bluuebunny/crossref_metadata_2025 huggingface dataset:
The plasma pharmacokinetics and cerebral spinal fluid penetration of intravenous topiramate in newborn pigs
Authors: Galinkin Jeffrey L. , Kurth C. Dean , Shi Heng , Priestley Margaret A. , Loepke Andreas W. , Adamson Peter C.
Published: July 2004

Introduction—Pre‐clinical studies suggest that the anticonvulsant topiramate confers neurologic protection against ischemia. An intravenous formulation of topiramate has been developed for administration during conditions such as hypoxia‐ischemia when enteral absorption may be unpredictable. The plasma pharmacokinetics, cerebrospinal fluid (CSF) penetration and pharmacodynamics of intravenous topiramate were studied in an established piglet model of hypoxia‐ischemia.

Methods—The plasma pharmacokinetics of topiramate were studied in a group of chronically instrumented conscious piglets (n = 8), and in a group of piglets following an episode of hypoxia‐ischemia (n = 8). These groups were divided into equal dose cohorts in which two doses of intravenously administered topiramate, 5 and 40 mg/kg, were studied. The animals' heart rate, arterial pressure and EEG were monitored. Plasma for topiramate concentration was sampled for up to 26 h. A single CSF topiramate concentration was determined 1 h following drug administration. Topiramate was quantified using a specific LC/MS assay.

Results—The animals tolerated intravenous topiramate well, with no significant changes in physiologic and neurologic parameters. Plasma topiramate concentrations following an intravenous dose were best described by a bi‐exponential equation, with a mean clearance of 39±18 ml/h/kg, and a terminal half‐life of 14.3 (range 7.5–48.1) h. A dose of 5 mg/kg was sufficient to maintain plasma drug concentrations greater than 10 µM for 24 h. CSF topiramate concentration at 1 h was 12±1 µM and 109±26 µM at the 5 and 40 mg/kg doses, respectively.

Conclusion—Topiramate administered intravenously was well tolerated. Slow clearance of the drug allowed for maintenance of potential neuroprotective concentrations following a single dose of drug for 24 h. High drug penetration into the CSF is an ideal pharmacologic characteristic of any potential neuroprotective agent. The pharmacokinetic profile of intravenously administered topiramate, including its penetration into the CSF, appears to achieve this goal. Copyright © 2004 John Wiley & Sons, Ltd.
Prognostic value of age and sex in early gastric cancer
Authors: Bando E , Kojima N , Kawamura T , Takahashi S , Fukushima N , Yonemura Y
Published: July 2004

Background

The need for lymph node dissection in early gastric cancer (EGC) is controversial. The present study investigated the possibility of planning treatment for EGC according to age and sex rather than node status.

Methods

Overall survival rate and cause of death were analysed according to age (5-year increments) and sex in 4231 patients with EGC. Cox proportional hazard regression analyses were used to identify the most valuable predictor.

Results

In patients with EGC 5- and 10-year cancer-specific survival rates were 98·4 and 96·3 per cent respectively, whereas corresponding overall survival rates were 90·2 and 80·9 per cent. The critical age for determining prognosis was 70 years for men (χ2 = 131·34, P < 0·001) and 75 years for women (χ2 = 64·35, P < 0·001). For both sexes, the 10-year overall survival rate was less than 30 per cent in patients over 80 years old. Multivariate Cox stepwise regression analysis identified age as the most powerful prognostic indicator in EGC. The rate of death from causes unrelated to the tumour increased significantly with age, whereas that from recurrence was not affected by age.

Conclusion

Age is a better prognostic indicator than node status in both men and women with EGC. Age and sex should be taken into account as well as conventional clinicopathological variables related to lymph node metastases when determining appropriate therapy for EGC.
Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma
Authors: Poon R T P , Ho J W Y , Tong C S W , Lau C , Ng I O L , Fan S-T
Published: July 2004

Background

Vascular endothelial growth factor (VEGF) and endostatin stimulate and inhibit tumour angiogenesis respectively. Recent studies have demonstrated the prognostic value of serum levels of both VEGF and endostatin in patients with various types of cancer. Their significance in patients with hepatocellular carcinoma (HCC) remains unclear.

Methods

Serum VEGF and endostatin levels were measured by enzyme immunoassay in 108 patients with HCC before surgical resection and in 20 healthy controls. Preoperative serum VEGF and endostatin levels were correlated with clinicopathological features and long-term survival.

Results

Serum VEGF levels in patients with HCC were significantly higher than those in controls, but serum levels of endostatin were similar in the two groups. High serum levels of VEGF, but not endostatin, were significantly associated with venous invasion and advanced tumour stage. Patients with a serum VEGF level higher than median (over 245·0 pg/ml) had significantly worse overall and disease-free survival than those with a lower level (P = 0·012 and P = 0·022 respectively). On multivariate analysis, serum VEGF level was an independent prognostic factor (hazard ratio 1·86 (95 per cent confidence interval 1·10 to 3·92); P = 0·032). Serum endostatin levels did not have significant prognostic influence on overall or disease-free survival.

Conclusion

A high serum level of VEGF is a predictor of poor outcome after resection of HCC. Serum VEGF, but not endostatin, may be a useful prognostic marker in patients with HCC.
A fully automated amino acid analyzer using NBD‐F as a ﬂuorescent derivatization reagent
Authors: Aoyama Chiaki , Santa Tomofumi , Tsunoda Makoto , Fukushima Takeshi , Kitada Chieko , Imai Kazuhiro
Published: July 2004

A fully automated amino acid analyzer using NBD‐F (4‐ﬂuoro‐7‐nitro‐2,1,3‐benzoxadiazole) as a ﬂuorescent derivatization reagent was developed. The whole analytical process was fully automated from derivatization, injection to HPLC separation and quantitation. The derivatization reaction conditions were re‐evaluated and optimized. Amino acids were derivatized by NBD‐F for 40 min at room temperature in the borate buffer (pH 9.5). The derivatives were separated within 100 min and ﬂuorometrically detected at 540 nm with excitation at 470 nm. The detection limits for amino acids were in the range of 2.8–20 fmol. The calibration curves were linear over the range of 20 fmol to 20 pmol on column with the correlation coefﬁcients of 0.999. The coefﬁcients of variation were less than 5% at 3 pmol injection for all amino acids. Amino acids in rat plasma were determined by the proposed HPLC method. Copyright © 2004 John Wiley & Sons, Ltd.
Evaluation of 3‐hydroxy‐3‐methylglutaryl‐COA‐reductase, cholesterol‐7α‐hydroxylase and acyl‐COA:cholesterol acyltransferase activities: alternative chromatographic methods to separate metabolites
Authors: Montoudis Alain , Boileau Serge , Simoneau Lucie , Mounier Catherine , Lafond Julie
Published: July 2004

Alternative HPLC and solid‐phase extraction column methods were developed to separate metabolites of enzymes involved in cholesterol metabolism in rabbit liver microsomes: hydroxyl‐methylglutaryl‐CoA reductase, cholesterol‐7α‐hydroxylase and acyl‐CoA:cholesterol acyltransferase. A comparison method of thin‐layer chromatography and solid‐phase extraction column were assayed to separate substrate and metabolite of hydroxy‐methylglutaryl‐CoA reductase, whereas for cholesterol‐7α‐hydroxylase and acyl‐CoA:cholesterol acyltransferase, this comparison was done between thin layer chromatography and HPLC. The results obtained by the new analytical chromatographic methods are not signiﬁcantly different than those observed in literature. Moreover a larger percentage recovery was obtained for analysed metabolites. Our results demonstrate the reliability of these alternative chromatographic techniques and showed that they are valuable tools to precisely and rapidly measure the activity of those enzymes. Copyright © 2004 John Wiley & Sons, Ltd.
Inﬂuence of the sample preparation method on the serotonin determination in plasma and platelets
Authors: Morgadinho Maria T. , Fontes Ribeiro C. A. , Macedo Tice R. A.
Published: July 2004

Plasma or platelet serotonin concentration is commonly used to provide information about the serotonergic activity in various psychiatric or neurological diseases. Some difﬁculties have been described in the measurement of serotonin (5‐HT) levels in plasma or platelets. We describe an isocratic liquid‐chromatographic assay with amperometric detection for determination of 5‐HT in the platelet pellet and in platelet‐rich and platelet‐poor plasma (PRP and PPP) in sample sizes of 100 µL of plasma. The method uses an RP18 column and an amperometric detector with a thin‐layer type electrochemical ﬂow cell, with glassy carbon electrode maintained at a potential of +0.600 V vs an Ag/AgCl reference electrode. Determinations were performed in the presence or in the absence of plasma, since the biological matrix may affect the results. Different validation parameters were analysed: selectivity, accuracy, precision, linearity and stability. Reference values for 5‐HT concentration in healthy adults (n = 12) were 6.6 nmol/109 platelets, for the platelet pellet, and 5.5 nmol/109 platelets, for PRP. The 100 µL sample volume used for the preparation of PPP did not make possible the determination of 5‐HT levels with accuracy and precision. Copyright © 2004 John Wiley & Sons, Ltd.
Simultaneous determination of D‐ and L‐serine in rat brain microdialysis sample using a column‐switching HPLC with ﬂuorimetric detection
Authors: Fukushima Takeshi , Kawai Junko , Imai Kazuhiro , Toyo'oka Toshimasa
Published: July 2004

Both d‐ and l‐serine in rat brain microdialysis sample were simultaneously determined by pre‐column ﬂuorescence derivatization with 4‐ﬂuoro‐7‐nitro‐2,1,3‐benzoxadiazole (NBD‐F), separation of the derivatives on ODS column, TSKgel ODS‐80TsQA, followed by Pirkle type chiral columns, Sumichiral OA‐2500 (S), which gave a sufﬁcient enantiomeric separation of NBD–d‐serine and NBD‐l‐serine, and ﬂuorimetric detection at a wavelength of 540 nm with an excitation wavelength of 470 nm. The peaks of NBD–d‐serine and NBD–l‐serine in the rat brain microdialysis sample were clearly found, and the validation study showed satisfactory results; the precision and accuracy were within 5.14 and 109%, respectively. Using the proposed HPLC method, the time‐course proﬁle of d‐serine concentration in rat prefrontal cortex following intraperitoneal administration of d‐serine was investigated. As a consequence, d‐serine appeared to be rapidly distributed in the brain, and then decreased gradually with time in the extracellular ﬂuid of the rat prefrontal cortex. The proposed HPLC method will be useful for in vivo studies on d‐serine, which acts as a coagonist for N‐methyl‐d‐aspartate receptor, to the extracellular ﬂuid of rat brain. Copyright © 2004 John Wiley & Sons, Ltd.
Separation and determination of two sesquiterpene lactones in Radix inulae and Liuwei Anxian San by microemulsion electrokinetic chromatography
Authors: Gao Wenhua , yaowen Chen , Yin Yegao , Chen Xingguo , Hu Zhide
Published: July 2004

A novel microemulsion electrokinetic chromatography (MEEKC) method for separating and determining two sesquoterpene lactones, alantolactone (AL) and isoalantolactone (IAL), in Radix inulae and Liuwei Anxian San has been developed. The effects of several important factors such as internal organic phases, concentration of microemusion, concentration of acetonitrile, injection time and running voltage were systematically investigated to determine the optimum conditions. The optimum microemulsion system was composed of n‐hexane (0.32% w/w), SDS (1.24% w/w), 1‐butanol (2.64% w/w), acetonitrile (10% w/w) and 10 mm sodium tetraborate buffer (85.80% w/w, pH 9.2). The applied voltage was 20 kV. The analytes were detected at 214 nm. Regression equations revealed linear relationships (correlation coefﬁcients 0.9950 for AL and 0.9946 for IAL) between the peak area of each analyte and the concentration. The limits of detection (deﬁned as a signal‐to‐noise ratio of about 3) were approximately 0.45 µg/mL for AL and 0.56 µg/mL for IAL. The levels of the analytes were successfully determined with recoveries ranging from 98.2 to 104.3%. Furthermore, a simple and effective extraction method, with methanol in an ultrasonic water bath for 60 min, was used for sample preparing. Also, MEEKC was compared with micellar electrokinetic chromatography (MEKC) and shown better separation results. Copyright © 2004 John Wiley & Sons, Ltd.
Direct determination of S‐(−)‐ and R‐(+)‐propranolol glucuronide in rat hepatic microsomes by RP‐HPLC
Authors: Yu Lushan , Luan Lianjun , Shao Qing , Zeng Su
Published: July 2004

Propranolol, available commercially as a racemic mixture, is a non‐selective β‐adrenergic blocking agent used in the treatment of hypertension, angina pectoris and cardic arrhythmias. We have developed and validated an RP‐HPLC assay method for direct determination of R‐(+)‐ and S‐(−)‐propranolol glucuronide in rat hepatic microsomes to investigate the enantioselectivity of propranolol glucuronidation metabolism. A baseline separation of propranolol glucuronide enantiomers was achieved on a 5 µm reversed‐phase ODS column, with a mixture of phosphate buffer (pH 3.5, 0.067 mol/L) and methanol (55:45, v/v) as mobile phase. Ultraviolet detection was set at 220 nm, and p‐nitrobenzoic acid was used as internal standard. The standard curve of assay for R‐(+)‐ and S‐(−)‐propranolol glucuronide in spiked microsomal incubate showed good linearity throughout the concentration range from 0.50 to 20.0 µmol/L. The analytical method affords average recovery of 99.8 and 100.1% for R‐(+)‐ and S‐(−)‐propranolol glucuronide, respectively. The method provides a high sensitivity and good precision for R‐(+)‐ and S‐(−)‐propranolol glucuronide (RSD < 10%). The LOD was 0.15 µmol/L and the LOQ was 0.5 µmol/L (RSD < 8%, n = 5) for both R‐(+)‐ and S‐(−)‐propranolol glucuronide. The method is simple, precise and accurate, and is suitable for quantifying the propranolol glucuronides enantiomers in rat hepatic microsomes. Copyright © 2004 John Wiley & Sons, Ltd.
Diastereoselective Remote CH Activation by Hydroboration
Authors: Varela Jesús A. , Peña Diego , Goldfuss Bernd , Denisenko Dmitri , Kulhanek Jiri , Polborn Kurt , Knochel Paul
Published: July 2004

Hydroboration of tetrasubstituted or trisubstituted alkenes with BH3 and subsequent thermolysis allows remote diastereoselective CH activation of neighboring aryl rings. Tetrasubstituted and trisubstituted 1,1‐diphenylethylene derivatives undergo a highly stereoselective 1,2‐rearrangement followed by remote CH activation to lead, after oxidative workup, to a diol in which the relative stereochemistry of two stereocenters has been controlled. The mechanism of this remote activation has been studied and extended to related molecules that undergo this stereoselective CH activation, namely alkenylbiphenyl systems or alkenes with only one phenyl ring, such as alkenylbenzenes, or bicyclic systems. We have shown that this reaction allows diastereoselective synthesis of molecules with up to three contiguous chiral centers.
Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S.
Authors: Yuan Jian‐Min , Govindarajan Sugantha , Arakawa Kazuko , Yu Mimi C.
Published: July 2004

BACKGROUND

Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse.

METHODS

A population‐based, case–control study of HCC was conducted during 1984–2002. The study involved 295 HCC cases and 435 age‐, gender‐, and race‐matched control subjects among Hispanic and non‐Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in‐person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers.

RESULTS

Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17–909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7–5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6–4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6–5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9–7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7–6.9).

CONCLUSIONS

Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Cancer 2004. © 2004 American Cancer Society.
Prospective validation of serum CYFRA 21‐1, β‐2‐microglobulin, and ferritin levels as prognostic markers in patients with nonmetastatic nasopharyngeal carcinoma undergoing radiotherapy
Authors: Ma Brigette B. Y. , Leungm Sing F. , Hui Edwin P. , Mo Frankie , Kwan Wing H. , Zee Benny , Yuen Joyce , Chan Anthony T. C.
Published: July 2004

BACKGROUND

Patients with undifferentiated nasopharyngeal carcinoma (NPC) have elevated serum levels of CYFRA 21‐1 (CYFRA), ferritin, and β‐2‐microglobulin (β2M) compared with healthy control individuals. The prognostic value of these markers has never been validated prospectively.

METHODS

Paired serum samples from 160 patients with newly diagnosed, nonmetastatic, undifferentiated NPC were collected before radiotherapy (RT) and at 4–6 weeks after the completion of RT. Pre‐RT and post‐RT levels of serum CYFRA, ferritin, and β2M were analyzed and correlated with overall survival (OS), progression‐free survival (PFS), time to locoregional recurrence, (TLR) and time to distant recurrence (TDR). The results of pre‐RT and post‐RT plasma Epstein–Barr virus (EBV) DNA levels available from a previous study were included in a Cox regression model together with age, tumor (T) classification, and lymph node (N) classification.

RESULTS

Sixty percent of patients had International Union Against Cancer Stage III–IV disease. At a median follow‐up of 116 weeks (range, 37–239 weeks), 38 patients had disease progression. On multivariate analysis, pre‐RT CYFRA and post‐RT EBV DNA levels were independent predictors of poor OS, post‐RT EBV DNA level and N classification predicted poor PFS and TDR; and only T classification predicted TLR. Patients who had pre‐RT CYFRA levels ≥ 1.5 U/mL were more likely to die (hazard ratio, 1.18; 95% confidence interval, 1.10–1.26) compared with patients who had pre‐RT CYFRA levels < 1.5 U/mL. There were no associations between age, post‐RT CYFRA levels and pre‐RT or post‐RT serum ferritin and β2M levels, and the survival and recurrence rates on multivariate analysis.

CONCLUSIONS

Serum CYFRA levels taken before RT predicted reduced survival in patients with nonmetastatic, undifferentiated NPC who underwent RT. Cancer 2004. © 2004 American Cancer Society.
Prognostic impact ofTP53mutation status for adult patients with supratentorial World Health Organization Grade II astrocytoma or oligoastrocytoma
Authors: Ständer Marko , Peraud Aurelia , Leroch Barbara , Kreth Friedrich W.
Published: July 2004

BACKGROUND

The goal of the current study was to retrospectively assess the prognostic impact ofTP53mutation status and P53 expression/accumulation on long‐term outcome for adult patients with supratentorial World Health Organization (WHO) Grade II astrocytoma or oligoastrocytoma.

METHODS

The authors revisited a previously published short‐term data set containing information on 159 consecutive patients who were treated between 1991 and 1998. Each patient was screened forTP53mutations and P53 overexpression/accumulation. The reference point for all analyses was the date of surgical treatment, and the date of last follow‐up examination was August 2002. Overall survival, progression‐free survival, postrecurrence survival, and time to malignant transformation were estimated using the Kaplan–Meier method, and potential prognostic factors were evaluated using the multivariate proportional hazards model.

RESULTS

The median follow‐up duration for survivors was 80.4 months (standard deviation, 33.0 months).TP53mutations, which were present in 49.1% of all tumors, occurred preferentially in gemistocytic tumors (P< 0.05). In addition, theTP53status of the primary tumor was predictive of theTP53status of the recurrent tumor in all cases of disease recurrence. The 5‐year overall and progression‐free survival rates were 77.5% and 43.2%, respectively, and the risk of malignant transformation at 5 years postsurgery was 32.7%. Unfavorable prognostic factors with respect to survival duration included older age (≥ 50 years;P< 0.002), gemistocytic subtype (P< 0.01), and positiveTP53mutation status (P< 0.05), all of which were also negatively associated with progression‐free survival (P< 0.05,P< 0.001, andP< 0.003, respectively). In contrast, positiveTP53mutation status was the only significant predictor of a reduction in time to malignant transformation (P< 0.03). P53 overexpression/accumulation did not exhibit prognostic relevance in any of the multivariate models constructed in the current study.

CONCLUSIONS

TP53mutations are common early events in the pathogenesis of WHO Grade II astrocytoma or oligoastrocytoma. In the current study, positiveTP53mutation status (but not P53 overexpression/accumulation) was found to be an independent unfavorable predictor of survival, progression‐free survival, and time to malignant transformation. The therapeutic implications of these findings have yet to be determined. Cancer 2004. © 2004 American Cancer Society.
Prevalence of vitamin B12 deficiency in patients with plasma cell dyscrasias
Authors: Baz Rachid , Alemany Carlos , Green Ralph , Hussein Mohamad A.
Published: July 2004

BACKGROUND

To the authors' knowledge, the prevalence of vitamin B12 deficiency among patients with plasma cell dyscrasias (PCD) is largely unknown. Identifying this vitamin deficiency in such patients could help improve their anemia and increase their tolerance to potentially neurotoxic agents.

METHODS

The authors retrospectively reviewed the charts and laboratory results of 664 consecutive patients diagnosed with PCD who had their vitamin B12 and folate status evaluated between 1997 and 2001 at the Cleveland Clinic Multiple Myeloma Research Program. The patients were screened for vitamin B12 deficiency using serum vitamin B12 and methylmalonic acid.

RESULTS

Of the 664 patients whose medical charts were reviewed, information on vitamin B12 status was available for 522 patients (78%). Among these 522 patients, 71 (13.6%) had laboratory‐defined vitamin B12 deficiency and the remaining 451 patients (86.4%) did not. On univariate analysis, vitamin B12 deficiency correlated with immunoglobulin A (IgA) PCD (P = 0.04), higher mean corpuscular volume (P = 0.008), and longer follow‐up (P = 0.048). In a covariate adjusted model, only the presence of IgA PCD was associated with an increased prevalence of vitamin B12 deficiency (P = 0.003).

CONCLUSIONS

Vitamin B12 deficiency was prevalent in patients with PCD, especially in patients with the IgA subtype. Serum vitamin B12 measurements should be part of the initial evaluation and subsequent workups for anemia in patients with PCD. Cancer 2004. © 2004 American Cancer Society.
Stroke in patients with diabetes mellitus
Authors: Mankovsky Boris N. , Ziegler Dan
Published: July 2004

The article's objective is to review the key advances in the scientific literature related to the association of stroke with diabetes mellitus and to summarize the current approaches to stroke prevention in diabetic patients. The key findings from the literature regarding stroke incidence in patients with diabetes, specific and nonspecific risk factors of stroke in the diabetic population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes duration, diabetic complications, insulin resistance/hyperinsulinemia, course and outcome of stroke in subjects with diabetes and/or hyperglycemia, and the peculiarities of type, site and size of stroke in diabetic patients are discussed. The results of recent clinical trials aimed at correcting hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with diabetes, are reviewed. The medical database Medline along with original articles from peer‐reviewed journals were used for analysis.

There is convincing evidence suggesting that diabetes mellitus represents a strong independent risk factor of stroke. The contribution of hyperglycemia to increased stroke risk is not proven. Data suggest an association of the full cluster of the insulin resistance syndrome and stroke. Diabetes is a risk factor mainly for ischemic stroke, while its association with hemorrhagic stroke remains controversial. Hyperglycemia is common in stroke patients, but it is not known whether it independently influences the course and outcome of stroke or merely reflects stroke severity and location. Aggressive control of arterial hypertension and dyslipidemia allows to decrease the risk of stroke in diabetic patients substantially, while the importance of glucose control for stroke prevention remains unproven. Copyright © 2004 John Wiley & Sons, Ltd.
Regulatory gamma delta T cells in Heymann nephritis express an invariant Vγ6/Vδ1 with a canonical CDR3 sequence
Authors: Wu Huiling , Knight John F. , Alexander Stephen I
Published: July 2004

γδ T cells are expanded in human IgA nephropathy and in a rat model of adriamycin (ADR)‐induced nephropathy. Despite different diseases and species, these renal γδ T cells use a restricted set of γδ T cell receptor (TCR) genes. To explore whether this phenomenon of post injury expansion of γδ T cells occurs in autoimmune‐mediated glomerulonephritis, we studied γδ TCR genes in Heymann nephritis (HN). γδ T cells were increased in HN kidneys (p<0.001). These γδ T cells predominantly expressed Vγ6/Vδ1 genes and used canonical matching sequences previously seen in the other models of renal injury. γδ T cells from the kidneys expressed high levels of TGF‐β, IL‐4 and IL‐5. The γδ T cells from both ADR‐treated and HN kidneys expressed NKG2D, the NK cell‐activating receptor. These results demonstrate that the majority of γδ T cells in the HN kidney use a canonical Vγ6/Vδ1 TCR – the γδ TCR previously described in the rat ADR‐treated kidney. The restriction in γδ TCR seen in two completely different models of kidney injury and the expression of an innate activating molecule NKG2D suggests that the γδ T cells may be responding to tissue stress from injury and producing a regulatory response.
Peritoneal and splenic B‐1 cells are separable by phenotypic, functional, and transcriptomic characteristics
Authors: Tumang Joseph R. , Hastings William D. , Bai Chunyan , Rothstein Thomas L.
Published: July 2004

B‐1 cells constitute a distinct B cell population with unique phenotypic and functional characteristics. Although the origin of B‐1 cells remains controversial, B‐1 cells in different locations are generally considered to be part of the same pool. To determine the validity of this assumption, we examined peritoneal and splenic B‐1 cells isolated by flow cytometric cell sorting from normal mice for several features. We found that splenic B‐1 cells differ from peritoneal B‐1 cells in terms of surface antigen expression, viability ex vivo, immunoglobulin secretion in vitro, stimulated cell cycle progression, and expression of Notch family, Notch‐dependent, and Notch‐associated genes. These results indicate that splenic and peritoneal B‐1 cells are not the same and thus dispute the notion that B‐1 cells are uniform, and may suggest that different subpopulations of B‐1 cells arise separately, home individually, and/or are heavily influenced by local environmental factors.
New Multifunctional Complexes [Ru(κ3‐L)(EPh3)2Cl]+ [E = P, As; L = 2,4,6‐Tris(2‐pyridyl)‐1,3,5‐triazine] Containing both Group V and Polypyridyl Ligands
Authors: Sharma Sanjeev , Chandra Manish , Pandey Daya Shankar
Published: July 2004

Synthesis, structure, reactivity and enzyme inhibitory activity of the new cationic ruthenium complexes [Ru(κ3‐L)(EPh3)2Cl]BF4 [L = 2,4,6‐tris(2‐pyridyl)‐1,3,5‐triazine (tptz); E = P (1), As (2)] and their substitution products [Ru(κ3‐tptz)(PPh3)(dtc)]Cl (3), [Ru(κ3‐tptz)(PPh3)(CN)2] (4), [Ru(κ3‐tptz)(AsPh3)(dtc)]BF4 (5), and [Ru(κ3‐tptz)(AsPh3)(CN)2] (6) are reported. The complexes were characterized by analytical and spectroscopic methods and the structures of the complexes 1, 2 and 3 determined by X‐ray diffraction studies. C−H···X (X = Cl, F and S), C−H···π and π−π interactions were observed in these complexes. Further studies indicated that the complexes [Ru(κ3‐L)(EPh3)2Cl]+ could find application as precursors in the synthesis of other ruthenium complexes or as metallo‐ligands. The complexes also interact with DNA, which was illustrated by absorption titration studies with CT‐DNA and inhibition of topoisomerase II of the filarial parasite Setaria cervi. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A novel reduction of sodium alkyl thiosulfates with InCl3(cat.)/Sm(0) system in aqueous media: Facile synthesis of disulfides
Authors: Li Pinhua , Wang Lei , Yang Yaner , Sun Xinhua , Wang Min , Yan Jincan
Published: July 2004

A novel reduction of sodium alkyl thiosulfates with InCl3(cat.)/Sm(0) system in aqueous media has been developed, which generates the corresponding disulfides in good yields. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:376–379, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20023
Synthesis and reactivity of sulfonamides containing boronate esters
Authors: He Xiao‐Feng , Zhang Haiwen , Vogels Christopher M. , Decken Andreas , Westcott Stephen A.
Published: July 2004

Sulfonamides containing pinacol protected boronate ester groups have been prepared by the addition of H2NC6H4Bpin (pin = O2C2Me4) to sulfonyl chlorides p‐RC6H4SO2Cl (R = CH3, NO2). Hydrogenation of the nitro derivatives afford the corresponding sulfanilamides without compromising the aryl‐Bpin bond. The sulfanilamides were further functionalized to afford novel platinum complexes containing boranosulfonamides. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:369–375, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20025
A straightforward synthesis of novel 4H‐thiazolo[3,2‐d][1,5]benzodiazepine derivatives
Authors: Janciene Regina , Vektariene Ausra , Stumbreviciute Zita , Kosychova Lidija , Klimavicius Algirdas , Puodziunaite Benedikta D.
Published: July 2004

The novel 4H‐thiazolo[3,2‐d][1,5]benzodiazepinium salts have been synthesized in a single step by the reaction of the variously substituted 2,3,4,5‐tetrahydro‐1,5‐benzodiazepine‐2(1H)‐thiones and bromoacetaldehyde diethyl acetal. Cyclization is obviously influenced by the nature of the substituents in the benzodiazepine system. Theoretical modeling and B3LYP DFT computational studies are presented. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:363–368, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20026
N‐ and C‐acyclic thionuleoside analogues of 1,2,3‐triazole
Authors: Al‐Masoudi Najim A. , Al‐Soud Yaseen A. , Abdul‐Zahra Asmehan
Published: July 2004

Cycloaddition of the azide derivative 5 with 1,4‐dihydroxybutyne afforded the N‐thio‐acyclic nucleoside 6, which prepared alternatively from coupling of the bromo derivative 8 with 2‐acetoxy‐ethylmercaptan. Deblocking of 6 gave the free nucleoside 7. Mesylation of 6 furnished the dimesylate 9, which gave three rearranged products 14–16 on treatment with chloride anion. These compounds might be obtained via the episulfonium ion 10, which is subjected to nucleophilic displacement and further sulfur participation. Deblocking of 14–16 afforded the free nucleoside analogues 17–19, and their structures were confirmed by COSY, ROESY, HMQC, and HMBC NMR techniques. Compound 16 was prepared alternatively from chlorination of alcohol 6 with Ph3P‐CCl4. Carbomoylation of 6 led to the carbamate 20, which gave the free nucleoside analogue 21 on deblocking. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:380–387, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20030
Synthesis, spectroscopic exploration, biocidal activities, and crystal structures of 3‐(3‐fluorophenyl)‐2‐phenylpropenoic acid and trimethyltin(IV) complex
Authors: Sadiq‐ur‐Rehman  , Ali Saqib , Parvez Masood , Mazhar M. , Badshah Amin
Published: July 2004

The ligand, 3‐(3‐fluorophenyl)‐2‐phenylpropenoic acid, [C15H11FO2] (I) was prepared by reacting equimolar amount of phenyl acetic acid with 3‐fluorobenzaldehyde (1:1) using Perkin condensation method. The trimethyltin(IV) carboxylate, [Me3SnO2FH10C15] (II) was synthesized by refluxing an equimolar (1:1) mixture of trimethyltin chloride and silver salt of the ligand acid, [C15H10FO2Ag] (Ia). The ligand and complex both were characterized by elemental analysis, IR, mass, 1H NMR, and X‐ray crystallographic data. On the basis of 1H NMR data, (2J[117/119Sn, 1H] and CSnC bond angle), it is concluded that the environment around the tin atom in solution is tetrahedral. The Infrared spectroscopic results showed that trimethyltin(IV) derivative has 5‐coordinated polymeric structure with bridging carboxylate groups in the solid state, which has been confirmed by the X‐ray crystallographic data. The crystal of ligand acid (I) is triclinic with space group Pbar1. However, the crystal of the complex (II) is monoclinic with space group C2/c. The geometry around the tin atom is distorted trigonal bipyramid with O(1) and O(2) atoms in apical positions. The ligand (I) and complex (II) were also tested for their biocidal activities. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:398–406, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20032
Heterocyclizations of hydroxyketones with two‐coordinated (trimethylsilylamino)phosphines, (Me3Si)2NPESiMe3
Authors: Petrov Petar Y. , Angelov Christo M. , Petrov Galin , Alexiev Alexi , Cavell Ronald G.
Published: July 2004

The reaction of two‐coordinated (trimethylsilylamino)phosphines (Me3Si)2NPESiMe3 1 (E = N) and 2 (E = CH) with hydroxycarbonyl compounds proceeded with four‐ or five‐member heterocyclization to yield derivatives of oxaphosphetane, oxaphospholanes, and oxaphospholes. The reaction rate depends on the structure of hydroxyketones as well as on the type of the two‐coordinated phosphorus compound in accordance with the polarity of the P=N and P=C bonds. Thus, reaction was completed in 30 min in the case of the ortho carbonyl phenoxy derivatives with the phosphine 1, but required 2 h in the case of the alkyl hydroxy carbonyls. All reactions with the phosphine 2 took about 24 h. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:413–417, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20033
SERS‐active Ag/SiO2 colloids: photoreduction mechanism of the silver ions and catalytic activity of the colloidal nanoparticles
Authors: Muniz‐Miranda Maurizio
Published: July 2004

The formation of Ag clusters on silica colloidal nanoparticles was achieved by photoreduction of silver ions with visible laser irradiation. A mechanism of this process was proposed by observing the plasmon resonance bands of the silver clusters in UV–visible absorption spectroscopy. These Ag/SiO2 colloids are SERS‐active and can be used to detect products that could be formed by heterogeneous catalytic reactions of ligands adsorbed on the colloidal surface. Copyright © 2004 John Wiley & Sons, Ltd.
Reflective learning and on‐line management education: a comparison of traditional and on‐line MBA students
Authors: Hay Amanda , Peltier James W. , Drago William A.
Published: July 2004

In recent years higher education has witnessed dramatic changes brought on by the advent of diversified forms of management education.

Advances in multi‐media and Internet technologies have generated explosive growth in on‐line learning.

The ability to engage in reflective thinking is important for managers, especially during periods of change. An important aim of management education is to develop this ability.

On‐line education has been criticized for its inability to foster critical thinking in students. A case study of an American MBA programme at the University of Wisconsin‐Whitewater is presented which compares reflective learning in on‐line and traditional classes.

Evidence is presented which dispels the myth that on‐line management education is less effective for fostering reflective thinking. The findings do suggest that reflective thinking does take different paths in on‐line versus traditional management education delivery systems.

Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of monolithic columns for HPLC
Authors: Miyabe Kanji , Guiochon Georges
Published: July 2004

Monolithic stationary phases and columns have rapidly become highly popular separation media for liquid chromatography, in spite of their recent discovery. However, their most important features have not yet been completely clarified. A complete understanding of their performance and of their intrinsic characteristics will require the systematic acquisition of many series of reliable experimental data and their consistent analysis from different points of view. Progress in their design and production requires now that the chromatographic behavior of monolithic columns be studied in close connection with their physico‐chemical and structural properties. The main goal of this review is to summarize fundamental information on some physico‐chemical and chromatographic characteristics of monolithic stationary phases and columns for RPLC. The material reviewed deals only with silica‐based monolithic columns. First, structural information on the porosities and the size of the pores in monolithic columns is reported. Second, results of chromatographic studies that deal with the characterization of monolithic columns are summarized. Third, results of detailed studies made on the adsorption equilibrium and the surface heterogeneity of monolithic stationary phases are presented. Finally, results on the mass transfer kinetics in monolithic columns derived from the applications of the classical random‐walk model and of the moment theory to a new model of the monolith are discussed.
Mass transfer characteristics of plasmids in monoliths
Authors: Zöchling Alfred , Hahn Rainer , Ahrer Karin , Urthaler Jochen , Jungbauer Alois
Published: July 2004

The hydrodynamic properties and pore‐structure of monoliths based on functionalized poly(glycidyl methacrylate‐ethylene dimethacrylate) were characterised by pulse response experiments using different probes representing a wide range of molecular mass. On a small scale, band spreading was found to be caused to the extent of more than 90% by extra‐column effects. These monoliths have large channel diameters, providing a suitable chromatography adsorbent for processing of large molecules. Dynamic and static binding capacity for plasmid DNA was investigated. For our model plasmid, consisting of 4.9 kbp, a capacity of 7 mg/mL was observed in comparison to 0.3 mg/mL for a conventional medium designed for protein separation. When plasmids were loaded on the monolith a gradual increase in pressure drop was observed. The channels filled up and the cross‐sectional area available for liquid flow decreased. Therefore, a higher pressure drop was observed during elution. This is caused by (i) shrinking of the channels as effect of the high salt concentration, (ii) high viscosity of the mobile phase due to high concentration of plasmids, and (iii) an increase of the hydrodynamic radius of the plasmid with salt concentration from 45 nm at 150 mM to 70 nm at 2 M NaCl, as measured by dynamic light scattering. These types of monoliths are considered to be the preferred adsorbents for plasmid separation.
Comparison of monolithic silica and polymethacrylate capillary columns for LC
Authors: Moravcová Dana , Jandera Pavel , Urban Jiří , Planeta Josef
Published: July 2004

Organic polymer monolithic capillary columns were prepared in fused‐silica capillaries by radical co‐polymerization of ethylene dimethacrylate and butyl methacrylate monomers with azobisisobutyronitrile as initiator of the polymerization reaction in the presence of various amounts of porogenic solvent mixtures and different concentration ratios of monomers and 1‐propanol, 1,4‐butanediol, and water. The chromatographic properties of the organic polymer monolithic columns were compared with those of commercial silica‐based particulate and monolithic capillary and analytical HPLC columns. The tests included the determination of H‐u curves, column permeabilities, pore distribution by inversed‐SEC measurements, methylene and polar selectivities, and polar interactions with naphthalenesulphonic acid test samples. Organic polymer monolithic capillary columns show similar retention behaviour to chemically bonded alkyl silica columns for compounds with different polarities characterized by interaction indices, Ix, but have lower methylene selectivities and do not show polar interactions with sulphonic acids. The commercial capillary and analytical silica gel‐based monolithic columns showed similar selectivities and provided symmetrical peaks, indicating no significant surface heterogeneities. To allow accurate characterization of the properties of capillary monolithic columns, the experimental data should be corrected for extra‐column contributions. With 0.3 mm ID capillary columns, corrections for extra‐column volume contributions are sufficient, but to obtain true information on the efficiency of 0.1 mm ID capillary columns, the experimental bandwidths should be corrected for extra‐column contributions to peak broadening.
Characterization of methacrylate monoliths for purification of DNA molecules
Authors: Benčina Mojca , Podgornik Aleš , Štrancar Aleš
Published: July 2004

The suitability of methacrylate based anion exchange monolithic supports for the separation and purification of plasmid and genomic DNA has been explored. The effect of the size of the channels, ionic strength of the solution, and ligand density on the dynamic binding capacity has been investigated. The dynamic binding capacity was found to be flow independent, at least up to a linear velocity of 700 cm h–1, and exceeded 9 mg mL–1 for all types of DNA. The recovery depends on the pH value of the mobile phase and its ionic strength as well as on the density of the active groups. Under optimal conditions recoveries exceeding 80% were obtained even for genomic DNA. Finally, the suitability of this approach is demonstrated by purification of a real‐life sample.
Rapid, low pressure, and simultaneous ion chromatography of common inorganic anions and cations on short permanently coated monolithic columns
Authors: Connolly Damian , Victory Danielle , Paull Brett
Published: July 2004

Short permanently coated reversed‐phase silica based monolithic columns have been investigated for the rapid separation of inorganic anions and cations. One 2.5×0.46 cm column was permanently coated with didodecyldimethylammonium (DDAB), for anion analysis; and a second 5.0×0.46 cm column was coated with dioctylsulphosuccinnate (DOSS), for cation analysis. The use of a single combined eluent of 2.5 mM phthalate/1.5 mM ethylenediamine, at flow rates of between 4.0 and 8.0 mL/min, resulted in the rapid separation of 8 anions (in under 100 s) and 5 cations (in under 100 s) on the above columns when used individually, with detection limits for common anions ranging from approximately 0.25 to 5 mg/L, and between 2.5 and 50 mg/L for alkaline earth metals, by direct and indirect conductivity detection, respectively. However, with both columns subsequently connected in parallel, with the eluent delivered using a flow splitter from a single isocratic pump, the simultaneous analysis of anions and cations was also possible, based on a single conductivity detector. The potential of this system for the rapid, complete screening of water samples for multiple common anions and cations is shown.
A computational study of the porosity effects in silica monolithic columns
Authors: Gzil Piotr , Vervoort Nico , Baron Gino V. , Desmet Gert
Published: July 2004

We report on a theoretical study of the influence of the through‐pore porosity on the main chromatographic performance parameters (reduced theoretical plate height, flow resistance, and separation impedance) of silica monoliths. To investigate this problem devoid of any structural uncertainties, computer‐generated structural mimics of the pore geometry of silica monolithic columns have been studied. The band broadening in these synthetic monoliths was determined using a commercial Computational Fluid Dynamics (CFD) software package. Three widely differing external porosities (ε = 0.38, ε = 0.60, and ε = 0.86) are considered and are compared on the basis of an identical intra‐skeleton diffusivity (D s = 5×10–10m2/s), internal porosity (εint = 0.5), and for the same phase retention factor (k ´ = 1.25). Since the data are obtained for perfectly ordered structures, the calculated plate heights and separation impedances constitute the ultimate performance ever to be expected from a monolithic column. It is found that, if silica monoliths could be made perfectly homogeneous, domain size‐based reduced plate heights as small as h min ≈ 0.8 (roughly independent of the porosity) and separation impedances as small as Emin ≈ 130 (ε = 0.60) and Emin ≈ 40 (ε = 0.86) should be achievable with pure water as the working fluid. The data also show that, although the domain size is a much better reduction basis than the skeleton size, the former is still not capable of bringing the van Deemter curves of different porosity columns into perfect agreement in the C term dominated velocity range. It is found that, in this range, large porosity monoliths can be expected to yield smaller domain size‐based reduced plate heights than small porosity monoliths.
Ion exchange properties of monolithic and particle type iminodiacetic acid modified silica
Authors: Sugrue Edel , Nesterenko Pavel , Paull Brett
Published: July 2004

A 10 cm silica monolith has been modified with iminodiacetic acid (IDA) groups and characterised for its selectivity toward alkali, alkaline earth, and selected transition metal cations. Physical characterisation of the modified monolith found non‐homogeneous modification along the length of the monolith, although sufficient capacity was achieved to facilitate significant retention of alkaline earth and transition/heavy metal ions over a range of eluent pH and ionic strength conditions. For alkaline earth and transition/heavy metal ions, selectivity of the 10 cm IDA monolith closely matched that seen with a 25 cm IDA modified silica gel particle packed column, although the separation of alkali metal ions was noticeably poorer on the monolithic column. Peak efficiencies for most metal ions were of a similar order for both column types, except for Zn(II), which showed significant peak broadening on the IDA monolithic column.