bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of cadmium ions on blood pressure, dopamine-β-hydroxylase activity and on the responsiveness of in vivo preparations to sympathetic nerve stimulation, noradrenaline and tyramine
Authors: FADLOUN Z , LEACH G D H 
Published: April 2011

Abstract
Changes in sympathetic nervous function of the rat caused by acute and chronic treatment with cadmium (Cd2+) have been studied in vivo by measurement of changes in blood pressure and plasma dopamine-β-hydroxylase (DBH) activity. In anaesthetized animals, acute injection of Cd2+ (0·1–1 μm) caused an initial fall followed by a rise in both diastolic and systolic blood pressure, plasma DBH activity increased in a dose-dependent manner. Animals subjected to repeated treatment with Cd2+ (0·5, 1 μm) daily for 12 days became markedly hypertensive, the increases in the systolic pressure being greater than those seen in the diastolic pressure. In pithed animals the blood pressure responses of the treated animals to electrical stimulation of the lower sympathetic outflow (T10-L1) and tyramine injection (35, 70, 140 nmol kg−1) were markedly decreased, whilst responses to low doses of noradrenaline (NA) (7, 15, 30 nmol kg−1) were potentiated compared with untreated animals. In addition, plasma DBH activities following sympathetic outflow stimulation and tyramine administration were markedly increased and decreased respectively compared with untreated controls. The data suggest that a correlation exists between changes in sympathetic nervous function and the induction of hypertension caused by Cd2+.
A comparative study on the performance of asbestos-free depth-filters for removal of pyrogens from infusion fluids
Authors: BAGGERMAN C , BRANDSEMA C , HUMER M , VISSER J 
Published: April 2011

Abstract
Three asbestos-free depth-filters were compared with traditionally used asbestos-containing depth-filters for chemical integrity, physical integrity and pyrogen retention. With chemical and physical integrity only minor differences between the various filter types were seen. One asbestos-free depth-filter, based on charcoal, showed poor pyrogen-retention; this might be due to a high flow rate used. Asbestos-free depth-filters based on kieselguhr or on a mixture of kaolin and alumina proved to be good alternatives; these filters have proved to be suitable for the removal of pyrogens from electrolyte- or carbohydrate-containing infusion fluids.
A semi-empirical model of aerosol deposition in the human respiratory tract for mouth inhalation
Authors: GONDA IGOR 
Published: April 2011

Abstract
A mathematical model for regional deposition of aerosols following inhalation via mouth has been developed. The model is in the form of algebraic equations which make it particularly efficient for computation of deposition of polydisperse aerosols. The parameters of the model were derived from average experimental data for‘head’ and tracheobronchial deposition which were supplemented by results of previous theoretical calculations and mass balance considerations. An example is presented to illustrate an application of the model to a problem in formulation of inhalation aerosols. To make the calculations more reliable for particular patho-physiological groups of patients, some modifications of the parameters used in the model are necessary. The model may be suitable, e.g. for testing the changes in regional deposition which would be likely to result from modification of particle size and related formulation properties of inhalation aerosols.
Circular dichroic examination of the interaction of some planar acidic drugs with tryptophan-modified human serum albumin
Authors: VALLNER J J , PERRIN J H 
Published: April 2011

Abstract
The single tryptophan region in human serum albumin was investigated for its involvement in binding planar hydrophobic and acidic drug molecules. The lone tryptophan was alkylated with a selective and specific agent, 2-hydroxy-5 nitrobenzyl bromide. The subsequent interaction of four drug molecules with tryptophan modified, and normal albumin was examined by circular dichroism (CD). In all cases the CD signal of tryptophan modified albumin was perturbed at low drug concentrations. The predominantly α-helical structure of the albumin remained intact. It is suggested that the primary binding site of these four acidic planar drugs does involve the tryptophan region.
Optical isomerization of R(−)-clidanac to the biologically active S(+)-isomer in guinea-pigs
Authors: TAMURA SHIGEO , KUZUNA SEIJI , KAWAI KIYOHISA , KISHIMOTO SHOJI 
Published: April 2011

Abstract
Optical isomerization of clidanac (RS-6-chloro-5-cyclohexyl-1-indancarboxylic acid, I), an anti-inflammatory drug having a chiral centre in its molecule, was evaluated in guinea-pigs. After oral administration of R(−)-I, the biologically active S(+)-isomer was detectable in the plasma, in the early stages. At 3 h after dosing R(−)-I, the plasma contained above 90% of the S(+)-isomer. Little conversion of S(+)-I to R(−)-I was observed. This may account for the equivalent in vivo activities of R(−)- and S(+)-I in this species. Determination of the enantiomeric composition required derivatization of the enantiomers to their diastereomeric amides after which thin layer chromatography (t.l.c.) was used for the separation. The quantitative determination of the compounds so-separated was accomplished by in situ measurements of the u.v.-reflectance. The t.l.c.-u.v.-densitometric procedure was also used to determine the plasma concentration of I.
Secoverine hydrochloride is a muscarinic antagonist in human isolated gastrointestinal muscle and myometrium
Authors: SANGER G J , BENNETT A 
Published: April 2011

Abstract
Secoverine is a new antimuscarinic agent thought to be selective for smooth muscle. We have found it to be a potent anticholinergic antagonist of acetylcholine in strips of human gastrointestinal and uterine muscle. The pA2 values in gut longitudinal and circular muscle and myometrium were 9·1, 9·3 and 8·6 respectively.
The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle
Authors: DOGGRELL SHEILA A , VINCENT LYNN 
Published: April 2011

Abstract
The effects of antidepressants of tricyclic (amitriptyline, nortriptyline, protriptyline, doxepin, imipramine, and desipramine) and atypical (maprotiline, nomifensine, tandamine, viloxazine, CGP 6085A, and YM-08054-1) structures on contractile responses to exogenously applied acetylcholine and (−)-noradrenaline were studied in rat isolated anococcygeus muscle previously incubated with 6-hydroxydopamine. Atropine, amitriptyline, protriptyline, doxepin, imipramine, maprotiline and nortriptyline inhibited contractile responses to acetylcholine whereas desipramine, nomifensine, tandamine, viloxazine, CGP 6085A and YM 08054-1 did not. The contractile responses to (−)-noradrenaline were inhibited by low concentrations of tricyclic antidepressants and by higher concentrations of the atypical agents. These results illustrate that, in the preparation, the order of potency of antidepressants as muscarinic and as postsynaptic α-adrenoceptor antagonists is similar. The ability of tricyclic, but not atypical agents, to increase the concentration of noradrenaline bound to postsynaptic α-adrenoceptors may be severely limited by the antagonistic effect these agents have at this receptor.
Membrane damage by bile salts: the protective function of phospholipids
Authors: MARTIN GARY P , MARRIOTT CHRISTOPHER 
Published: April 2011

Abstract
The direct toxicity of sodium deoxycholate (SDC) and lysophosphatidylcholine (LPC) to biological membranes was assessed by measurement of goldfish overturn time. When phosphatidylcholine (PC) was incorporated into the aqueous media, the toxicity of both SDC and LPC was reduced, as indicated by increased overturn time. Fish were also pretreated for various times in media containing (a) 1 mM SDC and (b) 1 mM SDC with 1 mM PC. Subsequent transfer to solution, 100 mg litre−1 quinalbarbitone sodium showed that reciprocal overturn times for fish treated using method (a) increased linearly with duration of pretreatment up to a limiting value, obtained after 20 min exposure; 40 min exposure to 1 mM SDC was directly toxic. Fish pretreated using regimen (b) survived longer when challenged with barbiturate, and the reciprocal overturn times were a linear function of time of pretreatment up to at least 40 min. PC also provided protection against membrane damage caused by the synthetic surfactant sodium dodecyl sulphate. Mixed micelle formation between PC and surfactant is thought to account for the protective effects. The results are of significance in the consideration of reflux hypotheses for the aetiology of gastric ulceration and also to the possible formulation of drug delivery systems intended to enhance absorption whilst minimizing gastrointestinal damage.
Presynaptic α-block and inhibition of noradrenaline and 5-hydroxytryptamine reuptake by a series of compounds related to mianserin
Authors: NICKOLSON VICTOR J , WIERINGA JOOP H 
Published: April 2011

Abstract
A structure-activity relationship study was undertaken for a variety of structural analogues of the tetracyclic antidepressant mianserin. Presynaptic α-blocking activity in vitro was evaluated measuring the potentiation of depolarization-induced noradrenaline (NA) release from rat cerebral cortex slices. Inhibition of NA and 5-hydroxytryptamine reuptake was measured in rat hypothalamic or striatal synaptosomes, respectively. Presynaptic α-blockade was only found in molecules with an overall bent shape. Flat rigid molecules or flexible ones were not active. Six-membered, chair-formed D-rings (containing the -NCH3 moiety) appeared better than 5- or 7-membered ones. Heteroatom substitution, but not hydroxylation or methylation, of the bridge between the two aromatic rings left presynaptic α-blockade unaffected. N-Demethylation and aromatic methyl- or chlorine-subsitution reduced presynaptic α-blockade. In pyridine ring-substituted analogues the localization of the heteroatom appeared to be crucial. 5-Hydroxytryptamine reuptake inhibitory activity was only found in desmethylmianserin. NA reuptake inhibition was found in many mianserin analogues, especially those with an exocyclic -N(CH3)2 moiety. Structure activity relationships for NA reuptake inhibition differed from those for presynaptic α-blockade and were generally less stringent. For both properties simple additivity relationships appeared to be absent.
Pressor effect of L-threo-3,4-dihydroxyphenylserine in rats
Authors: ARAKI HIROMASA , TANAKA CHIKAKO , FUJIWARA HIROSHI , NAKAMURA MASAFUMI , OHMURA IPPEI 
Published: April 2011

Abstract
The pressor effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in rats and its decarboxylation in vivo have been examined. On i.v. administration, it produces a slow-onset and long-lasting pressor response, but no significant change in heart rate or e.c.g. The pressor effect was markedly reduced by inhibition of peripheral decarboxylase and by blockade of α-adrenoceptors. The slow-onset and long-acting pressor effect was also evident when the drug was given orally, while intracerebroventricular administration produced a long-lasting decrease in blood pressure. Noradrenaline (NA) concentrations in the plasma were significantly increased by both i.v. and oral administration of L-threo-DOPS. Elevation of plasma NA concentration by L-threo-DOPS given i.v. was suppressed by inhibition of decarboxylase. The plasma concentration of the drug was highest immediately after its i.v. administration. Its pressor effect was enhanced in rats made hypotensive by chemical sympathectomy with 6-hydroxydopamine (6-OHDA), compared with control rats, nevertheless, L-threo-DOPS produced the same increase in plasma NA concentrations in sympathectomized rats as in the controls. These results indicate that L-threo-DOPS is gradually converted to NA by L-aromatic amino acid decarboxylase in vivo. These findings suggest that L-threo-DOPS may be clinically useful as an oral pressor agent for the treatment of certain disorders related to hypotension.
Tests for foreign particles in metered-dose aerosols
Authors: LEA A R , DREW R M , WONG S S L , HAILEY D M 
Published: April 2011

Abstract
A simple method for the determination of foreign particulate matter in metered-dose aerosols (MDA's) has been developed. The method compares favourably with a procedure currently used in pharmaceutical industry and has the advantage of providing information on container to container variation. A linear relationship between log particle count and particle size was found for a number of MDA's, although there was considerable product-to-product variation. On the basis of the results obtained in this study, commercially available MDA's would in general comply with a limit for foreign particles greater than 100 μm of not more than 150 particles per container with the sum of the mean count and twice the standard deviation not more than 200.
The design and use of an instrumented mG2 capsule filling machine simulator
Authors: JOLLIFFE I G , NEWTON J M , COOPER D 
Published: April 2011

Abstract
The problems of instrumenting a continuous motion dosator nozzle capsule filling machine (mG2 type) are discussed and the construction of an mG2 simulator is described. A standard filling turret is employed with mechanical modification so that the dosator does not rotate. This allows instrumentation in the form of a strain gauged dosator piston, to measure compression and ejection stresses during filling, as well as distance transducers, to measure the corresponding piston and dosator movements. An experimental method is described for using this machine to study the filling of lactose powders.
Time-course of the effects of chronic Δ9-tetrahydrocannabinol on behaviour, body temperature, brain amines and withdrawal-like behaviour in the rat
Authors: TAYLOR D A , FENNESSY M R 
Published: April 2011

Abstract
The effects of clomipramine HCl (15 mg kg−1 i.p.) on behaviour, body temperature and brain amines were investigated in rats that had been chronically treated twice daily with increasing doses of Δ9-tetrahydrocannabinol (Δ9-THC, 2–6 mg kg−1 i.v.). Δ9-THC produced a biphasic change in behaviour, stimulation followed by depression, and a pronounced hypothermia. Tolerance developed rapidly to these effects of Δ9-THC. Chronic treatment with Δ9-THC reduced the levels of homovanillic acid, 5-hydroxytryptamine and noradrenaline. The level of dopamine was not altered with chronic treatment and tolerance appeared to develop to the increased level of 5-hydroxyindoleacetic acid induced by Δ9-THC. Injection of clomipramine, 12–14 h after 2, 5 or 10 days of Δ9-THC treatment induced characteristic changes in the rats behaviour which consisted of writhes, backward kicking, wet shakes, jumps, ataxia and front paw and whole body tremor. The severity of the behavioural changes appeared to be dependent on the period of Δ9-THC administration and they were not accompanied by a change in body temperature or consistent changes in brain amines or metabolites. The results indicate that physical dependence on Δ9-THC may occur since clomipramine is able to precipitate changes in behaviour, indicative on an abstinence syndrome, in rats chronically treated with Δ9-THC. It is suggested that tryptaminergic mechanisms are altered during chronic Δ9-THC treatment and that clomipramine induces the behavioural changes by interacting with an altered tryptaminergic system.
On the preferred rotameric conformation for dopamine agonist action: an illusory quest?
Authors: COSTALL B , LIM S K , NAYLOR R J , CANNON J G 
Published: April 2011

Abstract
Putative dopamine agonists from the 2-aminotetrahydronaphthalene and trans-octahydrobenzo (f) and (g) quinoline series were shown to inhibit the spontaneous locomotor activity of mice. Marked potency differences were observed between the α- and β-rotameric conformations, compounds having the α-rotameric conformation having the greater potency. Thus, 2-di-n-propylmino-5,6-dihydroxytetrahydronaphthalene was 339 times more potent than the 6,7-dihydroxy isomer, and 2-n-propylamino-5,6-dihydroxy-compound was respectively 79 times and 179 times more potent than 6,7-hydroxy- and 7,8-dihydroxycompounds. trans-7,8-Dihydroxy-1-n-propyl-1,2,3,4,4a,9,10,10b-octahydrobenzo(f)quinoline was 11 times more potent than the β-rotamer, the 6,7-dihydroxy compound, and within the trans-octahydrobenzo(g)quinoline series the α-rotameric N-propyl derivative was 467 times more potent than the β-rotamer, and the α-rotameric &gt;N–H analogue was 46 fold more potent than the β-rotamer. Thus, the α-rotamer appears the more potent in causing the present functional dopaminergic change. The dopaminergic nature of the response was indicated by its sensitivity to spiroperidol but not to yohimbine or prazosin. The possibility that a difference in behavioural potency between the α- and β-rotamers may reflect a differential metabolism by catechol-O-methyl transferase was assessed by administration of different agonists after pyrogallol pre treatment. This potentiated the activity of 2-di-n-propylamino-6,7-dihydroxytetrahydro-naphthalene but not that of the 5,6-dihydroxy analogue. However, changes in the effects of N-propyl derivatives of trans-octahydrobenzo(f) and (g)quinoline were not marked and, in all experiments, pyrogallol treatment failed by orders of magnitude to shift the dose-response curves of the β-rotamers to indicate a comparable potency to the α-rotameric forms.
Multiple compression of powders in a tablet press
Authors: ARMSTRONG N A , ABOURIDA N M A H , KRIJGSMAN L 
Published: April 2011

Abstract
Lactose, magnesium carbonate, phenacetin, microcrystalline cellulose and directly compressible starch compacts were repeatedly compressed in a tablet press, the tablets not being ejected from the die between compressions. When the interval between compressions was 1.3 s, all substances showed a decrease in the maximum force exerted by the tablet press, this being attributed to the formation of a structure of lower porosity. As the intervals between compressions is increased, the decrease in force is reduced, and in the case of microcrystalline cellulose and directly compressible starch, the force exerted at the second compression is greater than that exerted by the first.
A high performance liquid chromatographic method for determination of the radiochemical purity of iodohippuric acid [123I] injection
Authors: MILLAR A M 
Published: April 2011

Abstract
A method for the separation of the radiopharmaceutical iodohippuric acid ([123I]IHA) from the two impurities produced in the labelling reaction, iodide (123I−) and iodobenzoic acid ([123I]IBA) has been developed using reversed-phase high performance liquid chromatography (h.p.l.c). The effect of eluent pH on the separation of the three compounds was studied. An eluent consisting of methanol: 0.1 M acetic acid (30:70) adjusted to pH 4.0 with NaOH gave optimum phase capacity ratios of −0.21 for I−, 0.93 for IHA and 1.54 for IBA. On the chromatograph used, this corresponded to an analysis time of 4 min per sample. To recover 123I− from the column with a good peak shape, it was found necessary to include sodium iodide (1 mg/100 ml) in the eluent. The recoveries of 123I− 123IHA and 123IBA from the column were found to be 100.6% (s.d. 1.3), 100.2% (s.d. 2.1) and 98.1% (s.d. 1.2) respectively (n = 10 for each compound). H.p.l.c. was compared with the standard thin layer chromatographic (t.l.c.) method of analysis on 10 preparations of [123I]IHA which gave a mean radiochemical purity of 99.1% (± 0.2 s.e.) by h.p.l.c. and 98.3% (± 0.2 s.e.) by t.l.c. This difference was found to be significant (P &lt;0.05) and an explanation for this difference is proposed. A coefficient of variation of 0.1% on the results from the repeated analysis (n = 20) of one preparation of [123I]IHA, demonstrated that the h.p.l.c. method was capable of very high precision.
Clonidine-induced potentiation of reflex vagal bradycardia in anaesthetized cats
Authors: CONNOR HELEN E , DREW G M , FINCH L 
Published: April 2011

Abstract
The interactions between clonidine and the selective α1- and α2-adrenoceptor antagonists, prazosin and yohimbine, on the angiotensin-induced reflex vagal bradycardia have been investigated in propranolol-treated chloralose-anaesthetized cats. Clonidine (1–10 μg intracisternally) had little effect on the pressor responses to angiotensin, only slightly increased the peak but markedly increased the duration of the reflex bradycardia. Neither prazosin nor yohimbine (200 μg intracisternally of either antagonist) had any effect on the reflex bradycardia to angiotensin. Yohimbine greatly diminished the clonidine-induced potentiation of the response, but prazosin was without effect. Clonidine appears to potentiate the vagal reflex bradycardia by stimulating central α2-adrenoceptors.
Involvement of histaminergic mechanisms in the cataleptogenic effect of morphine in mice
Authors: MULEY M P , BALSARA J J , JADHAV J H , CHANDORKAR A G 
Published: April 2011

Abstract
Intraperitoneally administered morphine induced catalepsy in mice. Morphine pretreatment however, failed to antagonize apomorphine-induced cage climbing behaviour thereby ruling out the possibility of its possessing DA receptor blocking activity. Pretreatment with L-histidine, a precursor of histamine, and atropine, potentiated the cataleptic effect of morphine whilst pretreatment with chlorcyclizine, an H1 receptor blocker, and naloxone, a morphine antagonist, antagonized morphine-catalepsy. Pretreatment with metiamide, an H2 receptor blocker, and methysergide, a 5-HT antagonist, did not significantly alter the cataleptic effect of morphine. The results with L-histidine and chlorcyclizine suggest an involvement of central histaminergic mechanisms in the cataleptogenic effect of morphine in mice. Further, as the cataleptic effect of morphine was also antagonized by naloxone it appears that the interaction of morphine with the central histaminergic mechanisms is mediated through specific opiate receptors.
Specification of limits for particulate contamination in pharmaceutical dosage forms
Authors: HAILEY D M , LEA A R , KENDALL C E 
Published: April 2011

Abstract
Limits for the control of particulate contamination in large volume parenteral solutions and metered-dose aerosols are discussed. It is suggested that it would be desirable to use limits based on measurement of both the mean and the standard deviation of the particle counts obtained for each of the containers tested. Use of the statistic sT, assuming a target value of zero, is considered to be an appropriate means of measuring the container to container variation in particulate contamination.
Mechanism of drug dissolution rate enhancement from β-cyclodextrin-drug systems
Authors: CORRIGAN O I , STANLEY C T 
Published: April 2011

Abstract
The influence of β-cyclodextrin on the physicochemical properties of bendrofluazide, chlorothiazide, hydrochlorothiazide and hydroflumethiazide was investigated using solubility, X-ray powder diffraction, differential scanning calorimetry (DSC) and intrinsic dissolution rate methods. The solubility of each drug was enhanced in the presence of β-cyclodextrin, the effect being greatest with bendrofluazide. X-ray diffraction data on equimolar freeze dried systems indicated the formation of a solid state inclusion complex only in the case of bendrofluazide. The relative increase in initial dissolution rate of drug from freeze dried systems varied from sixty fold for bendrofluazide to three fold for hydroflumethiazide. The observed dissolution rates were intermediate between those predicted by the classical two component soluble complex model and a carrier controlled model. It was concluded that the enhanced drug dissolution rates, which are above those predicted by the soluble complex model, are due to an extension of carrier phase dissolution control to higher drug weight fractions than predicted by the soluble complex model and that this was a consequence of the disparate solubilities of the carrier and drug.