bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative pharmacokinetics of tetrahydropyranyl-doxorubicin and doxorubicin in rat isolated lung
Authors: Dumas Monique , Dubuet Aleth , D'Athis Philippe , Camus Philippe , Escousse André 
Published: April 2011

Abstract
Rat isolated perfused lungs (Sprague-Dawley rats, n = 20) were studied to compare the pulmonary uptake of a new anthracycline, tetrahydropyranyl-doxorubicin (THP-DXR) with that of doxorubicin (DXR). Lung perfusions were initiated with a constituted medium containing either drug at concentrations of 1, 10 or 100 μm. Lungs were perfused by recirculation for 60 min. Thirteen perfusate samples were collected over 60 min and subjected to HPLC for assay. The perfusate concentration of THP-DXR decreased to 24 ± 5% of the initial concentration and to 8 ± 2%, 20 and 60 min after the beginning of the infusion, respectively. Corresponding values for DXR were 77 ± 16 and 52 ± 15%, respectively (P &lt; 0·05). During the THP-DXR perfusion, the area under the perfusate concentration vs time curve (AUC) was decreased to one-third and the clearance was increased 3-fold (P &lt; 0·05). The pulmonary concentration of THP-DXR reached 0·032 ± 0·01 μmol g−1 60 min after the beginning of a perfusion of 1 μm of the drug. This concentration increased to 0·379 ± 0·11 μmol g−1 when the initial dose concentration was 10 μm. Corresponding lung concentrations for DXR were 0·013 ± 0·001 and 0·150 ± 0·04 μmol g−1, respectively (P &lt; 0·05). The perfusate concentration/initial concentration ratio decreased by the same amount whether a 1 or 10 μm initial concentration of either drug was used. An initial concentration of 100 μm of THP-DXR, unlike DXR, consistently induced oedema in the perfused lung. No metabolite of either drug was revealed during the course of our study. These findings suggest: (1) a higher lung affinity for THP-DXR; (2) a correlation between lung uptake and dose consistent with a passive diffusion transport mechanism for both drugs; (3) a higher acute toxicity induced by THP-DXR; (4) the absence of metabolic activity in the lung with regards to both anthracyclines.
Evaluation of starch obtained from Ensete ventricosum as a binder and disintegrant for compressed tablets
Authors: Gebre-Mariam Tsige , Nikolayev Alexander S 
Published: April 2011

Abstract
The binding and disintegrant properties of starch obtained from Ensete ventricosum Musaceae have been evaluated. The effect of the starch on the physical properties such as crushing strength, friability and disintegration time of tablets of chloroquine phosphate, dipyrone and paracetamol was compared with tablets prepared with potato starch. The results show that enset starch can be used both as a tablet binder and disintegrant and the indication is that enset starch has a better binding ability and less disintegrating power than potato starch.
Microspheres of Human Serum Albumin with Barbiturates: Effect of Drug Partition Coefficient on Preparation and Drug Release
Authors: Filipović-Grĉić J , Jalsšenjak I 
Published: April 2011

Abstract
Human serum albumin microspheres were prepared with a series of barbiturates by the thermal denaturation method. The barbiturates were of similar general physicochemical properties but different partition coefficients. The total drug content of microspheres was dependent on the partition coefficient, and an increase in the partition coefficient caused a decrease in the drug content of finished microspheres due to drug migration to the outer organic phase during preparation. The ensemble drug release from microspheres was followed by the paddle method and by potentiometric titration with a pH-stat. Nonlinear regression analysis showed the best fit for the spherical Higuchi equation, especially first-order kinetics (bi-phasic). The drug partition coefficient affected the release in such a way that drugs with higher partition coefficients were released faster and to a greater extent than those with lower coefficients.
Effects of Cromakalim (BRL 34915) in Trachea Isolated from Actively Sensitized Guinea-pigs
Authors: Cortijo J , Pedrós C , Ortiz J L , Morcillo E J 
Published: April 2011

Abstract
The effects of cromakalim were examined in tracheal strips isolated from normal (unsensitized) guinea-pigs and from animals actively sensitized to bovine serum albumin. Sensitized tracheae exhibited hyper-responsiveness to KCl, acetylcholine and histamine. In normal and sensitized tracheae, cromakalim (0·01–10 μm) produced a concentration-related suppression of spontaneous tone. The ability of cromakalim to relax tracheal strips was reduced when tone was raised by KCl (25 Mm), acetylcholine (0·1 Mm) or histamine (0·1 Mm) and lost against KCl (120 Mm)-induced spasm. Procaine (5 Mm) abolished the relaxant effect of cromakalim whilst tetraethylammonium (8 Mm) was without effect. These effects were similar in normal and sensitized tissues. Cromakalim (10 μm) produced minor alterations of the concentration-effect curves of KCl (1–100 Mm), acetylcholine (1 Nm–1 Mm) and histamine (1 Nm–1 Mm) in normal and sensitized tissues. The results from this pharmacomechanical study do not support the hypothesis that altered properties of cromakalim-sensitive K+ channels underlie the airway hyper-reactivity induced by active sensitization to bovine serum albumin.
Effect of metadoxine on striatal dopamine levels in C57 Black mice
Authors: Fornai Francesco , Alessandri Maria Grazia , Bonuccelli Ubaldo , Scalori Vera , Corsini Giovanni U 
Published: April 2011

Abstract
In the present study, we examined the effect of metadoxine on striatal levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites in male C57 Black mice. Striatal content was assayed after systemic administration of metadoxine ranging from 1 μg kg−1 to 500 mg kg−1. Striatal dopamine increased 1 h after treatment with metadoxine (150 mg kg−1), but the most notable effect was obtained 24 h after the drug administration. At this time a plateau was reached; the two major metabolites of dopamine showed the same trend. Seven days after metadoxine administration, striatal dopamine approached the control values. Over the same time intervals, striatal 5-HT increased to a lesser extent and 5-hydroxy-indoleacetic acid did not differ significantly from controls. Striatal dopamine increased significantly at a dose of 250 μg kg−1 up to a dose of 1 mg kg−1 metadoxine; no further increment was observed between 1 and 500 mg kg−1 metadoxine. Administration of each component at doses equimolar to 1 mg metadoxine showed that pyridoxine produced only a mild increase in striatal dopamine compared with controls. We suggest that the metadoxine-induced striatal dopamine increase is obtained by increasing synthesis of dopamine.
Biocompatibility of Wound Management Products: A Study of the Effects of Various Polysaccharides on Murine L929 Fibroblast Proliferation and Macrophage Respiratory Burst
Authors: Schmidt Richard J , Chung Lip Yong , Andrews Andrea M , Spyratou Olga , Turner Terence D 
Published: April 2011

Abstract
An in-vitro screening method to examine the biocompatibility of materials used in wound management has been evaluated. This involved the use of a macrophage respiratory-burst assay and a fibroblast proliferation assay to represent respectively the inflammatory and the granulation phases in wound healing. Standard polysaccharides (calcium and sodium alginates, ŗ-carrageenan, chitin, chitosan lactate, chondroitin sulphate and pectic acid) were used as test compounds. None of the polysaccharide samples caused a significant increase in L929 fibroblast cell numbers relative to control after 6 days incubation. The overall effect of exposure of the fibroblast cultures to the alginates, carrageenan and chondroitin sulphate was an extension of lag phase followed by an enhanced rate of cell proliferation in the logarithmic phase. Only calcium and sodium alginates and chondroitin sulphate enhanced the respiratory burst activity of murine macrophages; ŗ-carrageenan and chitosan lactate were markedly inhibitory. The results suggest that a macrophage activity assay should be included as part of an in-vitro screening program to evaluate the biocompatibility of wound management materials and to detect intrinsic biological activity.
Anti-inflammatory activities of Emblica officinalis Gaertn leaf extracts
Authors: Asmawi M Z , Kankaanranta H , Moilanen E , Vapaatalo H 
Published: April 2011

Abstract
Emblica officinalis Gaertn, a tree growing in subtropical and tropical parts of China, India, Indonesia and the Malay Peninsula, has been used for anti-inflammatory and antipyretic treatments of rural populations in these areas. In the present study, we examined the effects of Emblica officinalis extracts on carrageenan- and dextran-induced rat hind paw oedema. Anti-inflammatory activity was found in the water fraction of methanol extract of the plant leaves. The effects of the same fraction were tested on the synthesis of mediators of inflammation such as leukotriene B4 (LTB4), platelet-activating factor (PAF) and thromboxane B2 (TXB2), and on LTB4- and N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-induced migration of human polymorphonuclear leucocytes (PMNs) in-vitro. The water fraction of the methanol extract inhibited migration of human PMNs in relatively low concentrations. It did not inhibit LTB4 or PAF synthesis in human PMNs or TXB2 synthesis in human platelets during clotting, suggesting that the mechanism of the anti-inflammatory action found in the rat paw model does not involve inhibition of the synthesis of the measured lipid mediators.
Prazosin-induced Blockade of Extraneuronal Uptake Facilitates Dopaminergic Modulation of Muscle Twitches in Rat Vas Deferens
Authors: Elmallah Ahmed I , Sharabi Fouad , Omar Amal G , El-Mas Mahmoud M 
Published: April 2011

Abstract
Preliminary findings in our laboratory have shown that prazosin augmented the inhibitory effects of dopamine on the electrically-evoked muscle twitches in rat vas deferens. In this study, we opted to investigate the underlying mechanism and whether a prazosin-induced blockade of extraneuronal uptake process may be involved.
Cumulative additions of dopamine (1.8 times 10−7-4.4 times 10−5m) elicited slight (&lt;30%) but dose-related inhibition of electrically-evoked (0.05 Hz, 1 ms duration and supramaximal voltage) muscle twitches of the vas deferens. Pretreatment with cocaine (10 μm), prazosin (50 nm) or oestradiol (10 μm) produced comparable potentiation of the inhibitory responses of dopamine; the pD2 values to dopamine amounted to 4.47 ± 0.20, 4.72 ± 0.21 and 4.56 ± 0.19, respectively. A lower concentration of prazosin (5 nm) failed to alter dopaminergic responses. Further potentiation of dopamine responses was demonstrated in tissues preincubated with a combination of cocaine plus prazosin (50 nm), or cocaine plus oestradiol (pD2, 5.40 ± 0.11 and 5.42 . 0.05, respectively). However, a mixture of all three drugs failed to elicit any further increase in dopamine responses, a finding that may suggest an extraneuronal uptake blocking activity for prazosin. Inhibition of muscle twitches evoked by bromocriptine, a dopaminoceptor agonist which is not a substrate for extraneuronal uptake, was not affected by prazosin (50 nm) pretreatment.
The findings presented in this study emphasize the role of dopamine in modulating noradrenergic neurotransmission in rat vas deferens. More importantly, the results suggest that prazosin may act to block the extraneuronal uptake at noradrenergic sites, an effect that may account for its capability to facilitate dopaminergic modulation of noradrenergic neurotransmission.
Availability and Mean Transit Times of Phenol and Its Metabolites in the Isolated Perfused Rat Liver: Normal and Retrograde Studies Using Tracer Concentrations of Phenol
Authors: Ballinger Linsay N , Cross Sheree E , Roberts Michael S 
Published: April 2011

Abstract
Phenolic compounds are frequently detoxified by the formation of sulphate and glucuronic acid conjugates in the liver. These conjugates are formed in the hepatocytes and then either transported into the bile or back into the blood. In this study, we examined the transport kinetics of phenol and its metabolites in the isolated perfused rat liver by monitoring the outflow profiles of these compounds after a bolus input in a single pass preparation.
Phenol was almost exclusively metabolized to phenyl sulphate (97%) at the trace concentrations used, with the amount of phenol and metabolites excreted into the bile being minimal (3.5%). The metabolite formed was rapidly transported back into the perfusate, with mean transit times of 17.4 and 12.3 s anterograde and 24.9 and 24.2 s retrograde at flow rates of 15 and 30 mL min−1 respectively, which were intermediate between those of Evans blue and water. The outflow concentration-time profile for phenyl sulphate formation was unaffected by the addition of another organic anion (bromosulphophthalein).
The effect of enzyme zonation on outflow concentration-time profiles was also investigated using retrograde perfusions. The transit time ratios for generated metabolite to water for anterograde perfusions (0.6) was found to be more than twice that for retrograde perfusions (0.23) at 15mL min−1 and approximately 1.6 times greater at 30mL min−1, being 0.58 and 0.37 respectively. The relative ratios obtained are consistent with previous findings that normalized variance of solutes in the retrograde perfusions is greater than that for anterograde perfusions.
Frusemide and Its Acyl Glucuronide Show a Short and Long Phase in Elimination Kinetics and Pharmacodynamic Effect in Man
Authors: Vree Tom B , Van Den Biggelaar-Martea Magdalena , Verwey-Van Wissen Corrien P W G M 
Published: April 2011

Abstract
The pharmacokinetics of 80 mg frusemide given orally were investigated in normal subjects using a direct HPLC method for parent drug and its acyl glucuronide conjugate.
Two half-lives could be distinguished in the plasma elimination of both frusemide and its conjugate, with values of 1.25 ± 0.75 and 30.4 ± 11.5 h for frusemide and 1.31 ± 0.60 and 33.2 ± 28.0 h for the conjugate. The renal excretion rate-time profile showed two phases; the rapid elimination phase lasted from 0–15 h and the second and slow phase, from 15–96 h. During the first 15 h, 33.3 ± 4.8% of the dosed frusemide was excreted; in the remaining period 15–96 h, 4.6 ± 1.5% was excreted. In the same two periods the excretion of the glucuronide was 13.4 ± 4.7 and 1.9 ± 1.1%, respectively. The mean renal clearance of frusemide was 90.2 ± 16.9 mL min−1 during the first period and 91.5 ± 29.3 mL min−1 in the remaining period, during which the stimulation of urine production was absent. The renal clearance of the acyl glucuronide was 702 ± 221 mL min−1 in the first period, but only 109 ± 51.0 mL min−1 in the second period. The stimulated urine production in the first 6 h after administration amounted to 2260 ± 755 mL (measured urine production minus baseline value of 1 mL min−1 (360 mL). During the second or rebound period (6–96 h after drug administration), the quantity of urine was 990 ± 294 mL lower than what would have been expected from the baseline production of 5400 mL. This reduced production (0.82 mL min−1) is equivalent to an 18% reduction in the average urine flow rate of 1 mL min−1.
Effects of Clonidine Pretreatment on the Local Anaesthetic Activity of Bupivacaine in Mice
Authors: Attolini Laurence , Gantenbein Manon , Grignon Sylvain , Bruguerolle Bernard 
Published: April 2011

Abstract
This study was designed to document possible changes in bupivacaine local anaesthetic activity in mice after a single injection of clonidine (0.1 or 1 mgkg−1, i.p.). The local anaesthetic activity was evaluated during 60 min, according to a previously reported technique, using sciatic nerve blockade by injection of bupivacaine in the area of the sciatic nerve.
Clonidine pretreatment modified the local anaesthetic activity of bupivacaine dose-dependently. The time of recovery was higher for clonidine-pretreated mice (40.00±7.24 min, 0.1 mgkg−1 clonidine: 50.0±9.35 min, 1 mgkg−1 clonidine) compared with controls (27.22±1.21 min, P = 0.02). The maximal effect (Emax) was significantly lower for the pretreated group (1.15±0.13 units, 0.1 mgkg−1; 1.35±0.09 units, 1 mgkg−1) compared with the control group (1.72±0.13, P = 0.01).
Our data indicate a significant decrease in the duration of anaesthetic activity of bupivacaine in clonidine-pretreated mice.
Cardiovascular Effects of NT-1, a New Patch Form of Nitroglycerin, Alone and in Combination with Nifedipine in Conscious Dogs
Authors: Kanda Atsuhiro , Yoshida Masumi , Kanou Mayumi , Yamaguchi Kazumasa , Kyuki Kohei 
Published: April 2011

Abstract
The cardiovascular effects of NT-1, a new patch form of nitroglycerin, alone and in combination with nifedipine in conscious dogs were examined.
NT-1 (2.5mgkg−1 nitroglycerin) decreased systolic blood pressure by 10–15%, while diastolic blood pressure and heart rate were not affected. Coronary blood flow and calculated rate-pressure product were decreased. These parameter changes occurred at 30 min after NT-1 application and remained constant for 8 h until NT-1 was removed. After administration of NT-1 in combination with nifedipine, systolic blood pressure was significantly decreased to a greater extent, and heart rate and coronary blood flow showed a tendency to increase compared with nifedipine alone. Rate-pressure product was not changed compared with that obtained on administration of nifedipine alone.
These results suggest that NT-1 may be applicable as a transdermal sustained release medication, and show that in combination with nifedipine, NT-1 can induce a large increase in coronary blood flow without further increasing rate-pressure product.
Absorption of Phenol Red and Bromphenol Blue as Model Drugs from the Peritoneal Cavity around the Liver Surface in Rats
Authors: Nishida Koyo , Amagishi Hiroaki , Sasaki Hitoshi , Nakamura Junzo 
Published: April 2011

Abstract
The importance of the injection site on the pharmacokinetics of phenol red and bromphenol blue as model drugs after intraperitoneal administration into rat was examined.
Their absorption rate from the peritoneal cavity was faster after intraperitoneal administration to the liver surface than that after intraperitoneal administration to the distal small intestine, as shown by the increase in maximum concentration and decrease in mean residence time in plasma. A similar tendency was observed in the biliary excretion pattern. The enhanced absorption rate was supported by the significantly smaller amount of both drugs remaining in the peritoneal cavity at 15 min after liver surface administration than that after small intestine administration. The liver concentration of the model drugs at 15 min after liver surface administration was 1.5–2.0 times that after small intestine administration.
Accordingly, liver surface administration was shown to be effective with good absorption and efficient drug delivery to the liver.
The Factors that Influence Skin Penetration of Solutes
Authors: Abraham Michael H , Chadha Harpreet S , Mitchell Robert C 
Published: April 2011

Abstract
In this study, human skin permeation data are analysed using a number of physicochemical descriptors.
It is shown that the equilibrium distribution of compounds between the stratum corneum and water (log Km) can be correlated with either water-octanol partition coefficients (log Poct) or Abraham solute descriptors. The latter reveals that partitioning of compounds is governed by solute size and hydrogen-bond acidity that favour the stratum corneum, and solute dipolarity/polarizability, and hydrogen-bond basicity that favour water.
For water-skin permeation coefficient (log kp) data it is demonstrated that log Poct cannot be used as a descriptor across a wide range of chemical families, but that log kp can be correlated using Abraham solute descriptors. These disclose that log kp values are increased by solute size and decreased by solute dipolarity/polarizability, hydrogen-bond acidity and hydrogen-bond basicity. It is suggested that different solutes travel through the stratum corneum by the same route, which cannot be distinguished as an intercellular or transcellular mechanism.
Backward skin permeation is examined and it is demonstrated that factors governing this process can be rationalized. Furthermore, it is shown that using the Abraham analysis, log Poct can be corrected to correlate log kp over a wide range of compounds.
The determination of solute descriptors is also described, indicating that Abraham solute descriptors can be obtained by substructure summation and partition coefficient measurements, so that dermatological properties can be predicted for solutes without the necessity for synthesis.
An Attempt to Clarify the Mechanism of the Penetration Enhancing Effects of Lipophilic Vehicles with Differential Scanning Calorimetry (DSC)
Authors: Leopold Claudia S , Lippold Bernhard C 
Published: April 2011

Abstract
In a previous in-vivo skin penetration study, it was observed that certain lipophilic liquid vehicles enhanced drug penetration, whilst others did not.
To clarify the mechanism of skin penetration enhancement, isolated sheets of human stratum corneum were measured by differential scanning calorimetry (DSC), either untreated or after pretreatment with various lipophilic liquids (highly purified light mineral oil, isopropyl myristate, caprylic/capric acid triglycerides containing 5% phospholipids, dibutyl adipate, dimethicone 100, cetearyl iso-octanoate, caprylic/capric acid triglycerides), commonly used in ointment bases.
All samples were analysed over a heating range of at least — 10–130°C. All DSC curves were evaluated with regard to the phase-transition enthalpies (peak areas) and peak maximum temperatures of the lipid-phase transitions at ca 75 and 85°C.
With the exception of dimethicone 100, cetearyl iso-octanoate and caprylic/capric acid triglycerides, all vehicles showed characteristic alterations of the phase-transition temperatures and enthalpies of the stratum corneum lipids. Mineral oil and isopropyl myristate caused a reduction of the enthalpy and a decrease of the phase-transition temperatures. These two vehicles are thought to fluidize the lamellar-gel phase of the stratum corneum lipids, and possibly partially dissolve the lipids. Dibutyl adipate and caprylic/capric acid triglycerides containing 5% phospholipids decreased the phase-transition enthalpy only, probably due to dissolution or extraction of the stratum corneum lipids.
These DSC results provide an explanation for the in-vivo penetration-enhancing effects observed previously.