bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated leptin expression in a rat model of fracture and traumatic brain injury
Authors: Wei Yongzhong , Wang Lei , Clark Jonathan C M , Dass Crispin R , Choong Peter F M 
Published: October 2010

Abstract
A few studies have reported a relationship between leptin induced by brain injury and healing of bone tissue. Our objective was to measure serum and callus leptin expression within the setting of fracture and traumatic brain injury (TBI). Sixty-four male Sprague-Dawley rats were randomised equally into four groups: control, TBI group, fracture group and fracture/TBI group. Rats were sacrificed at 2, 4, 8 and 12 weeks after fracture/TBI. Serum leptin was detected using radio-immunoassay, and callus formation was measured radiologically. Callus leptin was analysed with immunohistochemistry. Serum leptin was significantly increased in the fracture, TBI and combined fracture/TBI groups compared with the control group at 2 weeks (P &lt; 0.05). Serum leptin was significantly higher in the combined fracture/TBI group than in the fracture and TBI groups at 4 and 8 weeks (P &lt; 0.05). The percentage of leptin-positive cells in the callus and callus volume were significantly higher in the fracture/TBI group than in the fracture-only group (P &lt; 0.001). Thus, we demonstrated elevated leptin expression within healing bone, particularly in the first 8 weeks of a rat model combining fracture and TBI. A close association exists between leptin levels and the degree of callus formation in fractures.
Total triterpene acids, active ingredients from Fructus Corni, attenuate diabetic cardiomyopathy by normalizing ET pathway and expression of FKBP12.6 and SERCA2a in streptozotocin-rats
Authors: Qi Min-You , Liu Hao-Ran , Dai De-Zai , Li Na , Dai Yin 
Published: October 2010

Abstract
Total triterpene acids (TTAs) isolated from Cornus officinalis Sieb., one of the herbs contained in Liuwei Dihuang decoction, were aimed at alleviating diabetic cardiomyopathy. We hypothesized that the benefits of TTAs may result from suppressing the endothelin-reactive oxidative species (ET-ROS) pathway in the myocardium. Diabetes was produced by a single injection of streptozotocin (STZ, 60 mg kg−1, i.p.) in rats. Assessment of cardiac function, calcium handling proteins, endothelin-1 (ET-1) and redox system was conducted 8 weeks after STZ injection. Medication with TTAs (50 mg kg−1, i.g.) was installed in the last 4 weeks. The compromised cardiac function was characterized by depressed contractility (LVSP and LV+dp/dtmax) and relaxation (LVEDP and -LVdp/dtmin) in association with hyperglycaemia (30.2 ± 2.6 mmol L−1) in STZ-injected rats. Down-regulated expression of FKBP12.6 (calstabin 2), sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and phospholamban (PLB) were also found. These changes occurred in connection with an increased ET-1, up-regulated mRNA of propreET-1 and endothelin converting enzyme (ECE), and a state of oxidant stress was found by increased malondialdehyde (MDA), decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity, and an enhanced activity and expression of inducible nitric oxide synthase (iNOS) in the diabetic myocardium. After 4 weeks of treatment with TTAs, these changes were alleviated dramatically despite a mild reduction in hyperglycaemia (26.9 ± 3.4 mmol L−1). In conclusion, TTAs, as active ingredients of Liuwei Dihuang decoction, alleviated diabetic cardiomyopathy by normalizing the abnormality of FKBP12.6 and SERCA2a and ET-ROS pathway in the myocardium rather than by hypoglycaemic activity.
Effects of cytochrome P450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats: involvement of CYP2C11, 2E1, 3A1 and 3A2 in furosemide metabolism
Authors: Yang Kyung H , Choi Young H , Lee Unji , Lee Joo H , Lee Myung G 
Published: October 2010

AbstractObjectivesIt has been reported that the non-renal clearance of furosemide was significantly faster in rats pretreated with phenobarbital but was not altered in rats pretreated with 3-methylcholanthrene. However, no studies on other cytochrome P450 (CYP) isozymes have yet been reported in rats.MethodFurosemide 20 mg/kg was administered intravenously to rats pretreated with various CYP inducers –3-methylcholanthrene, orphenadrine citrate and isoniazid, inducers of CYP1A1/2, 2B1/2 and 2E1, respectively, in rats – and inhibitors – SKF-525A (a nonspecific inhibitor of CYP isozymes), sulfaphenazole, cimetidine, quinine hydrochloride and troleandomycin, inhibitors of CYP2C6, 2C11, 2D and 3A1/2, respectively, in rats.Key findingsThe non-renal clearance of furosemide was significantly faster (55.9% increase) in rats pretreated with isoniazid, but slower in those pretreated with cimetidine or troleandomycin (38.5% and 22.7% decreases, respectively), than controls. After incubation of furosemide with baculovirus-infected insect cells expressing CYP2C11, 2E1, 3A1 or 3A2, furosemide was metabolized via CYP2C11, 2E1, 3A1 and 3A2.ConclusionsThese findings could help explain possible pharmacokinetic changes of furosemide in various rat disease models (where CYP2C11, 2E1, 3A1 and/or CYP3A2 are altered) and drug–drug interactions between furosemide and other drugs (mainly metabolized via CYP2C11, 2E1, 3A1 and/or 3A2).
Review: doxorubicin delivery systems based on chitosan for cancer therapy
Authors: Tan Mei Lin , Choong Peter F M , Dass Crispin R 
Published: October 2010

AbstractObjectivesThis review sheds insight into an increasingly popular polymer that has been widely explored as a potential drug delivery system. The abundant, biodegradable and biocompatible polysaccharide chitosan, with many other favourable properties, has been favoured as a drug delivery system for the purposes of encapsulating and delivery of doxorubicin with reduced side-effects.Key findingsDoxorubicin is frequently used as a frontline chemotherapeutic agent against a variety of cancers. It has largely been able to demonstrate anti-tumour effects, though there are major shortfalls of doxorubicin, which include serious side-effects such as cardiomyopathy and myelosuppression, and also an ever-present danger of extravasation during drug administration. In view of this, drug delivery systems are currently being explored as alternative methods of drug delivery in a bid to more effectively direct doxorubicin to the specific lesion site and reduce its systemic side-effects. Liposomes and dendrimers have been tested as potential carriers for doxorubicin; however they are not the focus of this review.SummaryRecent advancements in doxorubicin and chitosan technology have shown some preliminary though promising results for cancer therapy.
Novel mucoadhesive nasal inserts based on chitosan/hyaluronate polyelectrolyte complexes for peptide and protein delivery
Authors: Luppi Barbara , Bigucci Federica , Mercolini Laura , Musenga Alessandro , Sorrenti Milena , Catenacci Laura , Zecchi Vittorio 
Published: October 2010

Abstract

Objectives
The purpose of this study was the preparation and characterisation of mucoadhesive nasal inserts based on chitosan/hyaluronate polyelectrolyte complexes prepared at various pHs and at different molar ratios.

Methods
A suspension of chitosan/hyaluronate complexes with or without the model drugs (vancomycin or insulin) was lyophilised into small inserts. Complexation yield, FT-IR spectra and thermogravimetric analysis were used to study the degree of interactive strength between polyions. In-vitro swelling, mucoadhesion and release tests were performed in order to investigate delivery of vancomycin and insulin in the nasal cavity.

Key findings
The results indicated that the selection of complex preparative conditions allows modulation of insert swelling and mucoadhesion ability. Nasal inserts containing vancomycin or insulin had showed completely different drug release behaviour.

Conclusions
Chitosan/hyaluronate polyelectrolyte complexes can be used for the formulation of mucoadhesive nasal inserts for the delivery of peptide and protein drugs.
Anti-African trypanocidal and antimalarial activity of natural flavonoids, dibenzoylmethanes and synthetic analogues
Authors: dos Santos Djalma A P , Braga Patricia A de C , da Silva M Fátima das G F , Fernandes João B , Vieira Paulo C , Magalhães Aderbal F , Magalhães Eva G , Marsaioli Anita J , Moraes Valéria R de S , Rattray Lauren , Croft Simon L 
Published: October 2010

Abstract

Objectives
The known anti-protozoal activity of flavonoids has stimulated the testing of other derivatives from natural and synthetic sources.

Methods
As part of our efforts to find potential lead compounds, a number of flavonoids isolated from Neoraputia paraensis, N. magnifica, Murraya paniculata, (Rutaceae), Lonchocarpus montanus, L. latifolius, L. subglaucescens, L. atropurpureus, L. campestris, Deguelia hatschbachii (Leguminosae), dibenzoylmethanes from L. subglaucescens and synthetic analogues were tested for in-vitro activity against chloroquine-sensitive Plasmodium falciparum and Trypanosoma brucei rhodesiense bloodstream form trypomastigotes. An assay withKB cells has been developed inorder tocompare in-vitro cytotoxicityof flavonoids with a selective action on the parasites.

Key findings
Thirteen of the compounds tested had IC50 values ranging from 4.6 to 9.9 μM against T. brucei rhodesiense. In contrast, a small number of compounds showed significant activity against P. falciparum; seven of those tested had IC50 values ranging from 2.7 to 9.5 μM. Among the flavones only one had IC50 &lt; 10 μM (7.6 μM), whereas against T. brucei rhodesiense seven had IC50 &lt; 10 μM. Synthetic dibenzoylmethanes were the most active in terms of number (five) of compounds and the IC50 values (2.7–9.5 μM) against P. falciparum.

Conclusions
Dibenzoylmethanes represent a novel class of compounds tested for the first time as antimalarial and trypanocidal agents.
Galactose-grafted chylomicron-mimicking emulsion: evaluation of specificity against HepG-2 and MCF-7 cell lines
Authors: Jain Vikas , Nath Banashree , Gupta Girish K , Shah Parag P , Siddiqui Maqsood A , Pant Aditya B , Mishra Prabhat R 
Published: October 2010

Abstract

Objectives
A chylomicron-mimicking lipid emulsion was prepared and loaded with paclitaxel (paclitaxel-CM) and was further grafted with galactose (paclitaxel-GCM) using palmitoyl-galactosamine, which was synthesized by reacting galactosamine hydrochloride with N-hydroxy succinimide ester of palmitic acid. Palmitoyl-galactosamine was used as a ligand for asialoglycoprotein receptors.

Methods
The uptake characteristics of the emulsions were evaluated in HepG-2 cells (human hepatocarcinaoma), which express asialoglycoprotein receptors, and MCF-7 (breast cancer) cells, which are devoid of these receptors.

Key findings
The incorporation efficiency of paclitaxel-CM was 68.05 ± 4.80% and that of paclitaxel-GCM was 72.10 ± 3.93% when the emulsion was prepared with 7.5% (w/w) paclitaxel/lipid phase. The globule size of paclitaxel-GCM and paclitaxel-CM was 124 ± 8.67 and 96.45 ± 5.78 nm, respectively. The release of paclitaxel from both of the formulations was fairly sustained: 50 ± 3.2% of paclitaxel in 24 h. The cytotoxicity and uptake of paclitaxel-GCM were significantly higher (P &lt; 0.05) in HepG-2 cells than MCF-7 cells, while for paclitaxel-CM cytotoxicity and uptake were similar in the two cell lines. This study clearly demonstrates that upon surface modification palmitoyl-galactosamine remains an integral part of the formulation. Paclitaxel solubility can be improved using optimum paclitaxel/lipid phase ratios. The paclitaxel-GCM formulation recognizes asialoglycoprotein receptors over-expressed on HepG-2 cells.

Conclusions
Under our experimental conditions, the proposed paclitaxel-GCM formulation is an ideal delivery vehicle for specific targeting to liver cancer cells, which is anticipated to result in improved efficacy and reduced toxicity to normal cells.
Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin
Authors: Yang Lingling , Hao Jianrong , Zhang Jing , Xia Wenjun , Dong Xifeng , Hu Xiaoyan , Kong Feng , Cui Xing 
Published: October 2010

Abstract

Objectives
It has been hypothesized that the accumulation of beta-amyloid peptide (Aβ) in the brain is a triggering event leading to the pathological cascade of Alzheimer's disease. The steady-state levels of Aβ are determined by the metabolic balance between anabolic and catabolic activity and the dysregulation of this activity leads to Alzheimer's disease. Recent evidence has shown that neprilysin (NEP) is the rate-limiting enzyme in the Aβ degradation in the brain. Ginseng, the root of Panax ginseng C.A. Meyer, is widely used as a tonic for the prevention and treatment of age-related disorders in China. We aimed to investigate the basis of this use.

Methods
In this study, we investigated the effect of ginsenoside Rg3, one of the major active components of ginseng, on the metabolism of Aβ40 and Aβ42 in SK-N-SH cells transfected with Swedish mutant β-amyloid precursor protein (SweAPP).

Results
The ELISA result showed that Rg3 significantly reduced the levels of Aβ40 and Aβ42, 19.65 ± 6.05%, 23.61 ± 6.74%, respectively (P &lt; 0.01). The Western blot analysis showed that Rg3 reduced the levels of Aβ40 and Aβ42 through enhancing NEP gene expression, and real-time PCR assay showed that 50 μM Rg3 could significantly enhance NEP gene expression (2.9 fold at 48 h).

Conclusions
Our findings suggest that the Rg3 compound of ginseng may be useful for treating patients suffering with Alzheimer's disease.
Effects of anticancer agents and scavengers on CMV-promoter-driven exogenous gene expression in genetically modified cells
Authors: Kinoshita Atsushi , Kobayashi Daisuke , Saitoh Yukiya , Komada Fusao 
Published: October 2010

Abstract

Objectives
This study aimed to investigate whether the levels of rsGFP mRNA and the fluorescence levels of cytomegalovirus (CMV)-promoter-driven rsGFP (red-shifted green fluorescent protein) could be changed by using anticancer agents and also to examine the effects of co-treatment with anticancer agents and scavengers.

Methods
The pQBI25 vector, which encodes the CMV promoter and the cDNA for rsGFP, was transfected into FR cells (rat skin fibroblast cell line). FR-pQBI25 cells were then exposed to doxorubicin, 5-fluorouracil, methotrexate or paraquat with or without scavengers such as N-acetyl cysteine (NAC) and edaravone for 48 h.

Key findings
The levels of rsGFP mRNA were found to be significantly higher following doxorubicin, 5-fluorouracil and paraquat treatment but were not changed by methotrexate. These levels of rsGFP mRNA were found to be significantly lower after paraquat/edaravone co-treatment compared with paraquat alone. The fluorescence levels of rsGFP were found to be significantly higher following doxorubicin and paraquat treatment but were not changed by 5-fluorouracil and methotrexate. The levels were also found to be significantly lower after paraquat/edaravone co-treatment compared with paraquat alone and also after doxorubicin/NAC co-treatment compared with doxorubicin alone.

Conclusions
These findings suggest that CMV-promoter-driven exogenous gene expression may be partly regulated by reactive oxygen species.
Metabolism of two new benzodiazepine-type anti-leishmanial agents in rat hepatocytes and hepatic microsomes and their interaction with glutathione in macrophages
Authors: Thi M Dao Duong , Grant M Helen , Mullen Alexander B , Tettey Justice N A , MacKay Simon P , Clark Rachel L 
Published: October 2010

Abstract

Objectives
To measure the metabolism and toxicity of 7-chloro-4-(cyclohexylmethyl)-1-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (BNZ-1) and 4-cyclohexylmethyl-1-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (BNZ-2), two new benzodiazepine analogues found to be effective against Leishmania amastigotes in vitro.

Methods
The metabolism of BNZ-1 and -2 was investigated in isolated rat hepatocytes and rat liver microsomes. The toxicity of the compounds was assessed in a murine macrophage cell line by determining cell viability and reduced glutathione (GSH) content. The metabolism and toxicity of flurazepam was assessed for comparison.

Key findings
BNZ-1 and BNZ-2 underwent similar metabolic transformations by the liver systems, forming N-demethylated and hydroxylated metabolites, with subsequent O-glucuronidation. Flurazepam and both analogue compounds depleted macrophage GSH levels without affecting cell viability at the concentrations used (up to 100 μM), but only flurazepam inhibited glutathione reductase activity, indicating that it is acting by a different mechanism.

Conclusions
The exact mechanism responsible for GSH depletion is unknown at present. Further experiments are needed to fully understand the effects of BNZs on the parasite GSH analogue, trypanothione, which may be a direct or indirect target for these agents. Pharmacokinetic evaluation of these compounds is required to further progress their development as potential new treatments for leishmaniasis.
The sacred lotus (Nelumbo nucifera)– phytochemical and therapeutic profile
Authors: Mukherjee Pulok K , Mukherjee Debajyoti , Maji Amal K , Rai S , Heinrich Michael 
Published: October 2010

Abstract

Objectives
Nelumbo nucifera Gaertn. (Nymphaeaceae), also known as sacred lotus, is a well known medicinal plant. This article reviews the traditional uses, phytochemistry and therapeutic reports on different parts of N. nucifera viz. the seeds, rhizomes, leaves and flowers. This review also describes various compounds isolated from different parts of this plant and the therapeutic benefits derived from those phytoconstituents.

Key findings
There are several therapeutic benefits of this plant for which different parts are used. The extracts of rhizomes, seeds, flowers and leaves have been reported to have varied therapeutic potential. Several bioactive compounds have been derived from these plant parts belonging to different chemical groups, including alkaloids, flavonoids, glycosides, triterpenoid, vitamins etc., which all have their own therapeutic impact. Thus, the pharmacological effects and various active ingredients of different parts of N. nucifera are well understood.

Summary
In this review we explore the current pharmaceutical, phytochemical and pharmacological knowledge about this well known plant species as well as several emerging aspects for research on N. nucifera.
A study on the effect of inorganic salts in transungual drug delivery of terbinafine
Authors: Nair Anroop B , Sammeta Srinivasa M , Vaka Siva Ram K , Murthy S Narasimha 
Published: October 2010

Abstract

Objectives
The poor success rate of topical therapy in nail disorders is mainly because of the low permeability of keratinized nail plates. This can be overcome by utilizing potent perungual drug penetration enhancers that facilitate the drug permeation across the nail plate. This study evaluated the efficacy of inorganic salts in enhancing the trans-nail permeation using a model potent antifungal agent, terbinafine hydrochloride.

Methods
Permeation studies were carried out across human cadaver nail in a Franz diffusion cell using terbinafine solution (1 mg/ml; pH 3). Preliminary studies were carried out to assess the effect of salts (0.5 m) on the terbinafine permeation into and through the nail. Further, the influence of salt concentration (0.25–3 m) on permeation, the mechanism for the enhancement and the suitability of developing a formulation were also studied.

Key findings
Terbinafine permeation (3–5 fold) through the nail and drug load (4–7 fold) in the nail were enhanced significantly when salts were used at 0.5 m concentration. Increase in salt concentration up to 1 m increased the permeation, which decreased with further increase in salt concentration (&gt;1 m). Mechanistic studies revealed that the enhanced permeation by salts was mainly due to their ability to increase the nail hydration and also to increase the thermodynamic activity of the drug. The cumulative amount of terbinafine permeated at 24 h from the formulated gel (9.70 ± 0.93 μg/cm2) was comparable with that of a solution (11.45 ± 1.62 μg/cm2).

Conclusions
Given the promising results from the permeation and drug load studies, it was concluded that inorganic salts could be used as potent transungual permeation enhancers.
Effects of concurrent administration of nevirapine on the disposition of quinine in healthy volunteers
Authors: Soyinka Julius O , Onyeji Cyprian O , Omoruyi Sharon I , Owolabi Adegbenga R , Sarma Pullela V , Cook James M 
Published: October 2010

AbstractObjectivesNevirapine and quinine are likely to be administered concurrently in the treatment of patients with HIV and malaria. Both drugs are metabolised to a significant extent by cytochrome P450 (CYP)3A4 and nevirapine is also an inducer of this enzyme. This study therefore evaluated the effect of nevirapine on the pharmacokinetics of quinine.MethodsQuinine (600 mg single dose) was administered either alone or with the 17th dose of nevirapine (200 mg every 12 h for 12 days) to 14 healthy volunteers in a crossover fashion. Blood samples collected at predetermined time intervals were analysed for quinine and its major metabolite, 3-hydroxquinine, using a validated HPLC method.Key findingsAdministration of quinine plus nevirapine resulted in significant decreases (P &lt; 0.01) in the total area under the concentration–time curve (AUCT), maximum plasma concentration (Cmax) and terminal elimination half-life (T1/2β) of quinine compared with values with quinine dosing alone (AUC: 53.29 ± 4.01 vs 35.48 ± 2.01 h mg/l; Cmax: 2.83 ± 0.16 vs 1.81 ± 0.06 mg/l; T1/2β: 11.35 ± 0.72 vs 8.54 ± 0.76 h), while the oral plasma clearance markedly increased (11.32 ± 0.84 vs 16.97 ± 0.98 l/h). In the presence of nevirapine there was a pronounced increase in the ratio of AUC(metabolite)/AUC (unchanged drug) and highly significant increases in Cmax and AUC of the metabolite (P &lt; 0.01).ConclusionsNevirapine significantly alters the pharmacokinetics of quinine. An increase in the dose of quinine may be necessary when the drug is co-administered with nevirapine.
Discrepancies between predicted and observed rates of intravenous gentamicin delivery for neonates
Authors: Sherwin Catherine M T , McCaffrey Frances , Broadbent Roland S , Reith David M , Medlicott Natalie J 
Published: October 2010

Abstract

Objectives
This study aimed to investigate intravenous infusions as used in the neonatal intensive care setting, to determine the effect of gentamicin dose (mg), gentamicin concentrations (mg/ml), flow rate (ml/h) and flush volume (ml) upon the length of infusion time.

Methods
Intravenous infusions were set up to simulate administration of gentamicin to neonates. Dextrose (10%, w/v) was administered as the primary intravenous fluid at 3.8 or 18.7 ml/h. Gentamicin doses (0.5 mg/0.2 ml, 2 mg/0.2 ml, 2.5 mg/1.0 ml, or 10 mg/1.0 ml) were delivered into the intravenous line at a T-connection using a Graseby pump over 35 min. This was followed by a saline flush of 1 or 2 ml over a further 35 min. At the end of each experiment a 2 ml 0.9% saline bolus was given. Analysis of gentamicin collected at 5-min intervals was by an HPLC method.

Key findings
The experiment demonstrated that under the infusion conditions neonates weighing 2.5 kg would receive only 80% of the drug at 60 min, increasing to 90–95% by 75 min. In extremely low birth weight neonates (0.5 kg), even lower percentage of gentamicin recovery occurred. At 60 min only 60% of the intended gentamicin dose had been delivered and this increased to only 70% by 75 min.

Conclusions
The delivery of gentamicin administered by intravenous infusion is substantially extended in extremely low birth weight neonates. This appeared to be primarily due to the small volumes and low infusion rates used in these patients.