bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relaxant Effect of Extract of Phyllanthus urinaria in the Guinea-pig Isolated Trachea. Evidence for Involvement of ATP-sensitive Potassium Channels
Authors: Paulino Niraldo , Cechinel-Filho Valdir , Yunes Rosendo A , Calixto João B 
Published: April 2011

Abstract
This study analyses the relaxation induced by the hydroalcoholic extract of stems, leaves and roots from Phyllanthus urinaria (Euphorbiaceae) in the guinea-pig trachea (GPT) pre-contracted by carbachol.
The hydroalcoholic extract of P. urinaria (0.1–10 mg mL−1) caused a graded relaxation in GPT with or without epithelium, with mean EC50 values of 1.94 (1.41-2.67) and 2.00 (1.47-2.78) mg mL−1 and Emax of 717 mg (± 16) and 627 mg (± 12), respectively. The relaxation in response to hydroalcoholic extract, like that to cromakalim (EC50 3.57 (2.75-4.64 μM) in GPT without epithelium, was fully abolished in the presence of high KCl concentrations (80 mM), and was significantly attenuated by tetraethylammonium (10 or 30 mM) or glibenclamide (0.1 or 3 μM). However, the relaxation caused by the hydroalcoholic extract was unaffected by apamin (0.1 or 1.0 μM), nitro-L-arginine (L-NOARG, 100 μM), methylene blue (10 μM) or by calcitonin gene-related peptide (CGRP) (8–37) (a CGRP antagonist, 0.1 μM). Both propranolol (1 or 3 μM) and [D-p-Cl-Phe6,Leu17]VIP (a vasoactive intestinal peptide (VIP) receptor antagonist, 0.1 μM) produced a significant displacement to the right (about 2-fold) of the relaxation response to hydroalcoholic extract of P. urinaria.
Thus, the present results indicate that the ATP-activated potassium channels sensitive to glibenclamide, but not the small conductance calcium-activated potassium channels sensitive to apamin, largely contribute to the relaxation effect of the hydroalcoholic extract of P. urinaria in GPT. In addition, both β2 and VIP-mediated responses seem to account, at least in part, for the relaxation effect of the hydroalcoholic extract, as its relaxant response was partially attenuated by both propranolol and VIP receptor antagonist.
Reversible Inhibition of Cholinesterases by Opioids: Possible Pharmacological Consequences
Authors: Galli Alessandro , Ranaudo Esterina , Giannini Laura , Costagli Chiara 
Published: April 2011

Abstract
The inhibitory potency of opioids belonging to different structural categories on electric eel and rat brain acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE) was investigated.
The phenylazepine meptazinol, the pyrrolo-[2,3-b]-indole derivative eseroline and the benzomorphan normetazocine were the most potent inhibitors of AChE among the compounds tested. These were followed by (-)-metazocine, N-allylnorcyclazocine, 3-(1,3-dimethyl-3-pyrrodinyl)-phenol, levallorphan, levorphanol and pentazocine. The opioids which inhibited horse serum BuChE were in order of potency: meptazinol, methadone, profadol, levallorphan and 1,2,3-trimethyl-3-(3-hydroxyphenyl)-piperidine. The results of this work appear consistent with the fact that the anticholinesterase activity of the opioids is not confined to specific structural categories, although conformationally constrained molecules, like those of morphinans, benzomorphans or pyrrolo-[2,3-b]-indoles, appear to favour affinity for AChE, whereas highly flexible molecules, like those of acyclic opioids, inhibit BuChE in a rather selective way. In all cases, the inhibitory action of opioids markedly differed from that of carbamates or organophosphorous compounds, in that it was time-independent and immediately reversible on dilution.
In general the anticholinesterase action of opioids does not seem to influence appreciably the pharmacological properties of the drugs since it is evidenced at drug doses higher than those which are analgesic. However, in the case of mixed agonist/antagonist opioids with rather weak analgesic activity, the enzyme inhibition caused by the levels of circulating drugs can be so marked as to exert also a cholinergic component of action.
Study of Interaction Effects of Polyacrylic Acid Polymers (Carbopol 940) on Antimicrobial Activity of Methyl Parahydroxybenzoate Against Some Gram-negative, Gram-positive Bacteria and Yeast
Authors: Scalzo Marcello , Orlandi Clelia , Simonetti Nicola , Cerreto Felice 
Published: April 2011

Abstract
Cosmetic or pharmaceutical formulations containing hydrophilic polymers of natural or synthetic origin, may be more exposed to successful microbial contamination because of a polymer-preservative interaction. The experimental data reported in this paper relate to the possible interference of Carbopol 940 with methyl parahydroxybenzoate.
Results show that this hydrophilic polymer, widely employed in many formulations, exerts, on the contrary, an interesting synergism on microbicidal activity of the preserving agent against E. coli and P. Aeruginosa.
A reduction in microbicidal activity against S. aureus and C. albicans is observed for a polymer concentration higher than that needed for anti-Gram-negative synergy.
Influence of pH on Skin Permeation of Amino Acids
Authors: Hatanaka Tomomi , Kamon Toshihiko , Uozumi Chisato , Morigaki Setsuko , Aiba Tetsuya , Katayama Kazunori , Koizumi Tamotsu 
Published: April 2011

Abstract
Skin permeation of amino acids through excised rat skin was measured at various pH values.
The permeabilities varied with the donor pH and amino acid, indicating that each ionic species of amino acid may have a different permeability. The permeability coefficient of each ion was estimated from the permeability-pH profiles using the dissociation constants. The estimated values for mono-cation and uncharged zwitterion were not dependent on the lipophilicity but on the size of the amino acid, suggesting a porous mechanism of transport. The permeability coefficient was highest for di-cation, followed by mono-cation, positively charged, uncharged and negatively charged zwitterions. The electrical potential difference across the skin was too small to affect the permeation of ions.
The permselective property of skin thus seems to be determined by the difference of diffusivity in aqueous pores of skin due to the hydration of ions and other factors.
Immunological Detection of Type II Collagen Degradation: Use in the Evaluation of Anti-arthritic Therapies
Authors: Chichester C O , Barrach H-J , Srinivas G R , Mitchell P 
Published: April 2011

Abstract
Propagated Swarm rat chondrosarcoma cells, rabbit chrondrocytes (from articular cartilage of knee, shoulder and hip joints), and bovine nasal cartilage explant cultures were studied. Type II collagen (CII) and its peptide fragments were quantitated in cell medium and cell layer separately, using two previously developed assays; one assay employed a monoclonal antibody, C4F6, that reacts specifically with triple helical CII and the other assay used an antibody, E1E5, that reacts specifically with a peptide of CII.
A time-dependent increase in the content of CII and CII-derived peptides was observed in both rat and rabbit cultures. In both culture systems the majority of the native type II collagen is found associated with the cell layer (97% in rat cultures and 73% in rabbit cultures), while the major part of the CII peptides is found in the media (73% in rat cultures, 88% in the rabbit cultures). The concentration of peptides in the media reaches approximately 2 μg mL−1 in both chondrocyte monolayer cultures after 4 days.
The CII peptide assay employing E1E5 was well suited to quantitate articular cartilage collagen degradation in explant culture. Thus it can be used to evaluate potential therapeutic agents that can modify or inhibit cartilage degradation. The assay has the added potential that it could be used in-vivo to evaluate the effectiveness of potential metalloproteinase inhibitors in animal models of osteoarthritis or in clinical trials.
Preoperative Lymph-node Staining with Liposomes Containing Patent Blue Violet. A Clinical Case Report
Authors: Pump B , Hirnle P 
Published: April 2011

Abstract
A case study is reported using patent blue violet entrapped in liposomes to localize lymph nodes before surgery.
Liposomes containing 44 mg patent blue violet were injected into foot lymphatics of a patient due to undergo retroperitoneal staging-lymphonodectomy. Lymph nodes were readily visualized and removed, and urine and serum was collected for assay of the dye. The maximum concentration of patent blue violet in serum was 2.7 μg mL−1, 1.5 h after the termination of the injection; almost no dye was detectable by the time of the operation 24 h later.
In the first urine sample (2 h after the termination of the injection) the concentration of patent blue violet was 1.3 μg mL−1, and subsequently diminished, with the last urine sample to contain detectable dye being collected 20 h later. A total of 0.8 mg dye (2% of the injected amount) was excreted in the urine suggesting 10% of the circulating amount of dye was renally excreted.
Endolymphatic injection of patent blue violet simplifies the often difficult process of finding the lymph nodes and additionally reduces side-effects. All surgery cases demanding a radical lymphonodectomy may profit, including testicular or bladder cancers and many gynaecological tumours.
Suppression of Adjuvant Arthritis in Rats by Oral Administration of Type II Collagen in Combination with Type I Interferon
Authors: Yoshino Shin 
Published: April 2011

Abstract
The oral administration of 3 μg but not 300 μg of type II collagen (CII) significantly suppressed adjuvant arthritis in rats that was induced by immunization with Mycobacterium tuberculosis. Feeding 5000 units of type I interferon was also effective in downregulating the disease. More suppression of adjuvant arthritis was observed when both CII and interferon were orally given. Delayed-type hypersensitivity responses to M. tuberculosis were inhibited in interferon-but not in CII-fed animals. There were no delayed responses to CII in M. tuberculosis-immunized rats fed either CII or interferon. However, the delayed response to M. tuberculosis plus CII was significantly reduced by CII as well as interferon given orally. Feeding both CII and interferon was more effective in suppressing the delayed responses to M. tuberculosis plus CII. A similar suppression was observed in proliferative responses of lymph-node cells to M. tuberculosis, CII, or M. tuberculosis plus CII in-vitro.
These results suggest that the suppression of adjuvant arthritis by oral administration of CII is due to tolerance to CII in which a bystander suppression mechanism appears to be involved. Orally administered interferon seems to suppress nonspecifically cellular immune responses. The oral administration of CII in combination with interferon may be a novel way to treat T cell-mediated diseases.
The Disposition of Aspirin and Salicylic Acid in the Isolated Perfused Rat Liver: the Effect of Normal and Retrograde Flow on Availability and Mean Transit Time
Authors: Mellick George D , Roberts Michael S 
Published: April 2011

Abstract
The effect of changing the direction of perfusate flow from anterograde to retrograde on the disposition of acetylsalicylic acid (aspirin) and salicylic acid was studied in the single pass in-situ perfused rat liver. Mixtures of aspirin, [14C]salicylic acid and the inert reference solute [3H]sucrose were administered as boluses into the liver using red blood cell and albumin-free perfusate media at a flow rate of 30 mL min−1/liver. Hepatic availability (F), mean transit time (MTT) and normalized variance (CV2) for aspirin, preformed [14C]salicylic acid, salicylic acid produced from aspirin in the liver and [3H]sucrose were deduced from the outflow concentration profiles using statistical moment analysis.
The values for F, MTT and CV2 for the solutes under anterograde perfusion were: aspirin (0.73 ± 0.04, 15.13 ± 2.01 s, 0.33 ± 0.09, n = 5), preformed [14C]salicylic acid (1.05 ± 0.06, n=12, 43.19 ± 2.21 s, 1.08 ± 0.08, n = 5), salicylic acid from aspirin (0.33 ± 0.05, 42.82 ± 9.16 s, 0.73 ± 0.10, n = 5) and [3H]sucrose (1.05 ± 0.05, 16.88 ± 0.77 s, 0.74 ± 0.10, n = 5). The corresponding values for retrograde perfusions were: aspirin (0.73 ± 0.02, 17.41 ± 3.06 s, 0.32 ± 0.09, n = 5), preformed [14C]salicylic acid (1.14 ± 0.02, 44.42 ± 3.16 s, 0.95 ± 0.07, n = 5), salicylic acid from aspirin (0.33 ± 0.09, 36.47 ± 10.28 s, 0.58 ± 0.05, n = 5) and sucrose (1.01 ± 0.04, 18.08 ± 1.61 s, 0.76 ± 0.15, n = 5).
No significant differences in F or MTT were apparent between anterograde and retrograde perfusions for all solutes. The MTT and CV2 data for [14C]salicylic acid and salicylic acid produced from aspirin is suggestive of a permeability limitation for salicylic acid transport.
Alterations in Renal Uptake Kinetics of the Xanthine Derivative Enprofylline in Endotoxaemic Mice
Authors: Nadai Masayuki , Hasegawa Takaaki , Wang Li , Haghgoo Soheila , Okasaka Toshiki , Nabeshima Toshitaka , Kato Nobuo 
Published: April 2011

Abstract
The pharmacokinetics and renal uptake of enprofylline, which is primarily excreted into the urine by an active tubular secretion mechanism, were investigated in endotoxaemic mice by lipopolysaccharide isolated from Klebsiella pneumoniae.
Lipopolysaccharide (1 mg kg−1) was infused 2 h before starting the examination, thereby inducing a decrease in the systemic clearance and an increase in the steady-state volume of distribution of enprofylline while inducing no changes in the urinary recovery (&gt; 90%). The protein binding of enprofylline significantly decreased in the presence of lipopolysaccharide. Both the systemic clearance for unbound enprofylline and glomerular filtration rate decreased in the treated mice. A nonlinear relationship was found in both groups between the steady-state unbound plasma concentration and renal uptake of enprofylline after constant infusion for 1 h. The renal uptake rate of enprofylline decreased in the treated mice. Lipopolysaccaharide caused increases in the apparent maximum capacity for renal uptake (Vmax) from 17.3 to 32.2 μg h−1 g−1 of kidney and in the Michaelis–-Menten constant (Km) from 2.7 to 21.7 μg mL−1 and decrease in the nonsaturable uptake rate constant (Kd) from 0.87 to 0.43 mL h−1 g−1 of kidney.
These results indicate that lipopolysaccharide decreases the renal tubular secretion of enprofylline by inducing a decrease in the renal uptake ability.
Kinetics of Bupivacaine After Nicorandil Treatment in Mice
Authors: Gantenbein Manon , Attolini Laurence , Bruguerolle Bernard 
Published: April 2011

Abstract
Previous studies have reported interactions between potassium-channel agonists and bupivacaine. This study was designed to document possible changes in the pharmacokinetic behaviour of bupivacaine and its main metabolite, N-desbutylbupivacaine, in mice after a single 1 mg kg−1 intraperitoneal injection of nicorandil.
The kinetic variables of bupivacaine were determined after a single 20 mg kg intraperitoneal dose of bupivacaine in controls (group 1) and in nicorandil-treated mice (group 2). The maximal concentration in the serum (Cmax 0.618 ± 0.051 vs 0.408 ± 0.041 μg mL−1 for group 1 vs 2, P = 0.01) and the area under the concentration curve (AUC 1.039 ± 0.051 vs 0.758 ± 0.072 μg mL−1 h for group 1 vs 2, P = 0.013) of bupivacaine were significantly lower in nicorandil-treated mice, while CL (0.579 ± 0.025 vs 0.815 ± 0.079 for group 1 vs 2, P = 0.022) and Vd (0.506 ± 0.054 vs 0.981 ± 0.117 for group 1 vs 2, P = 0.1006) were increased in nicorandil-treated animals. The ratio of AUC for N-desbutylbupivacaine to AUC for bupivacaine, which may partially indicate the rate of metabolism, was higher in the presence of nicorandil (1.142 ± 0.017 compared with 0.877 ± 0.013, P = 0.0001).
Our data may indicate an increased metabolism of bupivacaine in nicorandil-treated mice. These results do not explain the previously reported enhanced anaesthetic activity of bupivacaine in the presence of nicorandil, but may participate, at least in part, in the relative protective effect of nicorandil against the previously reported bupivacaine-induced toxicity.
Molecular Biological Analysis of the Effects of Ginsenoside-Rb2 on Albumin mRNA in Streptozotocin-induced Diabetic Rats
Authors: Yokozawa Takako , Yasui Teruhito , Oura Hikokichi 
Published: April 2011

Abstract
The mechanisms of the mRNA synthesis-promoting action of ginsenoside-Rb2, were investigated at the gene level.
Rot analysis suggested that the previously reported increase in RNA polymerase activity as a result of administration of ginsenoside-Rb2 might be because of its effect on a specific gene. In this regard, albumin mRNA, which is expressed specifically in the liver, was assayed by northern blot hybridization using albumin cDNA in normal rats, diabetic control rats and diabetic rats given ginsenoside-Rb2. When the level of albumin mRNA in normal rats was set at 100, the level was reduced markedly to 32 in diabetic control rats. In contrast, in diabetic rats given ginsenoside-Rb2 the level was 0.54, significantly higher (69%) than that in diabetic rats given no ginsenoside-Rb2. In addition, poly(A)+RNA was purified from total RNA and subjected to hybridization, and poly(A)+RNA bands with different charges were measured by densitometry. The results of the measurement revealed changes dependent on the charge, and this was confirmed by autoradiography.
We found no significant difference in the transcription activity of albumin mRNA, however, it showed only a tendency to increase. This suggests that ginsenoside-Rb2 has some effect on post-transcriptional regulation of the stability of mRNA itself. The results of Rot analysis suggest that ginsenoside-Rb2 affects a specific gene alone.
Time-dependent Densification Behaviour of Cyclodextrins
Authors: Muñoz-Ruiz Angel , Paronen Petteri 
Published: April 2011

Abstract
Understanding of volume reduction mechanisms is a valuable aid in the development of robust cyclodextrin tablet formulations. The particle and powder properties of α-, β-, γ-and hydroxypropyl (HP) -β-cyclodextrins and their behaviour under compression were examined.
The cyclodextrins studied showed big differences in particle-size distribution and particle shape. The highest densification on tapping was found for cyclodextrins having the smallest particle size. Cyclodextrins were compressed using single-sided saw-tooth displacement-time profiles at rates of 3 and 300 mm s−1 with a compaction simulator. The densification of the powders was examined by Heckel treatment, using the tablet-indie and ejected-tablet methods. The cyclodextrins were denser at the beginning of the tableting process (at low pressures) if high rather than low velocity was used. Ranking according to their tendency toward total deformation and permanent plastic deformation was: HP-β-cyclodextrin &gt; β-cyclodextrin &gt; γ-cyclodextrin &gt; α-cyclodextrin. The ranking order in strain-rate sensitivity (SRS) of total deformation was HP-β-cyclodextrin γ-cyclodextrin ≥ α-cyclodextrin ≥ β-cyclodextrin. On the basis of the yield pressure values and the Heckel plot profiles, all the cyclodextrins were highly prone to plastic deformation. Cyclodextrins showed time-dependent consolidation behaviour manifested as increased yield pressure with decreased contact time.
A ratio was defined between the SRS of fast elastic recovery and total elastic recovery. The two materials with high ratios, HP-β-cyclodextrin and β-cyclodextrin, were especially prone to fast elastic recovery with increasing punch velocities; γ-cyclodextrin and α-cyclodextrin had low values and were less prone. On the basis of this parameter it might be possible to categorize pharmaceutical materials according to capping tendency.
The Preparation of Norfloxacin-loaded Liposomes and their In-vitro Evaluation in Pig's Eye
Authors: Lin Hung-Hong , Ko Shiu-Man , Hsu Li-Ren , Tsai Yi-Hung 
Published: April 2011

Abstract
The effectiveness of norfloxacin as an antibacterial agent in ophthalmology is limited by poor drug delivery and limited ocular bioavailability. Liposomes containing norfloxacin have been prepared from different phospholipids using a novel technique with an encapsulation efficiency sixteen times greater than that of a conventional film method. The in-vitro release of the norfloxacin and the transcorneal characteristics of the liposomes have been evaluated. Differential scanning calorimetry was used to determine the interaction occurring between liposomes and cornea.
The release of liposome-entrapped norfloxacin was affected by the pH of the environment. In the in-vitro corneal perfusion studies, norfloxacin-loaded liposome was transferred through the cornea at a slower rate than was the free drug. Norfloxacin-loaded liposomes were accumulated primarily in the cornea. The drug corneal retention of the lipids increased in the order dirnyristoyl-L-α-phosphatidylcholine &lt; dipalmitoyl-L-α-phospha-tidylcholine &lt; distearoyl-L-α-phosphatidylcholine. In the corneal drug-elimination study, liposomal norfloxacin increased the loading of the drug in cornea; the maximum value of the loading occurred 5 h after dosing. The drainage of liposomes from the cornea was somewhat slower than the solution form.
Accumulation of norfloxacin in the cornea was greater for the liposome-entrapped drug. The results suggest that norfloxacin-loaded liposomes are absorbed by the cornea via endocytosis.
The Sources of Ca2+ for Muscarinic Receptor-induced Contraction in the Rat Ileum
Authors: Elorriaga Martin , Anselmi Elsa , Hernandez Jose M , D'Ocon Pilar , Ivorra Dolores 
Published: April 2011

Abstract
The contractile responses obtained by activation of different muscarinic receptor subtypes in the longitudinal muscle of the rat ileum and especially the responses of this muscle to acetylcholine in a Ca2+-free medium have been investigated.
In Ca2+-containing solution, acetylcholine elicited similar concentration-dependent contractile responses in the duodenum, jejunum and ileum strips of the rat intestine. The response to a maximal concentration of the agonist (1 μM) consisted of a rapid phasic response followed by a slower tonic one. Nifedipine completely relaxes or inhibits the sustained response and only partially diminishes the phasic one, which suggests that the phasic contraction depends on the release of internal Ca2+ as well as Ca2+ entry from the extracellular space through voltage-dependent Ca2+ channels, but that the tonic contraction only depends on the influx of the external ion. In Ca2+-free medium, acetylcholine (1 μM) induced phasic contractions that depend on the release of this ion from internal stores.
Participation of different subtypes of receptors (M1, M2 and M3) in these responses depends on the inhibitory action shown by methoctramine, 4−DAMP and atropine but not by pirenzepine in two different experimental models.