bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric and Duodenal Anti-ulcer Activity of SKF 38393, a Dopamine D1-Receptor Agonist in Rats
Authors: Desai Jagruti K , Goyal Ramesh K , Parmar Narayan S 
Published: April 2011

Abstract
The effect of SKF 38393 (1-phenyl-7,8-diol-2,3,4,5-tetrahydro-1H-3-benzazepine), a specific dopamine D1-receptor agonist, was studied on pylorus-ligation and water immersion plus restraint stress-induced gastric ulcers, and cysteamine-induced duodenal ulcers in rats.
Repeated administration of SKF 38393 (5 and 10 mg kg−1, p.o.) for six days was found to be effective in the prevention of gastric ulceration induced by water immersion plus restraint stress in rats. In 19-h pylorus-ligated rats, repeated treatment with SKF 38393 showed a significant reduction in the number and severity of ulcers. SKF 38393 did not alter the total gastric-mucosal carbohydrates: protein ratio; however, the gastric content volume and the free and total acidity were significantly reduced. In cysteamine-induced duodenal ulcers, the treatment with SKF 38393 for 6 days prevented the duodenal lesions.
Our data suggests the involvement of dopamine D1 receptors in the anti-ulcer activity of SKF 38393, which could be largely attributed to its anti-secretory effect. Its anti-ulcer activity against water immersion plus restraint, also points towards a central mode of action, but its failure to alter the carbohydrate: protein ratio rules out any protective effect through the strengthening of the gastric mucosal barrier.
The Role of Nitric Oxide and Sulphydryls in Gastric Mucosal Protection Induced by Sodium Cromoglycate in Rats
Authors: Mobarok Ali A T M 
Published: April 2011

Abstract
The role of endogenous nitric oxide and sulphydryls in gastric protection afforded by sodium cromoglycate against ethanol-induced gastric lesions was studied in rats. Drugs were administered either intraperitoneally (i.p.) or subcutaneously (s.c.) 30, 45 or 60 min before oral administration of ethanol.
Administration of cromoglycate before ethanol dose-dependently inhibited ethanol-induced gastric lesions. Pretreatment with NG-nitro-l-arginine methyl ester (L-NAME), an inhibitor of nitric oxide biosynthesis, dose-dependently aggravated gastric lesions and reduced cromoglycate-induced gastric protection. The attenuating effect of L-NAME on gastric protection elicited by cromoglycate was reversible by pretreatment with l-arginine but not by d-arginine. On the other hand, ethanol-induced gastric lesions were found to be associated with a reduction of nonprotein sulphydryl content of glandular stomachs. Pretreatment with cromoglycate prevented non protein sulphydryl depletion and afforded protection. Pretreatment with N-ethylmaleimide, a sulphydryl blocker, caused dose-dependent enhancement of ethanol-induced gastric lesions and further depletion of non protein-sulphydryl. Treatment with N-ethylmaleimide before cromoglycate reduced the gastric protection that was associated with depletion of nonprotein sulphydryls. Furthermore, combined N-ethylmaleimide and L-NAME pretreatment caused a greater aggravation of ethanol-induced gastric lesions and significantly produced a higher reduction of the protective effects of cromoglycate. However, pretreatment with l-arginine only partially restored the protective effects of cromoglycate.
These results suggest that the protective effects of cromoglycate may be dependent on the maintenance of a critical level of both endogenous nitric oxide and nonprotein sulphydryls in the gastric mucosa.
Evidence that the Secretory Response of Rat Intestine to 5-Hydroxytryptamine In-vivo Involves More than One 5-Hydroxytryptamine-receptor Subtype
Authors: Hardcastle J , Hardcastle P T 
Published: April 2011

Abstract
The transintestinal potential difference (PD) across rat mid-small intestine and proximal colon was measured in-vivo. The 5-hydroxytryptamine (5-HT)-induced increase in PD, which reflects a stimulation of electrogenic Cl secretion, was mimicked by both 2-methyl-5-hydroxytryptamine (2-CH3-5-HT), an agonist at 5-HT3 receptors, and 5-methoxytryptamine (5-MT), an agonist that lacks affinity for 5-HT3 receptors. The 5-HT3 antagonist granisetron caused a marked inhibition of the response to 2-CH3-5-HT in both regions, but only produced a small inhibition of the small intestinal response to 5-HT, with a more pronounced effect in the colon. The failure of granisetron to produce a marked antagonism of the 5-HT-induced rise in the transintestinal PD, coupled with the ability of 5-MT to induce a secretory response, indicates that 5-HT3 receptors are not the only ones involved in the stimulation of Cl secretion.
The 5-HT2 antagonist ketanserin failed to influence the response to 5-HT in either the small intestine or the colon, but it did inhibit the action of 5-MT, having a much greater effect in the small intestine. In the presence of granisetron however, ketanserin also inhibited the small intestinal response to 5-HT, having only a minimal effect in the colon. This suggests that 5-HT2 receptors can also play a role in the activation of Cl secretion.
These observations suggest that both 5-HT2 and 5-HT3 receptors contribute to the stimulation of electrogenic Cl secretion by 5-HT, with 5-HT2 receptors playing a more prominent role in the small intestine and 5-HT3 receptors being more important in the colon.
Effect of KBT-3022, a New Diphenylthiazole Derivative, on Platelet Functions
Authors: Yokota Koichi , Yamamoto Noriko , Morimoto Yasuo , Yamashita Akira , Oda Minoru 
Published: April 2011

Abstract
The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo.
KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid.
Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid.
These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.
Comparative Study of Separation of Non-encapsulated Drug from Unilamellar Liposomes by Various Methods
Authors: Dipali Satish R , Kulkarni Shirish B , Betageri Guru V 
Published: April 2011

Abstract
The purpose of this study was to compare the various methods available to separate non-encapsulated drug from large unilamellar liposomes (LUV). Multilamellar liposomes (MLV) were prepared by thin film hydration using distearoylphosphatidylcholine:cholesterol (2:1 molar ratio). MLVs were passed through a 0.2-μm polycarbonate membrane using an extruder to prepare LUVs. Particle size of liposome preparations was characterized using a submicron particle-size analyser. The non-encapsulated drug was separated by: filtering through Centrifree tubes; passing through gel (Sepharose-4B and Sephadex G-25M); passing through minicolumn; ficoll density gradient; protamine aggregation; or dialysis.
The dialysis method was found to be unsuitable for separation of non-encapsulated drug due to equilibration of encapsulated drug as the free drug was dialyzed. The upper limit for lipid concentration was 5 mg mL−1 using the Centrifree method. Separation using gel chromatography led to dilution of liposome preparation. Minicolumn and density gradient techniques did not lead to sample dilution, however the minicolumn method was tedious. The time required for separation of liposomes by protamine aggregation was longer for neutral liposomes.
Thus it was concluded that the Centrifree was the fastest method to estimate encapsulation; the density gradient method was ideal to separate non-encapsulated drug; and protamine aggregation was the least expensive method to estimate encapsulation efficiency.
The Influence of Moisture Content on the Consolidation Properties of Hydroxypropylmethylcellulose K4M (HPMC 2208)
Authors: Nokhodchi Ali , Ford James L , Rowe Philip H , Rubinstein Michael H 
Published: April 2011

Abstract
The effect of moisture content, compression speed and compression force on the compaction properties of HPMC K4M has been evaluated.
As the moisture content increased from 0 to 14.9% w/w, the thickness of HPMC K4M compacts increased at constant compression force and speed. This increase in moisture content also resulted in a marked increase in the tensile strength of the tablets. At a speed of 15 mm s−1 and force of 10 kN, as the moisture content increased from 0 to 14.9% w/w, the tensile strengths increased from 1.34 to 8.54 Mpa. Equivalent tensile strengths could be obtained with less compression force as the moisture content in the polymer was increased. Increasing the compression speed generally decreased the tensile strength of HPMC K4M tablets.
The dependence of tablet porosity and tensile strength on compression speeds showed that HPMC K4M is consolidated by plastic deformation. At all compression speeds, an increase in moisture content reduced the percentage elastic recovery of HPMC compacts due to greater tablet consolidation. The lowest elastic recovery (1.18%) was found for tablets made at 15 mm s−1 and 5 kN, containing 14.9% w/w moisture content.
Niosomal Plumbagin with Reduced Toxicity and Improved Anticancer Activity in BALB/C Mice
Authors: Naresh R A Raja , Udupa N , Devi P Uma 
Published: April 2011

Abstract
Plumbagin niosomes were prepared using a lipid layer hydration method, and drug entrapment was measured. The acute toxicity studies were conducted following treatment with free and niosomal plumbagin.
The antitumour activity of niosomal plumbagin in a solid tumour (sarcoma-180) and Ehrlich ascites model was evaluated. Niosome-encapsulated plumbagin was less toxic than free drug. The antitumour activity of the drug was also better after encapsulation.
The better anticancer activity can be justified with the help of LD50 survival studies and study of tumour volume doubling time.
Enhancing Effects of Unsaturated Fatty Acids with Various Structures on the Permeation of Indomethacin through Rat Skin
Authors: Morimoto Kazuhiro , Tojima Hideki , Haruta Tatsuo , Suzuki Masao , Kakemi Masawo 
Published: April 2011

Abstract
Effects of straight-chain, cis-type, unsaturated fatty acids with various structures (alkyl chain lengths, numbers of double bonds, position of double bonds and cis- and trans-positional isomers) on the skin permeation of indomethacin were examined by using rat skins in-vitro. Furthermore, the disordering degrees of the intercellular lipid domain in the stratum corneum, which were treated with preparations of unsaturated fatty acids, were measured by the Fourier transform infrared (FT-IR) method using excised rabbit ear skins.
Unsaturated fatty acids enhanced the permeation of indomethacin through rat skins. These permeation-enhancing effects by unsaturated fatty acids were affected by changes of their alkyl chain length from C14 to C22. The lag-times on the permeation of indomethacin were shortened by unsaturated fatty acids in the following order: C20 = C18 = C22 &lt; C16 &lt; C14. These fluxes were increased by unsaturated fatty acids in the following order: C20 &gt; C22 = C18 = C13 &gt; C14. Therefore, gondoic acid (cis-11-eicosenoic acid; C20H38O2) mostly enhanced the skin permeation of indomethacin. However, the enhancing effects of unsaturated fatty acids (C18 chain) were not affected by their differences of position and numbers of double bonds.
These permeation-enhancing effects which were evaluated by flux were related to the degrees of wave-number shift in the frequency of the antisymmetric CH bond stretching absorbance (near 2920 cm−1) on FT-IR spectra of the fatty acid-treated stratum corneum. Therefore, the perturbation increase of lipid domain in the stratum corneum by these fatty acids probably was the cause of the enhancing effects of permeation of indomethacin.
Terbutaline Transdermal Delivery: Preformulation Studies and Limitations of In-vitro Predictive Parameters
Authors: Tenjarla Srini N , Puranajoti Porranee , Kasina Ram , Mandal Tarun 
Published: April 2011

Abstract
A transdermal dosage form of terbutaline may be useful to prevent nocturnal wheezing by providing prolonged duration of action. It will also improve patient compliance and bioavailability. Controlled input of the drug would be an additional advantage as this will reduce the intersubject variablity. Preformulation studies were conducted to determine the feasibility of a transdermal dosage form of terbutaline.
The drug solubility in propylene glycol was 6.3 mg mL−1. The apparent partition coefficient (n-octanol/deionized-water, pH 6.5) of terbutaline was 0.03. A pH-partition coefficient (octanol/buffer) profile indicated that the partition coefficient values were 0.02, 0.05 and 04 in buffers of pH 3, 7.4 and 9, respectively. The required drug flux through the human skin to attain therapeutic concentrations in the blood was calculated to be 3.3 μg cm−2 h−1 for a 10-cm2 transdermal delivery system. Rabbit, guinea-pig and human skin was tested as the penetration barrier using modified Franz diffusion cells. Terbutaline flux values through the rabbit and guinea-pig skin were 8.3 and 7.7 μg cm−2 h−1, respectively. The flux through human full-thickness skin and human epidermis were 0.6 and 3.6 μg cm−2 h−1. Azone (3% w/v), a skin penetration enhancer, significantly increased the drug flux through all the membranes tested.
Based on these studies, transdermal delivery of terbutaline appears to be promising.
Improved Ocular Bioavailability of Indomethacin by Novel Ocular Drug Carriers
Authors: Calvo Pilar , Alonso María J , Vila-Jato José L , Robinson Joseph R 
Published: April 2011

Abstract
The ability of different drug carriers to improve the ocular bioavailability of drugs was investigated in the rabbit eye. The assayed drug carriers were suspensions of nanoparticles, nanocapsules and microparticles made of poly-ε-caprolactone (PECL) and a submicron emulsion.
Results indicated that the three submicron systems, nanoparticles, nanocapsules and emulsion, increased more than 3-fold the indomethacin concentration in the cornea, aqueous humour and iris-ciliary body at 0.5 and 1 h post-instillation. Furthermore, an increased indomethacin ocular bioavailability of 300% was observed after instillation of the submicron systems in comparison with the value obtained for a commercial solution. In contrast, the microparticles hardly increased the ocular bioavailability of indomethacin. The mechanism of interaction of the colloidal carriers with the corneal epithelium was investigated by confocal laser scanning microscopy. Confocal images indicated that submicron particles penetrate into the corneal epithelium cells by an endocytic mechanism. The similar behaviour of the three colloidal carriers suggests that any of their specific ingredients (PECL, lecithin and oil) acts as a penetration enhancer or an endocytotic stimulator. On the other hand, the favourable ocular penetration of indomethacin when encapsulated in the colloidal carriers, but not in the microparticles, led us to assume that the colloidal nature of these carriers is the main factor responsible for the increased ocular bioavailability of indomethacin.
PECL nanoparticles and nanocapsules as well as submicron emulsions are shown to be novel corneal drug carriers, thus representing a useful approach for increasing the ocular bioavailability of drugs.
The Acute Effects of FK-506 on Renal Haemodynamics, Water and Sodium Excretion and Plasma Levels of Angiotensin II, Aldosterone, Atrial Natriuretic Peptide and Vasopressin in Pigs
Authors: Golbækdal K , Nielsen C B , Pedersen E B 
Published: April 2011

Abstract
FK-506 has been shown to be an effective immunosuppressive drug with possible nephrotoxic side effects. In this study we have investigated the acute effects of FK-506 on renal haemodynamics, water, sodium and lithium excretion rates and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and vasopressin in 29 anaesthetized Lancaster/Yorkshire female pigs. A continuous intravenous infusion was given over a 2-h period to 4 groups: A: 0.075 mg kg−1 (n = 7), B: 0.15 mg kg−1 (n = 8), C: 0.3 mg kg−1 (n = 6) and P: placebo vehicle (n = 8). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125-I-iothalamate and 131-I-hippuran as reference substances. Hormonal parameters were measured by radioimmunoassay.
In all three FK-506 groups, fractional lithium excretion was significantly decreased 2 h after FK506 infusion (P: + 0.4%, A: − 8.8% (P &lt; 0.05), B: −12.9% and C: −11.2% (P &lt; 001 for both). Mean arterial blood pressure (MBP) was significantly increased in the two highest dosage groups (B,C) at 2 h of infusion: (MBP; P: +2.9%, A: +3.5%, B: +12.0%, C: + 15.3% (P &lt; 0.01 for both). GFR and RPF showed minor and inconsistent changes while all other parameters measured showed similar or no changes.
In conclusion, acute infusion of FK-506 to pigs does not change overall renal function significantly, but increases mean arterial blood pressure and decreases fractional excretion of lithium.
Transport and Metabolic Pathway of Thymocartin (TP4) in Excised Bovine Nasal Mucosa
Authors: Lang Steffen , Langguth Peter , Oschmann Rainer , Traving Birgit , Merkle Hans P 
Published: April 2011

Abstract
Thymocartin (TP4, Arg-Lys-Asp-Val) is the 32–35 fragment of the naturally occuring thymic factor (thymopoietin). Here studies on the nasal transport and metabolism of TP4 were performed. Freshly excised bovine nasal mucosa was taken as a model membrane. For permeation studies typical donor-receiver experiments (side-by-side) and finite-dose experiments with small volumes of highly concentrated solutions were carried out.
The metabolic pathway of TP4 in nasal mucosa was found to occur according to a typical aminopeptidase cleavage pattern, stepwise forming Lys-Asp-Val and Asp-Val. TP4 metabolism experiments under reflection kinetics showed a saturation profile above 0.5 μmol mL−1. A non-linear kinetic model consisting of three steps in sequence was sufficient to describe the kinetics: for the first step saturable Michaelis-Meat kinetics, and for the second and the third step first-order kinetics were assured. The model was capable of simultaneously fitting the data for the full range of initial concentrations from 0.1 up to 1.0 μmol mL−1. Saturation kinetics was also found to be the prominent feature of the permeation experiments performed. In the lower concentration range (&lt;0.4 μmol mL−1), transport of TP4 across nasal mucosa was controlled by metabolism, in the higher concentration range (&gt;0.85 μmol mL−1) diffusion control became more important.
We conclude that enhancement of absorption can be achieved when nasal aminopeptidases are saturated, e.g. at high TP4 concentrations.
In-vivo Clearance Study of Vancomycin in Rats
Authors: Nakamura Tsutomu , Takano Mikihisa , Yasuhara Masato , Inui Ken-Ichi 
Published: April 2011

Abstract
The renal handling of vancomycin in rats and the effects of various drugs (probenecid, cimetidine and quinidine) on urinary excretion of the antibiotic were investigated by in-vivo clearance.
The vancomycin-to-inulin excretion ratio (ER) was greater than unity at various infusion rates of vancomycin. Quinidine, co-administered with vancomycin, significantly decreased the total, renal and net secretory clearance of the antibiotic. Cimetidine also decreased, though not significantly, the secretory clearance of vancomycin by about 20%, but probenecid did not.
These results suggested that vancomycin is secreted in renal tubules in rats, and that quinidine decreases the total clearance of vancomycin partly by inhibiting its tubular secretion in the kidney.
The Effect of Gamma-irradiation on the Antibacterial Activity of Honey
Authors: Molan P C , Allen K L 
Published: April 2011

Abstract
There is increasing usage of honey as a dressing on infected wounds, burns and ulcers, but there is some concern that there may be a risk of wound botulism from the clostridial spores sometimes found in honey. It is well-established that the antibacterial activity is heat-labile so would be destroyed if honey were sterilized by autoclaving, but the effect of gamma-irradiation on the antibacterial activity of honey is not known. Therefore an investigation was carried out to assess the effect on the antibacterial activity of honey when the honey was subjected to a commercial sterilization procedure using gamma-irradiation (25 kGy).
Two honeys with antibacterial activity due to enzymically-generated hydrogen peroxide and three manuka honeys with non-peroxide antibacterial activity were investigated. The honeys were tested against Staphylococcus aureus in an agar well diffusion assay. There was no significant change found in either type of antibacterial activity resulting from this form of sterilization of honey, even when the radiation was doubled (to 50 kGy).
Testing of honey seeded with spores of Clostridium perfringens and C. tetani (10 000 and 1000 spores g−1 of honey, respectively) showed that 25 kGy of gamma-irradiation was sufficient to achieve sterility.
Antitumour Activity of Mitoxantrone-loaded Chitosan Microspheres Against Ehrlich Ascites Carcinoma
Authors: Jameela S R , Latha P G , Subramoniam A , Jayakrishnan A 
Published: April 2011

Abstract
Glutaraldehyde cross-linked chitosan microspheres containing the antineoplastic agent mitoxantrone were prepared and the antitumour activity was evaluated against Ehrlich ascites carcinoma in mice by intraperitoneal injections. The tumour inhibitory effect was followed by monitoring animal survival time and change in body weight for a period of 60 days.
While the mean survival time of animals which received 2 mg and 1 mg of free mitoxantrone intraperi-toneally was 2.1 and 4.6 days, respectively, animals which received 2 mg mitoxantrone via microspheres showed a mean survival time of 50 days. Five out of 8 animals treated using microspheres lived beyond 60 days. The percentage ratio mean survival time of the treated group divided by the mean survival time of the untreated group for animals treated using mitoxantrone-loaded chitosan microspheres containing 2 mg of the drug was 290 compared with 12.2 for those which received 2 mg of the free drug.
The antitumour effect of mitoxantrone-loaded microspheres against Ehrlich ascites carcinoma was much higher than that of doxorubicin-loaded microspheres reported by previous workers. Our data demonstrate the potential of mitoxantrone-loaded chitosan microspheres for sustained drug delivery to minimize drug toxicity and maximize therapeutic efficacy.