bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Antibiotics on Epithelial Ion Transport in the Rabbit Distal Colon In-vitro
Authors: Goldhill J M , Rose K , Percy W H 
Published: April 2011

Abstract
One side-effect of the therapeutic use of antimicrobial agents is respiratory paralysis as a result of inhibition of skeletal neuromuscular transmission; cholinergic neuro-effector motor transmission in the gastrointestinal tract is inhibited by the same classes of antimicrobial agent. Study of the effects of several classes of antibiotic compound on intestinal motility has suggested that antibiotic-induced alterations of intestinal motility may be related to the onset of diarrhoea or the development of antibiotic-associated colitis. These compounds may, however, also initiate or exacerbate diarrhoea by altering control of epithelial function, a possibility that has not previously been rigorously investigated. This series of experiments investigated the effect of six antibiotics on rabbit distal colonic epithelial ion transport.
Of all the antibiotics studied, only ampicillin was without effect. Clindamycin, erythromycin, gentamicin and lincomycin, each reduced the response of the epithelium to electrical field stimulation. In addition, the lincosamides clindamycin and lincomycin reduced basal short circuit current and the epithelial response to acetylcholine. Vancomycin had no effect on the response to electrical field stimulation or acetylcholine but enhanced the secretory action of prostaglandin E2.
These data suggest that, in addition to their ability to alter intestinal motility, a number of potential antibiotic interactions with the epithelium and its innervation may contribute to the pathogenesis of antibiotic-associated diarrhoea and colitis.
Measurement of Molecular Association in Drug: Cyclodextrin Inclusion Complexes with Improved 1H NMR Studies
Authors: Loukas Yannis L 
Published: April 2011

Abstract
The molecular association of haloperidol with hydroxypropyl-β-cyclodextrin, expressed by the binding constant of the inclusion complex formed, was calculated from the changes on the 1H NMR spectra of the drug in the presence of the cyclodextrin.
The stoichiometry of the complex was calculated by use of the continuous variation method (Job plot), and found to be 1:1. The binding constant for the 1:1 complex was calculated using improved non-linear models, which were solved by non-linear least-squares regression analysis, applying an iteration procedure.
Three improved mathematical models for more accurate calculation of binding constants are proposed. The models are free from any assumptions and from practical or theoretical shortcomings.
Nebulized Interleukin 2 Liposomes: Aerosol Characteristics and Biodistribution
Authors: Khanna Chand , Waldrep J Clifford , Anderson Peter M , Weischelbaum Ralph W , Hasz Diane E , Katsanis Emmanuel , Klausner Jeffrey S 
Published: April 2011

Abstract
Although interleukin 2 (IL-2) has been associated with modest anti-tumour responses in man, treatment-related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non-toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes.
The aerosol droplet size distribution and the physical stability of interleukin 2 liposomes were examined in-vitro using an Andersen cascade impactor and studies of liposome entrapment of interleukin 2 before and after nebulization. The biological stability of interleukin 2 liposomes after nebulization was demonstrated using the CTLL-2 bioassay for interleukin 2. In-vivo studies of pulmonary biodistribution and clearance of inhaled technetium (99mTc)-labelled interleukin 2 liposomes were undertaken in a normal dog. Aerosols of free interleukin 2 and of interleukin 2 liposomes were compared in both in-vitro and in-vivo experiments. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of interleukin 2 liposomes were 1–98 μm and 202, respectively. Independent analysis of aerosol particle-size distribution using the constitutive components of the interleukin 2 liposomes (interleukin 2: lipid: HSA) demonstrated a close correlation of size distributions (r = 0.9445; P &lt; 0.001). The entrapment of interleukin 2 in liposomes was 93 ± 4.3% before nebulization and 90 ± 8.9% after. After delivery to an anaesthetized dog, interleukin 2 liposome aerosols were deposited evenly throughout the lung (mean ± s.d. central lung-to-peripheral lung deposition was 1–12 ± 0.03). After approximately 24 h inhalation, interleukin 2 liposomes were retained within the lung and were taken up in part by the spleen.
The results of this study are indicative of the stability of this interleukin 2 liposome formulation to nebulization. Such nebulization might be an attractive immunotherapeutic strategy for treatment of pulmonary metastases and primary lung cancers.
Effects of Meloxicam, Compared with other NSAIDs, on Cartilage Proteoglycan Metabolism, Synovial Prostaglandin E2, and Production of Interleukins 1, 6 and 8, in Human and Porcine Explants in Organ Culture
Authors: Rainsford K D , Ying C , Smith F C 
Published: April 2011

Abstract
Some non-steroidal anti-inflammatory drugs (NSAIDs) can accelerate joint damage in osteoarthritis by enhancing the production of pro-inflammatory cytokines or inhibiting cartilage proteoglycan synthesis. Meloxicam, a new NSAID, was compared with standard NSAIDs for its effect on proteoglycan synthesis and degradation in human and porcine cartilage explants, as well as the production of prostaglandin E2 (PGE2) and interleukins 1 and 6 by human synovial tissue explants in-vitro.
Meloxicam at submicromolar concentrations inhibited synovial PGE2 production but, up to therapeutic drug concentrations (≤ 4 μm), did not affect synovial production of the pro-inflammatory cytokine IL-1. In contrast, hydrocortisone, 10 μm, a positive control, inhibited release of this cytokine, and indomethacin, 100 μm, increased its production. The lack of effects of meloxicam were evident irrespective of intrinsic IL-1 bioactivity of the synovia, production of IL-1 inhibitors or time of incubation. Production of the part antiinflammatory cytokine IL-6, was significantly increased by therapeutic concentrations of meloxicam, as well as by indomethacin. Another major pro-inflammatory cytokine, IL-8, was unaffected by therapeutic concentrations of meloxicam. Meloxicam, 0.1–4.0 μm, did not affect cartilage proteoglycan production whereas indomethacin, 100 μm, significantly reduced synthesis of these macromolecules.
Thus meloxicam, at concentrations within the therapeutic range and at which pronounced inhibition of prostaglandin production is evident, affects neither cartilage proteoglycan production nor the production of those cytokines likely to be important in cartilage destruction.
Evidence of Hydroxyl Free Radical Generation by Calcium Overload in Rat Myocardium
Authors: Obata Toshio , Tamura Minoru , Yamanaka Yasumitsu 
Published: April 2011

Abstract
Although calcium (Ca2+) is important in cardiac dysfunction and has also been reported as a source of oxidative toxicity, the connection between Ca2+ overload and oxygen free radicals in the myocardium is not clear. We have investigated whether Ca2+ overload generates hydroxyl free radicals in rat ventricle.
HPLC with electrochemical detection was used to measure the levels of 2,3- and 2,5-dihydroxybenzoic acid (DHBA) formed when the hydroxyl free radical reacts with salicylate. Ringer's solution containing salicylic acid (0.5 nmol μL− min−) was infused through a microdialysis probe in the region of the left anterior descending coronary artery of the rat ventricle. A positive linear correlation was obtained between Ca2+ and hydroxyl free radical formation trapped as 2,3-DHBA (r2 = 0.976) and 2,5-DHBA (r2 = 0–982) in the myocardial dialysate. The administration of ouabain (1 mg kg−, i.v.), a Ca2+ elevator, into the femoral vein significantly increased the level of 2,3- and 2,5-DHBA.
These results indicate that Ca2+ overload generates hydroxyl free radicals in rat heart.
The Predominant Contribution of Oligopeptide Transporter PepT1 to Intestinal Absorption of β-Lactam Antibiotics in the Rat Small Intestine
Authors: Tamai Ikumi , Nakanishi Takeo , Hayashi Kiyomi , Terao Toshimitsu , Sai Yoshimichi , Shiraga Toshiyuki , Miyamoto Ken-Ichi , Takeda Eiji , Higashida Haruhiro , Tsuji Akira 
Published: April 2011

Abstract
Although recent evidence suggests that certain β-lactam antibiotics are absorbed via a specific transport mechanism, its nature is unclear. To confirm whether peptide transport in the rat can be largely ascribed to the intestinal oligopeptide transporter PepT1, the transporter has been functionally characterized and its significance in the intestinal absorption of β-lactam antibiotics was evaluated.
For evaluation of transport activity complementary RNA (cRNA) of rat PepT1 was synthesized in-vitro and expressed in Xenopus laevis oocytes. cRNA induced uptake of several β-lactam antibiotics and the dipeptide [14C]glycylsarcosine; this was specifically inhibited by various dipeptides and tripeptides but not by their constituent amino acids or by terra- or pentapeptides. The transport activity of PepT1 for β-lactam antibiotics correlated well with their in-vivo intestinal transport and absorption. Furthermore, mutual inhibitory effects on uptake were observed between glycylsarcosine and β-lactam antibiotics. Hybrid depletion of the functional expression of rat PepT1 in oocytes injected with rat intestinal epithelial total mRNA was studied using an antisense oligonucleotide corresponding to the 5′-coding region of PepT1. In oocytes injected with rat mRNA pre-hybridized with the antisense oligonucleotide against rat PepT1, the uptake of [14C]glycylsarcosine was almost completely abolished, whereas its uptake was not influenced by a sense oligonucleotide for the same region of PepT1. Similarly, the uptake of β-lactam antibiotics was also reduced by the antisense oligonucleotide against rat PepT1.
These results demonstrate that the intestinal proton-coupled oligopeptide transporter PepT1 plays a predominant role in the carrier-mediated intestinal absorption of β-lactam antibiotics and native oligopeptides in the rat.
Antinociceptive Effect of the Hydroalcoholic Extract of Bauhinia splendens Stems in Mice
Authors: Filho Arnaldo Willain , Breviglieri Eduardo , Filho Valdir Cechinel , Santos Adair R S 
Published: April 2011

Abstract
The analgesic effect of the hydroalcoholic extract of the stems of Bauhinia splendens (Leguminosae) has been investigated in chemical and thermal models of nociception in mice.
The hydroalcoholic extract of B. splendens, 3–60 mg kg− intraperitoneally or 50–400 mg kg− orally, caused dose-related, and long-lasting (up to 3 h) inhibition of acetic acid-induced abdominal constriction in mice, with ID50 values of 3.2 and 177.6 mg kg− and maximum inhibition of 95 ± 2 and 61 ± 6%, respectively. In the formalin test, the extract given intraperitoneally (1.60 mg kg−) or orally (50–400 mg kg−) caused graded inhibition of both phases of formalin-induced pain, being about 5- to 6-fold more potent in attenuating the second phase of pain. The calculated mean ID50 values for the first and the second phases were 11.5 and 2.5 mg kg−, respectively, for intraperitoneal administration and &gt; 200 and 70 mg kg−, respectively, for oral administration; the percentages of maximum inhibition for the first and the second phases were 68 ± 6 and 99 ± 1, respectively, for intraperitoneal administration and 37 ± 6 and 69 ± 9, respectively, for oral administration. However, at the same doses the extract did not significantly affect the oedematogenic response induced by formalin. The treatment of animals with naloxone (5 mg kg−, i.p.) completely reversed the analgesic effect caused by morphine (5 mg kg−, s.c), but had no effect against the antinociceptive effect of the hydroalcoholic extract of B. splendens (60 mg kg−, i.p.) when assessed against acetic acid-induced abdominal constrictions. Furthermore, the extract, in contrast with morphine, had no analgesic effect in the hot-plate test.
These data show that the hydroalcoholic extract of B. splendens has significant analgesic action when assessed against several models of pain. The mechanism underlying its analgesic effect still remains unknown, but seems to be unrelated to interaction with opioid systems.
Garlic Compounds Protect Vascular Endothelial Cells from Oxidized Low Density Lipoprotein-induced Injury
Authors: Ide Nagatoshi , Lau Benjamin H S 
Published: April 2011

Abstract
Oxidation of low density lipoprotein (LDL) has been recognized as playing an important role in the initiation and progression of atherosclerosis. In this study, the effects of aged garlic extract and one of its major compounds, S-allylcysteine, on oxidized LDL-induced cell injury were studied.
Pulmonary artery endothelial cells were pre-incubated with the garlic extract (1, 2.5 and 5 mg mL−) or 5-allylcysteine (01, 1, 10 and 20 mm) at 37°C and 5% CO2 for 24 h, washed, and then exposed to 01 mg mL− oxidized LDL for 24 h. Lactate dehydrogenase release as an index of membrane damage, methylthiazol tetrazolium assay for cell viability and thiobarbituric acid reactive substances indicating lipid peroxidation were determined. Preincubation of endothelial cells with the extract or S-allylcysteine significantly prevented membrane damage, loss of cell viability and lipid peroxidation.
The data indicate that these compounds can protect vascular endothelial cells from injury caused by oxidized LDL, and suggest that they may be useful for prevention of atherosclerosis.
Effects of the Calcium Antagonist AE0047 on the Development of Neurological Deficit and Infarction after Middle Cerebral Artery Occlusion in Stroke-prone Spontaneously Hypertensive Rats
Authors: Shinyama Hiroshi , Kawamura Toru , Iwamoto Minori , Egi Yasuhiro , Tanaka Hideki , Kawabata Yoshiyasu , Nakamura Norifumi , Kagitani Yoshio 
Published: April 2011

Abstract
AE0047 [4-(4-benzhydrylpiperazino)phenethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate dihydrochloride] is a new dihydropyridine calcium antagonist with protective effects against cerebral ischaemia and the occurrence of stroke in several animal models. We investigated the effects of AE0047 on focal ischaemia induced by middle cerebral artery occlusion in stroke-prone spontaneously hypertensive rats.
AE0047 at a dose causing 20 or 40% systemic hypotension (1 or 3 mg kg−) was given orally twice, 15 min and 24 h after occlusion. The neurological status of animals was investigated 2, 24 and 48 h after occlusion. Infarct area of brain was measured 48 h after occlusion. Middle cerebral artery occlusion resulted in the progressive deterioration of neurological status and large infarction in middle cerebral artery territories with 40% mortality. AE0047 dose-dependently attenuated the deterioration of neurological status, and reduced mortality to 0 or 10%. AE0047 significantly reduced infarct size and left/right hemispheric area ratio, an index of brain swelling.
These results suggest that AE0047 has the ability to ameliorate ischaemic cerebral stroke in hypertensive patients.
Daunorubicin-induced Smooth Muscle Contraction: Involvement of Ca2+ Entry Mechanism
Authors: Masui Hidehisa , Wakabayashi Ichiro , Yoshimoto Sachiko , Sakamoto Kunihiro 
Published: April 2011

Abstract
The mechanisms of the smooth muscle contractile action of daunorubicin were investigated using guinea-pig aortae, and the involvement of the Ca2+ entry mechanism was compared among different smooth-muscle preparations.
In the aorta, daunorubicin showed a concentration-dependent contractile action at concentrations of 10–200 μm. The contractile response to daunorubicin was completely dependent on extracellular Ca2+, but only slightly sensitive to verapamil or nifedipine. Trifluoperazine abolished the contraction by daunorubicin, but no significant effect was noted with amiloride, phentolamine, indomethacin or staurosporine. The order of potency (sensitivity) for daunorubicin-induced smooth muscle contraction was oesophagus = gall bladder = iliac artery &gt; bronchus = aorta, while that of maximum reactivity was iliac artery = aorta &gt; bronchus = oesophagus = gall bladder. In the portal vein, daunorubicin showed no contractile action. Although the smooth muscle contraction induced by daunorubicin was strongly dependent on extracellular Ca2+ in the aorta, iliac artery, bronchus, oesophagus and gall bladder, its sensitivity to verapamil varied among the different smooth muscle preparations, with the sensitivity being iliac artery = gall bladder &gt; bronchus = oesophagus &gt; aorta.
These results suggest that daunorubicin has contractile action on various kinds of smooth muscle, mainly via the transplasmalemmal Ca2+ entry mechanism, but the degree of involvement of the voltage-dependent Ca2+ channel differs among the different smooth muscle preparations.
Absorption of Ciprofloxacin and Norfloxacin when Administered as Niosome-encapsulated Inclusion Complexes
Authors: D'Souza S A , Ray J , Pandey S , Udupa N 
Published: April 2011

Abstract
An attempt has been made to design suitable niosome-encapsulated drug delivery system for ciprofloxacin and norfloxacin. Encapsulation of ciprofloxacin and norfloxacin in niosomes was investigated and the nasal and intestinal absorption of the products studied.
More than 80% of the drugs were successfully encapsulated to give products with sustained release characteristics. Encapsulation in niosomes also improved the stability of the antibacterial compounds.
Although the systemic availability of these niosome-encapsulated antibacterial compounds was not increased after nasal administration, intestinal absorption was significantly higher in comparison with that of plain inclusion complexes.
Renal Excretion of Vancomycin in Rats with Acute Renal Failure
Authors: Nakamura Tsutomu , Kokuryo Toshiyuki , Takano Mikihisa , Inui Ken-Ichi 
Published: April 2011

Abstract
We have investigated the renal excretion of vancomycin in rats with acute renal failure (ARF) induced by uranyl nitrate or cisplatin.
The renal clearance of the antibiotic after uranyl nitrate or cisplatin injection was separately evaluated by calculating the glomerular filtration rate (GFR) and secretory clearance. The reduced renal clearance of vancomycin in these ARF rats was a result of a decrease in both GFR and secretory clearance. The extents of the decreases in GFR and in secretory clearance were not, however, proportional, the extent of the decrease in secretory clearance being more pronounced.
These results suggest that the renal tubular secretion of vancomycin was reduced more predominantly than glomerular filtration in these ARF models.
Comparison of HPLC and Enzymatic Recycling Assays for the Measurement of Oxidized Glutathione in Rat Brain
Authors: Sian J , Dexter D T , Cohen G , Jenner P G , Marsden C D 
Published: April 2011

Abstract
Glutathione (reduced, GSH and oxidized, GSSG) concentrations were analysed in rat cerebellar homogenate using high performance liquid chromatography with ultraviolet detection (HPLC-UV) or enzymatic recycling assays.
GSSG levels found using the HPLC-UV assay were 200-fold higher than those obtained with the enzymatic recycling procedure. Reduction of synthetic GSSG by glutathione reductase showed total conversion to GSH as assessed by HPLC-UV analysis. In contrast, only approximately 50% of the HPLC peak for GSSG could be reduced by glutathione reductase. Increasing the period of incubation with glutathione reductase for longer than 15 min did not alter GSSG levels.
These results suggest that another substance present in brain tissue is derivatized and eluted at the same time as GSSG using the HPLC-UV assay, thus contributing to the apparently high GSSG levels found employing this technique.
Modelling of the Void Space of Tablets Compacted Over a Range of Pressures
Authors: Ridgway Cathy J , Ridgway Kenneth , Matthews G Peter 
Published: April 2011

Abstract
A previously developed computer model, named Pore-Cor, has been used to simulate the changes in the void-space dimensions which occur during the compaction of tablets over a range of pressures.
The tablets were made by mixing pharmaceutical grade crystalline lactose and an anti-inflammatory compound in the proportion 4:1. Compacts were made by placing a weighed amount of the mixed powder into a stainless-steel die and applying pressure with a hand-operated calibrated hydraulic press. Compacts were prepared at eight pressures over the hydraulic pressure range 1 to 8 ton in−2 (15.4–123.2 MPa) in 1 ton in−2 increments. Mercury-intrusion curves were measured for the eight samples by use of a porosimeter and the Pore-Cor package was then used to simulate the mercury-intrusion curves and generate void-space models of the correct porosity.
The experimental and simulated characteristic throat diameter, the experimental and simulated porosity, and the simulated permeability of the tablets have all been shown to follow expected trends. The successful modelling of void-structure parameters, which are difficult or impossible to measure experimentally, opens the way to an improved understanding of the strength of compacts.
Effects of Grinding and Humidification on the Transformation of Conglomerate to Racemic Compound in Optically Active Drugs
Authors: Piyarom Sujimon , Yonemochi Etsuo , Oguchi Toshio , Yamamoto Keiji 
Published: April 2011

Abstract
The effects of grinding and humidification on the transformation of conglomerate to racemic compound have been investigated by X-ray powder diffraction (XPD), differential scanning calorimetry (DSC) and infrared (IR) spectroscopy for leucine, norleucine, valine, serine, tartaric acid and malic acid.
Racemic physical mixtures were prepared by physical mixing of equimolar quantities of d and l crystals using a mortar and pestle. Ground mixtures were obtained by grinding the physical mixtures with a vibrational mill. Humidification was performed by storing the physical mixtures and the ground mixtures in a desiccator containing saturated aqueous salt solutions at 40°C.
When physical mixtures of malic acid, tartaric acid and serine were ground, the XPD peaks of the racemic compounds were observed. The XPD patterns of humidified physical mixtures of these compounds also showed the formation of the racemic compounds. This indicated that grinding or humidification of malic acid, tartaric acid and serine induced the transformation of conglomerate to racemic compound crystals. When, on the other hand, the physical mixtures of valine, leucine and norleucine were ground, peaks of racemic compounds were not detected in the XPD pattern. After humidification of the ground mixtures of valine, leucine and norleucine, however, the XPD peaks of racemic compounds were observed. DSC and IR studies revealed consistent results.
We concluded that grinding or humidification of malic acid, tartaric acid and serine could induce the transformation of a conglomerate to racemic compound. In contrast, humidifying after grinding was needed to bring about the transformation in leucine, norleucine and valine.