bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chiral aspects of the metabolism of ethosuximide
Authors: Millership Jeffrey S. , Collier Paul S. , Hamilton John T. G. , McRoberts W. Colin , Mifsud Janet 
Published: January 2005

AbstractEthosuximide is a chiral drug substance primarily indicated for the treatment of absence seizures. This drug is used clinically as the racemate. The urinary metabolites of ethosuximide (following i.p. administration of the racemate or individual enantiomers to rats) have been studied using chiral gas chromatography (GC) and gas chromatography‐mass spectroscopy (GCMS). The metabolites identified were unchanged ethosuximide enantiomers, all four stereoisomers of 2‐(1‐hydroxyethyl)‐2‐methylsuccinimide, and a single stereoisomer of 2‐ethyl‐3‐hydroxy‐2‐methylsuccinimide [derived from (R)‐ethosuximide]. Preliminary quantitative studies indicate a degree of stereoselectivity in the fate of ethosuximide since the ratio of (R)‐ to (S)‐ethosuximide in the urine was found to be 0.77:1 (0–24 h sample), 0.64:1 (24–48 h sample), and 0.83:1 (48–72 h sample). This would suggest that the (R)‐isomer is preferentially metabolised. Results obtained following the administration of individual enantiomers of ethosuximide indicate that the 2‐(1‐hydroxyethyl)‐2‐methylsuccinimide diastereoisomers derived from (R)‐ethosuximide are produced in approximately equal proportions [ratio 1.05:1 (0–24 h sample), 1.10:1 (24–48 h sample)], whilst those from (S)‐ethosuximide are produced in unequal proportions [ratio 1.65:1 (0–24 h sample), 1.74:1 (24–48 h sample)]. © 1995 Wiley‐Liss, Inc.
Solvent selectivity in chiral chromatography using a β‐cyclodextrin‐bonded phase
Authors: Piperaki Stavroula , Tsantili‐Kakoulidou Anna , Parissi‐Poulou Maria 
Published: January 2005

AbstractA β‐cyclodextrin‐bonded phase has been used to investigate the separation of the enantiomers of atenolol, oxprenolol, celiprolol, tertatolol, terbutaline, fluoxetine, norfluoxetine, and zopiclone, focusing on the importance of solvent selectivity. With cyclodextrin (CD)‐bonded phases, chiral discrimination occurs because the two enantiomers of a racemate form inclusion complexes of different strengths within the CD cavity. The organic modifier molecules tend to compete with solutes for a definite number of adsorption sites on the stationary phase. Moreover, the ternary complex formation may play an important role in chiral recognition. In this study, it was of interest to estimate the influence of mobile phase modifiers with respect to solvent type (i.e., ACN, MeOH, EtOH, THF, i‐PrOH, PrOH and t‐BuOH), size and shape, and concentration. Solvent selectivity has been investigated by using different organic modifiers in mobile phases with the same polarity, and relationships were established between the logarithm of solvent partition coefficient (log Ps) and the three most important chromatographic parameters: retention time (t), resolution (R), and enantioselectivity (α). Thus, it seems that the hydrophobicity of the organic modifier becomes one of the dominant factors affecting the inclusion process phenomena. Further, the apparent partition coefficients of the compounds under study have been determined and a comparison has been attempted regarding the degree of their enantiomeric resolution. © 1995 Wiley‐Liss, Inc.
Lack of metabolic racemisation of ropivacaine, determined by liquid chromatography using a chiral AGP column
Authors: Arvidsson Torbjörn , Bruce Heidi Forsmo , Halldin Magnus M. 
Published: January 2005

AbstractRopivacaine hydrochloride monohydrate (ropivacaine) is a new local anaesthetic agent which is administered exclusively as the (‐)‐(S)‐form. The aim of the study was to determine whether metabolic racemisation of (‐)‐(S)‐ropivacaine occurs. This was tested in man, rat, dog, and sheep after different routes of administration. The enantiomers of ropivacaine and two of the major metabolites, 3‐hydroxy‐ropivacaine and 2′,6′‐pipecoloxylidide (PPX), were determined in urine samples by liquid chromatography on a Chiral AGP column after liquid–liquid extraction. It was possible to detect <1% of the (+)‐(R)‐enantiomer of both ropivacaine and the two major metabolites. In the samples examined, no trace of metabolic racemisation was observed. In pharmacokinetic, pharmacodynamic, toxicological, and metabolic studies, therefore, nonchiral assays are considered to be adequate. © 1995 Wiley‐Liss, Inc.
Comparative toxicity of (+)‐(R)‐ and (−)‐(S)‐1,2‐dibromo‐3‐chloropropane
Authors: Kouzi Samir A. , Søderlund Erik J. , Dybing Erik , Meerman John H. N. , Nelson Sidney D. 
Published: January 2005

AbstractThe haloalkane 1,2‐dibromo‐3‐chloropropane (DBCP), an environmental pollutant that was widely used as a soil fumigant, is a carcinogen and a mutagen and displays target‐organ toxicity to the testes and the kidneys. Because little is known about effects of stereochemistry on the metabolism and toxicity of halogenated alkyl compounds and because DBCP, which has a chiral center at C‐2, may show enantioselectivity in its metabolism and/or toxicities, the optically pure enantiomers of DBCP were tested in vivo in rats for organ toxicity as well as for bacterial mutagenicity. Organ toxicity studies showed that (S)‐DBCP was slightly more renal toxic than (R)‐DBCP but was not significantly more toxic than the racemate, and that no significant differences were observed in the extents of testicular necrosis and atrophy caused by either enantiomer or the racemate. In contrast, (R)‐DBCP was more mutagenic than either (S)‐DBCP or the racemate to Salmonella typhimurium (S. typhimurium) strains TA 100 and TA104. However, there was little or no enantioselectivity in glutathione S‐transferase (GST)‐catalyzed conjugation reactions of glutathione with DBCP based on the lack of selectivity in the rates of disappearance of the enantiomers of DBCP in the presence of glutathione (GSH) and GSTs as monitored by chiral gas chromatography (GC). © 1995 Wiley‐Liss, Inc.
Determination of the enantiomers of citalopram, its demethylated and propionic acid metabolites in human plasma by chiral HPLC
Authors: Rochat B. , Amey M. , Van Gelderen H. , Testa B. , Baumann P. 
Published: January 2005

AbstractA stereoselective HPLC assay has been developed to analyze the enantiomers of citalopram and of its three main metabolites in plasma after their separation on a Chiracel OD column. Using a fluorescence detector, the limit of quantification in plasma samples was 15, 4, 5, and 2 ng/ml for the enantiomers of citalopram (CIT), desmethylcitalopram (DCIT), didesmethylcitalopram (DDCIT), and for the citalopram propionic acid derivative (CIT‐PROP), respectively. Except for CIT, all metabolites were derivatized with achiral reagents. Identification of the enantiomers was realized with an optical rotation detector which showed that the enantiomers invert their rotation depending on the polarity and nature of the solvent. Under varying conditions, a racemization study has shown that the pure enantiomers of CIT and its demethylated metabolites are configurationally stable. Preliminary results obtained with five patients treated with CIT show a mean S/R ratio of 0.7 for both CIT and its active metabolite DCIT and of 3.6 for CIT‐PROP in plasma. This suggests that the pharmacologically relevant (+)‐(S)‐isomers of CIT and DCIT could be preferentially and steroselectively metabolized to CIT‐PROP. © 1995 Wiley‐Liss, Inc.
Racemization, enantiomerization, diastereomerization, and epimerization: Their meaning and pharmacological significance
Authors: Reist Marianne , Testa Bernard , Carrupt Pierre‐Alain , Jung Martin , Schurig Volker 
Published: January 2005

AbstractThe configurational lability of enantiomers can be characterized by different terms, each defining a specific process. Racemization relates to the macroscopic and statistical process of the irreversible transformation of one of the enantiomers into the racemic mixture. Enantiomerization refers to the microscopic and molecule process of the reversible conversion of one enantiomer into the other. Methods allowing the experimental determination of rate constants of racemization (krac) and enantiomerization (kenant) are discussed, and it is shown that kenant = 1/2 krac. Neglect of this fact is a source of some confusion in the literature. When two or more elements of chirality are present in a molecule and one of them is configurationally labile, epimerization occurs, a particular case of diastereomerization. These processes of interconversion between diastereomers are kinetically more complicated than racemization and enantiomerization since the rate constants of the forward and reverse reactions are always different (kdiast/A‐to‐B ≠ kdiast/B‐to‐A), however small the difference. An important aspect of the configurational lability of stereoisomeric drugs is the time scale of the phenomenon. When interconversion occurs to a significant extent during the residence time of a drug in the body, a pharmacological time scale is implied. In contrast, the pharmaceutical time scale refers to slower rates of interconversion that affect the configurational purity of a drug during its shelf‐life. © 1995 Wiley‐Liss, Inc.
In vitro fenoprofenyl–coenzyme a thioester formation: Interspecies variations
Authors: Soraci A. , Benoit E. 
Published: January 2005

AbstractIn vitro coenzyme A thioester formation from (−)‐(R)‐fenoprofen (FPF) and palmitic acid has been studied using liver microsomes from rat, guinea pig, sheep, and dog. In every species with both palmitic acid or (−)‐(R)‐fenoprofen, the Lineweaver–Burk plot was linear in the substrate concentration range used and as a consequence agrees with the involvement of only one isoenzyme (or different isoenzymes of similar Km values). The Vmax values for the thioesterification of (−)‐(R)‐fenoprofen present large species variations from 2.1 ± 1.0 with sheep liver microsomes to 60.6 ± 11 nmol/min/mg with dog liver microsomes. These values statistically significantly correlate (r = 0.94) to the Vmax values observed when palmitic acid was used as a substrate. Furthermore palmitic acid inhibited (−)‐(R)‐fenoprofen–CoA formation in the same extent in all animal species. The stereoselectivity of the thioesterification was also species dependent. © 1995 Wiley‐Liss, Inc.
Enantioselective influence of cyclodextrins on cleavage of chiralic esters
Authors: Beyrich Thorsten , Jira Thomas , Beyer Christine 
Published: January 2005

AbstractAssessing the reactivity of optical antipodes is of central importance in drug research. Using the model of 2‐methoxy‐2‐phenylacetic acid‐4‐nitrophenylester (MPE), the rate of hydrolysis in the presence of β‐cyclodextrin (CD), hydroxyethyl‐ and hydroxypropyl‐β‐CD, as well as methyl‐β‐CD is studied photometrically and by means of HPLC (Chiralcel‐OD‐R‐column). Both β‐CD and hydroxyalkylated‐β‐CD catalyze (−)‐(R)‐enantiomers to a larger extent than (+)‐(S)‐enantiomers, resulting in an enrichment of the latter. Methyl‐β‐CD stabilizes the ester trifold, thus abolishing chiral discrimination. © 1995 Wiley‐Liss, Inc.
Bevantolol hydrochloride (nc‐1400): Absolute configuration and direct separation of the enantiomers
Authors: Yamamoto Masao , Takayanagi Yukiko , Nihashi Susumu , Nomura Yutaka , Nohira Hiroyuki 
Published: January 2005

AbstractSynthesis of (−)‐bevantolol hydrochloride from 3,4‐dimethoxyphenethylamine and (S)‐(+)‐m‐tolyl glycidyl ether derived from (R)‐(−)‐epichlorohydrin established the absolute configuration of the (+) and (−) enantiomer as R and S, respectively. The purity of the enantiomers was determines using a chiral cellulose column (CHIRALCEL OD®) which allowed direct separation of the enantiomers. A separation factor (α) of 4.20 and a resolution factor (Rs) of 9.21 were obtained. © 1995 Wiley‐Liss, Inc.
Stereoselective disposition of hydroxychloroquine and its metabolites in rats
Authors: Wei Yimin , Nygard Gloria A. , Ellertson Shari L. , Khalil Shoukry K.W. 
Published: January 2005

AbstractRacemic hydroxychloroquine‐sulfate (HCQ‐sulfate) was administered to rats orally. Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue.The metabolism of HCQ in the rats was found to be stereoselective with R/S > 1 for the drug and < 1 for the metabolites. Gender‐specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant differences between dose groups. There were no observed differences in enantiomer ratios among the blood collection times. © 1995 Wiley‐Liss, Inc.
A pilot clinical trial of vaccination with dendritic cells pulsed with autologous tumor cells derived from malignant pleural effusion in patients with late‐stage lung carcinoma
Authors: Chang Gee‐Chen , Lan Haw‐Chang , Juang Shin‐Hun , Wu Yu‐Chen , Lee Hui‐Chen , Hung Yi‐Mei , Yang Hui‐Yu , Whang‐Peng Jacqueline , Liu Ko‐Jiunn 
Published: January 2005

AbstractBACKGROUNDThe authors conducted a pilot clinical trial to explore the vaccination of patients with late‐stage lung carcinoma with dendritic cells (DCs) pulsed with necrotic tumor cells derived from malignant pleural effusion specimens, and to evaluate the antitumor immune response induced by this therapy.METHODSAutologous DCs were generated by culturing adherent mononuclear cells with interleukin‐4 and granulocyte‐macrophage–colony‐stimulating factor for 7 days. Day‐7 DCs were cocultured overnight with autologous necrotic tumor cells derived from pleural effusion specimens to allow internalization of tumor antigens. DCs were then treated with tumor necrosis factor‐alpha for 16 hours. The antigen‐loaded DCs were injected into each patient's inguinal lymph nodes under sonographic guidance. Eight patients with late‐stage nonsmall cell lung carcinoma were treated in this manner. Patients were vaccinated once weekly for 4 weeks and then boosted twice biweekly.RESULTSThe authors found that there was no Grade II/III toxicity and autoimmune response in all patients after intranodal injection of the DC vaccine. Minor to moderate increases in T‐cell responses against tumor antigens were observed after DC vaccination in six of eight patients. Five patients had progressive disease. One patient had minor tumor response and two patients had stable disease. The two patients who had longer disease control also had better T‐cell responses.CONCLUSIONSThe results indicated that it was feasible to immunize patients with lung carcinoma intranodally with DCs pulsed with necrotic tumor cells enriched from pleural effusion specimens, and this approach may generate T‐cell responses and provide clinical benefit in some patients. Cancer 2005. © 2005 American Cancer Society.
Predictors of breast conservation therapy
Authors: Hiotis Karen , Ye Wei , Sposto Richard , Skinner Kristin A. 
Published: January 2005

AbstractBACKGROUNDDespite the National Institutes of Health consensus statement in 1991 that breast‐conserving surgery (BCS) followed by radiotherapy is an appropriate approach to the treatment of early‐stage breast carcinoma, studies have shown a relatively low rate of BCS in the United States. The current study investigated predictors of breast conservation therapy in a large, diverse patient population.METHODSBetween 1990 and 1998, 43,111 patients underwent surgery for breast carcinoma and were entered into the Cancer Surveillance Program database for Los Angeles County. Of these, 29,666 (68.3%) had complete data on patient demographics, staging, surgeon, type of surgery, and hospital. Data were collected regarding extent of disease, lymph node status, tumor size, age, race, socioeconomic status (SES), surgeon specialization, surgeon volume, hospital specialization, and hospital volume. Univariate and multivariate analyses were performed.RESULTSUnivariate analysis showed that extent of disease, lymph node status, tumor size, age, race, SES, surgeon and hospital specialization, and surgeon and hospital volume all were significantly associated with surgery type (P < 0.0001). Multivariate analysis showed that not only did extent of disease impact choice of surgery, but so did race, SES, hospital volume, surgeon volume, and surgeon specialization (P < 0.0001).CONCLUSIONSThese results suggest that not only does the extent of locoregional disease play a role in the likelihood of a woman undergoing breast conservation therapy, but patient age, socioeconomic status, racial/ethnic factors, and the experience of both the surgeon and hospital have an effect. Cancer 2005. © 2005 American Cancer Society.
Phase II study of transdermal estradiol in androgen‐independent prostate carcinoma
Authors: Bland Lisa B. , Garzotto Mark , DeLoughery Thomas G. , Ryan Christopher W. , Schuff Kathryn G. , Wersinger Emily M. , Lemmon Dianne , Beer Tomasz M. 
Published: January 2005

AbstractBACKGROUNDOral estrogen therapy has activity in patients with hormone‐naive and androgen‐independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids “first pass” liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC.METHODSPatients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24‐hour patches replaced every 7 days). Serum prostate‐specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals.RESULTSThree of 24 patients (12.5%; 95% confidence interval [CI], 0–26%) had a confirmed PSA reduction > 50%. The Kaplan–Meier estimate of median time to disease progression was 12 weeks (95% CI, 4.6–19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (±95% CI) serum estradiol level increased from 17.2 pg.mL (range, 14.8–19.6 pg/mL) to 460.7 pg/mL (range, 334.6–586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed.CONCLUSIONSIn patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors. Cancer 2005. © 2005 American Cancer Society.
Split sample comparison of ThinPrep and conventional smears in endoscopic retrograde cholangiopancreatography‐guided pancreatic fine‐needle aspirations
Authors: Siddiqui Momin T. , Gokaslan Sefik T. , Saboorian M. Hossein , Ashfaq Raheela 
Published: January 2005

AbstractFine‐needle aspiration (FNA) of pancreatic lesions is a common procedure to establish a tissue diagnosis before chemotherapy or surgery. In this study, the authors attempt to compare the diagnostic value of the ThinPrep (TP) method with conventional smears (CSs) in samples obtained by endoscopic retrograde cholangiopancreatography (ERCP)‐guided pancreatic FNAs. Material obtained, prospectively, from ERCP‐guided pancreatic FNAs was split to prepare CSs (2–5 slides) first, the remainder being rinsed in PreservCyte, and in the laboratory, 1 TP slide was prepared. The diagnostic categories of unsatisfactory, benign, reactive, suspicious for malignancy, and malignant were compared. Fifty‐one pancreatic FNAs prepared by split sample method yielded the following results: TP yielded unsatisfactory, 6 cases; benign, 3 cases; reactive, 5 cases; suspicious for malignancy, 11 cases; and malignant, 26 cases; in contrast, CS yielded unsatisfactory, 13 cases; benign, 4 cases; reactive, 3 cases; suspicious for malignancy, 13 cases; and malignant, 18 cases. Histological follow‐up was available in 21 cases (reactive, 8 cases; suspicious for malignancy, 1 case, and malignant, 12 cases). The foregoing data indicate a higher sensitivity in detection of pancreatic adenocarcinoma by the TP method (TP, 91% vs. 58% CS) with equivalent specificity (100%). In addition, TP provides better preservation and cytological detail. Diagn. Cytopathol. 2005;32:70–75. © 2005 Wiley‐Liss, Inc.
Patient with immunoproliferative disease and lung carcinoma: A case report
Authors: Radman Ivo , Sučić Mirna , Serventi‐Seiwerth Ranka , Boban Dubravka , Marković‐Glamočak Mirjana , Ries Sunčica , Gjadrov‐Kuveždić Koraljka , Petković Dražen , Jakić‐Razumović Jasminka , Šćukanec‐Špoljar Mira , Seiwerth Sven , Sučić Zvonimir , Papa Jurica 
Published: January 2005

AbstractThere are a number of reports on collision occurrance of non‐hematologic cancers and Non‐Hodgin's lymphoma (NHL) and multiple myeloma. In this report we present a case of patient with immunoproliferative disease, extramedullary plasmocytoma and NHL‐lymphoplasmocytoid lymphoma (LPL) and squamous cell carcinoma of the lung. After diagnosis of extramedullary plasmocytoma cytostatic therapy was commenced and the patient was well. Five years after patient was clinically worse and diagnostic evaluation this time revealed lymphoplasmocytoid cells in bone marrow. Five months later malignant morphologically undifferentiated cells were found in bone marrow which were by immunocytochemistry established as CD38 positive. After the patient's death, disseminated NHL‐LPL and squamous cell carcinoma of lung was confirmed. In the report, we compared clinical course and diagnostic findings of our patient with literature data. We have also discussed the possible relationship of multiple B‐cell lymphoid tumors and squamous cell carcinoma concluding that multidiscplinary diagnostic tools are essential not only for carcinoma diagnosis and follow‐up, but also for further understanding of carcinogenesis. Diagn. Cytopathol. 2005;32:97–102. © 2005 Wiley‐Liss, Inc.
Unusual finding in a nipple discharge of a female dog: Dirofilariasis of the breast
Authors: Manuali E. , Eleni C. , Giovannini P. , Costarelli S. , Ciorba A. 
Published: January 2005

AbstractWe report a case of dirofilariasis of the breast occurring in a 6‐yr‐old Bernese female dog living in central Italy presenting with a breast lump, diagnosed on cytological examination of nipple secretion fluid smears. The direct smears of nipple discharge revealed clusters of glandular cells characterized by mild pleomorphic appearance and the presence of some nematodes of about 350 μm in length in the background. The smears also contained several inflammatory cells, including eosinophils. Both the Knott and the antigen tests were negative for Dirofilaria immitis. The morphological features of this round worm is compatible with that of Dirofilaria repens. The case describes an unusual finding of dirofilariasis presenting as a breast lump, simulating an inflammatory breast carcinoma. Diagn. Cytopathol. 2005;32:108–109. © 2005 Wiley‐Liss, Inc.