bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling Global and Regional Net Primary Production under Elevated Atmospheric CO2: On a Potential Source of Uncertainty
Authors: El Maayar Mustapha , Ramankutty Navin , Kucharik Christopher J. 
Published: January 2006

AbstractTerrestrial ecosystem models are built, among several reasons, to explore how the Earth’s biosphere responds to climate change and to the projected continual increase of atmospheric CO2 concentration. Many of these models adopt the Farquhar et al. approach, in which leaf carbon assimilation of C3 plants is regulated by two limitations depending on the rate of Rubisco activity and ribulose-1, 5-bisphosphate regeneration (RuBP). This approach was expanded upon by others to include a third limitation that expresses the occurrence, in some plant species, of a photosynthetic downregulation under high concentrations of ambient CO2. Several ecosystem models, however, constrain leaf photosynthesis using only two limitations according to the original formulation of Farquhar et al. and thus neglect the limitation that represents the downregulation of photosynthesis under elevated atmospheric CO2. In this study, the authors first reviewed the effect of elevated CO2 on photosynthesis of C3 plants, which illustrated that short-term observations are likely to considerably underestimate the number of plant species that exhibit a photosynthetic downregulation. Several recent long-term field observations have shown that such downregulation starts to be effective only after several seasons/years of plant exposure to elevated CO2. Second, an ecosystem model was used to illustrate that neglecting the photosynthetic downregulation may significantly bias predictions of net primary production of the middle and high latitudes under high atmospheric CO2 concentrations. Based on both review of field observations and results of simulations, the authors conclude that a more appropriate representation of plant physiology and choice of plant functional types may be required in ecosystem models in order to accurately simulate plant responses to changing environmental conditions.
Long-Term Risk of Cardiovascular Disease in 5-Year Survivors of Testicular Cancer
Authors: van den Belt-Dusebout Alexandra W. , Nuver Janine , de Wit Ronald , Gietema Jourik A. , ten Bokkel Huinink Wim W. , Rodrigus Patrick T.R. , Schimmel Erik C. , Aleman Berthe M.P. , van Leeuwen Flora E. 
Published: January 2006

Purpose To evaluate the long-term risk of cardiovascular disease (CVD) in survivors of testicular cancer (TC). Patients and Methods We compared CVD incidence in 2,512 5-year survivors of TC, who were treated between 1965 and 1995, with general population rates. Treatment effects on CVD risk were quantified in multivariate Cox regression analysis. Results After a median follow-up of 18.4 years, 694 cardiovascular events occurred, including 141 acute myocardial infarctions (MIs). The standardized incidence ratio (SIR) for coronary heart disease was 1.17 (95% CI, 1.04 to 1.31), with 14 excess cases per 10,000 person-years. The SIR for MI was significantly increased in nonseminoma survivors with attained ages of less than 45 (SIR = 2.06) and 45 to 54 years (SIR = 1.86) but significantly decreased for survivors with attained ages of 55 years or older (SIR = 0.53). In Cox analysis, mediastinal irradiation was associated with a 3.7-fold (95% CI, 2.2- to 6.2-fold) increased MI risk compared with surgery alone, whereas infradiaphragmatic irradiation was not associated with an increased MI risk. Cisplatin, vinblastine, and bleomycin (PVB) chemotherapy (CT) was associated with a 1.9-fold (95% CI, 1.7- to 2.0-fold) increased MI risk, and bleomycin, etoposide, and cisplatin (BEP) CT was associated with a 1.5-fold (95% CI, 1.0- to 2.2-fold) increased CVD risk and was not associated with increased MI risk (hazard ratio = 1.2; 95% CI, 0.7 to 2.1). Recent smoking was associated with a 2.6-fold (95% CI, 1.8- to 3.9-fold) increased MI risk. Conclusion Nonseminomatous TC survivors experience a moderately increased MI risk at young ages. Physicians should be aware of excess CVD risk associated with mediastinal radiotherapy, PVB CT, and recent smoking. Intervention in modifiable cardiovascular risk factors is especially important in TC survivors. Whether BEP treatment increases CVD risk should be evaluated after more prolonged follow-up.
Comparison Between Patients With Philadelphia-Positive Chronic Phase Chronic Myeloid Leukemia Who Obtained a Complete Cytogenetic Response Within 1 Year of Imatinib Therapy and Those Who Achieved Such a Response After 12 Months of Treatment
Authors: Iacobucci Ilaria , Rosti Gianantonio , Amabile Marilina , Poerio Angela , Soverini Simona , Cilloni Daniela , Testoni Nicoletta , Abruzzese Elisabetta , Montefusco Enrico , Ottaviani Emanuela , Iuliano Francesco , Russo Domenico , Gobbi Marco , Alimena Giuliana , Martino Bruno , Terragna Carolina , Pane Fabrizio , Saglio Giuseppe , Baccarani Michele , Martinelli Giovanni 
Published: January 2006

Purpose Imatinib mesylate is a potent inhibitor of BCR-ABL, the constitutively active tyrosine kinase protein critical for the pathogenesis of chronic myeloid leukemia. Patients and Methods We reviewed 284 patients with late chronic-phase Philadelphia chromosome (Ph) –positive chronic myeloid leukemia treated with imatinib 400 mg daily after interferon-α failure. In a retrospective study, we evaluated the pattern and rapidity of the response to imatinib, comparing the cytogenetic and molecular responses, progression-free and overall survival rates in patients who obtained a complete cytogenetic response within 1 year of treatment (early responders), and in patients where a complete cytogenetic response was detected after 12 months (late responders). Results After 3 or 4 years of treatment, the molecular response of the late cytogenetic responders was similar to that of the early cytogenetic responders. At 36 months of treatment the amount of residual disease measured by standardized quantitative reverse-transcriptase polymerase chain reaction was 0.00047 in late responders versus 0.00022 in early responders, and at 48 months it was 0.00019 versus 0.00026 (median values, P value = nonsignificant). The estimated 4-year progression-free survival rate was 88% for early responders and 100% for late responders, while the estimated 4-year overall survival rates were 92% and 100% for early and late responders, respectively. Conclusion The sensitivity and the response (cytogenic and molecular) to imatinib may require 1 year or more. Long-term follow-up results continue to improve in terms of rates and durability of the complete cytogenetic response, major or complete molecular response, and progession-free and overall survival.
Phase II Study of Temozolomide and Thalidomide in Patients With Metastatic Neuroendocrine Tumors
Authors: Kulke Matthew H. , Stuart Keith , Enzinger Peter C. , Ryan David P. , Clark Jeffrey W. , Muzikansky Alona , Vincitore Michele , Michelini Ann , Fuchs Charles S. 
Published: January 2006

Purpose Standard, intravenous chemotherapy regimens for neuroendocrine tumors have been associated with limited response rates and significant toxicity. We evaluated the efficacy of an oral regimen of temozolomide and thalidomide in patients with metastatic carcinoid, pheochromocytoma, or pancreatic neuroendocrine tumors. Patients and Methods Twenty-nine patients were treated with a combination of temozolomide, administered at a dose of 150 mg/m2 for 7 days, every other week, and thalidomide at doses of 50 to 400 mg daily. Patients were followed for evidence of toxicity, biochemical response, radiologic response, and survival. Results Treatment with temozolomide and thalidomide was associated with an objective biochemical (chromogranin A) response rate of 40%, and a radiologic response rate of 25% (45% among pancreatic endocrine tumors, 33% among pheochromocytomas, and 7% among carcinoid tumors). The median duration of response was 13.5 months, 1-year survival was 79%, and 2-year survival was 61%. The median administered dose of temozolomide was 150 mg/m2, and the median administered dose of thalidomide was 100 mg daily. Grade 3-4 toxicities were uncommon, with the exception of grade 3-4 lymphopenia, which developed in 69% of the patient population. Opportunistic infections occurred in three patients (10%) during the time of lymphopenia, and included single cases of Pneumocystis carinii pneumonia, disseminated varicella zoster virus, and herpes simplex virus. Conclusion Orally administered temozolomide and thalidomide seems to be an active regimen for the treatment of neuroendocrine tumors. In this 29-patient study, this regimen appeared more active in pancreatic endocrine tumors than in carcinoid tumors.
Astragalus-Based Chinese Herbs and Platinum-Based Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Meta-Analysis of Randomized Trials
Authors: McCulloch Michael , See Caylie , Shu Xiao-juan , Broffman Michael , Kramer Alan , Fan Wei-yu , Gao Jin , Lieb Whitney , Shieh Kane , Colford John M. 
Published: January 2006

PurposeSystemic treatments for advanced non–small-cell lung cancer have low efficacy and high toxicity. Some Chinese herbal medicines have been reported to increase chemotherapy efficacy and reduce toxicity. In particular, Astragalus has been shown to have immunologic benefits by stimulating macrophage and natural killer cell activity and inhibiting T-helper cell type 2 cytokines. Many published studies have assessed the use of Astragalus and other Chinese herbal medicines in combination with chemotherapy. We sought to evaluate evidence from randomized trials that Astragalus-based Chinese herbal medicine combined with platinum-based chemotherapy (versus platinum-based chemotherapy alone) improves survival, increases tumor response, improves performance status, or reduces chemotherapy toxicity.MethodsWe searched CBM, MEDLINE, TCMLARS, EMBASE, Cochrane Library, and CCRCT databases for studies in any language. We grouped studies using the same herbal combinations for random-effects meta-analysis.ResultsOf 1,305 potentially relevant publications, 34 randomized studies representing 2,815 patients met inclusion criteria. Twelve studies (n = 940 patients) reported reduced risk of death at 12 months (risk ratio [RR] = 0.67; 95% CI, 0.52 to 0.87). Thirty studies (n = 2,472) reported improved tumor response data (RR = 1.34; 95% CI, 1.24 to 1.46). In subgroup analyses, Jin Fu Kang in two studies (n = 221 patients) reduced risk of death at 24 months (RR = 0.58; 95% CI, 0.49 to 0.68) and in three studies (n = 411) increased tumor response (RR = 1.76; 95% CI, 1.23 to 2.53). Ai Di injection (four studies; n = 257) stabilized or improved Karnofsky performance status (RR = 1.28; 95% CI, 1.12 to 1.46).ConclusionAstragalus-based Chinese herbal medicine may increase effectiveness of platinum-based chemotherapy when combined with chemotherapy. These results require confirmation with rigorously controlled trials.
Phase I Trial and Pharmacokinetic Study of the Farnesyltransferase Inhibitor Tipifarnib in Children With Refractory Solid Tumors or Neurofibromatosis Type I and Plexiform Neurofibromas
Authors: Widemann Brigitte C. , Salzer Wanda L. , Arceci Robert J. , Blaney Susan M. , Fox Elizabeth , End David , Gillespie Andrea , Whitcomb Patricia , Palumbo Joseph S. , Pitney Aaron , Jayaprakash Nalini , Zannikos Peter , Balis Frank M. 
Published: January 2006

PurposeThis pediatric phase I trial of tipifarnib determined the maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of tipifarnib in children with refractory solid tumors and neurofibromatosis type 1 (NF1) –related plexiform neurofibromas.Patients and MethodsTipifarnib was administered twice daily for 21 days, repeated every 28 days starting at 150 mg/m2/dose (n = 4), with escalations to 200 (n = 12), 275 (n = 12), and 375 (n = 6) mg/m2/dose. The MTD was also evaluated on a chronic continuous dosing schedule (n = 6). Pharmacokinetic sampling was performed for 36 hours after the first dose and peripheral-blood mononuclear cells (PBMCs) were collected at baseline and steady state for determination of farnesyl protein transferase (FTase) activity and HDJ-2 farnesylation.ResultsTwenty-three solid tumor and 17 NF1 patients were assessable for toxicity. The MTD was 200 mg/m2/dose, and dose-limiting toxicities on cycle 1 were myelosuppression, rash, nausea, vomiting, and diarrhea. The 200 mg/m2/dose was also tolerable on the continuous dosing schedule. Cumulative toxicity was not observed in the 17 NF1 patients who received a median of 10 cycles (range, 1 to 32 cycles). The plasma pharmacokinetics of tipifarnib were highly variable but not age dependent. At steady state on 200 mg/m2/dose, FTase activity was 30% compared with baseline, and farnesylation of HDJ-2 was inhibited in PBMCs.ConclusionOral tipifarnib is well tolerated in children receiving the drug twice daily for 21 days and a continuous dosing schedule at 200 mg/m2/dose, which is equivalent to the MTD in adults. The pharmacokinetic profile of tipifarnib in children is similar to that in adults, and at the MTD, FTase is inhibited in PBMC in vivo.
Characterization of pilocarpine-loaded chitosan/Carbopol nanoparticles
Authors: Kao Huei-Jen , Lo Yu-Li , Lin Hong-Ru , Yu Shi-Ping 
Published: January 2006

Abstract
Patients using ophthalmic drops are faced with frequent dosing schedules and difficult drop instillation. Therefore, a long-lasting pilocarpine-loaded chitosan (CS)/Carbopol nanoparticle ophthalmic formulation was developed. The physicochemical properties of the prepared nanoparticles were investigated using dynamic light scattering, zeta-potential, transmission electron microscopy, Fourier transform infrared ray spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The sustained-release effects of pilocarpine-loaded nanoparticles were evaluated using in-vitro release and in-vivo miotic tests, and compared with pilocarpine in solution, gel and liposomes. We found that the prepared nanoparticles were about 294 nm in size. DSC and FT-IR studies suggested that an electrostatic interaction between CS and Carbopol contributes at least in part to the stabilization of pilocarpine/CS/Carbopol nanoparticles. When compared with pilocarpine in solution, gel or liposomes, the best slow-release profile of pilocarpine from the prepared nanoparticles occurred in a dissolution test. In the in-vivo miotic study, pilocarpine-loaded CS/Carbopol nanoparticles showed the most significant long-lasting decrease in the pupil diameter of rabbits. The advantages of CS and Carbopol are good biocompatibility, biodegradability and low toxicity. CS is also a mucoadhesive polymer. Thus, pilocarpine/CS/Carbopol nanoparticles may provide an excellent potential alternative ophthalmic sustained-release formulation of pilocarpine for clinical use. CS/Carbopol nanoparticles may also be useful for a variety of other therapeutic delivery systems.
Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice
Authors: Sumiyoshi Maho , Kimura Yoshiyuki 
Published: January 2006

AbstractThree low molecular weight chitosans (molecular weight: 21, 46 and 130 kDa) obtained by enzymatic hydrolysis of a high molecular weight chitosan (average molecular weight: 650 kDa) had low viscosity and were water-soluble. The effects of these water-soluble chitosans on pancreatic lipase (in-vitro) and the elevation of plasma triacylglycerol concentration after the oral lipid tolerance test were examined in mice. The water-soluble 46-kDa chitosan was the most effective at inhibiting pancreatic lipase activity (in-vitro) and plasma triacylglycerol elevation after the oral lipid tolerance test. Based on this result, the effects of the 46-kDa chitosan on increases in bodyweight, various white adipose tissue weights, and plasma and liver lipids were examined in mice fed a high-fat diet for 20 weeks. Water-soluble 46-kDa chitosan (300 mg kg−1, twice daily) prevented increases in bodyweight, various white adipose tissue weights and liver lipids (cholesterol and triacylglycerol) in mice fed a high-fat diet, and further increased the faecal bile acid and fat. The results suggest that the lipid-lowering effects of the 46-kDa chitosan may be mediated by increases in faecal fat and/or bile acid excretion resulting from the binding of bile acids, and by a decrease in the absorption of dietary lipids (triacylglycerol and cholesterol) from the small intestine as a result of the inhibition of pancreatic lipase activity. Water-soluble 46-kDa chitosan (100 and 300 mg kg−1, twice daily) did not cause liver damage with the elevation of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, or kidney damage with the elevation of blood nitrogen urea. It was concluded that watersoluble 46-kDa chitosan is a safe functional food.
Synthesis and binding profile of constrained analogues ofN-[4-(4-arylpiperazin-1-yl)butyl]-3-methoxybenzamides, a class of potent dopamine D3 receptor ligands
Authors: Leopoldo Marcello , Lacivita Enza , Colabufo Nicola A , Berardi Francesco , Perrone Roberto 
Published: January 2006

AbstractWe recently reported on a series of N-[4-(4-arylpiperazin-1-yl)butyl]-3-methoxybenzamides, endowed with high affinity for dopamine D3 receptors, but lacking of selectivity over D4, D2, 5-HT1A, and α1-receptors. To improve the D3-receptor affinity and selectivity, without causing a considerable increasing in the lipophilicity, the flexible butyl linker was replaced by a more conformationally constrained cyclohexyl linker. The new cis- and trans-N-[4-(4-aryl-1-piperazinyl)cyclohexyl]-3-methoxybenzamides (Aryl = 2,3-di-Cl-Ph, 2-CH3O-Ph, 4-Cl-Ph, 2,3-di-CH3-Ph) were tested in-vitro for their binding affinity for D3, D4, D2, 5-HT1A, and α1-receptors. The trans- derivatives were found to be more potent at D3 receptor than the corresponding cis- isomers, but less potent than the opened counterparts. This reflected negatively on the selectivity over the other studied receptors. Derivative trans-N-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]cyclohexyl}-3-methoxybenzamide (trans-7) showed high D3-receptor affinity (Ki = 0.18 nm) and a relevant selectivity over D4, D2, 5-HT1A, and α1-receptors (&gt;200-fold). This compound was characterized as a full agonist at D3 receptor when tested in the Eu-GTP binding assay.
In-vitro and in-vivo antitumour activity of physalins B and D from Physalis angulata
Authors: Magalhães Hemerson Iury Ferreira , Torres Márcia Rocha , Costa-Lotufo Letícia Veras , De Moraes Manoel Odorico , Pessoa Cláudia , Veras Maria Leopoldina , Pessoa Otília Deusdênia Loiola , Silveira Edilberto Rocha , Alves Ana Paula Negreiros Nunes 
Published: January 2006

Abstract
We have evaluated the in-vitro and in-vivo antitumour activity of physalin B and physalin D isolated from the aerial parts of Physalis angulata. In-vitro, both compounds displayed considerable cytotoxicity against several cancer cell lines, showing IC50 values in the range of 0.58 to 15.18 μg mL−1 for physalin B, and 0.28 to 2.43 μg mL−1 for physalin D. The antitumour activity of both compounds was confirmed in-vivo using mice bearing sarcoma 180 tumour cells. The in-vivo antitumour activity was related to the inhibition of tumour proliferation, as observed by the reduction of Ki67 staining in tumours of treated animals. Histopathological examination of the kidney and liver showed that both organs were affected by physalin treatment, but in a reversible manner. These compounds were probably responsible for the previously described antitumour activity of ethanol extracts of P. angulata, and their identification and characterization presented here could explain the ethnopharmacological use of this species in the treatment of cancer.
Effects of Ginkgo biloba extract on blood pressure and vascular endothelial response by acetylcholine in spontaneously hypertensive rats
Authors: Kubota Yoko , Tanaka Naoko , Kagota Satomi , Nakamura Kazuki , Kunitomo Masaru , Shinozuka Kazumasa , Umegaki Keizo 
Published: January 2006

Abstract
We previously demonstrated that Ginkgo biloba extract (Ginkgo) produced vasodilation via the nitric oxide pathway in aortic segments isolated from Wistar rats. In this study, we have analysed the effects of daily long-term oral Ginkgo treatment on blood pressure, vascular tone, and calcium mobilization to evaluate the clinical availability. Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were fed either a control diet or a diet containing 0.05%–0.5% Ginkgo for 30 days. Administration of Ginkgo did not change systolic blood pressure in WKY, but significantly decreased systolic blood pressure in SHR. In thoracic aortic preparations isolated from SHR, diminished relaxation in response to acetylcholine was improved by a Ginkgo-containing diet. This diet significantly decreased the EC50 value and significantly increased maximum relaxation in response to acetylcholine in SHR. In aortic segments isolated from WKY, acetylcholine-induced relaxation was not affected by a Ginkgo-containing diet. Sodium nitroprusside-induced relaxation was unchanged by a Ginkgo-containing diet in SHR and WKY. We also examined the effects of a Ginkgo-containing diet on the intracellular calcium level of aortic endothelium using a fluorescent confocal microscopic imaging system. Calcium Green 1/AM preloading indicated that acetylcholine significantly increased the endothelial intracellular calcium level. The Ginkgo-containing diet significantly enhanced this increase in the aortic endothelium of SHR, but did not change that of WKY. The results suggested that Ginkgo enhanced endothelium-dependent vasodilation and elevation of the endothelial intracellular Ca2+ level in SHR, resulting in hypotension. This accelerative effect of Ginkgo on Ca2+ mobilization seemed to be associated with restoration of impaired dilatory function induced by acetylcholine in endothelial cells.
Protective effects of Swertia longifolia Boiss. and its active compound, swerchirin, on paracetamol-induced hepatotoxicity in mice
Authors: Sadeghi Zhina , Elmi Sara , Elmi Azadeh , Ghazi-Khansari Mahmoud , Hajimehdipoor Homa , Amanzadeh Yaghoub , Sadat-Ebrahimi Seyyed-Esmaeal 
Published: January 2006

Abstract
Aerial parts of Swertia longifolia Boiss. (Gentianaceae), which grows in the north of Iran, were screened for hepatoprotective activity against paracetamol (acetaminophen)-induced hepatotoxicity in Swiss mice. Pretreatment with total plant extract and swerchirin, the major component of the plant, significantly reduced the elevation of biochemical parameters, AST (aspartate aminotransferase), ALT (alanine aminotransferase) and ALP (alkaline phosphatase), the enzymes that are increased by liver damage (P &lt; 0.001). Our results indicated that total plant extract and swerchirin were hepatoprotective in the range of 6–50 mg kg−1 orally.