bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model
Authors: Sreemantula Satyanarayana , Nammi Srinivas , Kolanukonda Rajabhanu , Koppula Sushruta , Boini Krishna M 
Published: January 2005

Abstract
Background
The aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity.

Methods
For the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals.

Results
Daily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner.

Conclusion
The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders.
Differential effects of IL-10 on prostaglandin H synthase-2 expression and prostaglandin E2 biosynthesis between spleen and bone marrow macrophages
Authors: Shibata Yoshimi , Nishiyama Akihito , Ohata Hiroyoshi , Gabbard Jon , Myrvik Quentin N , Henriksen Ruth Ann 
Published: January 2005

AbstractDifferent populations of mononuclear phagocytes (MØ) show considerable diversity of cellular function including prostaglandin E2 (PGE2) biosynthesis. Certain bacterial components enhance PGE2 biosynthesis differentially in selected populations of MØ. Interleukin (IL)-10 is proposed to inhibit modulation of PGE2 biosynthesis by down-regulating prostaglandin G/H synthase-2 (PGHS-2) expression. To assess whether IL-10 regulates PGE2 biosynthesis and PGHS-2 expression, splenic and bone marrow MØ were isolated from IL-10-deficient (IL-10−/−), C57Bl/6 [wild-type (WT) control], and Balb/c (comparison control) mice and were treated with lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) as a model of bacterial inflammation. LPS-induced PGHS-2 expression was similar for splenic MØ isolated from the three strains of mice. However, PGE2 released by LPS-treated splenic MØ was significantly higher in IL-10−/− and Balb/c than in WT cells. In the presence of LPS and IFN-γ, PGHS-2 expression and PGE2 release by IL-10−/− and Balb/c splenic MØ were enhanced compared with stimulation with LPS alone or IFN-γ alone. However, there was no significant increase in PGE2 release from WT splenic MØ treated with LPS plus IFN-γ despite increased PGHS-2 expression. In sharp contrast, PGHS-2 expression and PGE2 release by bone marrow MØ were greatly enhanced in IL-10−/− cells compared with control cells. Our results indicate that IL-10 regulation of MØ PGE2 biosynthesis and PGHS-2 expression is compartment-dependent and that PGE2 production is not linked directly to PGHS-2 levels. Furthermore, our findings emphasize strain-specific differences between C57Bl/6 and Balb/c mice, and Balb/c appears more similar to the IL-10−/− than to the C57Bl/6 with respect to prostanoid production.
Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis
Authors: Popat S. , Hubner R. , Houlston R.S. 
Published: January 2005

Purpose A number of studies have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Although many have reported a better survival with MSI, estimates of the hazard ratio (HR) among studies differ. To derive a more precise estimate of the prognostic significance of MSI, we have reviewed and pooled data from published studies. Methods Studies stratifying survival in CRC patients by MSI status were eligible for analysis. The principal outcome measure was the HR. Data from eligible studies were pooled using standard techniques. Results Thirty-two eligible studies reported survival in a total of 7,642 cases, including 1,277 with MSI. There was no evidence of publication bias. The combined HR estimate for overall survival associated with MSI was 0.65 (95% CI, 0.59 to 0.71; heterogeneity P = .16; I2 = 20%). This benefit was maintained restricting analyses to clinical trial patients (HR = 0.69; 95% CI, 0.56 to 0.85) and patients with locally advanced CRC (HR = 0.67; 95% CI, 0.58 to 0.78). In patients treated with adjuvant fluorouracil (FU) CRCs with MSI had a better prognosis (HR = 0.72; 95% CI, 0.61 to 0.84). However, while data are limited, tumors with MSI derived no benefit from adjuvant FU (HR = 1.24; 95% CI, 0.72 to 2.14). Conclusion CRCs with MSI have a significantly better prognosis compared to those with intact mismatch repair. Additional studies are needed to further define the benefit of adjuvant chemotherapy in locally advanced tumors with MSI.
Randomized Phase II Study of Two Doses of Gefitinib in Hormone-Refractory Prostate Cancer: A Trial of the National Cancer Institute of Canada-Clinical Trials Group
Authors: Canil C.M. , Moore M.J. , Winquist E. , Baetz T. , Pollak M. , Chi K.N. , Berry S. , Ernst D.S. , Douglas L. , Brundage M. , Fisher B. , McKenna A. , Seymour L. 
Published: January 2005

Purpose Overexpression of the epidermal growth factor receptor has been demonstrated in advanced prostate cancer and is associated with a poor outcome. A multi-institutional, randomized, phase II study was undertaken by the National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of two doses of oral gefitinib in patients with minimally symptomatic, hormone-refractory prostate cancer (HRPC). Patients and Methods Between July and November 2001, 40 patients with HRPC and increasing prostate-specific antigen (PSA) or progression in measurable disease who had not received prior chemotherapy were randomly assigned to 250 mg (n = 19) or 500 mg (n = 21) oral gefitinib daily continuously. The primary end points were PSA response rate and objective measurable response. Functional Assessment of Cancer Therapy Prostate Cancer Subscale (FACT-P) quality-of-life questionnaires were completed at baseline and during treatment. Results None of the patients demonstrated a PSA or objective measurable response. Five (14.3%) of 35 assessable patients had stable PSA (one patient at 250 mg and four patients at 500 mg), and five patients (14.3%) had a best response of stable disease (duration, 2.5 to 16.8 months). No significant effect on the rate of increase in PSA was seen. The most common drug-related nonhematologic toxicities observed were grade 1 to 2 diarrhea (250 mg, 65%; 500 mg, 56%), fatigue (250 mg, 29%; 500 mg, 33%), and grade 1 to 2 skin rash (250 mg, 24%; 500 mg, 39%). FACT-P scores decreased during treatment, indicating worsening of symptoms compared with baseline. Conclusion Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC.
Role of Anti-Hepatitis C Virus (HCV) Treatment in HCV-Related, Low-Grade, B-Cell, Non-Hodgkin's Lymphoma: A Multicenter Italian Experience
Authors: Vallisa Daniele , Bernuzzi Patrizia , Arcaini Luca , Sacchi Stefano , Callea Vittorio , Marasca Roberto , Lazzaro Antonio , Trabacchi Elena , Anselmi Elisa , Arcari Anna Lisa , Moroni Carlo , Bertè Raffaella , Lazzarino Mario , Cavanna Luigi 
Published: January 2005

PurposeHepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated.Patients and MethodsThirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months.ResultsOf the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 ± 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response.ConclusionThis experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.
Phase I Clinical Trial of Mafosfamide in Infants and Children Aged 3 Years or Younger With Newly Diagnosed Embryonal Tumors: A Pediatric Brain Tumor Consortium Study (PBTC-001)
Authors: Blaney Susan M. , Boyett James , Friedman Henry , Gajjar Amar , Geyer Russ , Horowtiz Marc , Hunt Daniel , Kieran Mark , Kun Larry , Packer Roger , Phillips Peter , Pollack Ian F. , Prados Michael , Heideman Richard 
Published: January 2005

Purpose A phase I trial of intrathecal (IT) mafosfamide was performed to determine the optimal dose, dose-limiting toxicities, and incidence and severity of other toxicities when administered in association with concomitant multiagent systemic chemotherapy to children younger than 3 years with newly diagnosed embryonal tumors. Patients and Methods Twenty-five assessable patients received IT mafosfamide at one of six dose levels ranging from 5 mg to 17 mg. Patients were premedicated with dexamethasone (0.15 mg/kg) and morphine (0.1 mg/kg) before receiving IT mafosfamide. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. Results Irritability, presumably secondary to pain or headache during mafosfamide administration, was dose limiting in two of three patients at the 17-mg dose level. The maximum-tolerated dose of IT mafosfamide following premedication with dexamethasone and morphine was 14 mg. Conclusion The maximum tolerated dose and recommended phase II dose of IT mafosfamide in patients younger than 3 years with newly diagnosed embryonal CNS tumors is 14 mg. A trial to assess the efficacy of regional therapy with IT mafosfamide administered with intensive systemic chemotherapy in children younger than 3 years with primary intracranial embryonal tumors is now in progress.
Advanced-Stage Large-Cell Lymphoma in Children and Adolescents: Results of a Randomized Trial Incorporating Intermediate-Dose Methotrexate and High-Dose Cytarabine in the Maintenance Phase of the APO Regimen: A Pediatric Oncology Group Phase III Trial
Authors: Laver Joseph H. , Kraveka Jacqueline M. , Hutchison Robert E. , Chang Myron , Kepner James , Schwenn Molly , Tarbell Nancy , Desai Sunil , Weitzman Sheila , Weinstein Howard J. , Murphy Sharon B. 
Published: January 2005

Purpose The Pediatric Oncology Group adopted a histology-based approach to non-Hodgkin's lymphoma and treated patients with advanced large-cell lymphoma on a separate protocol (doxorubicin, vincristine, prednisone, 6-mercaptopurin, and methotrexate; APO regimen). In this study, we assessed the effects of an intense antimetabolite therapy alternating with APO on overall survival (OS) and event-free survival (EFS) and looked into biologic correlates. Patients and Methods From December 1994 to April 2000, we enrolled 180 eligible pediatric patients with stage III/IV large-cell lymphoma (LCL); 90 patients were randomly assigned to the intermediate-dose methotrexate (IDM) and high-dose cytarabine (HiDAC) arm, 85 patients to the APO arm, and five patients directly to the APO arm by study design due to CNS involvement. Planned therapy duration was 12 months. Results The 4-year EFS for all patients was 67.4% (SE, 4.2%), and OS was 80.1% (SE, 3.6%) without any significant difference between the two arms. The 4-year EFS and OS were 71.8% (SE, 6.1%) and 88.1% (SE, 4.4%), respectively, for patients with anaplastic large-cell lymphoma, and 63.8% (SE, 10.3%) and 70.3% (SE, 9.0%), respectively, for patients with diffuse large B-cell lymphoma. Only 11 patients required radiation (due to unresponsive bulky disease or CNS involvement). The IDM/HiDAC arm was associated with more toxicity. Conclusion The efficacy of incorporating IDM/HiDAC in the treatment plan of pediatric and adolescent patients with advanced-stage LCL was inconclusive as to its effect on EFS, regardless of the lymphoma phenotype. It cannot be excluded that with a higher number of patients, one treatment could prove superior and future studies will build on these data.
Platinum-Etoposide Chemotherapy in Elderly Patients With Small-Cell Lung Cancer: Results of a Randomized Multicenter Phase II Study Assessing Attenuated-Dose or Full-Dose With Lenograstim Prophylaxis—A Forza Operativa Nazionale Italiana Carcinoma Polmonare and Gruppo Studio Tumori Polmonari Veneto (FONICAP-GSTPV) Study
Authors: Ardizzoni Andrea , Favaretto Adolfo , Boni Luca , Baldini Editta , Castiglioni Federico , Antonelli Paola , Pari Franca , Tibaldi Carmelo , Altieri Alfonso M. , Barbera Sante , Cacciani Giancarlo , Raimondi Mario , Tixi Lucia , Stefani Micaela , Monfardini Silvio , Antilli Antonio , Rosso Riccardo , Paccagnella Adriano 
Published: January 2005

Purpose Small-cell lung cancer (SCLC) is increasingly diagnosed in elderly patients, who are at higher risk of treatment-related morbidity and mortality. We conducted a randomized two-stage phase II study to assess the therapeutic index of two different platinum/etoposide regimens, attenuated-dose (AD) and full-dose (FD) plus prophylactic lenograstim. Patients and Methods SCLC patients older than 70 years were randomized to receive four courses of cisplatin 25 mg/m2 on days 1 and 2, and etoposide 60 mg/m2 on days 1, 2, and 3 every 3 weeks (AD); or cisplatin 40 mg/m2 on days 1 and 2, and etoposide 100 mg/m2 on days 1, 2, and 3 every 3 weeks, plus lenograstim 5 mg/kg days 5 through 12, every 3 weeks (FD). A combined primary end point named therapeutic success (TS), which took into account activity, toxicity, and compliance, was used. Results Ninety-five patients were enrolled. Seventy-five percent and 72% of the patients in the AD and FD arms, respectively, completed the treatment as per protocol. Response rate was 39% and 69% in the AD and FD arms, respectively, and 1-year survival probability was 18% and 39%, respectively. Treatment was well tolerated in both groups, with no grade 3 to 4 myelotoxicity in the AD arm, and 12% myelotoxicity in the FD arm. Overall, the observed TSs were 10 (36%) of 28 patients and 42 (63%) of 67 patients for AD and FD treatments, respectively. Conclusion In elderly patients with SCLC a full-dose cisplatin/etoposide regimen combined with prophylactic lenograstim is active and feasible, while attenuated doses of the same regimen are associated with a poor therapeutic outcome.
Quality-of-Life Assessment in the Symptom Management Trials of the National Cancer Institute-Supported Community Clinical Oncology Program
Authors: Buchanan David R. , O'Mara Ann M. , Kelaghan Joseph W. , Minasian Lori M. 
Published: January 2005

Purpose To examine how quality of life (QOL) is prospectively conceptualized, defined, and measured in the symptom management clinical trials supported by the National Cancer Institute Community Clinical Oncology Program (CCOP). Methods All QOL research objectives, rationales, assessment instruments, symptoms treated, and types of interventions from the CCOP symptom management portfolio of clinical trials were extracted and analyzed. Results QOL assessments were proposed in 68 (52%) of the 130 total CCOP symptom management trials initiated since 1987. A total of 22 global QOL instruments were identified. Both the frequency of symptom management trials and the frequency of QOL assessment have increased significantly over time. The Functional Assessment of Cancer Therapy and Uniscale instruments were the most widely used QOL instruments, included in 55% of trials assessing QOL. The conceptual framework for QOL inclusion was limited to univariate relationships between symptom relief and global improvements in QOL. No consistent associations were found between QOL assessment and either the symptoms targeted or types of interventions. Conclusion To advance the state of the science, research protocols need to provide more explicit rationales for assessing QOL in symptom management trials and for the selection of the QOL instrument(s) to be used. Conceptual frameworks that specify the hypothesized links between the specific symptom(s) being managed, interactions with other symptoms, different domains of QOL, and global QOL also need to be more precisely described. Methodologic and conceptual advances in QOL symptom management trials are critical to fulfill the promise of alleviating suffering and improving the QOL of cancer patients.
Chronic Cocaine Administration Switches Corticotropin-Releasing Factor2Receptor-Mediated Depression to Facilitation of Glutamatergic Transmission in the Lateral Septum
Authors: Liu Jie , Yu Baojian , Orozco-Cabal Luis , Grigoriadis Dimitri E. , Rivier Jean , Vale Wylie W. , Shinnick-Gallagher Patricia , Gallagher Joel P. 
Published: January 2005

Corticotropin-releasing factor (CRF) and urocortin (Ucn I) are endogenous members among a family of CRF-related peptides that activate two different and synaptically localized G-protein-coupled receptors, CRF1and CRF2. These peptides and their receptors have been implicated in stress responses and stress with cocaine abuse.In this study, we observed significant alterations in excitatory transmission and CRF-related peptide regulation of excitatory transmission in the lateral septum mediolateral nucleus (LSMLN) after chronic cocaine administration. In brain slice recordings from the LSMLN of control (saline-treated) rats, glutamatergic synaptic transmission was facilitated by activation of CRF1receptors with CRF but was depressed after activation of CRF2receptors with Ucn I. After acute withdrawal from a chronic cocaine administration regimen, CRF1activation remained facilitatory, but CRF2activation facilitated rather than depressed LSMLN EPSCs. These alterations in CRF2effects occurred through both presynaptic and postsynaptic mechanisms. In saline-treated rats, CRF1and CRF2coupled predominantly to protein kinase A signaling pathways, whereas after cocaine withdrawal, protein kinase C activity was more prominent and likely contributed to the CRF2-mediated presynaptic facilitation. Neither CRF nor Ucn I altered monosynaptic GABAA-mediated IPSCs before or after chronic cocaine administration, suggesting that loss of GABAA-mediated inhibition could not account for the facilitation. This switch in polarity of Ucn I-mediated neuromodulation, from a negative to positive regulation of excitatory glutamatergic transmission after chronic cocaine administration, could generate an imbalance in the brain reward circuitry associated with the LSMLN.
The Rates of the Elementary Reactions of NH(a1Δ) with NH3(X̃) and HN3(X̃). The Temperature Dependences
Authors: Adam L. , Hack W. , Olzmann Matthias 
Published: January 2005

Abstract
The reactions NH(a) + HN3(X̃) → prod. (1)
and NH(a) + NH3(X̃) → prod. (2)
were studied in a quasi-static reaction cell in the temperature range 293 ≤ T/K ≤ 501 at a pressure of 10 mbar and 20 mbar, respectively, with He as the main carrier gas. The electronically excited reactant NH(a) was generated by laser-flash photolysis of HN3, at λ = 308 nm and detected by laser-induced fluorescence (LIF). Also the ground state species NH(X) was detected by LIF.
From the measured concentration-time profiles of NH(a) under pseudo-first order conditions, the rate coefficients k
1(T) and k
2(T) were obtained.
For the rate coefficient k
1 a positive temperature dependence was observed:

k
1(T) = (8.1 ± 0.5) × 1013 exp[(−0.76 ± 0.05)/RT] cm3/mol s
with a small activation energy of E
A = 0.76 kJ/mol.
For reaction (2) the rate coefficient

k
2(T) = (8.6 ± 0.6) × 1013 (T/298)−(0.6 ± 0.1) cm3/mol s
with a negative temperature dependence was measured indicating that the intermediate N2H4, which decomposes to 2 NH2, is formed without a barrier.
The rate of the quenching channel
NH(a) + NH3 → NH(X) + NH3 (2q)
has the same temperature dependence as the rate of the overall reaction (2). The contribution k
2

q
/k
2 = 0.008 over the temperature range 293 ≤ T/K ≤ 501.