bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vitro interaction of l-dopa with bacterial adhesins of Helicobacter pylori: an explanation for clinicial differences in bioavailability?
Authors: Niehues Michael , Hensel Andreas 
Published: October 2010

Abstract

Objectives
Recent investigations on the pharmacokinetics of levodopa (l-dopa) indicated that the presence of Helicobacter pylori in patients with Parkinson's disease, orally treated with l-dopa, influences the absorption of this compound, which consequently leads to decreased plasma levels. Therefore this work aims to study a potential in-vitro interaction of l-dopa with H. pylori and its surface adhesins.

Methods
Solutions containing l-dopa of different concentrations were incubated with H. pylori at different bacterial densities and time intervals. Free l-dopa was quantified from the incubation supernatants by HPLC. A flow cytometric assay with fluorescence labelled H. pylori was used to investigate the influence of l-dopa on the bacterial adhesion of H. pylori: FITC-labelled bacteria were pre-incubated with l-dopa, followed by incubation with gastric epithelial cells (AGS cells) and FACS quantification of adhering bacteria.

Key findings
Evaluation of time- and concentration-dependent incubation experiments indicated a significant decrease in l-dopa concentrations when coming into contact with H. pylori. The reduction in l-dopa concentrations was determined as 47 to 12%, referred to the initial starting concentration, with time-dependency and dependency of the H. pylori density. FITC-labelled H. pylori, pre-incubated with differing l-dopa concentrations, were shown to have a significantly reduced bacterial adhesion to AGS cells, with a maximum reduction of 22 ± 9%. These results demonstrate a direct interaction of l-dopa with the outer membrane proteins of H. pylori responsible for the adhesion to gastric epithelial cells. By this interaction the unbound l-dopa concentration in bacterial suspension was strongly reduced.

Conclusions
This study suggests a potential in-vitro interaction of l-dopa with H. pylori adhesins, confirming the clinical changes found in pharmacokinetics of l-dopa therapy by H. pylori-positive patients with Parkinson's disease.
Effect of intestinal ischaemia/reperfusion on P-glycoprotein-mediated ileal excretion of rhodamine 123 in the rat
Authors: Tomita Mikio , Takizawa Yusuke , Kishimoto Hisanao , Hayashi Masahiro 
Published: October 2010

AbstractObjectivesWe have shown that ischaemia/reperfusion in the small intestine at an early phase, such as 1 h after reperfusion, induced not only functional changes in the membrane, such as P-glycoprotein (P-gp) dysfunction, but also decreased expression of P-gp protein and mdr1a mRNA. In the present study we examined whether intestinal ischaemia/reperfusion modifies the P-gp-mediated ileal excretion transport system in rats beyond 1 h after reperfusion.MethodsTo evaluate the contribution of P-gp-mediated transport to the ileal excretion of rhodamine 123, we used Western blotting to measure the expression of P-gp protein levels isolated from the ileum at different reperfusion times after 60 min of ischaemia. We also measured the expression of inducible nitric oxide synthase (iNOS) mRNA using real-time RT-PCR.Key findingsIleal excretion of rhodamine 123 decreased at 3 h after reperfusion and had recovered at 24 h. Changes in villi structure at 3 h and its recovery at 24 h were also observed. Verapamil, a competitive inhibitor of P-gp, significantly inhibited ileal clearance of rhodamine 123 to the lumen at 24 h after reperfusion, suggesting that P-gp was working at this time. These results suggest that intestinal ischaemia/reperfusion-induced decrease in P-gp-mediated ileal excretion of rhodamine 123 was probably due to impaired P-gp-mediated transport. Levels of P-gp protein and iNOS mRNA in the ileum decreased 3 h after ischaemia/reperfusion and returned to control levels after 24 h.ConclusionsThese findings suggest that intestinal ischaemia/reperfusion markedly decreases P-gp-mediated ileal excretion of rhodamine 123, probably by decreasing the expression of P-gp protein, which is likely to be due to increased lipid peroxidation via iNOS.
Therapeutic index of methotrexate depends on circadian cycling of tumour necrosis factor-α in collagen-induced arthritic rats and mice
Authors: To Hideto , Irie Sadaharu , Tomonari Mari , Watanabe Yuko , Kitahara Takashi , Sasaki Hitoshi 
Published: October 2010

Abstract

Objectives
Rheumatoid arthritis is an autoimmune disorder of unknown aetiology. Morning stiffness, a characteristic feature of rheumatoid arthritis, shows a 24-h rhythm. Noticing this rhythm, we hypothesized the presence of a similar rhythm for a rheumatoid arthritis indicator, in addition to dosing-time dependency of the anti-rheumatic effect of methotrexate in arthritis induced by collagen in rats and mice, which reflect the symptomatology of rheumatoid arthritis patients.

Methods
To measure tumour necrosis factor (TNF)-α concentration, blood was taken at different times (2, 6, 10, 14, 18 or 22 h after the light was turned on (HALO)) in collagen-induced arthritic mice. Methotrexate was administered at two different dosing times based on these findings to estimate arthritis.

Key findings
The arthritis score was significantly lower in the 22 HALO-treated group than in the control and 10 HALO-treated groups in collagen-induced arthritic rats and mice. Plasma TNF-α concentrations showed obvious 24-h rhythms, with higher levels at light phase and lower levels at dark phase after rheumatoid arthritis crisis. Arthritis was relieved after administration of methotrexate during the dark phase in synchronization with the 24-h rhythm.

Conclusions
Our findings suggest that choosing an optimal dosing time associated with the 24-h cycling of TNF-α could lead to effective treatment of rheumatoid arthritis by methotrexate.
Comparative study between the effect of the peroxisome proliferator activated receptor-α ligands fenofibrate and n-3 polyunsaturated fatty acids on activation of 5′-AMP-activated protein kinase-α1 in high-fat fed rats
Authors: Motawi Tarek M Kamal , Hashem Reem M , Rashed Laila A , El-Razek Sabry M Abd 
Published: October 2010

Abstract

Objectives
Obesity is a risk factor for type 2 diabetes mellitus. It results from an energy imbalance in which energy intake exceeds energy expenditure. The cellular fuel gauge 5′-AMP-activated protein kinase (AMPK) is a heterotrimeric protein consisting of one catalytic subunit (α) and two non-catalytic subunits (β and γ), and approximately equal levels of α1 and α2 complexes are present in the liver. AMPK regulates metabolic pathways in response to metabolic stress and in particular ATP depletion to switch on energy-producing catabolic pathways such as β-oxidation of fatty acids and switch off energy-depleting processes such as synthesis of fatty acid and cholesterol. A high-fat diet alters AMPK-α1 gene expression in the liver and skeletal muscle of rats and results in body weight gain and hyperglycaemia. The aim of this study was to investigate and compare the potential effects of peroxisome proliferator-activated receptor (PPAR)-α agonists fenofibrate and n-3 polyunsaturated fatty acids (PUFAs) in modulation of AMPK-α1 activity in liver and skeletal muscle of high-fat diet fed rats.

Methods
Reverse transcription–polymerase chain reaction was used for determination of AMPK-α1 in liver and soleus muscle and both PPAR-α and CPT-1 in hepatic tissues. Serum, total cholesterol, triacylglycerol, fatty acid and fasting blood glucose were determined colorimetrically.

Key findings
Both PPAR-α agonists, fenofibrate and n-3 PUFA, increased the mRNA expression of AMPK-α1 activity in liver and skeletal muscle of obese diabetic rats. Fenofibrate was superior in its activation of hepatic mRNA expression of AMPK-α 1 to exert more lipolytic effect and body weight reduction, as estimated through the decrease of triacylglycerol output and serum levels of fatty acid on the one hand and the increase in CPT-1 mRNA expression, the key enzyme in β-oxidation of fatty acid, on the other hand. n-3 PUFA activated AMPK-α1 mRNA expression in skeletal muscle much more than fenofibrate to reveal more hypoglycaemic effect.

Conclusions
The PPAR-α agonists fenofibrate and n-3 PUFA could efficiently activate AMPK-α1 mRNA expression in liver and skeletal muscle to exert body weight reduction and hypoglycaemic effect, respectively.
Enhanced anticancer activity of glutamate prodrugs of all-trans retinoic acid
Authors: Cui Chunying , Zhang Yunwei , Wang Lili , Liu Hu , Cui Guohui 
Published: October 2010

Abstract

Objectives
All-trans retinoic acid (ATRA), an active metabolite of vitamin A, is widely used in the treatment of acute promyelocytic leukaemia and myelodysplastic syndrome. However, its high lipophilicity is thought to be responsible for the slow dissolution and low bioavailability following oral administration. In order to obtain compounds with better solubility characteristics to improve the transportation and bioavailability of ATRA, derivatives of ATRA containing glutamic acid or its sodium salt were synthesised.

Methods
The ATRA derivatives synthesised – all-trans retinoyl glutamate (RAE) and all-trans retinoyl sodium glutamate (RAENa2) – were characterised in terms of melting point, optical rotation, mass spectrometry, NMR and partition coefficient. A liposomal preparation formed from RAE was characterised by particle size and zeta potential. The anti-tumour activity of RAE and RAENa2 was compared with that of ATRA in mice bearing S180 tumours and their effects on the cell cycle were determined in human pro-myelocytic leukaemia HL-60 cells.

Key findings
RAE and RAENa2 were more active than ATRA against tumour growth. Flow cytometry indicated that RAE and RAENa2 induced HL-60 cell cycle arrest, similar to ATRA. DNA fragmentation studies suggested that apoptosis may be one of the mechanisms responsible for the anti-tumour activities.

Conclusions
The two derivatives of ATRA, RAE and RAENa2, exhibited improved aqueous solubility and were more effective in mice bearing S180 tumours.
Hepatoprotective effects of salidroside on fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide in mice
Authors: Wu Yan-Ling , Lian Li-Hua , Jiang Ying-Zi , Nan Ji-Xing 
Published: October 2010

Abstract

Objectives
The aim was to investigate the protective effect of salidroside isolated from Rhodiola sachalinensis A. Bor. (Crassulaceae) on d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.

Methods
Hepatotoxicity was induced by an intraperitoneal injection of d-galactosamine (700 mg/kg) and lipopolysaccharide (10 μg/kg); salidroside (20, 50 and 100 mg/kg) was administered intraperitoneally 1 h before induction of hepatoxicity. Liver injury was assessed biochemically and histologically.

Key findings
Salidroside attenuated the induced acute increase in serum aspartate aminotransferase and alanine aminotransferase activities, and levels of tumour necrosis factor-alpha levels and serum nitric oxide. It restored depleted hepatic glutathione, superoxide dismutase, catalase and glutathione peroxidase activities, decreased malondialdehyde levels and considerably reduced histopathological changes. Histopathological, immunohistochemical and Western blot analyses also demonstrated that salidroside could reduce the appearance of necrotic regions and expression of caspase-3 and hypoxia-inducible factor-1α in liver tissue.

Conclusions
Salidroside protected liver tissue from the oxidative stress elicited by d-galactosamine and lipopolysaccharide. The hepatoprotective mechanism of salidroside appear to be related to antioxidant activity and inhibition of hypoxia-inducible factor-1α.
Penetration of oseltamivir and its active metabolite into the brain after lipopolysaccharide-induced inflammation in mice
Authors: Oshima Shigeru , Nemoto Eiichi , Kuramochi Mika , Saitoh Yukiya , Kobayashi Daisuke 
Published: October 2010

Abstract

Objectives
Oseltamivir phosphate is used for the treatment of influenza virus infections. Recently, oral intake has been associated with abnormal behaviour. The present study examined the brain penetration of oseltamivir phosphate and oseltamivir carboxylate, its active metabolite, during inflammation.

Methods
Male C57BL/6 mice were given three i.p. injections of lipopolysaccharide (LPS) or saline. We studied the concentration of Evans blue (a marker of blood–brain barrier function) and oseltamivir phosphate and its active metabolite in the brain and plasma.

Key findings
The brain-to-plasma ratio of Evans blue compared with saline-treated control mice increased significantly with LPS dose. LPS-induced inflammation increased the permeation of drugs through the blood-brain barrier. The concentration of oseltamivir phosphate in both brain and plasma was 2-fold higher in mice treated with LPS than in control mice. Although the plasma concentration of the active carboxylate was not significantly altered by inflammation, the brain concentration was increased 2.7-fold in mice treated with LPS compared with control mice.

Conclusions
Administration of oseltamivir phosphate in the presence of inflammation increased the brain concentration of both parent drug and active metabolite, which may explain the central nervous system side-effects observed with this agent.
Antimalarial compounds isolated from plants used in traditional medicine
Authors: Bero Joanne , Frédérich Michel , Quetin-Leclercq Joëlle 
Published: October 2010

Abstract

Objectives
This review covers the compounds with antiplasmodial activity isolated from plants published from 2005 to the end of 2008, organized according to their phytochemical classes. Details are given for substances with IC50 values ≤ 11 μM.

Key findings
Malaria is a major parasitic disease in many tropical and subtropical regions and is responsible for more than 1 million deaths each year in Africa. The rapid spread of resistance encourages the search for new active compounds. Nature and particularly plants used in traditional medicine are a potential source of new antimalarial drugs as they contain molecules with a great variety of structures and pharmacological activities.

Summary
A large number of antimalarial compounds with a wide variety of structures have been isolated from plants and can play a role in the development of new antimalarial drugs. Ethnopharmacological approaches appear to be a promising way to find plant metabolites that could be used as templates for designing new derivatives with improved properties.
Non-phenolic radical-trapping antioxidants
Authors: Foti Mario C , Amorati Riccardo 
Published: October 2010

Abstract

Objectives
The aim of this review article is to introduce the reader to the mechanisms, rates and thermodynamic aspects of the processes involving the most biologically relevant non-phenolic radical-trapping antioxidants.

Key findings
Antioxidant defences in living organisms rely on a complex interplay between small molecules and enzymes, which cooperate in regulating the concentrations of potentially harmful oxidizing species within physiological limits. The noxious effects of an uncontrolled production of oxygen- and nitrogen-centered radicals are amplified by chain reactions (autoxidations), sustained mainly by peroxyl radicals (ROO•), that oxidize and alter essential biomolecules such as lipids, lipoproteins, proteins and nucleic acids.

Summary
Non-phenolic antioxidants represent an important and abundant class of radical scavengers in living organisms. These compounds react with peroxyl radicals through various mechanisms: (i) formal H-atom donation from weak X-H bonds (X = O, N, S), as in the case of ascorbic acid (vitamin C), uric acid, bilirubin and thiols; (ii) addition reactions to polyunsaturated systems with formation of C-radicals poorly reactive towards O2, for example β-carotene and all carotenoids in general; (iii) co-oxidation processes characterized by fast cross-termination reactions, for example γ-terpinene; and (iv) catalytic quenching of superoxide (O2•−) with a superoxide dismutase-like mechanism, for example di-alkyl nitroxides and FeCl3. Kinetic data necessary to evaluate and rationalize the effects of these processes are reported. The mechanisms underlying the pro-oxidant effects of ascorbate and other reducing agents are also discussed.
Montmorillonite adsorbs uric acid and increases the excretion of uric acid from the intestinal tract in mice
Authors: Ma Zhao , Long Li-hui , Liu Jing , Cao Yong-xiao 
Published: October 2010

Abstract

Objectives
The aim was to evaluate the adsorbing effect of montmorillonite on uric acid, promoting diffusion of uric acid from blood to intestine, preventing absorption of uric acid in intestine and reducing uric acid level in serum.

Methods
The adsorbing effect of montmorillonite on uric acid was observed in vitro. The intestine and blood vessel of rats were circularly perfused with intestinal perfusate and vascular perfusate, respectively. A model of hyperuricaemia in mice was prepared by intraperitoneal injection of hypoxanthine and potassium oteracil. The concentration of uric acid was determined by the method of urate oxidase and peroxide enzyme.

Key findings
The results showed that different concentrations of montmorillonite could adsorb uric acid in a concentration-dependent manner. The adsorbing effect was fast. The adsorptive rate was high in acid solution and was low in alkaline solution. When blood vessels were circularly perfused by vascular perfusate containing uric acid, the concentration of uric acid in vascular perfusate was decreased and the concentration of uric acid in intestinal perfusate was increased, suggesting that uric acid in blood vessels diffused into the intestine. When the intestine was perfused with intestinal perfusate containing uric acid, the uric acid concentration in vascular perfusate was increased, but the uric acid concentration of intestinal perfusate was decreased, suggesting that uric acid was absorbed in the intestine. The uric acid concentrations of intestinal perfusate and vascular perfusate in montmorillonite 0.5 and 1.0 g/kg groups were lower than the control group. Concentrations of uric acid in serum and urine in the montmorillonite 1 and 2 g/kg groups were lower compared with mice in the hyperuricaemic group.

Conclusions
The results suggested that montmorillonite adsorbed uric acid and promoted diffusion of uric acid from blood vessels to intestine, prevented absorption of uric acid in intestine and decreased uric acid level in serum.
Efficacy of different doses of aspirin in decreasing blood levels of inflammatory markers in patients with cardiovascular metabolic syndrome
Authors: Gao Xiu-ren , Adhikari Chandar M , Peng Long-yun , Guo Xiao-gang , Zhai Yuan-sheng , He Xu-yu , Zhang Li-Yuan , Lin Jun , Zuo Zhi-yi 
Published: October 2010

Abstract

Objectives
Inflammation and platelet aggregation and activation are key processes in the initiation of a cardiovascular event. Patients with metabolic syndrome have a high risk of cardiovascular events. This study determined whether small and medium doses of aspirin have anti-inflammation and antiplatelet aggregation effects in patients with metabolic syndrome.

Methods
One hundred and twenty-one consecutive patients with metabolic syndrome were randomized into three groups, receiving 100 mg/day of aspirin, 300 mg/day of aspirin or a placebo, respectively, for 2 weeks. The blood levels of thromboxane B2 (TXB2), a stable product of the platelet aggregation mediator TXA2, 6-keto-prostaglandin F1-α (6-keto-PGF1-α), a stable product of the endogenous cyclooxygenase metabolite prostaglandin I2, and inflammatory mediators including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were determined by ELISA and radioimmunoassay.

Key findings
The blood levels of hs-CRP, TNF-α, IL-6 and TXB2 were significantly decreased after 2 weeks of treatment with 300 mg/day of aspirin. Patients who received 100 mg/day of aspirin had decreased blood levels of hs-CRP and TXB2. The blood level of IL-6 in the 300 mg/day aspirin group was significantly lower than that in the other two groups after 2 weeks of therapy. Aspirin at either dose did not affect the blood level of 6-keto-PGF1-α.

Conclusions
Aspirin at all doses suppresses the blood levels of inflammatory markers and the platelet aggregation mediator TXA2 in Chinese patients with metabolic syndrome. Since the suppression induced by 300 mg/day of aspirin was greater than that induced by 100 mg/day of aspirin, these data suggest that 300 mg/day of aspirin may be beneficial in decreasing the risk of cardiovascular events in Chinese patients with metabolic syndrome.
Catecholamine-induced myocardial fibrosis and oxidative stress is attenuated by Terminalia arjuna (Roxb.)
Authors: Kumar Santosh , Enjamoori Rajesh , Jaiswal Amardeep , Ray Ruma , Seth Sandeep , Maulik Subir Kumar 
Published: October 2010

Abstract

Objectives
Myocardial fibrosis and oxidative stress accompany a number of cardiac disorders such as hypertrophic cardiomyopathy, hypertensive heart disease and cardiac failure. Stem bark of Terminalia arjuna has been advocated for cardiac ailments. The present study evaluated the effects of T. arjuna bark extract on myocardial fibrosis and oxidative stress induced by chronic beta-adrenoceptor stimulation.

Methods
Aqueous extract of T. arjuna bark was evaluated at 63, 125 and 250 mg/kg given orally for antifibrotic and antioxidant effects in rats given the selective β-adrenoceptor agonist isoprenaline (5 mg/kg s.c.) for 28 days. Captopril (50 mg/kg per day, given orally), an inhibitor of angiotensin-converting enzyme used as a standard cardioprotective drug, was used as a positive control.

Key findings
Isoprenaline caused fibrosis, increased oxidative stress and cardiac hypertrophy (increased heart weight: body weight ratio and cardiomyocyte diameter). The T. arjuna bark extract and captopril significantly prevented the isoprenaline-induced increase in oxidative stress and decline in endogenous antioxidant level. Both also prevented fibrosis but not the increase in heart weight: body weight ratio.

Conclusions
T. arjuna protects against myocardial changes induced by chronic beta-adrenoceptor stimulation.
Review: physical chemistry of solid dispersions
Authors: Janssens Sandrien , Van den Mooter Guy 
Published: October 2010

Abstract

Objectives
With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state.

Key findings
After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life.

Conclusions
Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development.