bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of Procarbazine as an Inhibitor In-vitro of Rat Semicarbazide-sensitive Amine Oxidase
Authors: Holt Andrew , Sharman Dennis F , Callingham Brian A , Kettler Rolf 
Published: April 2011

Abstract
Procarbazine (N-isopropyl-α-(2−methyl hydrazino)-p-toluamide hydrochloride) inhibited more powerfully the deamination of benzylamine by semicarbazide-sensitive amine oxidase (SSAO) of rat brown adipose tissue than the deamination of 5−hydroxytryptamine and benzylamine by rat liver monoamine oxidase-A or -B activities, respectively. Inhibition of SSAO, but not monoamine oxidase, was time-dependent. Use of metabolic inhibitors, and an enzyme dilution technique, suggested that any conversion of procarbazine to an active species must be as a result of the action of SSAO itself and not of any other enzyme. The non-competitive kinetics and the time-dependence of inhibition were indicative of a suicide interaction between procarbazine and SSAO. The slow reversal of inhibition by dialysis was evidence in favour of the involvement of tight binding, rather than covalent bonding. High concentrations of benzylamine afforded the enzyme significant protection from the action of procarbazine, indicating that the interaction is at or near the active site. If the properties of procarbazine, evident in in-vitro studies, are retained in-vivo, these data suggest that procarbazine might be suitable for the examination of SSAO activities, both in-vivo and ex-vivo.
Effects In-vitro of Procarbazine Metabolites on Some Amine Oxidase Activities in the Rat
Authors: Holt Andrew , Sharman Dennis F , Callingham Brian A 
Published: April 2011

Abstract
The effects were examined of four metabolites of the anticancer agent, procarbazine (N-isopropyl-α-(2−methyl hydrazino)-p-toluamide hydrochloride) on semicarbazide-sensitive amine oxidase (SSAO) and monoamine oxidase-A and -B (MAO-A and -B) activities in rat brown adipose tissue and liver homogenates, respectively. Azoprocarbazine (AZO) and monomethylhydrazine (MMH) inhibited selectively the deamination of benzylamine by SSAO, when compared with their effects on MAO activities. The IC50 values against SSAO, of 32·7 Nm (AZO) and 7·0 Nm (MMH), were more than three orders of magnitude lower than those exhibited against MAO. Neither isomer of azoxyprocarbazine was an effective inhibitor of rat amine oxidase activities. The inhibition of SSAO by AZO was reversed very slowly by dialysis, in contrast to results seen for MMH. The non-competitive kinetics of MMH and the ability of B24, a rapidly reversible SSAO inhibitor, to protect SSAO against inhibition by MMH are consistent with the view that this compound binds to the enzyme cofactor at, or near, the active site.
Effect of ryanodine on histamine release from rat peritoneal mast cells induced by anti-IgE
Authors: Takei Masao , Ueno Mokoto , Endo Koichi 
Published: April 2011

Abstract
Ryanodine strongly inhibited histamine release from rat peritoneal mast cells induced by anti-IgE. Ryanodine also inhibited Ca2+-mobilization from the intracellular Ca2+-store as well as histamine release in mast cells activated by anti-IgE. These results suggest that the effect of ryanodine on histamine release from rat mast cells might be due to the inhibition of Ca2+ release from the intracellular Ca2+ store.
Supersensitivity to morphine after chronic sympathetic denervation in guinea-pig colon
Authors: Marino F , Marcoli M , Lecchini S , Frigo G M 
Published: April 2011

Abstract
The possible role of opioid systems in the adaptive changes which follow chronic sympathetic denervation in the guinea-pig colon has been studied by comparing the effects of the opioid agonist morphine in control animals and after chronic sympathetic denervation. Supersensitivity to the inhibitory effects of morphine on the peristaltic reflex was observed after chronic sympathetic denervation, while the potency against acetylcholine release was unmodified. Our results suggest that a modification of the opioid system occurs after sympathetic denervation in the guinea-pig colon. Supersensitivity to endogenous opioids at a site different from that regulating acetylcholine release could account for the counter-regulation of intestinal motility after chronic sympathetic denervation.
Sulphasalazine fails to prevent development of mucosal ulceration and 5-lipoxygenase activity in guinea-pigs with chronic inflammatory bowel disease induced by combined bacterial immunization and oral carrageenin
Authors: Oestreicher P , Nielsen S T , Rainsford K D 
Published: April 2011

Abstract
A model of inflammatory bowel disease in guinea-pigs involving a 14 day initial treatment with formalin-killed Bacteroides vulgatus subcutaneously and oral carrageenin plus live B. vulgatus for 10 days was used to determine the effects of sulphasalazine 100 mg kg−1 day−1 b.i.d., p.o. given for 4, 7 and 10 days after cessation of the bacterial/carrageenin treatment on the morphological and histological states of the established disease and on the production of the principal 5−lipoxygenase products, 5−hydroxyeico-satetraenoic acid and leukotriene B4. The drug treatment did not cause any significant changes in this established disease as measured by these parameters.
Influence of changes in protein binding on the central activity of antidepressants
Authors: Torres I , Gomez E , Garcia E , Suárez E , Rodriguez-Sasiaín J M , Calvo R 
Published: April 2011

Abstract
The central effect (expressed as analgesic response), protein binding and brain uptake of mianserin were measured in mice receiving drug intraperitoneally. A significant decrease of the central effect of mianserin (30 mg kg−1) was seen in mice with experimental inflammation when compared with control animals (reaction time (s)= 12·12 ± 1·22 vs 25·56 ± 2·92; P &lt; 0·001) and the dose-analgesia response curve (10−60 mg kg−1) was significantly shifted to the right in mice with inflammation. In serum of mice with inflammation, unbound concentration of mianserin was decreased from 19·37 ± 0·73 to 17·83 ± 0·30% (P &lt; 0·05) and seromucoid levels were significantly increased (P &lt; 0·001). Following the intraperitoneal administration of 30 mg kg−1 of mianserin, brain uptake decreased in diseased mice when compared with control animals (P &lt; 0·02), suggesting that the decrease in analgesia was secondary to a decrease in drug delivery to the brain because of increased protein binding.
Hydrolysis Kinetics of Phospholipids in Thermally Stressed Intravenous Lipid Emulsion Formulations
Authors: Herman C J , Groves M J 
Published: April 2011

Abstract
A model 20% w/v emulsion, prepared with either a commercially available pharmaceutical grade soy oil or a highly purified grade of oil from the same origin and stabilized with a commercially available mixture of egg yolk phospholipids was passed through a Microfluidics homogenizer until the mean particle size fell below 500 nm diameter. Samples stored in sealed all-glass ampoules were thermally stressed over a temperature range of 5–90°C and samples taken at appropriate intervals for analysis by HPLC. Hydrolysis degradation kinetics were in conformation with the Arrhenius equation. The energy of activation for phosphatidylcholine was virtually identical for emulsions prepared with either pharmaceutical or purified oil (65 and 63 kJ mol−1, respectively). For phosphatidylethanolamine itself the respective activation energies were 53 and 54 kJ mol−1, suggesting that the source of the oil used in preparing the emulsions had no significance in the degradation processes of the resulting systems.
Di-iodo-l-tyrosine-labelled Dextrans as Molecular Size Markers of Nasal Absorption in the Rat
Authors: Fisher A N , Illum L , Davis S S , Schacht E H 
Published: April 2011

Abstract
A series of fractionated di-iodo-l-tyrosine-labelled dextrans (DIT dextrans), with a narrow range of number average molecular weights from 1260 to 45 500 Da, was administered intranasally and intravenously to anaesthetized rats. The nasal absorption of these compounds ranged from 0·6 to 52·7%. There was an inverse relationship between molecular size and the proportion of an intranasal dose absorbed. The study demonstrated the usefulness of DIT dextrans as molecular weight markers and confirmed the relationship between molecular size and nasal absorption for highly water soluble compounds. These results also supported the proposition that there is a continuous range of aqueous pores in the nasal mucosa.
Interaction Between Cicletanine and the Eicosanoid System in Human Subcutaneous Resistance Arteries
Authors: Calder J A , Schachter M , Sever P S 
Published: April 2011

Abstract
In human subcutaneous resistance arteries in-vitro, the relaxation produced by the novel furopyridine compound cicletanine (30 μm) was inhibited by 51% (P &lt; 0·0001) in the presence of 20 μm of the cyclo-oxygenase inhibitor indomethacin. Maximal cicletanine-induced relaxation was reduced by both the cyclo-oxygenase inhibitor mefenamic acid and the relatively specific blocker of prostacyclin synthetase, tranylcypromine by 55% (P &lt; 0·0005) and 43% (P &lt; 0·01), respectively. The potassium channel blocker, glibenclamide (100 μm), did not affect the relaxation produced by cicletanine but did inhibit the relaxation produced by the potassium channel blocker cromakalim (P &lt; 0·0001). Cromakalim-induced relaxation was inhibited in the presence of indomethacin; relaxation induced by cromakalim (30 μm) was reduced by 22% (P &lt; 0·02). The relaxation produced by the hypotensive agonists sodium nitroprusside, hydrochlorothiazide, bumetanide and nicardipine was unaffected by incubation with indomethacin. The results suggest that the vascular eicosanoid system, specifically prostacyclin, may be involved in the mechanism of the acute vasodilator action of cicletanine. Although at high doses, cicletanine is a diuretic, in this model it did not act like either a thiazide or a loop diuretic. The acute vasodilator action of the thiazide diuretic, hydrochlorothiazide was a novel finding of this study. Cromakalim showed a reduced response in the presence of indomethacin suggesting an involvement of the eicosanoid system in its mechanism of action.
Enhancement of the stability of thrombin by polyols: microcalorimetric studies
Authors: Boctor Amal M , Mehta Surendra C 
Published: April 2011

Abstract
Glycerol increased the transition temperature (Tm) of thrombin in a concentration-dependent fashion up to a concentration of 50% glycerol in aqueous buffer solution. Glycerol showed a comparable effect on Tm of trypsin. This effect on Tm of thrombin was not seen in the presence of excess sodium chloride (1·2 m) in aqueous buffer solution. The stabilizing effect of glycerol may be due to increased energy demand to unfold the protein molecule, as reflected by an increase in Tm. This stabilizing effect, as measured by Tm, was seen for other polyols, including sucrose, and was also dependent on the concentration of the stabilizing agent. Micro-calorimetry may be used as an effective tool to screen for the protective action of compounds in enzyme stabilization studies before conducting the time-consuming and expensive stability studies of proteins in the presence of additives under different storage conditions.
Effect of exogenous copper on lipid peroxidation in rat hepatocytes. Possible involvement of protein kinase C
Authors: Mudassar S , Andrabi K I , Khullar M , Ganguly N K , Walia B N S 
Published: April 2011

Abstract
We have investigated the direct effect of copper on malondialdehyde formation in rat isolated hepatocytes. Copper was found to decrease the cell viability with concomitant production of ujalondialdehyde in a time related manner. In addition the protein kinase C activator, PMA, was found to have a synergistic effect with copper on rat hepatocytes. These results indicate that protein kinase C may be important in mediating hepatotoxicity after exposure to copper.
An in-vitro comparison of controlled release aminophylline tablets: phyllocontin Continus and Pecram
Authors: Smart J D , Barnes M S , Norris M J 
Published: April 2011

Abstract
It has been suggested that two controlled release preparations containing aminophylline, Phyllocontin Continus and Pecram, are clinically equivalent and are therefore interchangeable. In this study, an in-vitro evaluation of the two preparations was completed using the British Pharmacopoeia dissolution apparatus, initially using water and then an acid/buffer medium to provide a similar pH environment to that within the gastrointestinal tract. Similar release profiles were found when water was used as the dissolution medium, with very little variation between tablets within each group. Good fits were obtained for dissolution-controlled release and diffusion-controlled release models. When the acid/buffer solution was used as the dissolution medium a reduction in the rate of release was observed with Phyllocontin. It was predicted that if this was repeated in-vivo then differences in the peak plasma levels between the two formulations would be seen, although these may be masked by the other variables encountered.
Transport Characteristics of Cephalosporin Antibiotics Across Intestinal Brush-border Membrane in Man, Rat and Rabbit
Authors: Sugawara Mitsuru , Toda Takaki , Iseki Ken , Miyazaki Katsumi , Shiroto Hiroshi , Kondo Yukifumi , Uchino Jun-Ichi 
Published: April 2011

Abstract
The uptake of orally active cephalosporins, ceftibuten and cephradine, by intestinal brush-border membrane vesicles isolated from man, rat and rabbit was studied. In the presence of an inward H+ gradient, ceftibuten but not cephradine was taken up into intestinal brush-border membrane vesicles of man and rat against the concentration gradient (overshoot phenomenon). In rabbit jejunal brush-border membrane vesicles, the uptake of both cephalosporins in the presence of an inward H+ gradient exhibited the overshoot phenomenon. In human and rat vesicles, the initial uptake of ceftibuten was strongly inhibited by compound V, an analogue of ceftibuten, but the uptake of cephradine was not affected by any of the cephalosporins tested, whereas in the rabbit brush-border membrane vesicles, initial uptake of both ceftibuten and cephradine were markedly inhibited by all cephalosporins and dipeptides used. These results suggest that the transport characteristics of human and rat intestinal brush-border membrane for cephalosporins are comparable, and that rabbit is an inadequate animal for investigating the transport characteristics of β-lactam antibiotics.
Transport of Paraquat and Mexiletine from the Blood into the Rat Intestinal Lumen and Peritoneal Cavity
Authors: Arimori Kazuhiko , Deshimaru Megumi , Furukawa Emiko , Nakano Masahiro 
Published: April 2011

Abstract
Transport of paraquat and mexiletine from the blood into the intestinal lumen and the peritoneal cavity was examined after their intravenous administration (paraquat: 20 mg kg−1, mexiletine: 10 mg kg−1) to rats. The average amounts of paraquat transferred into the intestinal lumen and the peritoneal cavity were 1·39 and 22·8% of the dose in 120 min, respectively. The average amounts of mexiletine transferred into the intestinal lumen and the peritoneal cavity were 6·1 and 2·5% of the dose in 120 min, respectively. The transfer rate of 3H2O into the peritoneal cavity after intravenous administration (1·85 MBq) was greater than that into the intestinal lumen. In view of the hydrophilic nature of paraquat cation, a solvent drag effect due to movement of water might contribute to transport of paraquat from the blood to the peritoneal cavity. Differences in transport behaviour across the two membranes could be due to differences in the geometrical factors such as the surface area and the distribution of blood vessels. Differences might also be due to differences in physicochemistry and pharmacological effects of both substances.
L-Dopa-like Regulatory Actions of l-threo-3,4-Dihydroxyphenylserine on the Release of Endogenous Noradrenaline Via Presynaptic Receptors in Rat Hypothalamic Slices
Authors: Yue Jin-Liang , Goshima Yoshio , Nakamura Shinichi , Misu Yoshimi 
Published: April 2011

Abstract
Effects of l-threo-3,4-dihydroxyphenylserine (l-threo-DOPS) on the spontaneous release and the stimulus(2 Hz)-evoked release of endogenous noradrenaline were studied in rat hypothalamic slices with functioning l-aromatic amino acid decarboxylase (AADC) and with AADC inhibition. In non-inhibited slices, spontaneous release was not modified by l-threo-DOPS at 1 Pm-100Nm, tended to increase at 1–10 μm and increased at 100 μm. Noradrenaline tissue content slightly increased at 100 μm. Stimulated release was concentration-dependently facilitated at 1–1000 Pm and tended to decrease gradually from a maximum at 10 Nm-10 μm. Under AADC inhibition, spontaneous release concentration-dependently increased at 10–100 μm by 60% of the increase seen in slices without AADC inhibition. Increase in noradrenaline tissue content was abolished. l-threo-DOPS produced a triphasic pattern on stimulated release; concentration-dependent facilitation at 1–1000 Pm similar to that seen in slices with functional AADC, no facilitation at 10–1000 Nm, and a concentration-dependent increment at 10–100 μm. The facilitation at 1 Nm was stereoselective and was antagonized by (–)-propranolol 10 Nm, and no facilitation at 100 Nm was restored to the maximum by yohimbine 10 Nm, DG-5128 10 Nm or S-sulpiride 1 Nm. Furthermore, l-threo-DOPS (1–1000 Pm)-induced facilitation was competitively antagonized by l-dopa methyl ester, a competitive antagonist for l-dopa, with a pA2 value of 13·6, whereas it was noncompetitively antagonized by (–)-propranolol.
Cardiac Function in Rats with Acute Renal Failure
Authors: Robinson S C , Bowmer C J , Yates M S 
Published: April 2011

Abstract
Inotropic responses of isolated cardiac preparations from rats with glycerol-induced acute renal failure (ARF) were recorded, following a range of cardiac stimulants. Left atria of rats with ARF showed diminished inotropic responses only to the calcium agonist Bay K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5-carboxylate) whilst right ventricular strips exhibited reduced responses to isoprenaline, 3-isobutyl-1-methylxanthine, Ca2+ and Bay K 8644. Investigations of cardiac mitochondrial respiration indicated that there is a site-unspecific ‘pseudo’ uncoupling of oxidative phosphorylation in ARF but that electron transport is unaffected. This uncoupling of oxidative phosphorylation did not have any detectable effect on either levels of total adenine nucleotides and creatine phosphate or cellular energy charge. Measurements were also made of the activity of pyruvate dehydrogenase which provides an index of mitochondrial Ca2+ levels. The proportion of pyruvate dehydrogenase in its active form was threefold higher following isoprenaline injection in hearts of rats with ARF compared with controls. The results suggest that in hearts of rats with ARF there is a change in the number, affinity, efficacy or coupling of the dihydropyridine receptor on the L-type calcium channel. Moreover, in the ventricle, a defect in cellular Ca2+ control, resulting in an increase in mitochondrial Ca2+ uptake, may contribute to the depression of inotropic response to the range of cardiac stimulants tested.
Spectrophotometric Method for the Determination of Carbidopa Using Neotetrazolium Chloride
Authors: Issopoulos Prodromos B , Economou Pantelis T 
Published: April 2011

Abstract
A new high-sensitive spectrophotometric method for the determination of microquantities of carbidopa is described. The method is based on the reduction of neotetrazolium chloride by carbidopa in an alkaline ethanolic medium. The formazan formed exhibits an absorption maximum at λ = 507 nm, with an apparent molar absorptivity of = 6·63 × 104 m−1 cm−1 and a corresponding Sandell's sensitivity of 3·68 ng cm−2. Beer's law is obeyed over the range of 0·10–6·0 μg mL−1 while the optimum concentration range is 0·125–5·0 μg mL−1. The regression line equation was calculated as: A = 0·271C +0·0023 with a correlation coefficient of 1·0000 (n = 28). The accuracy and the precision of the method were considered as very satisfactory. The results obtained from the determination of carbidopa using both the described procedure and the corresponding USP. XXII and BP 1988 official methods were statistically compared by means of Student's t-test as well as by the variance ratio F-test, and no significant difference was observed.
Effect of Humidity on Solid-state Isomerization of Various Kinds of Lactose During Grinding
Authors: Otsuka Makoto , Ohtani Hiro , Otsuka Kuniko , Kaneniwa Nobuyoshi 
Published: April 2011

Abstract
The effect of humidity on isomerization during grinding of α-monohydrate, α-anhydrate and β-anhydrate of lactose was investigated. Samples were ground in an agate centrifugal ball mill at 270 rev min−1 at room temperature (21°C) and at 5 and 60% relative humidity. Crystallinity of the ground lactose was measured by Hermans' method from the powder X-ray diffraction profiles. The α- and β-lactose content of the ground lactose was measured by using angular rotation spectrophotometry. The crystalline lactose samples were transformed into noncrystalline solids by mechanical stress during grinding. After grinding, the adsorbed water content of all ground lactose samples increased, and the isomerized amount increased with increase of the water content during grinding at 5 and 60% relative humidity. The results suggest that the isomerization rate of α-monohydrate during grinding may depend on the crystallinity, but those of α-and β-anhydrate depend on the content of adsorbed water.
Investigation of Potential Genotoxic Effects of Low Frequency Electromagnetic Fields on Escherichia coli
Authors: Chahal R , Craig D Q M , Pinney R J 
Published: April 2011

Abstract
Exposure of growing cells of Escherichia coli strain AB1157 to a frequency of 1 Hz with field strengths of 1 or 3 kV m−1 did not affect spontaneous or ultraviolet light (UV)-induced mutation frequencies to rifampicin resistance. Neither did growth in the presence of charge alter the sensitivities of strains AB1157, TK702 umuC or TK501 umuC uvrB to UV. Similarly, although the resistance of strains TK702 umuC and TK501 umuC uvrB to UV was increased by the presence of plasmid pKM101, which carries DNA repair genes, pregrowth of plasmid-containing strains in electric fields did not increase UV resistance. Finally, growth in a low frequency field in the presence of sub-inhibitory concentrations of mitomycin C did not affect mitomycin C-induced mutation frequencies. It is concluded that low frequency electromagnetic fields do not increase spontaneous mutation, induce DNA repair or increase the mutagenic effects of UV or mitomycin C.
Inhibition of drug-induced contractions of guinea-pig ileum by Annona crassiflora seed extract
Authors: Weinberg Maria De Lourdes Duarte , Pires Virginia , Weinberg Julio , De Oliveira Alaide Braga 
Published: April 2011

Abstract
A hydro-alcoholic extract of dried Annona crassiflora seeds (AR.1) showed a non-specific inhibitory effect on drug-induced contractions of guinea-pig ileum. Maximum responses to histamine, acetylcholine and bradykinin were reduced increasingly with increasing doses of AR.1. Affinities of the gut to the above agonists, expressed as respective pD2 values were not changed by AR.1. Dose-response curves of calcium-induced contractions in depolarized preparations were shifted to the right but maximum responses were not changed by AR.1. It is suggested that the inhibitory effect of AR.1 is due to a decrease in membrane permeability to calcium. This inhibitory effect may be responsible for the effect of Annona crassiflora as a remedy against snake venom.