bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel 1,4 Substituted Piperidine Derivatives. Synthesis and Correlation of Antioxidant Activity with Structure and Lipophilicity
Authors: Alexidis Alexandros N , Rekka Eleni A , Demopoulos Vassilis J , Kourounakis Panos N 
Published: April 2011

Abstract
A series of novel piperidine derivatives was prepared and their lipophilicity was determined (as RM values). These compounds as well as two intermediate α-keto-esters were tested for antioxidant activity.
It was found that the cysteamine derivatives were efficient antioxidants, i.e. they could inhibit lipid peroxidation, act as hydroxyl radical scavengers and interact with 2,2-diphenyl-l-picrylhydrazyl radicals. This interaction could be attributed to the free SH group and this activity seemed to be favoured by increased lipophilicity.
Replacement of SH by NH2 or OH resulted in a decreased antioxidant activity of the compounds. However, the described activities seem not to be connected with any O−2· scavenging ability, at least under the experimental conditions applied. Furthermore, cysteamine derivatives seem to induce O−2· generation, a phenomenon often observed with thiol compounds.
The antioxidant activity of the intermediate α-keto-esters varied and is probably mediated by different mechanisms.
Behavioural Profile of Two Potential Antidepressant Pyridazine Derivatives Including Arylpiperazinyl Moieties in Their Structure, in Mice
Authors: Rubat Catherine , Coudert Pascal , Bastide Pierre , Tronche Pierre 
Published: April 2011

Abstract
The potential antidepressant effects of two pyridazine derivatives, 5-benzyl 6-methyl 2-[4-(3-trifluoro-methyl phenyl) piperazin-1-yl] methylpyridazin-3-one (PC4) and 5-benzyl 6-methyl 2-[4-(3-chlorophenyl) piperazin-1-yl] methylpyridazin-3-one (PCI3), were evaluated using classical psychopharmacological tests in mice.
The intraperitoneal LD50 values of PC4 and PC13 were respectively 1125·8 and 429-6mg kg−1. Only at intraperitoneal doses of 100mg kg−1 did PC4 or PC13 significantly decrease locomotor activity. Both compounds (5–20 mg kg−1, i.p.) reduced the duration of immobility of mice in the forced swimming test, antagonized reserpine (2–5 mg kg−1, i.p.)-induced ptosis, and potentiated reserpine (2–5 mg kg−1, i.p.)-induced hypothermia. PC4 and PCI3 (20mg kg−1, i.p.) partly reversed hypothermia induced by low dose apomorphine (5 mg kg−1, s.c.) but were less effective for higher doses of apomorphine (16 mg kg−1, s.c). At 200 mg kg−1, intraperitoneal PC13 enhanced the toxic effects of yohimbine (30 mg kg−1, s.c), while PC4 was inactive. Head twitches produced either by L-5-hydroxytryptophan (4 mg kg−1, i.p.) in mice pretreated with pargyline (100mg kg−1, i.p.) or by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3 mg kg−1, i.p.) were antagonized by both pyridazine derivatives (20 mg kg−1, i.p.). PC4 and PC13 showed analgesic properties in the phenylbenzoquinone-induced abdominal constriction test (50 &lt; ED50 &lt; 5-5mg kg−1, i.p.) and in the hot-plate test (10 to 37% of analgesia at 10 mg kg−1, i.p.). These antinociceptive effects were not significantly diminished by naloxone (1 mg kg−1, i.p.). Furthermore, acute intraperitoneal administration of both compounds (20 mg kg−1 for PC4 and 5mg kg−1 for PC13) potentiated morphine (7–5 mg kg−1, s.c.) analgesia in the hot-plate test.
Thus, these results suggest that PC4 and PC 13 possess potential antidepressant effects related to different aminergic mechanisms, especially at the 5-HT2 receptor level.
Plasma and Cerebrospinal Fluid Concentrations of Morphine and Morphine Glucuronides in Rabbits Receiving Single and Repeated Doses of Morphine
Authors: Mignat Christian , Jansen Ruth , Ziegler Albrecht 
Published: April 2011

Abstract
The pharmacokinetics of morphine in plasma and the distribution of morphine and its glucuronidated metabolites within the cerebrospinal fluid were investigated in rabbits.
After single morphine dosage, the plasma AUC ratio of morphine-3-glucuronide/morphine was 11·1 compared with 0·14 for morphine-6-glucuronide/morphine. The similar elimination half-lives of morphine (107 min), morphine-3-glucuronide (122 min), and morphine-6-glucuronide (105 min) suggested the glucuronidation to be the rate-limiting step, which was substantiated by the observation that morphine-3-glucuronide becomes eliminated four times faster when applied intravenously. Both after single and repeated morphine administration, the ratios of CSF and plasma levels of the parent drug were higher than those of morphine-3-glucuronide or morphine-6-glucuronide.
These data demonstrate a poor penetration of the glucuronides across the blood-brain barrier and do not support the previously postulated accumulation of morphine-6-glucuronide in the central nervous system during chronic morphine treatment.
Epidemiology and Susceptibilities to Mercury Preservatives of Staphylococci Isolated from Used Eye-Drops Preserved with Thiomersal
Authors: Du Bois S K , Davison A L , Pinney R J 
Published: April 2011

Abstract
Minimum inhibitory concentrations (MICs) of seven independent isolates of Staphylococcus hominis isolated in the same week from used eye-drops, preserved with thiomersal and collected from wards and clinics in the same hospital, ranged between 1 and 0·03 mg L−1 for thiomersal, 1 and 0·01 mg L−1 for phenyl mercuric nitrate and 10 and 3 mg L−1 for mercuric chloride.
Although MIC values determined on solid nutrient medium indicated a 100-fold variation in susceptibility to the bacteriostatic effect of phenyl mercuric nitrate, after 5 h in an aqueous solution containing the bactericidal concentration of 10 mg L−1 phenyl mercuric nitrate, the survival levels of the six S. hominis isolates were similar, with a mean of 13·4% (s.d. 11·0), compared with 100 and 0·8%, respectively, for the most resistant and most sensitive control staphylococcal strains tested. Antibiotic susceptibilities and plasmid profiles of the S. hominis isolates indicated they were the same strain.
It is concluded that laboratory indicators of preservative efficacy, such as MIC determination or susceptibility to bactericidal concentrations of preservatives, do not necessarily correlate with the epidemiology of contaminating bacterial strains or their survival in preserved pharmaceuticals.
Transdermal Delivery of Physostigmine. A Pretreatment Against Organophosphate Poisoning
Authors: Jenner J , Saleem A , Swanston D 
Published: April 2011

Abstract
Physostigmine absorption through isolated human skin and inhibition of plasma and red blood cell cholinesterases in guinea-pigs have been measured to assess the feasibility of its transdermal delivery as a pretreatment for organophosphate poisoning.
Penetration of radiolabeled physostigmine across human epidermis was measured in-vitro using glass diffusion cells and optimization of physostigmine delivery was achieved by changes in vehicle formulation and use of penetration enhancers.
Two-component vehicles consisting of propionic acid/isopropyl myristate (50:50) and propionic acid/oleic acid (50:50) produced the highest transdermal delivery of physostigmine. A comparison of formulations containing propionic acid alone with propionic acid plus oleic acid when applied to guinea-pigs, showed that inclusion of oleic acid allowed the amount of physostigmine and the size of the transdermal patch to be substantially reduced, whilst maintaining effective delivery rates. The formulation containing oleic acid was not irritant to guinea-pigs when applied to the skin for 48 h.
It is concluded that a mixture of propionic acid and oleic acid containing physostigmine is a good candidate for transdermal delivery of physostigmine as a pretreatment for organophosphate poisoning.
Do 5-HT4 Receptors Mediate the Intestinal Secretory Response to 5-HT in Rat In-vivo?
Authors: Franks C M , Hardcastle J , Hardcastle P T , Sanger G J 
Published: April 2011

Abstract
The involvement of the recently characterized 5-HT4 receptor in the actions of 5-hydroxytryptamine (5-HT) on jejunal, ileal and colonic electrogenic ion secretion was investigated in the rat in-vivo.
5-HT and the 5-HT1-, 5-HT2- and 5-HT4-receptor agonist 5-methoxytryptamine (5-MeOT), induced a rise in transintestinal PD in all regions of the gut. However, the 5-HT4-receptor agonists renzapride and cisapride had no effect. Furthermore, the 5-HT4-receptor antagonists SDZ 205–557 (2-diethylaminoethyl-[2-methoxy-4-amino-5-chloro] benzoate), tropisetron and SB 204070 ([1-butyl-4-piperidinylmethyl]-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate hydrochloride) did not affect the secretory response to either 5-HT or 5-MeOT in the jejunum, but did cause a small inhibition in the ileum and colon.
It is concluded that 5-HT4 receptors do not make a contribution to the electrically monitored 5-HT intestinal secretory response in the rat jejunum in-vivo, but may play a small role in the ileum and colon.
Amelioration of Cisplatin Nephrotoxicity with Glycine: Dose Dependency in Rats
Authors: Li Q , Bowmer C J , Yates M S 
Published: April 2011

Abstract
The effects of glycine (0·1-1·0 g μg kg−1, i.v.) on the acute changes in renal haemodynamics and nephrotoxicity produced by cisplatin (6·0 mg g kg−1, i.v.) were investigated in the rat.
Cisplatin produced decreases of 50% in the clearance of [3H] inulin (CIN) and renal blood flow (RBF), 110 min following its injection. Glycine at a dose of 0·1 g kg−1 produced no attenuation of the cisplatin-induced decrease in CIN or RBF. Furthermore, this dose of glycine provided no significant protection of renal function over a 7-day period following cisplatin injection.
By contrast, glycine at a dose of either 0·5 or 1·0 g kg−1 markedly attenuated cisplatin-induced falls in CIN and RBF, with the highest dose completely preventing any falls in these indices during the course of the experiment. Treatment with these higher doses of glycine produced prominent protection from the nephrotoxic actions of cisplatin, as evidenced by improvements in a range of indices of renal function which included plasma urea and creatinine concentrations, urine output, sodium excretion, CIN and the clearance of [14C]P-aminohippurate.
The results of experiments with an intermediate dose of 0·25 g kg−1 glycine revealed some degree of amelioration of acute renal haemodynamic effects of cisplatin, particularly with regard to CIN; whilst in the nephrotoxicity study, 0·25 g kg−1 glycine produced a modest but significant reduction in cisplatin-induced acute renal dysfunction.
The results have revealed a clear association between the acute renal haemodynamic effects produced by glycine in cisplatin-injected rats with the longer-term renal protective effects of glycine in cisplatin nephrotoxicity. The findings indicate that glycine's ability to prevent the falls in RBF and glomerular filtration rate produced by cisplatin plays an important role in the protective effect of glycine in cisplatin-induced nephrotoxicity.
Correlation of Pharmacological Properties of a Group of β-Blocker Agents by Molecular Topology
Authors: Garcá-March F J , Cercós-Del-Pozo R A , Pérez-Giménez F , Salabert-Salvador M T , Jaén-Oltra J , AntÓn-Fos G M 
Published: April 2011

Abstract
The molecular connectivity method has been applied to the study of pharmacological properties, among which are found the angor treatment dose, α-distribution half-life and intravenous LD50 in mouse, of a group of β-blocker agents, verifying its application in the prediction of theoretic values for said pharmacological properties.
To do this, the obtained multiple regression functions of the corresponding connectivity indices were used in relation with the experimental values of the properties, which are accompanied by the statistical parameters used in their selection criteria, as well as the corresponding random and cross-validation studies of said functions, which corroborate the good correlation of the selected equations.
Inhibitory Effect of 5-Hydroxytryptamine on Rat Stomach Fundus: Mediated Indirectly by Activation of Noradrenaline Release
Authors: Béjar E , Malone M H 
Published: April 2011

Abstract
Biphasic cumulative concentration-response curves to 5-hydroxytryptamine (5-HT) and α-methyl-5-hydroxytryptamine (α-Me-5-HT) using rat stomach fundus in the presence of 50 μm pargyline suggested two sites of interaction (high and low affinity).
The order of agonist potencies of 5-HT agonists for the high-affinity (contractile) response confirmed reports of a strong correlation of the 5-HT2B (contractile) receptor on fundus with reported rat brain (radioligand binding) pKd values at the 5-HT2C receptor (r = 0·94, b = 0·93 P &lt; 0·01). 1(1-Naphthyl)-piperazine and ketanserin antagonized the high-affinity responses. The order of potencies for the low affinity (inhibitory) response was: α-Me-5-HT &gt; 5-HT. Preincubation with mianserin or S-(—)propranolol, pretreatment with reserpine and removal of the mucosa layer resulted in amplification of the contractile effects and disappearance or reversal of the inhibitory effects of 5-HT.
Activation of a second receptor site inducing catecholamine release may explain this effect of 5-HT on rat stomach fundus.
Relaxant Activity of Three Aporphine Alkaloids from Annona cherimolia on Isolated Aorta of Rat
Authors: Chuliá S , Ivorra M D , Cavé A , Cortés D , Noguera M A , D'Ocón M P 
Published: April 2011

Abstract
In the present study we tested the relaxant effect of three aporphine alkaloids—roemerine, anonaine and dehydroroemerine—isolated from the roots of Annona cherimolia, on isolated strips of rat thoracic aorta.
All compounds completely relaxed KCl- and noradrenaline-induced contractions with different potencies depending on their structural characteristics. The experiments, carried out in Ca2+-free medium using two different agonists (noradrenaline and caffeine) which mobilize calcium intracellularly by different mechanisms of action, showed that the alkaloids made no contribution to intracellular calcium processes.
The present study provides evidence that the relaxant effects produced by aporphine alkaloids may be due to the blockade of calcium movements across the cell membrane, mainly through voltage-operated channels, and to the disruption of α1-adrenoceptors connected to receptor-operated channels.
The Prejunctional Inhibitory Effect of α-Methylnoradrenaline in the Rat Vas Deferens is Not Mediated via α2-Adrenoceptors
Authors: Oriowo Mabayoje A 
Published: April 2011

Abstract
In field-stimulated rat vas deferens, clonidine (10−9–10−7 m) and α-methylnoradrenaline (10−7–3 times 10−5 m) concentration-dependently inhibited twitch response to electrical field stimulation. The inhibitory effects of clonidine and α-methylnoradrenaline were similarly reduced by phenoxybenzamine (10−6 m). However, idazoxan (3 times 10−7 m) antagonized clonidine but not α-methylnoradrenaline-induced responses. The inhibitory effect of α-methylnoradrenaline was also not antagonized by phentolamine (3 times 10−7 m), SK&F 104856 (2-vinyl-7-chloro-3,4,5,6-tetrahydro-4-methylthienol[4,3,2 ef][3]benzazepine) 3 times 10−6 m) or yohimbine 3 times 10−7 m). These antagonists however, attenuated the twitch-inhibiting effect of clonidine. The -logKB values were 8·02 ± 0·05, 6·91 ± 0·10, and 7·58 ± 0·07 for phentolamine, SK&F 104856 and yohimbine respectively. In-vivo treatment of rats with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (6 mg kg−1), to inactivate prejunctional α2-adrenoceptors, attenuated clonidine, but not α-methylnoradrenaline-induced responses.
It was concluded that adrenoceptors are not involved in the prejunctional inhibitory effects of α-methylnoradrenaline in the rat vas deferens.
The Involvement of Cytosolic Chymotrypsin-like, Trypsin-like, and Cucumsin-like Activities in Degradation of Insulin and Insulin-like Growth Factor I by Epithelial Tissues
Authors: Bai Jane P F 
Published: April 2011

Abstract
Using specific substrates, benzyloxycarbonyl-Gly-Gly-Leu-p-nitroanilide, benzyloxycarbonyl-Gly-Gly-Arg-2-naphthylamide and benzyloxycarbonyl-Leu-Leu-Glu-2-naphthylamide, cytosolic chymotrypsinlike, trypsin-like and cucumsin-like activities were determined, respectively, in rat epithelial tissues and differentiated human Caco-2 cells.
The cytosolic fractions of rat colonic, rectal, nasal, and alveolar epithelial cells and differentiated human Caco-2 cells contained these three distinct enzyme activities. However, effects of enzyme inhibitors revealed that these three distinctive activities were not extensively involved in cytosolic or homogenate degradation of insulin and insulin-like growth factor I (IGF-I).
It is concluded that proteasome-like activities may not significantly limit nonparenteral absorption of peptide and protein drugs such as insulin and IGF-I.
Enhanced Effectiveness of Dimethyl-4,4‘-dimethoxy-5,6,5’,6‘-dimethylene dioxybiphenyl-2,2’-dicarboxylate in Combination with Garlic Oil against Experimental Hepatic Injury in Rats and Mice
Authors: Kim Sang Geon , Nam Seon Young , Chung Hye Chin , Hong Su Yeun , Jung Ki Hwa 
Published: April 2011

Abstract
The present study was designed to evaluate the effects of dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (PMC) in combination with garlic oil against chemical-induced hepatic injury in rats and mice.
Rats insulted with carbon tetrachloride were concomitantly treated with PMC and/or garlic oil (50 and 100 mg kg−1, respectively) for four weeks. Whereas treatment of animals with garlic oil alone was ineffective in suppressing carbon tetrachloride-induced hepatotoxicity, administration of PMC in combination with garlic oil more effectively protected the liver against the carbon tetrachloride-induced insult than PMC alone, as monitored by serum aminotransferase activity. Hepatoprotective effects of the formulation were further supported by the changes in the numbers of Kupffer cells and dead hepatocytes.
Although prior treatment of rats with PMC for three days failed to protect hepatotoxicity elicited by allyl alcohol, the formulation of PMC and garlic oil was capable of blocking allyl alcohol-induced hepatotoxicity by ∼ 40%.
To further examine the effect of the agents on lipid metabolism in the liver, hepatic triglycerides and cholesterol contents were assessed in mice after a diet containing PMC and/or garlic oil for one week followed by a single dose of carbon tetrachloride. Garlic oil appeared to be more effective in bringing hepatic lipid levels to those of control than PMC alone. Treatment of animals with PMC in combination with garlic oil synergistically improved chemical-induced impairment of hepatic triglycerides and cholesterol.
These results demonstrated that PMC in combination with garlic oil is effective in protecting (or treating) chemical-induced hepatic injury and that the formulation may be effective against chemical-induced fat-infiltration of the liver.
The Release of Isoconazole Nitrate from Different Suppository Bases: In-vitro Dissolution, Physicochemical and Microbiological Studies
Authors: Asikoglu M , Ertan G , Cosar G 
Published: April 2011

Abstract
The influence of the suppository base on the in-vitro release of isoconazole nitrate was studied by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. Vaginal suppository formulations containing 25 mg isoconazole nitrate for local treatment of vaginitis were prepared by a fusion method, using different hydrophilic and lypophilic suppository bases (PEG 6000, PEG 4000, PEG 1500, Witepsol H15, Novata BD and Cremao). In-vitro release rates were examined by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. In the physicochemical investigations the pH indicators (pH 1–14) erythrosin B, thymol blue, bromocresol green, chlorophenol red, phenol red, and alkali blue were added to agar gels. The discs were placed onto the agar gels and 21 h later, the coloured zone diameters were measured. In the microbiological investigations, the discs were put on the inoculated plates with the suspension of Candida albicans (Institute Pasteur 628). The inoculated plates were incubated at 37°C for 3 days, then the diameters of inhibition zones were measured.
In the dissolution investigations release rates were in the order PEG 6000 &gt; PEG 4000 &gt; PEG 1500 &gt; &gt; Witepsol H15 &gt; Cremao &gt; Novata BD. The diffusion distance of isoconazole nitrate in the physicochemical investigation was in the order polyethylene glycols &gt; Witepsol H15 &gt; Novata BD. In the microbiological studies release rates were found with polyethylene glycols &gt; Witepsol H15 &gt; Novata BD &gt; Cremao.
The findings in the in-vitro studies suggested that polyethylene glycols are suitable bases for vaginal suppositories.
The Release of Isoconazole Nitrate from Different Suppository Bases: In-vivo Release of Drug Labelled with 99mTc in Rabbits
Authors: Asikoglu M , Ertan G , Ercan M T , Duman Y 
Published: April 2011

Abstract
The influence of the suppository bases on the in-vivo release of 99mTc-labelled isoconazole nitrate was investigated. The single-dose vaginal suppository formulations for local treatment of vaginitis were prepared by a fusion method using polyethylene glycols, Witepsol H15, Novata BD and Cremao.
Prepared vaginal suppositories containing solid-labelled substance were applied to the vagina of rabbits and at 0, 2 and 24 h after administration, the amounts of radioactivity in the vagina were detected by the SPECT Gamma Camera and the release rates of the drug were calculated. The percent released was found to be in the following order; polyethylene glycol (PEG) 6000 &gt; PEG 4000 &gt; Witepsol &gt; PEG 1500 &gt; Novata BD &gt; Cremao. The results obtained in both in-vitro and in-vivo studies indicated that the vaginal suppository of isoconazole nitrate prepared with polyethylene glycols could confidently be used in therapy.
Anti-ulcer Activity of Higher Primary Alcohols of Beeswax
Authors: Carbajal Daisy , Molina Vivian , Valdés Suria , Arruzazabala Lourdes , Más Rosa 
Published: April 2011

Abstract
The anti-ulcer effects of a natural mixture of higher aliphatic primary alcohols, designated D-002, isolated from beeswax, were compared with those of cimetidine on indomethacin-, ethanol-, water-immersion-induced ulcers and on gastric secretion in rats.
D-002 (25–50 mg kg−1 p.o.) was similar to cimetidine in dose-dependently reducing the duration of indomethacin-induced ulcers while also being effective in preventing ethanol-induced ulcers, which are not affected by cimetidine. On the other hand, D-002 (100 mg kg−1) moderately decreased the volume of gastric basal secretion in pylorus-ligated rats, but not the acidity. Nevertheless, it inhibited gastric ulcer induced by pylorus-ligation at doses (50mg kg−1) that were ineffective in decreasing the volume. In addition, 100 mg kg−1 of D-002 prevented the formation of acute gastric ulcers induced in rats by water-immersion stress.
The results demonstrate the anti-ulcer activity of the preparation in different experimental models suggesting its potential value for ulcer therapy.