bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances and potential applications of chitosan derivatives as mucoadhesive biomaterials in modern drug delivery
Authors: Chopra Shruti , Mahdi Saiqa , Kaur Jasjeet , Iqbal Zeenat , Talegaonkar Sushma , Ahmad Farhan J 
Published: July 2006

Abstract
Pharmaceutical technologists have been working extensively on various mucoadhesive polymeric systems to create an intimate and prolonged contact at the site of administration. Chitosan is one of the most promising polymers because of its non-toxic, polycationic biocompatible, biodegradable nature, and particularly due to its mucoadhesive and permeation enhancing properties. Due to its potential importance in controlled drug delivery applications, pharmaceutical scientists have exploited this mucoadhesive polymer. However, chitosan suffers from limited solubility at physiological pH and causes presystemic metabolism of drugs in intestinal and gastric fluids in the presence of proteolytic enzymes. These inherent drawbacks of chitosan have been overcome by forming derivatives such as carboxylated, various conjugates, thiolated, and acylated chitosan, thus providing a platform for sustained release formulations at a controlled rate, prolonged residence time, improved patient compliance by reducing dosing frequency, enhanced bioavailability and a significant improvement in therapeutic efficacy. We have explored the potential benefits of these improved chitosan derivatives in modern drug delivery.
Anti-plasmodial and anti-leishmanial activity of conformationally restricted pentamidine congeners
Authors: Huang Tien L , Vanden Eynde Jean Jacques , Mayence Annie , Donkor Isaac O , Khan Shabana I , Tekwani Babu L 
Published: July 2006

Abstract
A library of 52 pentamidine congeners in which the flexible pentyldioxy linker in pentamidine was replaced with various restricted linkers was tested for in-vitro activity against two Plasmodium falciparum strains and Leishmania donovani. The tested compounds were generally more effective against P. falciparum than L. donovani. The most active compounds against the chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indochina) strains of P. falciparum were bisbenzamidines linked with a 1,4-piperazinediyl or 1, 4-homopiperazinediyl moiety, with IC50 values (50% inhibitory concentration, inhibiting parasite growth by 50% in relation to drug-free control) as low as 7 nM based on the parasite lactate dehydrogenase assay. Seven piperazine-linked bisbenzamidines substituted at the amidinium nitrogens with a linear alkyl group of 3–6 carbons (22, 25, 27, 31) or cycloalkyl group of 4, 6 or 7 carbons (26, 32, 34) were more potent (IC50 &lt; 40 nM) than chloroquine or pentamidine as anti-plasmodial agents. The most active anti-leishmanial agents were 4,4′-[1,4-phenylenebis(methyleneoxy)]bisbenzenecarboximidamide (2, IC50 ∼ 0.290 μM) and 1,4-bis[4-(1H-benzimidazol-2-yl)phenyl] piperazine (44, IC50∼0.410 μM), which were 10- and 7-fold more potent than pentamidine (IC50 ∼ 2.90 μM). Several of the more active anti-plasmodial agents (e.g. 2,31, 33, 36–38) were also potent anti-leishmanial agents, indicating broad antiprotozoal properties. However, a number of analogues that showed potent anti-plasmodial activity (1, 18, 21, 22, 25–28, 32, 43, 45) were not significantly active against the Leishmania parasite. This indicates differential modes of anti-plasmodial and anti-leishmanial actions for this class of compounds. These compounds provide important structure-activity relationship data for the design of improved chemotherapeutic agents against parasitic infections.
In-vitro and in-vivo studies on a topical formulation of sitamaquine dihydrochloride for cutaneous leishmaniasis
Authors: Garnier Tracy , Brown Marc B , Lawrence M Jayne , Croft Simon L 
Published: July 2006

Abstract
The efficacy of topical formulations of the 8-aminoquinoline, sitamaquine dihydrochloride, in both in-vitro and in in-vivo models of cutaneous leishmaniasis is reported. In-vitro parasite assays confirmed that sitamaquine dihydrochloride was active against a range of Leishmania species that cause either cutaneous or visceral leishmaniasis, with ED50 values against amastigotes over the range of 2.9 to 19.0μM. A range of topical sitamaquine dihydrochloride formulations (anhydrous gel, emulsions) were developed for studies on experimental cutaneous leishmaniasis using only topically acceptable excipients orthose currently undergoing regulatory approval. An uptake study into murine skin confirmed in-vitro skin penetration and retention. Several formulations were tested in-vivo against Leishmania major cutaneous lesions in BALB/c mice. None of the sitamaquine dihydrochloride formulations tested appeared to either slow lesion progression or reduce parasite burden.
Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
Authors: Lifschitz A , Ballent M , Virkel G , Sallovitz J , Lanusse C 
Published: July 2006

AbstractIvermectin (IVM), a macrocyclic lactone used as antiparasite agent, has been reported as a P-glycoprotein (P-gp) substrate. The participation of P-gp in the IVM excretion process has been previously demonstrated. Sex-related differences in the kinetic behaviour of some macrocyclic lactone compounds have been observed. The aim of this work was to characterize in-vivo the comparative gastrointestinal disposition of IVM in male and female rats. The sex-related influence on the itraconazole (ITZ) modulation of P-gp-mediated IVM intestinal transport was also assessed. Sixty Wistar rats (30 male, 30 female) received IVM alone or co-administered with ITZ. Rats were killed between 6 and 72h after treatment and blood, gastrointestinal tissues and lumen contents were collected. IVM concentrations were determined by high performance liquid chromatography. Substantial sex-related differences in the IVM disposition kinetics were observed. Higher IVM systemic availability was observed in female rats. The ITZ-mediated modulation of the IVM disposition kinetics had a differential impact between male and female rats. Co-administration with ITZ resulted in a marked increase in the IVM concentrations in the wall tissue from different portions of the gastrointestinal tract of male rats. The presence of ITZ induced drastic sex-related changes on the P-gp-mediated IVM gastrointestinal disposition.
Everolimus alters imatinib blood partition in favour of the erythrocyte
Authors: Prenen Hans , Guetens Gunther , De Boeck Gert , Highley Martin , van Oosterom Allan T , de Bruijn Ernst A 
Published: July 2006

AbstractThe signal transduction inhibitor imatinib is one of the latest breakthroughs in cancer pharmacotherapy. It is administered orally over prolonged periods of time for the treatment of gastrointestinal stromal tumours. Routine therapeutic drug monitoring of blood plasma versus red blood cells over several years by liquid chromatography coupled tandem mass spectrometry has highlighted a very intriguing phenomenon. Imatinib plasma availability decreases dramatically owing to a significant shift in the partition ratio of red blood cells versus plasma. The shift is enforced by combination with everolimus, another signal transduction inhibitor. These data warrant routine erythrocyte versus plasma monitoring to prevent unexpected alterations in drug efficacy during long-term treatment.
Effects of cranberry juice on nifedipine pharmacokinetics in rats
Authors: Uesawa Yoshihiro , Mohri Kiminori 
Published: July 2006

AbstractLittle information is available about drug interactions with cranberry juice (CJ). Using microsomes from the human liver and rat small intestine, this study was designed to determine whether CJ could inhibit CYP3A-mediated nifedipine (NFP) oxidase activity; it showed that CJ was a potent inhibitor of human and rat CYP3A. Preincubation with 10% vol/vol of CJ and 1 mM NADPH for 10 min resulted in significant inhibition of the NFP oxidation activity of human and rat CYP3A (18.2 and 12.6% decreases, respectively, compared with preincubation experiments without NADPH). In addition, the pharmacokinetic interaction between CJ and NFP in vivo was confirmed in rats. In comparison with a control group, the area under the concentration-time curve (AUC) of NFP was approximately 1.6-fold higher when CJ (2 mL) was injected intraduodenally 30 min before the intraduodenal administration of NFP (30 mg kg−1). However, the mean residence time, the volume of distribution and the elimination rate constant were not changed significantly. These data suggest that CJ component(s) inhibit the function of enteric CYP3A. In conclusion, it was found that CJ inhibits the CYP3A-mediated metabolism of NFP in both rats and humans. Furthermore, CJ alters NFP pharmacokinetics in rats.
Lidocaine metabolism in isolated perfused liver from streptozotocin-induced diabetic rats
Authors: Gawronska-Szklarz Barbara , Musial Heros David , Loniewski Igor , Paprota Bartosz , Drozdzik Marek 
Published: July 2006

Abstract
Insulin deficiency can trigger not only an altered glucose metabolic state but may also affect drug metabolism. The formation rate of the major lidocaine metabolite monoethylglycinxylidide (MEGX) has been shown to reflect the activity of CYP3A2 and CYP1A2. In the present study the effects of streptozotocin-induced diabetes on lidocaine elimination and MEGX formation in a model of isolated, non-recirculated, perfused rat liver with constant flow was evaluated. The parameters describing hepatic lidocaine elimination studied 10 days after streptozotocin administration, i.e. hepatic extraction coefficient (EH), hepatic clearance (ClH) and elimination rate (VL), were significantly decreased in diabetic livers in comparison with the controls. The EH in the controls varied between 0.88±0.07 and 0.93±0.06, whereas in diabetic livers it was markedly reduced to between 0.27±0.15 and 0.39±0.23. The ClH dropped to 8.04±4.12-11.66±2.99mLmin 1 in diabetic rats in comparison to 26.29±2.07–27.94±0.92 mL min−1 in the control animals. The VL was estimated to be 128.08±18.60–136.44±17.59 μg mL−1 in the controls and from 40.87±28.31 μg mL−1 to 56.83±22.16 μg mL−1 in diabetic perfused livers. The major lidocaine metabolite, i.e. MEGX, concentrations were significantly decreased in diabetic rats compared to the controls. The observed changes indicate an impairment of N-deethylation metabolic pathway in streptozotocin-induced diabetic rats, i.e. a possible decrease in the enzymatic activity of CYP3A2 and CYP1A2.
Characterization of fasted-state human intestinal fluids collected from duodenum and jejunum
Authors: Moreno Mariangeles Perez de la Cruz , Oth Marianne , Deferme Sven , Lammert Frank , Tack Jan , Dressman Jennifer , Augustijns Patrick 
Published: July 2006

Abstract
The solubility of drugs in the gastrointestinal tract is very challenging to simulate with artificial media due to the high complexity of human intestinal fluid (HIF). In particular, bile salt composition, pH and buffer capacity are very important characteristics of HIF, since they determine the solubility of drugs in-vivo. In this study, we have measured the concentrations of individual bile salts in human intestinal fluids (n = 6) collected from two different locations (duodenum and jejunum) in the fasted state. Total bile salt concentrations ranged from 570 to 5137 μM in the duodenum and from 829 to 5470 μM in the jejunum. The following rank order of relative bile salt concentration in duodenum was observed: taurocholic acid &gt; glycocholate &gt; glycochenodeoxycholate &gt; glycodeoxycholate &gt; taurochenodeoxycholate &gt; taurodeoxycholate. Cholic acid, tauroursodeoxycholate, chenodeoxycholic acid, and deoxycholic acid represented less than 1% of bile salts present in the samples. Ursodeoxycholate could not be detected in HIF. No statistically significant difference between bile salt composition of duodenal and jejunal aspirates was observed. The buffer capacity of HIF was compared with other media commonly used for solubility/dissolution determinations, indicating a relatively low buffer capacity of HIF (4–13 mmol L−1/pH). This low buffer capacity was reflected in the change in pH (between 4 and 9.5) that occurred in HIF after addition of model compounds covering a broad pKa range. Interindividual variability in pH, buffer capacity and bile salt contents of HIF will contribute to differences in the rate and extent of absorption of compounds for which dissolution/solubility is the rate limiting step. The variability observed warrants further research to explore the impact of intraluminal conditions on drug solubility.
The influence of rutin on the extracellular matrix in streptozotocin-induced diabetic rat kidney
Authors: Kamalakkannan N , Prince P Stanely Mainzen 
Published: July 2006

Abstract
We previously reported that rutin administration to streptozotocin (STZ)-induced diabetic rats decreased plasma glucose and increased plasma insulin levels. In this study, we have examined the role of rutin on matrix remodelling in the kidney of STZ-induced diabetic rats. STZ was administered intraperitoneally (50 mg kg−1) to male albino Wistar rats to induce experimental diabetes. Rutin (100 mg kg−1) was orally administered to normal and STZ-induced diabetic rats for a period of 45 days and its influence on the content of hydroxyproline and collagen and on the activity of matrix metalloproteinases (MMPs) were studied. We have also studied the levels of tissue inhibitors of metalloproteinases (TIMPs) in the kidney. STZ-induced diabetic control rats showed increased content of hydroxyproline and collagen, decreased activity of MMPs and increased levels of TIMPs in the kidney. These changes were positively modulated by rutin treatment in STZ-induced diabetic rats, thereby protecting the kidney. In normal rats treated with rutin, none of the parameters studied were significantly altered. From the results obtained, we could conclude that rutin influences MMPs and effectively protects kidney against STZ-induced damage in rats. The effects observed are due to the reduction of plasma glucose levels by rutin.
Inhibition of pancreatic lipase by poloxamer 407 may provide an adjunct treatment strategy for weight loss
Authors: Johnston Thomas P , Goldberg Ira J 
Published: July 2006

Abstract
This investigation was conducted to evaluate whether poloxamer 407 (P-407), a nonionic surface-active-agent that functions as a lipase inhibitor, could aid in weight loss by inactivating pancreatic lipase (PL) following oral administration to mice. Using a pH-titrimetric method, P-407 was evaluated for its ability to inhibit PL activity in-vitro. The palatability of drinking water containing P-407 (50 μM) was assessed in mice to determine whether inclusion of P-407 altered either the volume of water ingested, or the volume of urine produced, per day. P-407 at the same concentration was next evaluated for its potential to mediate weight loss over a one-month period in mice fed a high-fat diet. Faecal fat determinations and the potential for P-407 to lower plasma triacylglycerol concentrations following oral administration of a standard lipid emulsion were also conducted. P-407 was determined to have an IC50 of 15.9 μM in-vitro. Inclusion of P-407 in drinking water neither perturbed the daily volume of water ingested, nor the volume of urine produced. Over the course of one month, adult mice, which were fed the high-fat diet and treated with P-407, lost approximately 12.4±1.7% of their initial body weight, whereas, control mice fed the identical diet continued to slowly gain weight (7.3±0.5% of their initial body weight). The amount of total lipids excreted in the faeces of high-fat-fed, P-407-treated mice was approximately 45% greater than that observed for control mice eating the same diet. Lastly, plasma triacylglycerol concentrations following oral administration of the standard lipid emulsion containing P-407 were significantly lower than corresponding plasma triacylglycerol concentrations observed in mice administered the lipid emulsion alone. While not as potent as orlistat, P-407 may potentially represent an additional treatment strategy for weight loss, especially when combined with caloric restriction, regular exercise, and anti-obesity medications of other drug classes.
Vasorelaxing effect of levosimendan against 5-hydroxytryptamine-induced contractions in isolated human conduit bypass grafts
Authors: Pataricza János , Szolnoky Jenö , Krassói Irén , Hegedüs Zoltán , Kun Attila , Varró András , Papp Julius Gy 
Published: July 2006

Abstract
Levosimendan is a novel inodilator drug developed for the treatment of heart failure. The possible vasodilating property of the drug in human coronary artery bypass grafts was investigated. Isometric tensions of the left internal thoracic artery (LITA, n = 8) as well as the proximal and distal segments of the radial artery (RA, n = 8 and 8) were measured in isolated organ baths. Concentration-relaxation curves for levosimendan (0.009-1.14 μmol L−1) were obtained against 5-hydroxytryptamine (5-HT; serotonin, 0.002–9.3 μmol L 1)-induced contractions. 5-HT-induced contraction of LITA was considerably smaller than that of the proximal and distal RAs. Levosimendan relaxed the grafts in the following order of calculated maximum efficacies (Emax): LITA &gt; proximal RA &gt; distal RA (LITA 100.3 ±16.2% of 5-HT-induced maximum tension, proximal RA 86.9 ±8.6%, distal RA 59.4 ± 17.5%, P &lt; 0.05 LITA vs distal RA). The potency values of levosimendan, expressed as the negative logarithm of 50% effective concentrations (pD2), were comparable in the three bypass grafts (LITA −6.52 ± 0.44 log mol L−1, proximal RA −6.60 ± 0.49 log mol L−1, distal RA −6.85 ± 0.45 log mol L−1). The results suggest that levosimendan is an effective vasorelaxant of conduit bypass grafts and may serve as a new therapeutic tool, especially in the case of LITA and proximal RA grafts, for relieving perioperative spasm and subsequent graft failure.
Effect of leptin administration on membrane-bound adenosine triphosphatase activity in ethanol-induced experimental liver toxicity
Authors: Balasubramaniyan Vairappan , Viswanathan Periyaswamy , Nalini Namasivayam 
Published: July 2006

Abstract
Hepatic injury elicits intracellular stress that leads to peroxidation of membrane lipids accompanied by alteration of structural and functional characteristics of the membrane, which affects the activity of membrane-bound ATPases. We have explored the effect of leptin on hepatic marker enzyme and membrane-bound adenosine triphosphatases in ethanol-induced liver toxicity in mice. The experimental groups were control, leptin (230 μg kg−1, i.p. every alternate day for last 15 days), alcohol (6.32 g kg−1, by intragastric intubation for 45 days), and alcohol plus leptin. Ethanol feeding to mice significantly (P &lt; 0.05) elevated the plasma leptin, alanine transaminase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) and hepatic lipid hydroperoxides (LOOH), and plasma and hepatic total ATPases, Na+, K+-ATPase and Mg2+-ATPase. There was a significant decrease in Ca2+-ATPase and reduced glutathione (GSH). Leptin injections to ethanol-fed animals further elevated the levels of hepatic LOOH, plasma and hepatic total ATPases, Na+, K+-ATPase and Mg2+-ATPase, while the Ca2+-ATPase and GSH were decreased significantly. In addition, leptin administration was found to increase the plasma levels of leptin, ALT, ALP, GGT, Na+ and inorganic phosphorous, and decrease the levels of K+ and Ca2+ in ethanol-fed mice. These findings were consistent with our histological observations, confirming that leptin enhanced liver ailments in ethanol-supplemented mice.
Dose-response efficacy of caraway (Carum carvi L.) on tissue lipid peroxidation and antioxidant profile in rat colon carcinogenesis
Authors: Kamaleeswari Muthaiyan , Nalini Namasivayam 
Published: July 2006

Abstract
Colon cancer is a leading cause of cancer death and its prevention is of great interest throughout the world. This study was conducted to examine the efficacy of different doses of dietary caraway (Carum carvi L.) on tissue lipid peroxidation (LPO) and antioxidant profile in rat colon carcinogenesis. Wistar male rats were divided into 6 groups and were fed a modified pellet diet for the whole of 30 weeks. To induce colon cancer, rats were given a weekly subcutaneous injection of 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg−1 (based on body weight) for the first 15 weeks. Caraway was supplemented every day orally at doses of 30, 60 and 90 mg kg−1 for different groups of rats for the total period of 30 weeks. All rats were sacrificed at the end of 30 weeks, the colons were examined visually for masses and were subsequently evaluated histologically. The results showed diminished levels of intestinal, colonic and caecal LPO products, such as conjugated dienes (CD), lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and also the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione reductase (GR) in DMH treated rats, which were significantly reversed (P &lt; 0.05) on caraway supplementation. Moreover, enhanced activity of intestinal, colonic and caecal glutathione peroxidase (GPx), glutathione S-transferase (GST) and colonic ascorbic acid and α-tocopherol levels were observed in carcinogen-treated rats, which were significantly (P &lt; 0.05) reduced on caraway supplementation. Thus, our study showed that caraway supplementation at a dose of 60 mg kg−1 had a modulatory role on tissue LPO, antioxidant profile and prevented DMH-induced histopathological lesions in colon cancer rats.
Antibacterial, antiviral, antiproliferative and apoptosis-inducing properties of Brackenridgea zanguebarica (Ochnaceae)
Authors: Möller Maren , Suschke Ulrike , Nolkemper Silke , Schneele Jürgen , Distl Melanie , Sporer Frank , Reichling Jürgen , Wink Michael 
Published: July 2006

Abstract
Brackenridgea zanguebarica is a small tree that is used in traditional African medicine as a type of cure-all for many diseases, including the treatment of wounds. The yellow bark of B. zanguebarica was used for the preparation of an ethanolic extract, which was tested in various concentrations against eleven bacteria, Herpes simplex virus type 1 (HSV-1) and different human tumour cell lines. The extract that contains different polyphenolic substances like calodenin B. Cell growth inhibition, assessed via MTT-assay, was found in all tested human cell lines with IC50 values (concentration of extract that reduced cell viability by 50%) between 33 μg dry extract/mL for HL-60 human myeloid leukaemia cells and 93 μg dry extract/mL for HaCaT human keratinocytes. Staining with Annexin-V-FLUOS and JC-1 followed by subsequent analysis via flow cytometry revealed significant apoptosis-inducing properties. Analysis of caspase activity using a fluorogenic caspase-3 substrate showed a significant caspase activity in Jurkat T-cells after incubation with the extract. The bark extract had a pronounced activity against free HSV-1 and a strong antibacterial activity against Gram-positive strains (MICs: 6–24 μg dry extract/mL), which are often involved in skin infections. Additionally, no irritating properties of the extract could be observed in hen-egg test chorioallantoic membrane (HET-CAM) assay. These findings give a rationale for the traditional use of B. zanguebarica and are a basis for further analysis of the plant's components, their biological activity, and its use in modern phytotherapy.