

    1981-07-01

    In a double-blind, placebo controlled and randomised secretory study the effectiveness of pirenzepine, ranitidine, and their combination was compared intraindividually in eight healthy subjects receiving intravenous bolus injections. Pirenzepine (0.15 mg/kg) plus ranitidine (0.6 mg/kg) suppressed peptone-stimulated gastric acid secretion from 69 +/- 11 to 2 +/- 0.4 mmol H+/3 h; the mean percentage inhibition was 97%. Postprandial gastrin was unaffected. There were only minor side-effects in a few experiments (reduction of salivation, brief blurring of vision), but no prolactin stimulation after ranitidine or ranitidine plus pirenzepine. The combined application of ranitidine and pirenzepine inhibited meal-stimulated acid secretion more effectively and produced fewer side-effects than the combination of cimetidine plus pirenzepine studied previously. PMID:6114900

  3. Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

    International Nuclear Information System (INIS)

    We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig

  4. Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse

    DEFF Research Database (Denmark)

    Schjerning, Jeppe; Uhrenholt, Torben R; Svenningsen, Per; Vanhoutte, Paul M; Skott, Ole; Jensen, Boye L; Hansen, Pernille B L

    2013-01-01

    In arterioles, aldosterone counteracts the rapid dilatation ("recovery") following depolarization-induced contraction. The hypothesis was tested that this effect of aldosterone depends on COX-derived products and/or NOS inhibition. Recovery of the response to high K(+) was observed in mesenteric...... by aldosterone. Actinomycin-D abolished the effect of aldosterone indicating a genomic effect. The effect was blocked by indomethacin and by the COX-1 inhibitor valeryl salicylate but not by NS-398 (10(-6) mol/L) or the TP-receptor antagonist S18886 (10(-7) mol/L). The effect of aldosterone on...... recovery in arteries from wild type mice and the SNP-mediated dilatation in arteries from eNOS(-/-) mice was inhibited by the histamine H2 receptor antagonist cimetidine. RT-PCR showed expression of mast cell markers in mouse mesenteric arteries. The adventitia displayed granular cells positive for...

  5. 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. PMID:17913068

  6. 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.

  7. 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.

  8. 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.

  9. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    International Nuclear Information System (INIS)

    Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg−1) or co-administration with cimetidine (100 mg kg−1), which protects against GI damage. The 1H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg−1) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

  10. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

  11. 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

  12. 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.

  13. 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

    2010-08-01

    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

  14. Structure-activity relationship analysis of cytotoxic cyanoguanidines: selection of CHS 828 as candidate drug

    Directory of Open Access Journals (Sweden)

    Gullbo Joachim

    2009-06-01

    Full Text Available Abstract Background N-(6-(4-chlorophenoxyhexyl-N'-cyano-N''-4-pyridyl guanidine (CHS 828 is the first candidate drug from a novel group of anti-tumour agents – the pyridyl cyanoguanidines, shown to be potent compounds interfering with cellular metabolism (inhibition of nicotinamide phosphoribosyl transferase and NF-κB signalling. Substituted cyanoguanidines are also found in anti-hypertensive agents such as the potassium channel opener pinacidil (N-cyano-N'-(4-pyridyl-N''-(1,2,2-trimethylpropylguanidine and histamine-II receptor antagonists (e.g. cimetidine, N-cyano-N'-methyl-N''-[2-[[(5-methylimidazol-4-yl]methyl]thio]ethylguanidine. In animal studies, CHS 828 has shown very promising activity, and phase I and II studies resulted in further development of a with a water soluble prodrug. Findings To study the structural requirements for cyanoguanidine cytotoxicity a set of 19 analogues were synthesized. The cytotoxic effects were then studied in ten cell lines selected for different origins and mechanisms of resistance, using the fluorometric microculture cytotoxicity assay (FMCA. The compounds showed varying cytotoxic activity even though the dose-response curves for some analogues were very shallow. Pinacidil and cimetidine were found to be non-toxic in all ten cell lines. Starting with cyanoguanidine as the crucial core it was shown that 4-pyridyl substitution was more efficient than was 3-pyridyl substitution. The 4-pyridyl cyanoguanidine moiety should be linked by an alkyl chain, optimally a hexyl, heptyl or octyl chain, to a bulky end group. The exact composition of this end group did not seem to be of crucial importance; when the end group was a mono-substituted phenyl ring it was shown that the preferred position was 4-substitution, followed by 3- and, finally, 2-substitution as the least active. Whether the substituent was a chloro, nitro or methoxy substituent seemed to be of minor importance. Finally, the activity patterns in the

  15. Functional characteristics of histamine receptor-bearing mononuclear cells. I. Selective production of lymphocyte chemoattractant lymphokines with histamine used as a ligand.

    Science.gov (United States)

    Center, D M; Cruikshank, W W; Berman, J S; Beer, D J

    1983-10-01

    Mitogens and antigens have been the traditional ligands for activating lymphocytes in vitro for the elaboration of lymphokines. Recently, histamine, by interaction with histamine-type 2 receptors on T lymphocytes, has been found to induce the production of one lymphokine, histamine-induced suppressor factor (HSF), that inhibits lymphocyte proliferation and lymphokine production in vitro. Because the biologic effects of HSF appear to be confined to alterations in lymphocyte function, we assessed the ability of soluble products of histamine-stimulated human blood mononuclear cells to affect another lymphocyte function, motility. Utilizing a modified Boyden chamber assay to assess lymphocyte migration, we identified chemoattractant activity for human blood and rat splenic T lymphocytes in histamine-induced mononuclear cell supernatants. No neutrophil or monocyte chemoattractant activity was present. Sephadex G-100 gel filtration of histamine-induced supernatants showed the lymphotactic activity eluted with a 56,000 m.w. This activity was cationic as determined by its elution pattern from a Sephadex QAE anion exchange matrix with a single pl of 9.0 to 9.4 determined by isoelectric focusing in sucrose. Its biologic activity is predominantly chemokinetic in nature, is stable to heating at 56 degrees C for 30 min, but is sensitive to the effects of trypsin and neuraminidase. These physicochemical and functional characteristics establish it as identical to a recently described concanavalin A-induced (Con A) lymphotactic lymphokine (LCF). Mononuclear cells that did not adhere to a histamine affinity matrix were unable to produce LCF when subsequently stimulated with histamine or Con A. Mononuclear cells incubated with histamine and diphenhydramine produced LCF; the addition of cimetidine eliminated LCF production. In fact, supernatants from cells incubated with histamine and cimetidine significantly inhibited lymphocyte migration, a phenomenon explainable by the two regions

  16. Development and evaluation of a gastro-retentive delivery system for improved antiulcer activity of ginger extract (Zingiber officinale).

    Science.gov (United States)

    Kumar Singh, Pramod; Pal Kaur, Indu

    2011-11-01

    Aim was to develop and optimize multiunit gastro-retentive floating beads (FBs) intended for localized and prolonged release of ginger for treating gastric ulcers. Protective effect of ginger extract (GE) against ulcer is well documented, but therapeutic use is compromised due to poor bioavailability and physicochemical properties. GE was only slightly soluble (3.19 ± 0.38 mg/ml) in simulated gastric fluid (SGF; pH 1.2). The solubility decreased in water to 0.69 ± 0.03 mg/ml and further by 26% in the presence of calcium carbonate (0.5% w/v). We prepared FBs of GE using calcium carbonate and sodium alginate in different proportions. Beads were evaluated for diameter, buoyancy, entrapment, and porosity. In vitro dissolution showed a Fickian release with a cumulative release of >80% at 24 h. Preclinical evaluation was done in cold-restraint stress induced gastric ulcers, in albino rats, in terms of (i) ulcer index, hemorrhagic streaks (l), mucus content, (ii) oxido-nitrosative stress, and (iii) histopathology. GE loaded FBs (200 mg/kg) were significantly better than free GE and better/equivalent to cimetidine (10 mg/kg). The system was evaluated for therapeutic effect (curative), i.e. after the induction of ulcers. Most of the natural phytochemical or antioxidants show pretreatment effectiveness. We, however, developed and established GE FBs for sustained curative effect. PMID:21401390

  17. Other antiandrogens.

    Science.gov (United States)

    Schmidt, J B

    1998-01-01

    Various substances of steroidal or nonsteroidal structure may serve as an alternative for the antiandrogenic treatment of acne. Compounds with antiandrogenic properties like cimetidine or ketoconazole are rarely administered for acne due to their weak effects. In contrast, spironolactone is an effective antiandrogen that shows good treatment effects in hirsutism and acne. Side effects occur frequently and are dose dependent. Isotretinoin--the most effective agent in acne therapy--has been under discussion for additional antiandrogenic properties for years. At present there is additional evidence for the antiandrogenic effects of isotretinoin. Regarding substances acting on both levels, androgen receptor binding and 5 alpha-reductase inhibition, the question is raised whether the term 'antiandrogen' should be amplified by including the 5 alpha-reductase inhibitors. This would pay tribute to the biological aspect of antiandrogenicity that takes into account not only the mode of action but also the effects of the substance. Under this aspect type 1 5 alpha-reductase inhibitors may gain attention in the future. PMID:9557251

  18. 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. PMID:12566804

  19. Distribution of histaminergic neurons and their modulatory effects on oscillatory activity in the olfactory center of the terrestrial slug Limax.

    Science.gov (United States)

    Matsuo, Ryota; Fukata, Rena; Kumagai, Moeko; Kobayashi, Asuka; Kobayashi, Suguru; Matsuo, Yuko

    2016-01-01

    Terrestrial mollusks can form an odor aversion memory following the simultaneous presentation of a food odor and an aversive stimulus. The local field potential oscillation recorded on the surface of the procerebrum (PC; the higher olfactory center) exhibits a frequency change in response to the detection of a learned odor; such a change is thus considered to reflect the internal state of the brain during memory recall. Thus far, dopamine and serotonin have been demonstrated to change the oscillatory frequency. Other monoamines, however, have not yet been studied. In the present study, we investigated the possible involvement of histamine (HA). Immunohistochemical staining of HA and in situ hybridization against histidine decarboxylase revealed the location of the cell bodies of HAergic neurons in all ganglia of the brain. The majority of them were located at the medial aspect of the pedal ganglia, and the cerebral ganglia also contained numerous HAergic neurons in their posterior regions. The neuropil layers of the PC received HAergic innervation from the neurons in the cerebral ganglion, as well as from a few neurons located in the dorsomedial part of the cell mass layer of the PC. The HAergic fibers, however, innervated spatially limited regions of the PC, and seemed to affect a small fraction of the PC neurons. HA exerted accelerating effects on the LFP oscillation in a dose-dependent manner, and this effect was suppressed by an H2 blocker, cimetidine. Our results support the involvement of HA in the functioning of the PC. PMID:26105566

  20. 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.

  1. Clinical features, pathogenesis and management of drug-induced seizures.

    Science.gov (United States)

    Zaccara, G; Muscas, G C; Messori, A

    1990-01-01

    Many classes of pharmacological agents have been implicated in cases of drug-induced seizures. The list includes antidepressant drugs, lithium salts, neuroleptics, antihistamines (H1-receptor antagonists), anticonvulsants, central nervous system stimulants, general and local anaesthetics, antiarrhythmic drugs, narcotic and non-narcotic analgesics, non-steroidal anti-inflammatory drugs, antimicrobial agents, antifungal agents, antimalarial drugs, antineoplastic drugs, immunosuppressive drugs, radiological contrast agents and vaccines. For each of these classes of drugs, this article offers a revision of the literature and emphasises in particular the frequency of the adverse reaction, its clinical presentation, its presumed epileptogenic mechanism and the therapeutic strategy for the management of drug-induced seizures. An attempt is also made to distinguish seizures induced by standard dosages from those provoked by accidental or self-induced intoxication. For some classes of drugs such as antidepressants, neuroleptics, central nervous system stimulants (e.g. theophylline, cocaine, amphetamines) and beta-lactam antibiotics, seizures are a well recognised adverse reaction, and a large body of literature has been published discussing exhaustively the major aspects of the issue; sufficient data are available also for the other classes of pharmacological agents mentioned above. In contrast, several other drugs [e.g. allopurinol, digoxin, cimetidine, protirelin (thyrotrophin releasing hormone), bromocriptine, domperidone, insulin, fenformin, penicillamine, probenecid, verapamil, methyldopa] have not been studied thoroughly under this aspect, and the only source of information is the occasional case report. This review does not address the issue of seizures induced by drug withdrawal. PMID:2182049

  2. 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.

  3. Effect of Flabellaria paniculata Cav. extracts on gastric ulcer in rats

    Directory of Open Access Journals (Sweden)

    Sofidiya Margaret O

    2012-10-01

    Full Text Available Abstract Background The leaves and root of Flabellaria paniculata (Malpighiaceae are frequently used in the treatment of wounds and ulcers in Nigerian folk medicine. The purpose of this study was to compare the effect of ethanolic extracts from the leaves (FPL and root (FPR of F. paniculata on gastric ulcers in rats. Methods The effect of FPL and FPR (100, 200 and 400 mg/kg was evaluated in ethanol and indomethacin gastric ulcer models. Control groups for FPL and FPR were orally treated with 3% Tween 20 and distilled water respectively. FPL was further investigated in pylorus ligation model. Misoprostol and cimetidine were used as reference. Results FPL significantly (P 50 of FPL was estimated to be 4570 mg/kg while that of FPR was 2754 mg/kg. The LD50 in intraperitoneal injection was estimated to be 1202.26 and 1380.38 mg/kg for FPL and FPR respectively. The phytochemical investigation showed that both extracts possess triterpenoids and saponin, while the presence of flavonoid was detected only in FPL. Conclusions The results of this study indicated that FPL and not FPR is effective against experimentally induced gastric ulcers. The presence of varied phytochemical constituents probably influenced the pharmacological differences between the two extracts.

  4. Activity in the gastrointestinal tract after administration of bone-seeking radiopharmaceuticals. Experimental studies in mice

    International Nuclear Information System (INIS)

    Purpose: To test the possibility that (radio)activity of non-pertechnetate nature is excreted into the gastrointestinal tract at bone scintigraphy. Material and Methods: The distribution of a bone-seeking radiopharmaceutical (99mTc-HDP) was studied in an experimental mouse system by dissecting different organs and assessing their activity with a gamma-counter. Results: A comparison of the activity of the submandibular glands, which are assumed to accumulate only pertechnetate, and the gastrointestinal tract showed that a significant fraction of the activity excreted into the gastrointestinal tract did not consist of pertechnetate. Part of the excretion took place in the stomach. It was not connected to a specific bone-seeking agent or 99Mo/99mTc generator. Nor did it increase with time between make-up and injection. The excretion of the non-pertechnetate activity was reduced by cimetidine and omeprazole. These gastric-secretion blocking drugs did not reduce excretion of pertechnetate or significantly affect the general distribution of the radiopharmaceutical. Conclusion: There is a significant excretion of non-pertechnetate activity in the gastrointestinal tract. Part of this may be caused by excretion of the undegraded radiopharmaceutical by the stomach mucosa. (orig.)

  5. 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.

  6. 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. PMID:22807255

  7. 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. PMID:26907376

  8. Incompatibility of water soluble contrast media and intravascular pharmacologic agents: experimental study

    International Nuclear Information System (INIS)

    With the development of low osmolar and nonionic contrast media in clinical practice, radiologists have enjoyed increased clinical application along with other advantages such as improvement of patient comfort and safety. Recently, radiologists have introduced many intravascular pharmacologic agents to improve diagnostic quality and patient safety. Shortly after the introduction of these agents, however, it was observed that a precipitate results when a certain pharmacologic agent is mixed with a low osmolar contrast media. These observations have prompted testing of several other drugs used for incompatibility with contrast media. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro and observed them for visible precipitates after operating the high-speed centrifuge. The results were as fallows: The contrast media that produced incompatibilities with some pharmacologic agents were ioxaglate, diatrizote, and iothalamate in the order of frequency. The contrast media that produced no precipitate were iopromide and ioxithalamate. The pharmacologic agents that produced precipitate with some contrast media were Papaverine, Benadryl, Protamine, Cimetidine, Regitin, and Gentamicin. Therefore, we recommend that caution should be taken to recognize incompatibilities and avoid them when intravascular pharmacologic agents of any kind may be incompatible

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

    International Nuclear Information System (INIS)

    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

  11. Adoptive chemoimmunotherapy using ex vivo activated memory T-cells and cyclophosphamide: tumor lysis syndrome of a metastatic soft tissue sarcoma.

    Science.gov (United States)

    Gold, J E; Malamud, S C; LaRosa, F; Osband, M E

    1993-09-01

    Adoptively transferred immune cells in combination with chemotherapeutic agents form the basis for adoptive chemoimmunotherapy (ACIT) of neoplastic disease. Autolymphocytes (ALT-cells) are ex vivo activated peripheral blood lymphocytes (PBL) from tumor-bearing hosts (TBH) that consist primarily of tumor-specific CD45RO+ (memory) T-cells. These ALT-cells combined with cimetidine (CIM) as autolymphocyte therapy (ALT), have previously been demonstrated to be a safe and active form of outpatient adoptive immunotherapy (AIT) in human TBH with metastatic renal cell cancer (RCC). We have previously described an effective ACIT protocol using ALT and cyclophosphamide (CY) for patients with relapsed and refractory non-RCC solid tumors. We now report a case of a patient with a metastatic gastric leiomyosarcoma to the liver, who developed a clinical picture consistent with a tumor-lysis syndrome (TLS), following salvage therapy for his tumor with ACIT using ALT and CY. TLS is a well-known complication resulting from the treatment of rapidly proliferating hematopoietic tumors such as Burkitt's lymphoma and acute lymphocytic leukemia. TLS has also been rarely described in chronic lymphocytic leukemia, as well as certain solid tumors such as breast cancer, small cell lung cancer, and medulloblastoma. However, there have been no previous reports of TLS occurring either secondary to immunotherapy or in sarcomas. The nature of these unusual findings is discussed. PMID:8342564

  12. 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.

  13. Pharmacologic considerations for patients taking oral contraceptives.

    Science.gov (United States)

    Hassan, T

    1987-03-01

    This is a brief review of the theoretical and known drug reactions with oral contraceptives. There are at least 6 possible types of drug reactions that may affect the action of oral contraceptives, not including malabsorption related to changes in intestinal motility or flora. Ampicillin is an example of an antibiotic that may cause diarrhea, thereby reducing absorption of pill steroids. The steroids in orals are subject to enterohepatic circulation, which is in turn affected by the gut flora. Antibiotics known to suppress gut flora include: penicillins, cephalosporins, tetracyclines, sulfas, neomycin and erythromycin. Although controlled clinical trials of antibiotic intake with oral contraception have not shown significant interactions, anecdotal reports of pill failures have been published. The other important drug interaction affecting contraception by orals is enhanced hepatic degradation, as seen with rifampicin. Other drugs such as cimetidine, MAO-inhibitor antidepressants, chloramphenicol, influenza or BCG vaccine, isoniazid, warfarin, metronidazole and disulfiram may delay steroid metabolism and possibly increase side effects. When prescribing drugs it is important to realize that certain drugs decrease oral contraceptive concentrations: antibiotics anticonvulsants, griseofulvin, purgatives and rifampicin. PMID:3155374

  14. Macrolide antibacterials. Drug interactions of clinical significance.

    Science.gov (United States)

    von Rosensteil, N A; Adam, D

    1995-08-01

    Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine. PMID:7576262

  15. 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.

  16. 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. PMID:24632077

  17. Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat.

    Science.gov (United States)

    Zhang, C Y; Tan, B K

    1997-04-01

    The cardiovascular activities of crude water extract (WE) of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), its three semi-purified ethyl acetate (FA), n-butanol (FB) and aqueous (FC) fractions, as well as andrographolide, a major plant constituent, were elucidated in anaesthetized Sprague-Dawley (SD) rats for the very first time. FA and andrographolide, which possesses multiple pharmacological activities, elicited no drop in mean arterial blood pressure (MAP), while WE, FB and FC produced a significant fall in MAP in a dose-dependent manner without significant decrease in heart rate. The ED50 values for WE, FB and FC were 11.4, 5.0 and 8.6 mg/kg-respectively. These suggested that the hypotensive substance(s) of the crude water extract was concentrated in FB. Pharmacological antagonist studies were consequently only tested in FB (5 mg/kg). The hypotensive action of FB was not mediated through effects on the beta-adrenoceptor, muscarinic cholinergic receptor and angiotensin-converting enzyme, for it was not affected by propranolol, atropine and captapril, respectively. However, it seems to work via alpha-adrenoceptors, autonomic ganglion and histaminergic receptors, since the hypotensive effect of FB was negated or attenuated in the presence of phentolamine, hexamethonium as well as pyrilamine and cimetidine. PMID:9174969

  18. Cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide in the anaesthetised rat and isolated right atria.

    Science.gov (United States)

    Zhang, C; Kuroyangi, M; Tan, B K

    1998-12-01

    The cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide (DDA) from Andrographis paniculata (Burm.f.) Nees (Acanthaceae) was elucidated in anaesthetised Sprague-Dawley (SD) rats and isolated rat right atria. In anaesthetised rats, DDA produced significant falls in mean arterial blood pressure (MAP) and heart rate in a dose-dependent manner with the maximum decrease of 37.6 +/- 2.6% and 18.1 +/- 4.8%, respectively. The ED50 value for MAP was 3.43 mmol kg-1. Pharmacological antagonist studies were done using this dose. The hypotensive action of DDA was not mediated through effects on the alpha-adrenoceptor, muscarinic cholinergic and histaminergic receptors, for it was not affected by phentolamine, atropine as well as pyrilamine and cimetidine. However, it seems to work via adrenoceptors, autonomic ganglia receptor and angiotensin-converting enzyme, since the hypotensive effect of DDA was negated or attenuated in the presence of propranolol, hexamethonium and captopril. In the isolated right atria, DDA caused negative chronotropic action and antagonised isoproterenol-induced positive chronotropic actions in a non-competitive and dose-dependent manner. These results further supported the bradycardia-inducing and beta-adrenoceptor antagonistic properties of DDA in vivo. PMID:9990649

  19. A new approach for trace analysis of guanidine compounds in surface water with resorcinarene-based ion chromatography columns.

    Science.gov (United States)

    Panahi, Tayyebeh; Weaver, Douglas J; Lamb, John D; Harrison, Roger G

    2016-02-01

    Trace levels of pharmaceuticals have been detected in surface water and may pose a health risk to humans and other organisms. New chromatographic materials will help identify and quantify these contaminants. We introduce a new ion chromatographic (IC) material designed to separate cationic pharmaceuticals and report its ability to separate a group of guanidine compounds. Guanidine moieties are strongly basic and protonated under acid conditions, and therefore can potentially be separated on the newly designed stationary phase and detected by ion exchange chromatography. The new column packing material is based on glutamic acids bonded to resorcinarene moieties that in turn are bound to divinylbenzene macroporous resin. Detection limits in the range of 5-30 μg L(-1) were achieved using integrated pulsed amperometric detection (IPAD) for guanidine (G), methylguanidine (MG), 1,1-dimethylbiguanide (DMG), agmatine (AGM), guanidinobenzoic acid (GBA) and cimetidine (CIM). Suppressed conductivity (CD) and UV-vis detection resulted in limits of detection similar to IPAD, in the range of 2-66 μg L(-1), but were not able to detect all of the analytes. Three water sources, river, lake, and marsh, were analyzed and despite matrix effects, sensitivity for guanidine compounds was in the 100 μg L(-1) range and apparent recoveries were 80-96%. The peak area precision was 0.01-2.89% for IPAD, CD and UV-vis detection. PMID:26649362

  20. Crystal structure and theoretical study of IR and 1H and 13C NMR spectra of cordatin, a natural product with antiulcerogenic activity

    Science.gov (United States)

    Brasil, Davi S. B.; Alves, Cláudio N.; Guilhon, Giselle M. S. P.; Muller, Adolfo H.; Secco, Ricardo De S.; Peris, Gabriel; Llusar, Rosa

    Cordatin is a furan diterpenoid with a clerodane skeleton isolated from Croton palanostigma Klotzsch (Euphorbiaceae). This natural product shows significant antiulcerogenic activity, similar to cimetidine (Tagamet®), a compound used for the treatment of peptic ulcers. The crystal structure of cordatin was obtained by X-ray diffraction and its geometrical parameters were compared with theoretical calculations at the B3LYP theory level. The IR and NMR (1H and 13C chemical shifts and coupling constants) spectra were obtained and compared with the theoretical calculations. The B3LYP theory level, with the 6-31G(d,p) and 6-311G(d,p) basis set, provided IR absorption values close to the experimental data. Moreover, theoretical NMR parameters obtained in both gas phase and chloroform solvent at the B3PW91/DGDZVP, B3LYP/6-311+G(2d,p), and B3PW91/6-311+G(2d,p) levels showed good correlations with the experimental results.

  1. Cytokine-mediated bone resorption is cytochrome P-450 dependent. Student Research Award 1998.

    Science.gov (United States)

    Young, N; Chole, R

    1999-12-01

    Localized bone loss leads to much of the morbidity of chronic otitis media. Although the cellular events of bone remodeling have been well established, their regulation remains poorly understood. Various cytokines, including tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, used alone and in combination, are powerful inducers of bone resorption. One of the modulators of cytokine-induced bone resorption is nitric oxide (NO), a product of the action of NO synthase (NOS) on L -arginine to form NO. Cytochrome P-450, an enzyme that is similar to NOS both structurally and functionally, may also have a role in NO production in various cellular systems. The goal of this study was to elucidate a possible role of cytochrome P-450 in bone. In this study cytokine-induced bone resorption was blocked with cimetidine and clotrimazole, which are selective inhibitors of the cytochrome P-450 IIIA family and 7-ethoxyresorufin, a nonspecific cytochrome P-450 inhibitor. A concomitant reduction of NO was also observed. This effect may be explained by cytochrome P-450 being a preferred alternative pathway or providing an essential cofactor to NOS in bone. PMID:10580224

  2. Involvement of H1 and H2 receptors and soluble guanylate cyclase in histamine-induced relaxation of rat mesenteric collecting lymphatics

    Science.gov (United States)

    Kurtz, Kristine H.; Moor, Andrea N.; Souza-Smith, Flavia M.; Breslin, Jerome W.

    2014-01-01

    Objective This study investigated the roles of the H1 and H2 histamine receptors, nitric oxide (NO) synthase, and soluble guanylate (sGC) cyclase in histamine-induced modulation of rat mesenteric collecting lymphatic pumping. Methods Isolated rat mesenteric collecting lymphatics were treated with 1–100 μM histamine. Histamine receptors were blocked with either the H1 antagonist mepyramine or the H2 antagonist cimetidine. The role of NO/sGC signaling was tested using the arginine analog L-NAME, the sGC inhibitor ODQ, and sodium nitroprusside (SNP) as a positive control. Results Histamine applied at 100 μM decreased tone and contraction frequency (CF) of isolated rat mesenteric collecting lymphatics. Pharmacologic blockade of either H1 or H2 histamine receptors significantly inhibited the response to histamine. Pretreatment with ODQ, but not L-NAME, completely inhibited the histamine-induced decrease in tone. ODQ pretreatment also significantly inhibited SNP-induced lymphatic relaxation. Conclusions H1 and H2 histamine receptors are both involved in histamine-induced relaxation of rat mesenteric collecting lymphatics. NO synthesis does not appear to contribute to the histamine-induced response. However, sGC is critical for the histamine-induced decrease in tone and contributes to the drop in CF. PMID:24702851

  3. 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.

  4. 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.

  5. 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. PMID:26100666

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

    International Nuclear Information System (INIS)

    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

  7. 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.

  8. Pharmacological toxicological studies on certain drugs subjected to radiation or used radioprotective agents

    International Nuclear Information System (INIS)

    The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab

  9. Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations.

    Science.gov (United States)

    Jansen, J; De Napoli, I E; Fedecostante, M; Schophuizen, C M S; Chevtchik, N V; Wilmer, M J; van Asbeck, A H; Croes, H J; Pertijs, J C; Wetzels, J F M; Hilbrands, L B; van den Heuvel, L P; Hoenderop, J G; Stamatialis, D; Masereeuw, R

    2015-01-01

    The bioartificial kidney (BAK) aims at improving dialysis by developing 'living membranes' for cells-aided removal of uremic metabolites. Here, unique human conditionally immortalized proximal tubule epithelial cell (ciPTEC) monolayers were cultured on biofunctionalized MicroPES (polyethersulfone) hollow fiber membranes (HFM) and functionally tested using microfluidics. Tight monolayer formation was demonstrated by abundant zonula occludens-1 (ZO-1) protein expression along the tight junctions of matured ciPTEC on HFM. A clear barrier function of the monolayer was confirmed by limited diffusion of FITC-inulin. The activity of the organic cation transporter 2 (OCT2) in ciPTEC was evaluated in real-time using a perfusion system by confocal microscopy using 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+)) as a fluorescent substrate. Initial ASP(+) uptake was inhibited by a cationic uremic metabolites mixture and by the histamine H2-receptor antagonist, cimetidine. In conclusion, a 'living membrane' of renal epithelial cells on MicroPES HFM with demonstrated active organic cation transport was successfully established as a first step in BAK engineering. PMID:26567716

  10. Modeling uptake of selected pharmaceuticals and personal care products into food crops from biosolids-amended soil.

    Science.gov (United States)

    Prosser, Ryan S; Trapp, Stefan; Sibley, Paul K

    2014-10-01

    Biosolids contain a variety of pharmaceuticals and personal care products (PPCPs). Studies have observed the uptake of PPCPs into plants grown in biosolids-amended soils. This study examined the ability of Dynamic Plant Uptake (DPU) model and Biosolids-amended Soil Level IV (BASL4) model to predict the concentration of eight PPCPs in the tissue of plants grown in biosolids-amended soil under a number of exposure scenarios. Concentrations in edible tissue predicted by the models were compared to concentrations reported in the literature by calculating estimated human daily intake values for both sets of data and comparing them to an acceptable daily intake value. The equilibrium partitioning (EqP) portion of BASL4 overpredicted the concentrations of triclosan, triclocarban, and miconazole in root and shoot tissue by two to three orders of magnitude, while the dynamic carrot root (DCR) portion overpredicted by a single order of magnitude. DPU predicted concentrations of triclosan, triclocarban, miconazole, carbamazepine, and diphenhydramine in plant tissues that were within an order of magnitude of concentrations reported in the literature. The study also found that more empirical data are needed on the uptake of cimetidine, fluoxetine, and gemfibrozil, and other ionizable PPCPs, to confirm the utility of both models. All hazard quotient values calculated from literature data were below 1, with 95.7% of hazard quotient values being below 0.1, indicating that consumption of the chosen PPCPs in plant tissue poses de minimus risk to human health. PMID:25207852

  11. Antihistamines block radiation-induced increased intestinal blood flow in canines

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Gossett-Hagerman, C.J.

    1985-06-01

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H1 and H2 histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H1 and H2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systemic plasma histamine levels were determined simultaneously. Data obtained indicated that the H1 and H2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure.

  12. 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.

  13. 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.

  14. Exposure to heavy charged particles affects thermoregulation in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A.; Dalton, T.K.; Joseph, J.A.; Harris, A.H. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States); Rabin, B.M. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States)]|[Univ. of Maryland, Baltimore, MD (United States)

    1994-09-01

    Rats exposed to 0.1-5 Gy of heavy particles ({sup 56}Fe, {sup 40}Ar, {sup 20}Ne or {sup 4}He) showed dose-dependent changes in body temperature. Lower doses of all particles produced hyperthermia, and higher doses of {sup 20}Ne and {sup 56}Fe produced hypothermia. Of the four HZE particles, {sup 56}Fe particles were the most potent and {sup 4}He particles were the least potent in producing changes in thermoregulation. The {sup 20}Ne and {sup 40}Ar particles produced an intermediate level of change in body temperature. Significantly greater hyperthermia was produced by exposure to 1 Gy of {sup 20}Ne, {sup 40}Ar and {sup 56}Fe particles than by exposure to 1 Gy of {sup 60}Co {gamma} rays. Pretreating rats with the cyclo-oxygenase inhibitor indomethacin attenuated the hyperthermia produced by exposure to 1 Gy of {sup 56}Fe particles, indicating that prostaglandins mediate {sup 56}Fe-particle-induced hyperthermia. The hypothermia produced by exposure to 5 Gy of {sup 56}Fe particles is mediated by histamine and can be attenuated by treatment with the antihistamines mepyramine and cimetidine. 15 refs., 4 figs.

  15. Antihistamines block radiation-induced increased intestinal blood flow in canines

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Gossett-Hagerman, C.J.

    1985-01-01

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H/sub 1/ and H/sub 2/ histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H sub 1 and H sub 2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systematic plasma histamine levels were determined simultaneously. Data obtained indicated that the H sub 1 and H sub 2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure. (Author)

  16. Campylobacter pylori-associated gastritis: attempts to eradicate the bacteria by various antibiotics and anti-ulcer regimens.

    Science.gov (United States)

    Glupczynski, Y; Burette, A; Nyst, J F; De Prez, C; De Koster, E; Deltenre, M

    1988-01-01

    The efficacy of various antimicrobial and anti-ulcer agents on the eradication of Campylobacter pylori in patients with antral gastritis or duodenal ulcers was investigated by several open studies or double-blind, placebo-controlled protocols. Among the anti-ulcer agents, ranitidine, cimetidine or sucraflate had no effect on C. pylori. Colloidal bismuth subcitrate achieved clearance of C. pylori in 40% of treated patients at the end of therapy but a high relapse rate (14/16 patients) was observed after a 6-month follow-up period. The antibacterial agents doxycycline, minocycline, ofloxacin, clindamycin, paromomycin and nifuroxazide failed to eradicate C. pylori in most patients. By contrast, short term elimination of C. pylori could be achieved in more than 90% of patients treated with amoxycillin. However, relapse occurred as a rule in all amoxycillin-treated patients within one month after therapy. Overall, we observed no correlation between the in-vitro activity of the different antibacterial agents and their in vivo efficacy. Development of resistance during therapy does not seem to account for this discrepancy since it occurred only with ofloxacin. On the basis of these results, we conclude that long term eradication of C. pylori from the gastric antrum cannot be achieved after monotherapy either with antibiotics or with bismuth salts. PMID:2979039

  17. Influence of thyroid states on stress gastric ulcer formation

    International Nuclear Information System (INIS)

    This study was designed to test the hypothesis that thyroid states may affect the acute development of gastric lesions induced by cold-resistant stress. Normal (euthyroid), hyperthyroid and hypothyroid rats were used. Gastric lesion incidence and severity was significantly increased in hypothyroid rats, whereas in contrast hyperthyroid rats developed significantly less gastric lesions. As anticipated, plasma levels of thyroxin (T4) were significantly elevated in hyperthyroid rats, and undetectable in hypothyroid rats. Acute pretreatment with i.p. cimetidine, but not T4 1 h prior to stress completely prevented gastric lesions formation in hypothyroid rats. Finally, binding of 3H-dihydroalprenolol to β-adrenergic receptors on brain membranes prepared from frontal cortex was reduced by 20% in hypothyroid rats after 3 h of stress. These and other data contained herein suggest that thyroid hormones contribute to modulate the responsiveness of the gastric mucosa to stress. The increase rate of ulcerogenesis observed in hypothyroid rats appears to be mediated by gastric acid secretion. The central mechanism for this response may involve decreased brain nonadrenergic receptor function

  18. Influence of histamine of precursors of granulocytic leukocytes in murine bone marrow

    International Nuclear Information System (INIS)

    The effect of histamine on granulocytic progenitor cells in murine bone marrow was studied in vitro. When bone marrow cells were cultured for three days with the drug, 10-8 M to 10-5 M of histamine stimulated differentiation and proliferation of myeloid precursor cells. Subsequently, the number of descendant cells, such as metamyelocytes and neutrophils, increased dose-dependently. Co-existence of equimolar H2 blockers such as cimetidine and ranitidine completely suppressed this effect of histamine, though this was not the case with an H1 blocker/histamine combination. Significant increase in 3H-thymidine incorporation was observed almost exclusively in myeloblasts, promyelocytes and myelocytes after exposure to histamine at concentrations higher than 10-8 M. Also, selective incorporation of 3H-histamine into bone marrow cells was observed in myeloblasts and promyelocytes, but histamine incorporation was not influenced by the presence of either of histamine agonists of antagonists. While histamine, via H2 receptors, selectively increased the number of granulocytic colony forming units in culture (CFU-C), it had no such effect on macrophage colonies. 22 references, 5 figures, 4 tables

  19. Vascular responses to compound 48/80 in rat mesenteric vascular beds.

    Science.gov (United States)

    Jin, Honghua; Li, Zhen; Takatori, Shingo; Koyama, Toshihiro; Jin, Xin; Zamami, Yoshito; Kawasaki, Hiromu; Sun, Pengyuan

    2016-06-01

    A further investigation was performed on the vascular effect of endogenous histamine using the histamine releaser, compound 48/80, in rat mesenteric vascular beds with active tone. In preparations with intact endothelium, low concentrations of compound 48/80 (1.53 × 10(-5) - 3 × 1.53 × 10(-5) mg/mL) perfusion for 1 min only induced a small vasodilation. High concentrations of compound 48/80 (1.53 × 10(-4) - 3 × 1.53 × 10(-2) mg/mL) induced a biphasic vascular responses, an initial vasoconstriction followed a subsequent long-lasting vasodilation. The vasodilation induced by low concentrations of compound 48/80 and the vasoconstriction induced by high concentration of compound 48/80 was inhibited by olopatadine. However, cimetidine did not affect the responses induced by compound 48/80. Endothelium removal enlarged the compound 48/80-induced phase-2 vasoconstriction, while it attenuated the phase-3 vasodilation. Additionally, indomethacin and seratrodast significantly inhibited vasoconstriction but it did not affect the long-lasting vasodilation induced by high concentrations of compound 48/80. Ruthenium red inhibited the vasodilation induced by low concentrations and high concentrations of compound 48/80. These results suggest that the vasoconstriction induce by high concentrations of compound 48/80 is mediated by endogenous histamine released from mast cells. It is also suggested that thromboxane A2 released from mast cells is related to the vasoconstriction. PMID:26991394

  20. In vitro radioprotective effects of histamine H2 receptor antagonists against gamma-rays induced chromosomal aberrations in human lymphocytes

    International Nuclear Information System (INIS)

    Background: Radioprotective capability of histamine H2 receptor antagonists have been shown in several in vivo studies mainly using animal models. However, to verify the effectiveness of these agents in clinical applications, studies should be performed on human lymphocytes using metaphase analysis. Materials and Methods: In vitro metaphase analysis technique was used to test the effects of cimetidine, ranitidine and famotidine on radiation induced clastogenic effects. Lymphocytes in whole peripheral blood were exposed to 3 Gy gamma-rays at a dose rate of 73.7 c Gy/min in the presence or absence of various doses of the drugs used in this study. The frequency of chromosomal aberrations were determined after standard metaphase preparations and staining slides in 5% Giemsa. Results: Results show that radiation produced a high number of chromosomal aberrations in lymphocytes compared to controls (p2-receptor antagonists used in this study effectively reduced the clastogenic effects of radiation with a dose reduction factor of 1.5-2 in human lymphocytes in vitro. The way in which these drugs reduce the clastogenic effects of radiation might be via radical scavenging mechanism

  1. Immune-related intestinal Cl- secretion. I. Effect of histamine on the T84 cell line

    International Nuclear Information System (INIS)

    The mast cell mediator, histamine, induces a rapid and transient increase in chloride secretion across monolayers of the human colonic epithelial cell line, T84. Threshold stimulation occurred at 3 x 10-6 M histamine and a maximal effect at 10-4 M. The effect was reproduced by the H1 agonists 2-methylhistamine and 2-pyridylethylamine, but not by the H2 agonists 4-methylhistamine and dimaprit, suggesting the involvement of an H1 receptor. Additionally, histamine's action was inhibited by an H1 antagonist, diphenhydramine, but not by an H2 antagonist, cimetidine. Histamine treatment increased free cytosolic calcium levels, but not those of adenosine 3',5'-cyclic monophosphate (cAMP) or guanosine 3',5'-cyclic monophosphate (cGMP). The mechanism of chloride secretion induced by histamine resembled that of carbachol, in that both (1) were associated with an increase in free cytosolic calcium, (2) had a site of activation at a basolaterally localized K+ channel, and (3) were potentiated by both cAMP- and cGMP-mediated secretagogues. These results suggest that histamine may act as an intestinal secretagogue via direct interactions with epithelial cells

  2. Implication of prostaglandins and histamine H1 and H2 receptors in radiation-induced temperature responses of rats

    International Nuclear Information System (INIS)

    Exposure of rats to 1-15 Gy gamma radiation (60Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations

  3. 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.

  4. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    International Nuclear Information System (INIS)

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor

  5. 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.

  6. 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.

  7. Cardiac mast cells regulate myocyte ANP release via histamine H2 receptor in beating rabbit atria.

    Science.gov (United States)

    Li, Dan; Wen, Jin Fu; Jin, Jing Yu; Quan, He Xiu; Cho, Kyung Woo

    2009-06-01

    It has been shown that histamine inhibits atrial natriuretic peptide (ANP) release. Because cardiac mast cells are the principal source of histamine in the heart, we hypothesized that cardiac mast cells are involved in the regulation of atrial ANP release. To test the hypothesis, experiments were performed in perfused beating rabbit atria allowing atrial pacing and measurements of changes in atrial stroke volume, intraatrial pulse pressure and myocyte ANP release. Mast cell degranulation with Compound 48/80 decreased atrial myocyte ANP release, and the response was blocked by a selective histamine H(2) receptor blocker, cimetidine, indicating that histamine was responsible for the decrease in ANP release. Mast cell stabilization with cromolyn blocked the Compound 48/80-induced decrease in ANP release. These data suggest that mast cell-derived histamine is involved in the regulation of cardiac ANP release. Thus, the cardiac mast cell-cardiomyocyte communication via the histamine-ANP pathway may implicate in the cardiac disorder associated with mast cell degranulation such as in acute coronary syndrome or cardiac hypertrophy. PMID:19328828

  8. Successful treatment of florid cutaneous warts with intravenous cidofovir in an 11-year-old girl.

    Science.gov (United States)

    Cusack, Caitriona; Fitzgerald, Deborah; Clayton, Timothy M; Irvine, Alan D

    2008-01-01

    Cutaneous warts, commonly seen in children and the immunosuppressed are socially distressing and are often resistant to traditional treatments. Here, we report an 11-year-old girl with bilateral florid verrucous lesions on her hands, feet and chin, which were refractory to a number of standard treatments including cryotherapy, cantharidin preparations, topical salicylic acid, surgical debulking techniques, oral Cimetidine, and topical and intralesional Cidofovir. As the disfiguring lesions had a marked adverse effect on her quality of life, a trial of IV Cidofovir was instituted. We administered five cycles of IV Cidofovir with a 1-week interval between the first and second treatment, followed by 2-week intervals thereafter. This regime was well tolerated and we report dramatic resolution of the lesions with persistent clearance 6 months after completion of the fifth infusion. Resolution of recalcitrant warts with IV Cidofovir has been reported in a limited number of cases. Our experience supports its efficacy in this setting, and to the best of our knowledge this is the first report of successful treatment of cutaneous warts with IV Cidofovir in a pediatric case. PMID:18577053

  9. Treatment of molluscum contagiosum: a brief review and discussion of a case successfully treated with adapelene.

    Science.gov (United States)

    Scheinfeld, Noah

    2007-01-01

    Molluscum contagiosum occur in 2-8 percent of children. This infection is among the most common viral skin infections in children. Although the lesions will resolve spontaneously when puberty, there are several reasons to treat them. The lesions can be cosmetically unappealing. About 10 percent of those with this infection develop a pruritic eczematous eruption. In about 4 percent of children with molluscum, the lesions are numerous and recurrent with no other coexisting immunological problem. Patients who have atopic dermatitis may develop widespread involvement with molluscum. Treatment options include destruction, topical therapy, and oral therapy. Destructive treatment modalities include curettage, cryotherapy, expression or pricking with a sterile needle, electrodesiccation, photodynamic therapy, and laser ablation. Destructive therapy is poorly tolerated in children. Topical medical therapy includes salicylic acid, glycolic acid, tretinoin, tazortene, 5 percent sodium nitrite co-applied daily with 5 percent salicylic acid topical preparations, podofilox, liquefied phenol, tretinoin, cantharidin, and potassium hydroxide. Oral treatment of molluscum includes cimetidine. No therapy is universally effective. I report herein a case of generalized numerous and recurrent molluscum treated with minimal irritation with adapelene. PMID:18328209

  10. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

    International Nuclear Information System (INIS)

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in 51Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal 51Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol

  11. Implication of prostaglandins and histamine H1 and H2 receptors in radiation-induced temperature responses of rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A.; Mickley, G.A.

    1988-04-01

    Exposure of rats to 1-15 Gy gamma radiation (/sup 60/Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations.

  12. Dexamethasone: a potent blocker for radiation-induced taste aversion in rats

    International Nuclear Information System (INIS)

    Rats, trained to drink water during a single 30-min period each day, were then given 0.1% saccharin twice a week and water on other days for 30 min. If 20 rad of radiation (0.2 Gy) were given each time 30 to 40 min after the saccharin the rats developed a profound aversion to saccharin during the course of three weeks, whereas control groups failed to do so. This paradigm was then used to test the ability of drugs, given twice weekly immediately after the saccharin, to prevent the development during three weeks of an aversion when 20 rad was given, 30 to 40 min later. Insulin, domperidone, haloperidol, acetylsalicylic acid, naloxone, chlorpheniramine, cimetidine, and dimethyl sulphoxide were tested without notable success. However dexamethasone, at doses ranging from 0.013 mg/kg to 1.3 mg/kg, significantly attenuated the conditioned taste aversion by up to 60 percent. The results are discussed in terms of a search for an antinauseant and antiemetic drug effective against radiation in man

  13. Implication of prostaglandins and histamine h1 and h2 receptors in radiation-induced temperature responses of rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A.; Mickley, G.A .

    1988-01-01

    Exposure of rats to 1-15 Gy cobalt 60 gamma radiation induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxgenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H(1) and H(2) receptors may be involved in radiation-induced hypothermia since both the H(1) receptor antagonist, mepyramine, and H(2) receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggested that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations.

  14. Antihistamines block radiation-induced increased intestinal blood flow in canines

    International Nuclear Information System (INIS)

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H1 and H2 histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H1 and H2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systemic plasma histamine levels were determined simultaneously. Data obtained indicated that the H1 and H2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure

  15. 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.

  16. 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).

  17. Enzymatic sulfation of gastric mucous glycoprotein in rat--changes in glycoprotein sulfotransferase activity with stress and anti-ulcer agent, sofalcone

    International Nuclear Information System (INIS)

    Enzymatic sulfation of mucous glycoprotein (GP) was studied in gastric mucosa of rat. After rat stomach was incubated with [35S]-sulfate, incorporation of radioactivity into gastric mucosal APS (adenosine 5'-phosphosulfate), PAPS (3'-phosphoadenosine 5'-phosphosulfate) and endogenous GPs could be detected. The degree of sulfation of endogenous GPs was highest in the macromolecular GP (peak I) and lowest in the low molecular GP (peak III). By using a crude preparation of GP sulfotransferase from rat gastric mucosa, the transfer of [35S]-sulfate from [35S]-PAPS into macromolecular mucous GP was determined as being the activity of sulfotransferase. The activity of GP sulfotransferase was mainly distributed in the microsomal fraction, and was proportional to the incubation time, substrate (mucous GP) concentration and [35S]-PAPS concentration. The enzyme activity was significantly higher in the corpus than that in the antral mucosa. The activity of GP sulfotransferase was significantly decreased at 6 h and was significantly increased at 12 h after the stress load, compared with that of the non-stressed condition. Anti-ulcer agent, sofalcone, increased the GP sulfotransferase activity under the stressed condition. On the other hand, cimetidine showed a significant inhibitory effect under the same condition. Changes in the GP sulfotransferase activity with stress and anti-ulcer agents were consistent with those in the incorporation of [35S]-sulfate into macromolecular mucous GP. These results suggest the importance of GP sulfotransferase as a key enzyme regulating the sulfation of mucous GP

  18. Ussing chamber技术评价 P-糖蛋白及有机阳离子转运体对左氧氟沙星跨胃黏膜转运的影响%Evaluation of P-glycoprotein and organic cation transporter on the transport of levofloxacin by Ussing chamber

    Institute of Scientific and Technical Information of China (English)

    胡咏梅; 张珊珊; 张磊; 胡兴萍; 许建明

    2015-01-01

    目的:评价P-糖蛋白及有机阳离子转运体对左氧氟沙星跨胃黏膜转运的影响。方法用大鼠胃黏膜与Ussing chamber 技术建立胃黏膜体外模型,分为空白组及加入P-糖蛋白抑制剂(环孢素A)或有机阳离子转运体抑制剂(西咪替丁)的抑制剂组并进行双向转运实验,用高效液相色谱法对左氧氟沙星进行定量分析,计算其表观渗透系数( Papp )。结果加入环孢素 A 后,50μg· mL-1左氧氟沙星 Papp ( S -M )/Papp ( M -S )由2.20变为1.06(P<0.05);加入西咪替丁后,50μg · mL-1左氧氟沙星 Papp ( S -M)/Papp ( M-S)与空白组比较,差异无统计学意义。结论 P-糖蛋白参与左氧氟沙星跨胃黏膜转运过程,而有机阳离子转运体不参与左氧氟沙星跨胃黏膜转运过程。%Objective To evaluate the effect of P-glycoprotein (P-gp) and organic cation transporter ( OCTs) on the transport of levofloxacin by using a model in vitro.Methods A model in vitro was established by rat gastric mucosa combined with Ussing chamber.The concentrations of levofloxacin collected from the transport assay were determined by HPLC and the transport parameters such as apparent permeability coefficient [Papp(M-S) and Papp(S-M)] and the ratio of Papp(S -M) versus Papp(M -S) were calculated and compared when the levofloxacin was used solely and co -used with P -gp inhibitor cyclosporin A or OCTs inhibitor cimetidine.Results When cyclosporin A was added , the Papp(S-M)/Papp(M-S) of levofloxacin decreased from 2.20 to 1.06 ( P<0.05).There was no significant difference compared with the blank group while cimetidine was added.Conclusion The reasults indicated that P-glycoprotein might be involved in the transport of levofloxacin in this model in vitro, while the organic cation transporter probably not participated in.

  19. Measurement of canine gastric vascular permeability to plasma proteins in the normal and protein-losing states

    International Nuclear Information System (INIS)

    An isolated segment of the greater curvature of a dog's stomach was perfused at constant flow through a single cannulated artery with donor blood containing 131I-albumin, 125I-fibrinogen, and papaverine. Perfusion pressure was 30-50 mmHg, and venous pressure was set at 15 mmHg. Venous blood was collected in 1-min samples for 60 min. Filtration of fluid and loss of labeled proteins were calculated as the difference between measured arterial inflow and venous outflow. Permeability-surface area products (PS) were calculated for the proteins, and reflection coefficients (sigma) were calculated from solute flux and filtration. Intraarterial infusion of histamine (1.6-1.9 microgram . ml-1) increased filtration and PS and decreased sigma for albumin but not fibrinogen. When protein-losing was established by topical irrigation with 10 mM dithiothreitol in neutral solution, filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Irrigation of the mucosa with 10 mM salicylic acid in 100 mN HCl caused bleeding that was quantitated by addition of 51Cr-erythrocytes to perfusing blood. Filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Hematocrit of blood lost remained low during extensive mucosal damage. Effects of histamine infusion were attenuated or abolished by cimetidine (4 mg . kg-1 loading, 1.4 mg . kg-1 . h-1 continuous infusion) or by pyrilamine maleate (5 mg . kg-1 bolus injection at beginning of irrigation, repeated at 40-50 min). Pyrilamine attenuated or abolished effects of topical dithiothreitol or salicylic acid. We conclude that during protein loss caused by dithiothreitol or salicylic acid, histamine released within the mucosa causes increased vascular permeability for plasma proteins

  20. 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.

  1. 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. PMID:19497430

  2. 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. PMID:16926041

  3. Primary culture of secretagogue-responsive parietal cells from rabbit gastric mucosa

    International Nuclear Information System (INIS)

    A new procedure for isolation and primary culture of gastric parietal cells is described. Parietal cells from rabbit gastric mucosa are enriched to greater than 95% purity by combining a Nycodenz gradient separation with centrifugal elutriation. Cells are plated on the basement membrane matrix, Matrigel, and maintained in culture for at least 1 wk. Parietal cells cultured in this manner remain differentiated, cross-react with monoclonal H+-K+-ATPase antibodies, and respond to histamine, gastrin, and cholinergic stimulation with increased acid production as measured by accumulation of the weak base, [14C]aminopyrine. When stimulated, cultured cells undergo ultrastructural changes in which intracellular canaliculi expand and numerous microvilli are observed. These ultrastructural changes are similar to those previously found to occur in vivo and in acutely isolated parietal cells. Morphological transformations in living cells can also be observed with differential interference contrast optics in the light microscope. After histamine stimulation, intracellular canaliculi gradually expand to form large vacuolar spaces. When the H2 receptor antagonist, cimetidine, is added to histamine-stimulated cells, these vacuoles gradually disappear. The ability to maintain hormonally responsive parietal cells in primary culture should make it possible to study direct, long-term effects of a variety of agonists and antagonists on parietal cell secretory-related activity. These cultured cells should also prove to be useful for the study of calcium transients, ion fluxes, and intracellular pH as related to acid secretion in single cells, particularly since morphological transformations can be used to monitor physiological responses at the same time within the same cell

  4. Mechanisms of histamine stimulated secretion in rabbit ileal mucosa.

    Science.gov (United States)

    Linaker, B D; McKay, J S; Higgs, N B; Turnberg, L A

    1981-11-01

    Histamine is present in high concentrations in the intestine and we investigated the possibility that it might have a role here in intestinal transport. When added to the basal side of rabbit ileal mucosa in vitro histamine (10(-4)M) induced a short-lived increase in electrical potential difference and short circuit current. It inhibited net chloride absorption but did not influence sodium transport. Alkali secretion, measured by a pH stat technique, was inhibited, suggesting that bicarbonate secretion was reduced. Both the electrical and ion flux responses to histamine were blocked by the H1 receptor blocker diphenhydramine, but not by the H2 receptor blocker cimetidine. The presence of specific H1 histamine receptors was further supported by shifts in the dose-response curve to histamine by four different concentrations of diphenhydramine. Calculation of a pA2 value from these "Schild' plots provided a figure of 7.85, which is similar to that for H1 receptors in other tissues. Aminoguanidine, a histaminase blocker, had no electrical effects alone but shifted the histamine dose response curve to the left. These studies indicate that histamine inhibits chloride absorption and alkali secretion, possibly by influencing a chloride/bicarbonate exchange process, through specific mucosal H1 receptors. Enhancement of histamine effects by a histaminase inhibitor suggests that histaminases are present in the intestinal mucosa and supports the possibility of a role for endogenous histamine in influencing ion transport. The observations indicate a mechanism by which absorption might be impaired in diseases in which histamine is liberated locally in the intestine. PMID:7308851

  5. Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review.

    Science.gov (United States)

    Cohen, Shlomi; Bueno de Mesquita, Mirjam; Mimouni, Francis B

    2015-08-01

    Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was to review the reported adverse effects of pharmacological agents used in the treatment of paediatric GERD. We conducted this review using the electronic journal database Pubmed and Cochrane database systematic reviews using the latest 10-year period (1 January 2003 to 31 December 2012). Our search strategy included the following keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide, betanechol, erythromycin, baclofen, alginate. We used Pubmed's own filter of: 'child: birth-18 years'. All full articles were reviewed and we only included randomized controlled trials retrieved from our search. We addressed a summary of our search on a drug-by-drug basis with regard to its mechanism of action and clinical applications, and reviewed all of the adverse effects reported and the safety profile of each drug. Adverse effects have been reported in at least 23% of patients treated with histamine H2 receptor antagonists (H2 RAs) and 34% of those treated with proton pump inhibitors (PPIs), and mostly include headaches, diarrhoea, nausea (H2 RAs and PPIs) and constipation (PPIs). Acid suppression may place immune-deficient infants and children, or those with indwelling catheters, at risk for the development of lower respiratory tract infections and nosocomial sepsis. Prokinetic agents have many adverse effects, without major benefits to support their routine use. PMID:25752807

  6. 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.

  7. Nalbuphine Sedation in a Patient with Long Term, High Dose Chemotherapeutically Controlled Psychosis

    Science.gov (United States)

    Kelly, Maureen; Howell, Robert M.

    1985-01-01

    Consideration of which pharmacologic agent to use when a patient requires sedation prior to an oral surgery procedure entails a number of factors, including past medical history, current medications and dose level, duration of administration, pharmacologic interactions, and the dental needs of the patient. The case described in this report illustrates the importance of consideration of these factors in a patient who required sedation prior to oral surgery while taking 800 mg chlorpromazine, 300 mg amantadine hydrochloride, and 900 mg of cimetidine daily. The possible pharmacologic interactions which could occur from concomitantly administering either diazepam or a narcotic in the presence of these agents are numerous and significant. The choice of sedative agent was further complicated by the fact that the patient was prescribed chlorpromazine and amantadine in doses which far exceeded the usual therapeutic levels and had been maintained for an extended period of time, over 8 months. Consequently, any adverse reactions that may have resulted when sedating a patient taking chlorapromazine and amantadine hydrochloride in lower doses for a shorter duration would be more likely to occur with greater speed and severity in a patient receiving such high-dose, long-term therapy. Also, unusual reactions which have not been reported with usual therapeutic dose levels might also occur since these high doses approach toxic levels for some patients. Additionally, a sedative agent had to be used which would not interfere with the antipsychotic effects of chlorpromazine since the patient's psychiatric condition required maintenance of these unusually high therapeutic levels. The following case report gives the rationale and outcome of utilizing nalbuphine for obtunding pain and producing sedation during an oral surgery procedure under such complex therapeutic conditions. PMID:3866505

  8. Nalbuphine sedation in a patient with long-term, high-dose chemotherapeutically controlled psychosis.

    Science.gov (United States)

    Kelly, M; Howell, R M

    1985-01-01

    Consideration of which pharmacologic agent to use when a patient requires sedation prior to an oral surgery procedure entails a number of factors, including past medical history, current medications and dose level, duration of administration, pharmacologic interactions, and the dental needs of the patient. The case described in this report illustrates the importance of consideration of these factors in a patient who required sedation prior to oral surgery while taking 800 mg chlorpromazine, 300 mg amantadine hydrochloride, and 900 mg of cimetidine daily. The possible pharmacologic interactions which could occur from concomitantly administering either diazepam or a narcotic in the presence of these agents are numerous and significant. The choice of sedative agent was further complicated by the fact that the patient was prescribed chlorpromazine and amantadine in doses which far exceeded the usual therapeutic levels and had been maintained for an extended period of time, over 8 months. Consequently, any adverse reactions that may have resulted when sedating a patient taking chlorapromazine and amantadine hydrochloride in lower doses for a shorter duration would be more likely to occur with greater speed and severity in a patient receiving such high-dose, long-term therapy. Also, unusual reactions which have not been reported with usual therapeutic dose levels might also occur since these high doses approach toxic levels for some patients. Additionally, a sedative agent had to be used which would not interfere with the antipsychotic effects of chlorpromazine since the patient's psychiatric condition required maintenance of these unusually high therapeutic levels. The following case report gives the rationale and outcome of utilizing nalbuphine for obtunding pain and producing sedation during an oral surgery procedure under such complex therapeutic conditions. PMID:3866505

  9. 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.

  10. Malignant melanoma of nasal fossae, a propos of a case

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    Gómez-González JL

    2012-07-01

    Full Text Available Introduction: The melanoma of the nasal fossae represents a 4% of all sinonasal malignant tumors. The symptoms are unspecific, thus delaying diagnosis. We present a case of a woman of 80 years of age. She has hypertension and a degenerative heart disease, and presents nasal respiratory insufficiency, left otalgia and epistaxis of 8 months of evolution. Examination revealed a dark, polypoidal, fleshy mass. The CT revealed a mass that occupied that space, without bone erosion. A biopsy of the mass revealed that it was an amelanotic melanoma. Due to the age of the patient and her general pathology, endoscopic sinonasal surgery was applied. The pathological anatomic analysis confirmed that it was a malignant round cell melanoma with the following phenotype: positive for Vimentin, positive for nuclear S-100, focal positive for HMB-45, negative, melan A+ negative for HMB-45 with heterogeneous intensity, and negative for ENE and ALC. The patient did not present symptoms until a year later, when she discovered a small laterocervical adenopathy. A FNAP confirmed that the melanoma had metastatized. The patient underwent a radical neck dissection and remained 15 months without symptoms. She is currently going through monthly revisions. Discussion: The treatment of choice is surgery. Selective neck dissection is not justified. This tumor is radioresistant. Active immunotherapy (a combination of Interferon and Cimetidine and targeted chemotherapy have also been used, mainly in inoperable cases. Five-year survival ranges between 6.5% and 34%.Conclusion: We propose endoscopic surgery for non-infiltrating tumors or for patients who cannot undergo very aggressive surgery due to their general condition.

  11. 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.

  12. Homopterocarpin contributes to the restoration of gastric homeostasis by Pterocarpus erinaceus following indomethacin intoxication in rats

    Institute of Scientific and Technical Information of China (English)

    M Tolulope Olaleye; Afolabi C Akinmoladun; Olamide O Crown; Katty E Ahonsi; A O Adetuyi

    2013-01-01

    Objective:To investigate the restorative effect ofPterocarpus erinaceus (P. erinaceus) and homopterocarpin, an isoflavonoid isolated from it, on indomethacin-induced disruption in gastric homeostasis in rats.Methods:Adult rats were divided into five groups and fasted for48 h before treatment.Group1 received olive oil (vehicle), group2 received25 mg/kg indomethacin while groups3-5 received cimetidine (100 mg/kg), homopterocarpin (25 mg/kg) andP. erinaceus ethanolic stem bark extract (100 mg/kg) respectively.After1 h, all the groups except group 2 were administered25 mg/kg of indomethacin.One hour later, the rats were sacrificed and the ulcer index and other gastroprotective indices were evaluated.Results:Indomethacin caused significant injury to the stomach of the rats as reflected in the ulcer indices (9.0±1.4) as compared with that of control (2.0±0.0).Equally, there were significant increases in gastric acid concentration and malondialdehyde level in the stomachs of the ulcerated animals compared with the control.However mucus content, reduced gluthatione level and gastric pH were significantly reduced in the ulcerated animals compared with the control.Pretreatment with eitherPterocarpus bark extract or homopterocarpin reversed the effects of indomethacin on the evaluated parameters.Conclusions:These results indicate that both homopterocarpin and Pterocarpus extract offered gastroprotection against indomethacin-induced ulcer by antioxidativemechanism and the modulation of gastric homeostasis.The results also suggest that homopterocarpin might be responsible for, or contribute to the antiulcerogenic property ofP. erinaceus.

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

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    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. 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.

  15. 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.

  16. Effect of the radioprotector WR-2721 on operant behavior in the rat

    International Nuclear Information System (INIS)

    The effect of WR-2721 on performance maintained by a fixed-ratio 20 (FR-20) schedule for water reinforcement was studied in male Sprague-Dawley rats. Graded doses of WR-2721 (range 25-100 mg/kg) were administered IP immediately prior to a 60 min test session. WR-2721 had a dose dependent monotonic disruptive effect on FR responding, with significant effects at doses of 50, 75 and 100 mg/kg. WR-2721 also decreased postsession water consumption, but only one significant effect at the highest dose (100 mg/kg). Both slopes of the dose-response regression line are parallel in effect. These data indicate that WR-2721 may affect drinking motivation, which could disrupt operant performance, and WR-2721 affects motor behavior at lower doses than those that depress motivation to drink. The log dose-probit analysis on the all-or-none disruptive pattern of pause of responding observed from cumulative records disclosed that the slope of this regression line (s = 1.11) was also almost identical to that of reinforcer decrement analyzed from graded dose-response relationship (s = 1.14) and shared the same estimated ED50's (58.5 and 55.6 mg/kg, respectively). A preliminary study using a variety of pharmacological interventions was also carried out to ascertain if the general functional gastrointestinal disorders produced by WR-2721 may subserve the behavioral deficits. Subcutaneous pretreatments with various selective, peripherally active, gastroprotective drugs [cimetidine (30 and 60 mg/kg), pirenzepine (5 and 10 mg/kg) and domperidone (1, 5 and 10 mg/kg)] 30 min prior to challenge with WR-2721 at dose of 100 mg/kg, demonstrated that these drugs did not yield any apparent significant attenuative effects

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

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    Abigail A. Kindberg

    2014-12-01

    Full Text Available 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.

  18. Relation between acid back-diffusion and luminal surface hydrophobicity in canine gastric mucosa: Effects of salicylate and prostaglandin

    International Nuclear Information System (INIS)

    The stomach is thought to be protected from luminal acid by a gastric mucosal barrier that restricts the diffusion of acid into tissue. This study tested the hypothesis that the hydrophobic luminal surface of canine gastric mucosa incubated in Ussing chambers, impedes the back-diffusion of luminal acid into the tissue. Isolated sheets of mucosa were treated with cimetidine to inhibit spontaneous acid secretion, and incubated under conditions that prevented significant secretion of luminal bicarbonate. By measuring acid loss from the luminal compartment using the pH-stat technique, acid back-diffusion was continuously monitored; potential difference (PD) was measured as an index of tissue viability. Tissue luminal surface hydrophobicity was estimated by contact angle analysis at the end of each experiment. Addition of 16,16-dimethyl prostaglandin E2 to the nutrient compartment enhanced luminal surface hydrophobicity, but did not reduce acid back-diffusion in tissues that maintained a constant PD. 10 mM salicylate at pH 4.00 in the luminal compartment reduced surface hydrophobicity, but this decrease did not occur if 1 ug/ml prostaglandin was present in the nutrient solution. Despite possessing relatively hydrophilic and relatively hydrophobic surface properties, respectively, acid back-diffusion in the absence of salicylate was not significantly different between these two groups. Neither group maintained a PD after incubation with salicylate. Lastly, radiolabeled salicylate was used to calculate the free (non-salicylate associated) acid loss in tissues incubated with salicylate and/or prostaglandin. No significant correlation was found between free acid back-diffusion and luminal surface hydrophobicity. These data do not support the hypothesis that acid back-diffusion in impeded by the hydrophobic surface presented by isolated canine gastric mucosa

  19. Anti-ulcerogenic effect of cavidine against ethanol-induced acute gastric ulcer in mice and possible underlying mechanism.

    Science.gov (United States)

    Li, Weifeng; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Wang, Yu; Niu, Xiaofeng

    2016-09-01

    Cavidine, a major alkaloid compound isolated from Corydalis impatiens, has various pharmacological effects but its effect on gastric ulcer has not been previously explored. The current study aimed to investigate the possible anti-ulcerogenic potential of cavidine in the model of ethanol-induced gastric ulcer. Mice received cavidine (1, 5 or 10mg/kg, ig), cimetidine (CMD, 100mg/kg, ig) or vehicle at 12h and 1h before absolute ethanol administration (0.5mL/100g), and animals were euthanized 3h after ethanol ingestion. Gross and histological gastric lesions, biochemical, immunological and Western blot parameters were taken into consideration. The results showed that ethanol administration produced apparent mucosal injuries with morphological and histological damage, whereas cavidine pre-treatment reduced the gastric injuries. Cavidine pre-treatment also ameliorated the contents of malonaldehyde (MDA) and myeloperoxidase (MPO) activity, and increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and prostaglandin E2 (PGE2), relative to the model group. Also cavidine was able to decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), inhibit the up-regulation of cyclo-oxygenase-2 (COX-2) expression and activation of Nuclear factor-kappa B (NF-κB) pathway. Taken together, these results indicated that cavidine exerts a gastroprotective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, reduction of oxidative stress, suppression of NF-κB expression and subsequent reduced COX-2 and pro-inflammatory cytokines. PMID:27380619

  20. Effect of adenosine and adenosine analogs on ( sup 14 C)aminopyrine accumulation by rabbit parietal cells

    Energy Technology Data Exchange (ETDEWEB)

    Ota, S.; Hiraishi, H.; Terano, A.; Mutoh, H.; Kurachi, Y.; Shimada, T.; Ivey, K.J.; Sugimoto, T. (Univ. of Tokyo (Japan))

    1989-12-01

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on (14C)aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. (14C)Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated (14C)aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on (14C)aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased (14C)aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.

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

    International Nuclear Information System (INIS)

    Highlights: • A PVDF–TiO2 photocatalyst was fabricated by electrospinning and electrospraying. • The TiO2 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 (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 cm2 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

  2. Modulatory effects of taurine on jejunal contractility

    International Nuclear Information System (INIS)

    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

  3. Syzygium aromaticum water extract attenuates ethanol‑induced gastric injury through antioxidant effects in rats.

    Science.gov (United States)

    Jin, Seong Eun; Lee, Mee-Young; Shin, In-Sik; Jeon, Woo-Young; Ha, Hyekyung

    2016-07-01

    The aim of the present study was to investigate whether Syzygium aromaticum water extract (SAWE) has a protective effect against ethanol‑induced gastric injury in rats. Acute gastric injury was induced via intragastric administration of absolute ethanol at a dose of 5 ml/kg. SAWE (250 or 500 mg/kg/day) or cimetidine (100 mg/kg/day), which was used as a positive control, were administered to the rats 2 h prior to ethanol administration for 3 days. All rats were sacrificed 24 h following the final ethanol administration. To examine whether SAWE has a gastroprotective effect, assays were performed to assess the contents of malondialdehyde (MDA) and glutathione (GSH), the activities of catalase, glutathione‑S‑transferase and superoxide dismutase, and an immune-linked immunosorbent assay was performed for prostaglandin E2 (PGE2) production in gastric tissues by hematoxylin and eosin and periodic acid-Schiff staining. Histological assessment of the gastric wall was performed. Compared with ethanol treatment alone, treatment with SAWE at a dose of 250 mg/kg/day significantly decreased the gastric MDA content and increased the GSH content, catalase activity, and production of gastric PGE2. Histological assessment showed that SAWE attenuated inflammatory cell infiltration and the loss of epithelial cells. These findings suggested that SAWE protected against ethanol‑induced gastric mucosal injury in the rats. These effects appeared to be associated with antioxidant activity, activation of the production of PGE2, suppression of inflammatory cell infiltration and loss of epithelial cells in the gastric mucosa. Collectively, SAWE may be beneficial in the prevention of gastric disease associated to oxidative stress. PMID:27177078

  4. The relationship between Na+/H+ exchanger expression and tyrosinase activity in human melanocytes

    International Nuclear Information System (INIS)

    The activity of melanosome-associated tyrosinase in human melanocytes differs based on racial skin type. In melanocytes from Black skin, tyrosinase activity is high while in White melanocytes the activity of the enzyme is low. Recent studies suggest that low tyrosinase activity in White melanocytes may be due to an acidic pH environment within the melanosome. Because sodium/hydrogen (Na+/H+) exchangers (NHEs) are known to regulate intracellular pH, melanocytes were treated with NHE inhibitors to determine what effect this inhibition might have on tyrosinase activity. Treatment of Black melanocytes with ethyl-isopropyl amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity. This inhibition was not due to either direct enzyme inhibition or to a decrease in tyrosinase abundance. In contrast, treatment of White melanocytes with EIPA, cimetidine, or clonidine resulted in little inhibition of tyrosinase activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis showed that both Black and White melanocytes expressed mRNA and protein for NHE-1, NHE-3, NHE-5, NHE-6, and NHE-7. Immunohistochemical analysis showed that NHE-7 and NHE-3 co-localized with the melanosomal protein, Tyrosinase Related Protein-1 (TRP-1). In addition, the vesicular proton pump, vesicular ATPase (V-ATPase), was found to be present in both White and Black melanosomes, indicating that organelles from both racial skin types are capable of being acidified. The results suggest that one or more NHEs may help regulate melanosome pH and tyrosinase activity in human melanocytes

  5. Microscopic colitis

    Directory of Open Access Journals (Sweden)

    Gianluca Ianiro

    2012-01-01

    Full Text Available 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-epithelial 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.

  6. 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.

  7. Investigation of biological activity of polar extracts isolated from Phlomis crinita Cav ssp. mauritanica Munby.

    Science.gov (United States)

    Limem-Ben Amor, Ilef; Skandrani, Ines; Boubaker, Jihed; Ben Sghaïer, Mohamed; Neffati, Aicha; Bhouri, Wissem; Bouhlel, Ines; Chouchane, Nabil; Kilani, Soumaya; Guedon, Emmanuel; Ghoul, Mohamed; Ghedira, Kamel; Chekir-Ghedira, Leila

    2009-01-01

    The lyophilized infusion, the methanol, the ethyl acetate, and the total oligomer flavonoid (TOF)-enriched extracts prepared from the dried leaves of Phlomis crinita Cav. ssp. mauritanica Munby were investigated for the contents of flavonoids, tannins, coumarines and steroids. Antibacterial activity was investigated toward five bacterial strains. An inhibitory effect was observed against Staphyllococcus aureus and Enterococcus feacalis, and the minimal inhibitory concentrations ranged from 2.5 to 5 mg/mL of extract. The tested extracts exhibit an important free radical scavenging activity toward the 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical; with IC(50) values of 30.5, 6, 32, and 31.5 microg/mL, respectively, in the presence of lyophilized infusion, the TOF, the methanol, and the ethyl acetate extracts. Genotoxic and antigenotoxic properties of the different extracts were studied by using the SOS chromotest with Escherichia coli PQ37. The lyophilized infusion and TOF extracts obtained from P. crinita ssp. mauritanica showed no genotoxicity, whereas methanol and ethyl acetate extracts are considered as marginally genotoxic. On the other hand, we showed that each extract inhibited the mutagenicity induced by aflatoxin B1 (AFB1) (10 microg/assay) and nifuroxazide (NF) (10 microg/assay). The ethyl acetate extract showed the strongest level of protection toward the genotoxicity induced by both directly and indirectly genotoxic NF and AFB1. These tests proved that the lyophilized infusion possesses an antiradical activity likewise, it showed no genotoxic effect; that is why we choose this extract to assess its antiulcerogenic activity by using an ethanol-induced ulcerogenesis model in the rat. This test demonstrates that 300 mg/kg of a P. crinita ssp. mauritanica lyophilized infusion was more effective than the reference compound, cimetidine. PMID:19514937

  8. Size-dependent effects of nanoparticles on the activity of cytochrome P450 isoenzymes

    International Nuclear Information System (INIS)

    Nanoparticles are known to be able to interfere with cellular metabolism and to cause cytotoxicity and moreover may interfere with specific cellular functions. Serious effects on the latter include changes in liver cell function. The cytochrome P450 system is expressed in many cells but is especially important in hepatocytes and hormone-producing cells. The interaction of polystyrene nanoparticles with the most important drug-metabolizing cytochrome P450 isoenzymes, CYP3A4, CYP2D6, CYP2C9 and CYP2A1 expressed individually in insect cells (BACULOSOMES) was studied by the cleavage of substrates coupled to a fluorescent dye. The data obtained for individual isoenzymes were compared to metabolism in microsomes isolated from normal liver and from the hepatoma cell line H4-II-E-C3. Small (20-60 nm) carboxyl polystyrene particles but not larger (200 nm) ones reached high intracellular concentrations in the vicinity of the endoplasmic reticulum. These small particles inhibited the enzymatic activity of CYP450 isoenzymes in BACULOSOMES and substrate cleavage in normal liver microsomes. They moreover increased the effect of known inhibitors of the cytochrome P450 system (cimetidine, phenobarbital and paclitaxel). Substrate cleavage by the hepatoma cell line H4-II-E-C3 in contrast was undetectable, making this cell line unsuitable for this type of study. Our results thus demonstrate that nanoparticles can inhibit the metabolism of xenobiotics by the CYP450 system in model systems in vitro. Such inhibition could also potentially occur in vivo and possibly cause adverse effects in persons receiving medication.

  9. Intestinal Oxidative State Can Alter Nutrient and Drug Bioavailability

    Directory of Open Access Journals (Sweden)

    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.

  10. Effect of adenosine and adenosine analogs on [14C]aminopyrine accumulation by rabbit parietal cells

    International Nuclear Information System (INIS)

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on [14C]aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. [14C]Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated [14C]aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on [14C]aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased [14C]aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion

  11. Radioprotective properties of histamine H2 receptor antagonists. Present and Future prospects

    International Nuclear Information System (INIS)

    Various chemical agents were examined for their radioprotective capability to provide partial protection against radiation injury over the past 50 years. However, no suitable drug has yet been introduced for routine clinical use. In the present study, the radioprotective potential of H2 receptor antagonists was examined in in vivo and in vitro conditions. For this purpose, an in vivo micronucleus assay and an in vitro metaphase analysis were used to test the effects of cimetidine, ranitidine, and famotidine on radiation-induced clastogenic effects. For micronuclei assay, BALB/c mice were irradiated in the presence or absence of drugs, and slides were prepared from bone marrow cells. The frequency of micronuclei was determined in bone marrow erythrocytes. For the in vitro assay, lymphocytes in whole peripheral blood were exposed to radiation in the presence or absence of drugs, and the frequency of chromosomal aberrations were determined. The results show that radiation produced a high number of micronuclei in polychromatic erythrocytes (PCE) and chromosomal aberrations in lymphocytes. All three drugs used in this study effectively reduced the frequency of radiation-induced micronuclei and chromosomal aberrations at various doses. Famotidine was found to be more effective than the other two drugs. From the results obtained, it can be concluded that H2-receptor antagonists reduced the clastogenic effects of radiation with a dose reduction factor (DRF) of 1.5-2 in vivo and in vitro. The way in which these drugs reduce the clastogenic effects of radiation might be via a radical scavenging mechanism. (author)

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

    International Nuclear Information System (INIS)

    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

  13. Radioprotective effects of histamine H2 receptor antagonists famotidine and ranitidine on gamma ray induced chromosome damage

    International Nuclear Information System (INIS)

    Histamine H2 receptor antagonist such as Cimetidine, Famotidine and Ranitidine are used in the clinical treatment of peptic ulcer. In vitro metaphase analysis and micronucleus assay were used to test the effects of famotidine and ranitidine on Cobalt 60 γ-ray induced clastogenic effects. Heparinised whole blood was obtained from healthy non-smoker volunteers. Blood samples were irradiated at a dose of 3Gy and incubated at 37 deg C for 1h. Lymphocyte cultures were initiated for metaphase chromosomes and cytochalasin B blocked micronucleus analysis. Aqueous solution of Famotidine (150 g/ml) and Ranitidine (500 g/ml) was added to the whole blood cultures at 0h and 24h. Cultures were harvested and processed at 48h and 72h for chromosome aberrations and micronucleus analysis respectively. Cultures treated with Famotidine at 0h and 24h after 3Gy γ-ray irradiation induce 60.90% and 56.52% inhibition in dicentrics, 48.70% and 43.61% inhibition in total aberrations. Ranitidine at 0h and 24h after 3Gy γ-ray irradiation induce 52.17% and 43.47% inhibition in dicentrics, 33.60% and 46.15% inhibition in total aberrations, when compared with 3Gy γ-ray irradiation alone. 43-54% inhibition in Binucleated cells with micronuclei and 47.72% inhibition in micronuclei at 0h treatment respectively. In conclusion radioprotective effects of Histamine H2 receptor antagonists famotidine and ranitidine on γ-ray induced chromosome damage is observed and the drugs effectively reduced the frequency of radiation induced chromosome aberrations and micronucleus. Famotidine was found to be more effective. The mechanism in which these drugs reduce clastogenic effect of γ-radiation is not fully understood. It might be due to their antioxidant and free radical-scavenging properties. (author)

  14. Effects of radioprotectors on mutation in cultured mammalian cells by carbon beam

    International Nuclear Information System (INIS)

    The project goal is understand genotoxic effects of high linear energy transfer (LET) radiations, e.g. carbon, 290 MeV/nucleon: LET=100 KeV/μm [C290], and to identify chemicals that can prevent or decrease such pathologies in cultured cells and in exposed humans. We have now quantified effects of C290-induced genotoxicity of several chemicals including WR-1065, cimetidine, lycopene, RibCys [(R, S)-D-ribo(1', 2', 3', 4'-Tetrahydroxybutyl)-thiazolidine-4(R)-ca riboxylic acid, N-acetyl cysteine (NAC), Dimethyl sulfoxide (DMSO) and vitamin C, and combinations of DMSO plus Vitamin C. In vitro, vitamin C showed the most promise. It significantly reduced mutant induction by C290 and also reduced the yield of mutants displaying the cancer-related property of genomic instability even when added after radiation. Unfortunately vitamin C was less effective at doses below 5 mM, which is too high for use in humans. So we are turning to using non-toxic levels of vitamin C in combination with other chemicals. Our recent preliminary results and those of Dr. J. Kumagai indicate that NAC, at doses well tolerated by humans and which scavenge classical hydroxyl radicals, also effectively scavenge mutagenic, long-lived radicals (LLR). We plan, therefore, to evaluate the combined effect of NAC + vitamin C on X-ray mutagenicity (but not initially at Heavy Ion Medical Accelerator in Chiba (HIMAC)). If these experiments look promising we would like to propose experiments with high LET radiation at HIMAC in collaboration with Dr. Kumagai. (author)

  15. 药物联合治疗膀胱疼痛综合征/间质性膀胱炎的疗效及影响因素%Efficacy and prognositic factors of combined medical therapy for painful bladder syndrome/ interstitial cystitis

    Institute of Scientific and Technical Information of China (English)

    张宁; 张鹏; 王飚; 张小东; 杨勇

    2009-01-01

    史者、妇科手术或尿道手术史者疗效不佳.%Objective To evaluate the efficacy and prognostic factors of combined medical thera-py with amitriptyline, cimetidine and intravesical resiniferatoxin post-hydrodistention for patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Methods Twenty-nine patients with PBS/ IC according to NIDDK criteria were enrolled. There were 6 males and 23 females with average age of 52±14 years and average duration of symptoms of 3.7±1.9 years before diagnosis. The patients were divided into 2 groups. Non-concomitant disease group included 10 cases without concomitant disease and 7 cases with unrelated diseases such as hypertension and diabetes mellitus. Concomitant disease group included 5 cases with history of bladder neck incision, 3 cases with history of transurethral re-section of the prostate, 2 cases with history of gynecologic disease and 2 cases with history of gyneco-logic operation. Patients of concomitant disease group still had the painful bladder syndrome after 3 months when the primary disease had been cured. All patients were treated with amitriptyline (25 mg twice a day), cimetidine (800 mg per day) and intravesical resiniferatoxin (1-2 times) post-hydrodis-tention. The primary assessment index was O'Leary-Sant score. The secondary assessment index was pelvic pain score, mean voiding times per day and mean volume of each micturating. The data of pa-tients before treatment and after follow-up≥9 months were collected to evaluate the efficacy and prog-nostic factors of the combined treatment. Results The mean follow-up for all patients was 9.2±6.0 months. Patients were followed up at month 1 and month 6 after discharge. Then, patients would be followed up at each 6 months interval. The overall remission rate was 65.5% (19/29). Complete re-mission rate was 41.4% (12/29). Partial remission was 24. 1% (7/29). Non-remission rate was 34.5% (10/29). For all patients, the pre-treatment mean voiding

  16. Scintigraphic assessment of Barrett's esophagus

    International Nuclear Information System (INIS)

    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

  17. 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

  18. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  19. 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

  20. Efecto del OLEOZON® frente a lesiones gástricas inducidas por indometacina en ratas (Effect of OLEOZON® on gastric lesions induced by indomethacin in rats

    Directory of Open Access Journals (Sweden)

    González Alvarez Ricardo

    2007-03-01

    indomethacin. In the second experiment gastric lesions were induced by indomethacin and thereafter treated with Oleozon in the same range of doses. Gastric lesions were evaluated determining the ulceration index. Cimetidine was used as areference antiulcer drug. The results demonstrated that the pretreatment with Oleozon did not prevent gastric damageinduced by indomethacin and therefore did not exert cytoprotective effect. In contrast, the treatment with Oleozon induced reversionof gastric lesions induced previously by indomethacin. These results support the potential therapeutic effectiveness of Oleozon as antiulcer drug in this experimental model.

  1. Determination of the antiepileptics vigabatrin and gabapentin in dosage forms and biological fluids using Hantzsch reaction.

    Science.gov (United States)

    al-Zehouri, J; al-Madi, S; Belal, F

    2001-02-01

    A selective and sensitive method was developed for the determination of the anticonvulsants vigabatrin (I) (CAS 60643-86-9) and gabapentin (II) (CAS 60142-96-3). The method is based on the condensation of the drugs through their amino groups with acetylacetone and formaldehyde according to Hantzsch reaction yeilding the highly fluorescent dihydropyridine derivatives. The yellowish-orange color was also measured spectrophotometrically at 410 nm and 415 nm for I and II, respectively. The absorbance-concentration plots were rectilinear over the ranges 10-70 micrograms/ml and 20-140 micrograms/ml for I and II, respectively. As for the fluorescence-concentration plots, they were linear over the ranges 0.5-10 micrograms/ml and 2.5-20 micrograms/ml with minimum detection limits (S/N = 2) of 0.05 microgram/ml (approximately 2.1 x 10(-8) mol/l) and 0.1 microgram/ml (approximately 5.8 x 10(-7) mol/l) for I and II, respectively. The spectrophotometric method was applied to the determination of I and II in their tablets. The percentage recoveries +/- SD (n = 6) were 99.45 +/- 0.13 and 98.05 +/- 0.53, respectively. The spectrofluorimetric method was successfully applied to the determination of I and II in spiked human urine and plasma. The % recoveries +/- SD (n = 5) were 98.77 +/- 0.29 and 98.39 +/- 0.53 for urine and 99.32 +/- 0.74 and 98.90 +/- 0.96 for plasma, for I and II, respectively. No interference was encountered with the co-administered drugs: valproic acid (CAS 99-66-1), diphenylhydantoin (CAS 57-41-0), phenobarbital (CAS 50-06-6), carbamazepine (CAS 298-46-4), clonazepam (CAS 1622-61-3), clobazam (CAS 22316-47-8) or cimetidine (CAS 51481-61-9). A proposal of the reaction pathway is suggested. The advantages of the proposed methods over existing method are discussed. PMID:11258050

  2. Relato de um caso de latrodectismo ocorrido em Manaus, Amazonas, Brasil Report of a case of latrodectism occurred in Manaus, Amazonas, Brazil

    Directory of Open Access Journals (Sweden)

    Alcidéa R. B. de Souza

    1998-02-01

    Full Text Available Em 02/07/1995, foi atendido no Instituto de Medicina Tropical do Amazonas, paciente masculino, 11 anos, acidentado em Manaus, por picada na região retroauricular direita, clínicamente compatível com aquele causado por Latrodectus. Observavam-se abalos musculares, febre, calafrios e sudorese intensa. Instituída terapêutica com neostigmine precedido de atropina, gluconato de cálcio, cimetidina, diazepam e hidrocortisona. No terceiro dia apresentava-se melhorado, consciente, orientado e com diminuição importante do edema palpebral. A despeito de uma melhora progressiva diária, no quinto dia surgiu eritema máculo-pápulo-vesiculoso. Em 14/07/1995 teve alta, assintomático. O caso relatado é o primeiro descrito na região Amazônica, ocorrido na periferia de Manaus e pode ter sido uma consequência da expansão urbana das duas últimas décadas.In July 2, 1995 arrived at the Instituto de Medicina Tropical do Amazonas an eleven-year-old male with complaining of spider bite on his right retroauricular region, presenting typical findings of latrodectism. The accident was reported as having ocurred in the suburbs of Manaus. The patient was given neostigmine preceded by atropin, calcium gluconate, cimetidin, diazepan and hidrocortisone. Within three days the patient showed improvement, and was aware, orientated and with significant palpebral oedem reduction. Muscle spasms are still present, as well as fever, shivering, and intense sweating. In spite of a daily progressive improvement, at the fifth day appeared a spotted papular erythem. The patient was discharged without simptoms after the13th day. This is the first such reported case which took place in Amazonian region, it might have been happened a consequence of the urban sprawl wich has characterized the growth of the city of Manaus, in the last twenty years. It is not possible at this point to evaluate the epidemiolgical resounds of the event, but in any case, it seems plausible to

  3. Gynaecomastia: management in a developing country

    International Nuclear Information System (INIS)

    Gynaecomastia is a benign enlargement of male breast. It is common in the general population, resulting from various pathophysiological mechanisms. The aim of this study was to describe the presentation and outcome of treatment for gynaecomastia at a University Hospital in Pakistan. Methods: A three year retrospective study was carried out of one hundred men with gynaecomastia. Patients were evaluated in detail clinically and by appropriate investigations. They were counselled and kept on hormonal therapy for three months. Surgery was considered for patients with long standing gynaecomastia, failed medical therapy and for cosmetic reasons. Post operative complications and patient's satisfaction was assessed. Results: Most (90%) cases were idiopathic. Other causes were liver cirrhosis in 4 cases, testicular tumour in two, thyrotoxicosis in one and drug induced (use of cimetidine and Kushta) in two. Carcinoma of the breast was diagnosed in one patient. Most of the patients had bilateral, non tender lump in the breast. Three cases of idiopathic gynaecomastia resolved on danazol. Eighty-eight cases underwent surgical treatment. The mean age of patients who underwent surgery (n=88) was 30.5+-9.59 years. Most of the patients belonged to 21-30 years age group. Major indications for surgery were failure of medical treatment (45.5%) and cosmetic reasons (34.0%). Mean operating time for subcutaneous mastectomy was 42.2 +- 3.70 (36-48) minutes. Mean hospital stay after subcutaneous mastectomy was 5.2+- 2.44 (2-10) days. The only postoperative complication noted was wound infection (24%). Seventy-two (81.8%) were satisfied with the results of their surgical treatment. Conclusion: Gynaecomastia is the common condition affecting male breasts and most common cause of gynaecomastia is idiopathic. Secondary gynaecomastia may regress in size by treating the primary cause. Idiopathic gynaecomastia do not respond to danazol so they needed surgical treatment. Subcutaneous mastectomy

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

    Directory of Open Access Journals (Sweden)

    Hu XF

    2015-08-01

    Full Text Available Xiufen Hu,1,* Mohammad Ishraq Zafar,2,* Feng Gao2 1Department of Paediatrics, Tongji Hospital, 2Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: 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 (OVA323–339 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

  5. Úlcera gastroduodenal: problemática de la morbilidad

    Directory of Open Access Journals (Sweden)

    Luis Manuel Fernández Machín

    2000-10-01

    Full Text Available Se realizó un estudio descriptivo, restrospectivo en 4 consultorios atendidos por Médicos de la Familia, pertenecientes al Policlínico "Plaza de la Revolución" para señalar los principales problemas de salud que afectan la morbilidad por úlcera gastroduodenal, en el período comprendido desde enero de 1996 hasta diciembre de 1997. El sexo masculino representó el 65,7 % de la muestra en estudio y los grupos de edades de mayor prevalencia fueron de 31 a 40 años y de 51 a 60. El 42,1 % de los pacientes que refirieron antecedentes patológicos familiares de afecciones gastroduodenales desarrollaron úlcera gastroduodenal. La localización duodenal se presentó en un 77,1 % de los casos. El café fue el más frecuente de los hábitos tóxicos, siguiéndole el alcohol; entre los medicamentos ingeridos, la aspirina representó el 17,1 % de los casos. Los esquemas de tratamiento más empleados fueron la cimetidina y otros medicamentos (74,3 %, los regímenes lácteos (65,7 % y los antiácidos (62,9 %. La endoscopia y la radiología (40 % asociada a la endoscopia fueron los métodos más frecuentes para el diagnóstico. Asimismo, el sangramiento digestivo alto fue la complicación más observada (28,6 %A descriptive and retrospective study was conducted in 4 family physician?s offices from the Plaza de la Revolución? Polyclinic to stress the main health problems affecting morbidity from peptic ulcer between January, 1996, and December, 1997. Males accounted for 65,7 % of the sample under study, whereas the highest prevalence was observed in the age groups 31-40 and 51-60. 42,1 % of the patients who had pathological family history of gastroduodenal disorders developed peptic ulcer.The duodenal localization was present in 77,1 % of the cases. Coffee was the most frequent of the toxic habits, followed by alcohol. Among the drugs taken by the patients, aspirin represented 17,1 % of the cases. The most used schemes of treatment were cimetidine and

  6. Effects of Different Adjuvant on the Immune Responses to Recombi-nant Protein L2E7E6 of Human Papillomavirus Type 16 in Mice%不同佐剂对人乳头瘤病毒16型L2E7E6蛋白免疫效果的影响

    Institute of Scientific and Technical Information of China (English)

    任皎; 赵莉; 高孟; 姜云水; 郝明强; 谭文杰; 田厚文; 阮力

    2013-01-01

      Objective: To investigate the effects of CpG, freund adjuvant, poly I:C, levamisole and cimetidine on the immune responses to recombinant protein L2E7E6 of human papillomavirus type 16 in mice. Methods: C57BL/6 mice were immunized with recombinant protein L2E7E6 combined with or without CpG, freund adjuvant, poly I:C, levamisole or cimetidine through intramuscular. Then the humoral and cellular immune responses were detected by ELISA and ELISPOT respectively, and the effects of tumor growth regression were measured by using the TC-1 tumor bearing mice model. Results: All of groups mice immunized with the recombinant protein L2E7E6 combined with or without adjuvant could elicit high specific IgG antibodies titer against L2, E7 and E6 proteins (IgG1 antibodies were predominant), among which those with freund adjuvant could secret higher IgG and IgG1 antibodies against E6 antigen and higher IgG1 antibody against E7 antigen respectively(P<0.05), and those with CpG could secret higher Th1-associated IgG2a antibodies against E7 antigen(P<0.05), however those with cimeti⁃dine could secret lower IgG antibody against E7 antigen(P<0.05). Furthermore, the mice vaccinated with the re⁃combinant protein combined with CpG could elicit stronger T cell immune responses to peptides E7 and E6 re⁃spectively, and eliminate the established TC-1 tumors in 70% vaccinated mice. In addition, those mice vaccinated with freund adjuvant and poly I:C were able to elicit moderate cellular immune responses to peptide E7 and de⁃layed tumor appearance in tumor-bearing mice. Conclusion: Accompanied with CpG, freund adjuvant or poly I:C, the recombinant protein could be enhanced on the cellular immune response and the effects of tumor growth re⁃gression in immunized mice, and it could have better effects with the CpG, which will provide the basis to devel⁃ op the L2E7E6 protein as one promising candidate vaccine.%  目的:研究CpG佐剂、弗氏佐剂、聚肌胞苷酸佐剂

  7. 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

  8. 左氧氟沙星在人胃黏膜上皮细胞中的摄取特征%Study on the uptake of levofloxacin by gastric epithelial system cells

    Institute of Scientific and Technical Information of China (English)

    胡兴萍; 胡咏梅; 张磊; 张珊珊; 许建明

    2014-01-01

    Objective To investigate the uptake mechanisms of levoflox-acin by gastric epithelial system ( GES-1 ) cells.Methods The uptake of levofloxacin in GES-1 cells were determined by HPLC and coomassie brilliant blue.The influences of incubated time ,extracellular levofloxacin concentrations, pH, temperature, inhibitors of transporters on the uptake of levofloxacin by GES -1 cells were tested.Results The uptake of levofloxacin by GES-1 cells was increased sharply at 1-5 minutes then was increased moderately at 7.5 -15.0 minutes and reached a steady state after the start of the incubation.The accumulation of levofloxacin increased with the extracellar levels ,but which was not linearly.The up-take of levofloxacin reached a maximum when temperature was 37 ℃and pH was 7.4.The increase in levofloxacin accumulation by cyclosporin A and verapamil in GES -1 cells was by 2.81% -13.23%, 2.07% -10.28%, respectively ( P >0.05 ).Effect of the cimetidine was not same that the two drugs.Conclusion Levofloxacin enters into GES -1 cells in carrier-mediated transport manner.P-gp might be involved in the process of uptake of levofloxacin in GES -1 cells.%目的:研究左氧氟沙星在人胃黏膜上皮细胞(GES-1)中的摄取特征。方法 GES-1细胞与左氧氟沙星孵育后用高效液相色谱法和考马斯亮蓝法研究其在细胞内的药物摄取量,同时考察时间、药物浓度、温度、pH值和转运体抑制剂(环孢素A、维拉帕米和西咪替丁)对左氧氟沙星在GES-1细胞中摄取的影响。结果在GES-1细胞内,左氧氟沙星摄取量,在1~5 min明显增加,在7.5~15.0 min缓慢增加并达到稳态;摄取量随着细胞外左氧氟沙星浓度的增加而增加,但不呈线性增加。在37℃、pH 7.4时,摄取量最大。环孢素A和维拉帕米能增加细胞内药物摄取量,分别较对照组增加了2.81%~13.23%,2.07%~10.28%,但差异无统计学意义( P>0.05);西咪替丁对此均

  9. Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide

    Directory of Open Access Journals (Sweden)

    Jeong HU

    2015-01-01

    Full Text Available Hyeon-Uk Jeong,1 Mihwa Kwon,2 Yongnam Lee,3 Ji Seok Yoo,3 Dae Hee Shin,3 Im-Sook Song,2 Hye Suk Lee1 1College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea; 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea; 3Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea Abstract: We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1, OAT3, organic anion transporting polypeptide 1B1 (OATP1B1, OATP1B3, organic cation transporter 1 (OCT1, OCT2, P-glycoprotein (P-gp, and breast cancer resistance protein (BCRP. The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3 and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3. The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km =41.5 µM, maximum uptake rate (Vmax =46.2 pmol/minute, and intrinsic clearance (CLint =1.11 µL/minute. OATP1B1- and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 µL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µ

  10. Study on the Curative Effect of Esomeprazole Combined with Xylitol Infu-sion in the Treatment of Gastrointestinal Hemorrhage%埃索美拉唑联合木糖醇注射液治疗消化道出血疗效分析

    Institute of Scientific and Technical Information of China (English)

    张慧

    2015-01-01

    目的:分析消化道出血行埃索美拉唑与木糖醇注射液联合治疗的效果。方法回顾性分析2013年2月-2015年2月该院收治的消化道出血130例患者临床资料,按数字表法分为观察组和对照组,每组65例。对照组行西咪替丁治疗,观察组行埃索美拉唑与木糖醇注射液联合治疗,比较两组疗效。结果观察组总有效率96.92%显著比对照组70.77%高,且平均止血时间(1.50±0.02)d比对照组(3.65±2.36)d少,平均治疗时间(10.02±8.10)d比对照组(25.15±12.50)d少,比较差异均有统计学意义(P<0.05)。结论消化道出血患者行埃索美拉唑与木糖醇注射液联合治疗的效果显著,可有效止血。%Objective To analyze the effect of Esomeprazole combined Xylitol infusion in the treatment of gastrointestinal hemor-rhage. Methods The clinical data of 130 patients with gastrointestinal hemorrhage treated in our hospital between February 2013 and February 2015 were reviewed, and were randomly divided into an observation group and a control group, each with 65 cases. Patients in the control group received Cimetidine for treatment, whereas those in the observation group were given Esomeprazole and Xylitol infusion combined for treatment. The curative effect was compared between the two groups. Results The total rate treatment effectiveness in the observation group was 96.92%, significantly higher than that in the control group, which was 70.77%; And the mean time to hemostasis (1.50 ± 0.02) d d less than in the control group (3.65 ± 2.36), the mean duration of treatment (10.02 ± 8.10) d less than in the control group (25.15 ± 12.50) d, differences were statistically significant (P<0.05). Conclusion The combined therapy of Esomeprazole and Xylitol infusion is with significant curative effect for treating gastrointesti-nal bleeding, which can effectively stop the hemorrhage.

  11. 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

  12. Application of Combined Bacillus Subtilis and Enterococcus Faecium Granules with Multivitamines-Live in Treatment of Henoch Purpura in Children%枯草杆菌二联活菌颗粒在儿童腹型过敏性紫癜中的应用

    Institute of Scientific and Technical Information of China (English)

    左满凤; 艾柳; 舒琼璋; 董晶

    2012-01-01

    Objective:To observe the adjunctive effect of the viable organism praeparatum Combined Bacillus Subtilis and Enterococcus Faecium Granules with Multivitamines-Live(Medilae-Vita) in the treatment of henoch purpura in children. Methods: Together 139 children with henoch purpura as research subjects were divided into observation group and control group by random number table method. In the control group, children were treated with cimetidine, vitamin C, calcium, glucocorticosteroid; and antibiotics therapy was given to those who had combined infection. The observation group were given Medilac-Vita in addition to the same treatment as the control group. Aged 4~6 years, 1 g each time; aged - 12 years, 1. 5 g each time; all three times a day, 7 days as a course of treatment. The symptom changes of digestive tube ( stomachache, emesia, hemafecia), levels of salivary secretary IgA ( sIgA) and clinical effect after treatment in I week of the two groups were observed. Results: The extinction time of digestive tube symptoms in observation group was less than that of the control group (P0.05). The total effective rate in observation group was 95.71% , while that of the control group was 81.82% , there was significant difference in the two groups (x2 = 4. 978, P<0. 05). Conclusions: Viable organism praeparatum Medilac-Vila can enhance the immunity of mucous membrane. In the treatment of henoch purpura in children, it can relieve digestive tube symptoms quickly, prevent alimentary tract hemorrhage, and shorten the course of treatment%目的:观察枯草杆菌二联活菌颗粒在儿童腹型过敏性紫癜(HSP)治疗中的辅助作用.方法:将139例腹型HSP住院患儿中完成研究的125例纳入研究对象,采用随机数字表法随机分为观察组70例和对照组55例.对照组给予西咪替丁、维生素C、钙剂及糖皮质激素等综合治疗,合并感染者给予抗生素治疗,观察组在对照组治疗基础上加服枯草杆菌二联活菌颗粒,年龄4

  13. 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