bluuebunny/crossref_metadata_2025 huggingface dataset:
Industry Sponsorship and Authorship of Clinical Trials Over 20 Years
Authors: Buchkowsky Susan S , Jewesson Peter J
Published: March 2004

BACKGROUND

The pharmaceutical industry has become a major source of funding for biomedical research. Our general observation is that pharmaceutical industry employees are appearing with increasing frequency as coauthors of clinical trial publications.

OBJECTIVE

To characterize clinical trial funding, reporting, and sources; investigate author—industry affiliation; and describe clinical outcome trends over time.

METHODS

We reviewed 500 randomly selected clinical trials published in 5 influential medical journals over a 20-year period (1981–2000).

RESULTS

Of the 500 clinical trials reviewed, 181 (36%) involved pharmaceutical industry as an independent (n = 104) or joint (n = 77) sponsor and 180 (36%) involved a peer-review funding source; the balance (139; 28%) lacked any declared sponsorship. The percentage of industry-sponsored clinical trials increased to 62% during 1997–2000. The percentage of nonprofit sponsored clinical trials remained constant over time, while the percentage of those without funding declaration declined. Reported author affiliation with industry increased to 66% of clinical trials sponsored only by industry. An increase in the percentage of clinical trials with reported author—industry affiliation was observed for all journals. Regardless of funding source, the majority of clinical trials reported clinical outcomes that favored the study drug.

CONCLUSIONS

Pharmaceutical industry—sponsored and mixed-funding clinical trials are common, and the relative incidence of published trials with these declared funding sources in the 5 journals reviewed has increased. Industry employees are appearing as coauthors of clinical trial publications with increasing frequency.
Pediatric Constipation Therapy Using Guidelines and Polyethylene Glycol 3350
Authors: Bell Edward A , Wall Geoffrey C
Published: March 2004

OBJECTIVE

To review current guidelines on the treatment of functional constipation in pediatric patients, with an emphasis on the role of polyethylene glycol 3350 (PEG 3350).

DATA SOURCES

Primary medical literature published in English was identified by MEDLINE search (1980—May 2003).

STUDY SELECTION AND DATA EXTRACTION

Recently published treatment guidelines relating to pediatric functional constipation and its pharmacotherapy are assessed and compared. Published trials evaluating PEG 3350 in pediatric subjects are discussed and their results applied to the clinical role and use of this new agent.

DATA SYNTHESIS

Constipation is a common disorder among children. A number of factors may play a role. A variety of medications are commonly used for this disorder, although few treatments have undergone evaluation by controlled clinical trials. Consensus guidelines recommend either osmotic laxatives, mineral oil, or their combination for maintenance treatment in concert with patient and parental education and behavioral training. PEG 3350 solution (MiraLax) has been shown in recent clinical studies to be an effective maintenance treatment for pediatric constipation.

CONCLUSIONS

PEG 3350 is an effective and well-tolerated treatment choice for pediatric constipation, especially as an adjunct to education and behavioral training. PEG 3350 is an option for children with constipation who have failed or are intolerant of other pharmacotherapies. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-016-H01
Reversible Coma Secondary to Cefepime Neurotoxicity
Authors: Abanades Sergio , Nolla Juan , Rodríguez-Campello Ana , Pedro Carme , Valls Antonio , Farré Magí
Published: March 2004

OBJECTIVE

To describe a case of cefepime neurotoxicity associated with acute renal failure that resulted in nonconvulsive status epilepticus.

CASE SUMMARY

A 66-year-old woman with acute myeloid leukemia had fever on the third day of the initial chemotherapy cycle. Empiric antibiotic treatment with cefepime 2 g every 8 hours was started; fluconazole and vancomycin were subsequently added due to the persistence of fever. Ten days after initiation of cefepime, the patient developed acute renal failure followed by altered consciousness (Glasgow coma scale 6) associated with nonconvulsive status epilepticus. Cefepime was discontinued. Epileptiform activity in the electroencephalogram disappeared with clonazepam, and the patient regained consciousness 48 hours after cefepime withdrawal.

DISCUSSION

Acute renal impairment combined with the use of cefepime may account for nonconvulsive status epilepticus. An objective causality assessment revealed that the adverse event was probably due to cefepime. Cefepime's neurotoxic effects derive from high serum concentrations resulting from decreased renal clearance, increased unbound antibiotic, and blood–brain barrier dysfunction during uremia.

CONCLUSIONS

The combination of cefepime treatment and acute renal failure may induce drug-related neurotoxicity. Nonconvulsive status epilepticus frequently passes unnoticed in severely ill patients without a history of epilepsy. This disorder should be included in the list of potential causes of coma. In this patient, early detection of nonconvulsive status epilepticus and withdrawal of the antibiotic resulted in full recovery.
Combining Quinupristin/Dalfopristin with Other Agents for Resistant Infections
Authors: Brown Jack , Freeman Burgess B
Published: March 2004

OBJECTIVE

To review the resistance mechanisms of Enterococcus and Staphylococcus spp. and summarize quinupristin/dalfopristin's (QD's) effects on these resistant organisms when combined with other antibiotics via review of the literature and unpublished data.

DATA SOURCES

Data were identified by a PubMed search (1996—May 2003) using the search terms quinupristin/dalfopristin, synergy, in vitro, in vivo, vancomycin-resistant Enterococcus faecium (VREF), methicillin-resistant Staphylococcus aureus (MRSA), and individual antibiotic names. Bibliographies of the resultant PubMed searches were reviewed and included if applicable.

STUDY SELECTION AND DATA EXTRACTION

All studies reviewed were analyzed; specific drug data were included only if clinically pertinent. In vitro data from studies with adequate design were discussed, whereas all case reports and clinical trials were utilized.

DATA SYNTHESIS

In the treatment of VREF, available information seems conflicting, although some clear differences have become apparent. QD—ampicillin and QD—doxycycline combinations have demonstrated beneficial activity, usually displaying synergistic or additive effects even in macrolide-, lincosamine-, and streptogramin-resistant (MLSB) isolates. Vancomycin and chloramphenicol have shown some efficacy, but antagonistic or null results also have been observed. Regarding MRSA, results from many studies of QD combinations have been ambiguous. More common combinations displayed synergy or additive effects against MRSA, but only QD—rifampin showed consistent beneficial activity against MRSA and MLSB isolates. Most other combinations displayed antagonism when tested in vitro.

CONCLUSIONS

Data supporting the use of various QD—antibiotic combinations against VREF and MRSA are increasing, but further in vitro and in vivo data are needed to confirm the findings.
Low-Dose Granisetron for Postoperative Nausea and Vomiting Prophylaxis
Authors: Corman Shelby L , Skledar Susan J , Ansani Nicole T
Published: March 2004

OBJECTIVE

To evaluate the use of low-dose granisetron in postoperative nausea and vomiting prophylaxis.

DATA SOURCES

Clinical trials available through PubMed and OVID (1966—July 2003), as well as information supplied by the drug manufacturer, were accessed.

DATA SYNTHESIS

Safety concerns associated with droperidol and limited availability of other agents have created a need to restructure prophylaxis guidelines for postoperative nausea and vomiting. It has recently been proposed that granisetron may be effective at a dose that is one-tenth of the Food and Drug Administration—approved dose. Conflicting evidence for this regimen is evaluated.

CONCLUSIONS

Based on the scarcity of supporting data, this regimen is not recommended for prophylaxis in patients at risk for postoperative nausea and vomiting.
Diuretic Effects of Subcutaneous Furosemide in Human Volunteers: A Randomized Pilot Study
Authors: Verma Arun K , da Silva Jack H , Kuhl David R
Published: March 2004

BACKGROUND

Furosemide is usually administered by the oral or intravenous route to cardiac patients with hypertension and heart failure, as well as edema. Occasionally, furosemide cannot be administered by these routes.

OBJECTIVE

To evaluate the diuretic/natriuretic efficacy of subcutaneously administered furosemide in healthy volunteers.

METHODS

This single-center, double-blind, placebo-controlled, randomized, crossover pilot study compared the diuretic effect of subcutaneously administered furosemide and NaCl 0.9% (placebo) in 12 healthy volunteers. The study was conducted over 5 days. Baseline values were determined on day 1. On days 3 and 5, each volunteer was injected with either furosemide 20 mg (2 mL) or 2 mL of placebo subcutaneously. A washout period occurred on day 4. Fluid and dietary intake were controlled on all 3 data collection days. Primary outcome measures consisted of urine volume voided, urine sodium concentration, onset time and volume of initial urine output, and number of voids during 8 hours of urine collection.

RESULTS

All outcomes demonstrated statistically significant differences when treatment and placebo groups were compared (p < 0.05). Adverse effects most commonly reported by the participants were minor and included transient burning and stinging at the injection site.

CONCLUSIONS

This study demonstrates that subcutaneously administered furosemide is a viable alternative when the oral or intravenous route of administration is not desirable or possible in humans. However, the results of this study need to be corroborated in various patient populations.
Interpretation of Drug Risk and Benefit: Individual and Population Perspectives
Authors: Bjornson Darrel C
Published: March 2004

OBJECTIVE

To provide pharmacists with the necessary nomenclature and tools to interpret the medical literature on drug risks and benefits.

DATA SOURCES

Primary articles were identified by MEDLINE search (1990—December 2003) and through secondary sources.

STUDY SELECTION AND DATA EXTRACTION

All of the articles identified from the data sources were evaluated, and all information from secondary sources deemed relevant was included.

DATA SYNTHESIS

Articles in the primary and secondary literature were reviewed. The articles show that measurement of drug risks and benefits is consistently reported with similar terminology. However, the interpretation and subsequent balancing of risks and benefits can be difficult.

CONCLUSIONS

All drugs have concomitant risks and benefits. The medical literature documents those risks and benefits and it is this medical evidence that is typically used to make drug therapy decisions. Pharmacists who either manage individual patients or populations of patients (pharmacy benefit managers) may interpret this medical evidence more clearly by understanding the implications of various statistical methods used in studies.
Guidelines for Acute Decompensated Heart Failure Treatment
Authors: DiDomenico Robert J , Park Hayley Y , Southworth Mary Ross , Eyrich Heather M , Lewis Richard K , Finley Jamie M , Schumock Glen T
Published: March 2004

OBJECTIVE

To describe the development of guidelines for the treatment of acute decompensated heart failure (ADHF) in the emergency department/observation unit (ED-OU) setting for hospitals that are part of a group purchasing organization (GPO).

DATA SOURCES

A MEDLINE search (1966-March 2003) using the following search terms: cardiotonic agents; diuretic; dobutamine; heart failure, congestive; milrinone; natriuretic peptide, brain; nesiritide; nitroglycerin; vasodilator agents, was conducted.

STUDY SELECTION AND DATA EXTRACTION

Relevant articles in the English language were identified. All randomized studies and meta-analyses for each category of drugs were included.

DATA SYNTHESIS

A group consensus method was used to develop guidelines. An expert panel reviewed and revised the guidelines. The final guidelines were approved June 1, 2003, and are described here. They are organized based upon a patient's symptomatology at the time the diagnosis of ADHF is made. Patients with evidence of volume overload require intravenous diuretics and/or intravenous vasodilators to alleviate the symptoms of ADHF. Patients with signs and symptoms of low cardiac output require inotropic support to manage their ADHF. A timeline for diagnosis, treatment, reassessment, and disposition is provided and encourages an early, aggressive approach to treating patients with ADHF.

CONCLUSIONS

Hospitalization for ADHF is common and costly. Consensus guidelines for the treatment of ADHF did not previously exist, resulting in inconsistent and inefficient treatment. Consequently, hospitals struggling with the treatment of ADHF may find these guidelines and the process by which they were developed useful. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-015-H01
Multigene Reverse Transcription-PCR Profiling of Circulating Tumor Cells in Hormone-Refractory Prostate Cancer
Authors: O’Hara S Mark , Moreno Jose G , Zweitzig Daniel R , Gross Steve , Gomella Leonard G , Terstappen Leon W M M
Published: March 2004

Background: Circulating tumor cells (CTCs) represent a surrogate source of tissue and conceptually represent a “real-time” biopsy. We previously reported that the number of CTCs mirrors disease progression in hormone-refractory prostate cancer (HRPC). To improve characterization of CTCs we further investigated whether in vitro transcription-based multigene reverse transcription-PCR expression profiles could be obtained from CTCs in HRPC.

Methods: We evaluated the expression of 37 genes with potential utility for epithelial cell characterization from antisense RNA libraries constructed from immunomagnetically enriched CTCs from 7.5-mL blood samples from healthy donors and patients with HRPC.

Results: In the control group 13 of 37 genes were not expressed. The most notable of the genes expressed in CTCs of 23 blood specimens drawn from 9 patients with metastatic prostate cancer were prostate-specific antigen (20 of 23; 87%), prostate-specific membrane antigen (17 of 23; 74%), androgen receptor (16 of 23; 70%), human glandular kallikrein 2 (7 of 23; 30%), epidermal growth factor receptor (4 of 23; 17%), and prostate-specific gene with homology to G protein receptor (2 of 23; 9%). The number of CTCs in these samples ranged from 4 to 283 in 7.5 mL of blood (mean, 87; median, 89). Expression of some of the genes was low in the control samples and higher in the patient samples. In all 23 samples, cytokeratin 19, epithelial cell adhesion molecule, or mucin 1 was expressed. Because of background expression in the controls, expression of 13 of the 37 genes, including HER-2, p53, and BCL-2, could not be measured in CTCs.

Conclusion: Antisense RNA libraries can be constructed from CTCs and gene expression profiles of CTCs obtained from patients with HRPC. This could enhance the characterization of HRPC and facilitate the development of more effective therapies.
Determination of Absolute Configuration of Acyclic 1,2‐Diols with [Mo2(OAc)4], Part 2: New Structural Evidence toward a Rationale of the Method: What Remains of [Mo2(OAc)4] in DMSO Solution?
Authors: Bari Lorenzo Di , Pescitelli Gennaro , Salvadori Piero
Published: March 2004

The nature of the CD‐active species obtained by mixing dimolybdenum tetraacetate and a chiral 1,2‐diol in DMSO has been studied by different techniques (1D and 2D 1H NMR, CD, UV/Vis) with two substrates, (R)‐phenyl‐1,2‐ethanediol (1) and (R,R)‐butane‐2,3‐diol (2). The diol/dimolybdenum adducts have diagnostic CD spectra whose sign correlates with the absolute configuration of the organic substrate. It is demonstrated that, in DMSO solution, the acetate ligands of [Mo2(OAc)4] dissociate to a large extent under the action of the dissolved water, yielding acetic acid and a polyhydrated dimolybdenum species. Addition of a 1,2‐diol leads to chelation with formation of one main active species for 2 and two for 1, all with 1:1 stoichiometries at diol/dimolybdenum molar ratios less than 1.5. Only a small fraction (less than 20 %) of the 1,2‐diol is bound. The structures of the active complexes are estimated on the basis of NMR spectra, by correlating the observed chemical shifts with the quadruple bond diamagnetic anisotropy. In the predominating complexes for 1 and 2, the 1,2‐diol moiety bridges the Mo2 core forming a six‐membered ring.
Photocycloaddition of Some Difluoro(aminoenonato)boron Complexes with Arylalkenes
Authors: Itoh Kuniaki , Okazaki Kazuhiko , Chow Yuan L.
Published: February 2004

The photocycloaddition of some difluoro[(methylamino‐κN)alkenonato‐κO]boron complexes 1 with arylalkenes 2 is discussed. The resulting [2+2] photoaddition gave the cyclobutane and azetidine derivatives (Schemes 1, 3, and 5). Rearrangements of the cyclobutane gave 1,5‐diketones derivatives (Schemes 2, 4, and 5). The yields of the photoadducts were governed by the reduction and oxidation potentials. Furthermore, the configurations of the products established high regio‐ and stereoselectivity, suggesting the presence of a singlet exciplex. The reactivity and the stereochemistry were rationalized by means of FMO (frontier molecular orbital) calculations.
Synthesis and Triple‐Helix‐Stabilization Properties of Branched Oligonucleotides Carrying 8‐Aminoadenine Moieties
Authors: Aviño Anna , Grimau Marta G. , Frieden Miriam , Eritja Ramon
Published: February 2004

The synthesis of several branched oligonucleotides, i.e., of the parallel hairpins 5–8 and the Y‐shaped 9 is described, together with their use in the formation of pyrimidine⋅pyrimidine⋅purine triple helices. Special attention was paid to the optimization of the assembly of the second strand from asymmetric branching molecules. The presence of 8‐aminoadenine moieties in the WatsonCrick purine strand and 2′‐O‐methyl‐RNA in the Hoogsteen pyrimidine strand produced strong stabilization of the triplex.
Insulin Secretagogues from Moringa oleifera with Cyclooxygenase Enzyme and Lipid Peroxidation Inhibitory Activities
Authors: Francis Jayaraj A. , Jayaprakasam Bolleddula , Olson L. Karl , Nair Muraleedharan G.
Published: February 2004

Bioassay‐directed isolation and purification of the methanol extract of Moringa oleifera fruits yielded bioactive N‐benzyl thiocarbamates, N‐benzyl carbamates, benzyl nitriles, and a benzyl ester. Among these, methyl 2‐[4‐(α‐L‐rhamnopyranosyl)phenyl]acetate (2), N‐[4‐(β‐L‐rhamnopyranosyl)benzyl]‐1‐O‐α‐D‐glucopyranosylthiocarboxamide (3), 1‐O‐phenyl‐α‐L‐rhamnopyranoside (5), and 4‐[(β‐D‐glucopyranosyl)‐(1→3)‐(α‐L‐rhamnopyranosyl)]phenylacetonitrile (6) are novel, and their structures were determined by spectroscopic methods. The known compounds isolated and characterized from the MeOH extract were niazirin (=4‐(α‐L‐rhamnopyranosyl)phenylacetonitrile; 1), niazicin A (=methyl N‐{4‐[(4′‐O‐acetyl‐α‐L‐rhamnopyranosyl)benzyl]}thiocarbamate; 4), methyl N‐{4‐[(α‐L‐rhamnopyranosyl)benzyl]}carbamate (7), and methyl N‐{4‐[(4′‐O‐acetyl‐α‐L‐rhamnopyranosyl)benzyl]}carbamate (8). The combined yield of these compounds from dried M. oleifera fruits was 1.63%. In rodent pancreatic β‐cells (INS‐1), compounds 4, 5, 6, 7, and 8 at 100 ppm significantly stimulated insulin release. Cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2) enzyme inhibition assays revealed that 5 and 6 were most active at 83 ppm. Compound 6, however, demonstrated greater specificity for inhibition of COX‐2 enzyme (46%) than COX‐1 enzyme. Lipid peroxidation assays revealed that 4 and 6 at 50 ppm inhibited peroxidation reactions by 80 and 95%, respectively, while 3 and 8 inhibited lipid peroxidation by 35%. These compounds did not inhibit the cell growth when tested with human breast (MCF‐7), central nervous system (CNS, SF‐268), lung (NCI‐H460), or colon (HCT‐116) cancer cell lines. Moreover, these compounds were not cytotoxic at the concentrations tested.
Generation of Reactive Oxygen Species during the Photolysis of 6‐(Hydroxymethyl)pterin in Alkaline Aqueous Solutions
Authors: Cabrerizo Franco M. , Thomas Andrés H. , Lorente Carolina , Dántola María L. , Petroselli Gabriela , Erra‐Balsells Rosa , Capparelli Alberto L.
Published: February 2004

Photochemical studies of the reactivity of 6‐(hydroxymethyl)pterin (=2‐amino‐6‐(hydroxymethyl)pteridin‐4(1H)‐one; HPT) in alkaline aqueous solutions (pH 10.2–10.8) at 350 nm and room temperature were performed. The photochemical reactions were followed by UV/VIS spectrophotometry, thin‐layer chromatography (TLC), high‐performance liquid chromatography (HPLC), and an enzymatic method for H2O2 determination. In the presence of O2, 6‐formylpterin (=2‐amino‐3,4‐dihydro‐4‐oxopteridine‐6‐carboxaldehyde; FPT) was the only photoproduct detected. In the absence of O2, we observed a compound with an absorbance maximum at 480 nm, which was oxidized very rapidly by O2 in a dark reaction to yield FPT. The quantum yields of substrates disappearance and of photoproducts formation were determined. The formation of H2O2 during photooxidation was monitored, and the number of mol of H2O2 released per mol of HPT consumed corresponded to a 1 : 1 stoichiometry. HPT was also investigated for efficiency of singlet‐oxygen (1O2) production and quenching in aqueous solution. The quantum yield of 1O2 production (ΦΔ=0.21±0.01) was determined by measurements of the 1O2 luminescence in the near‐IR (1270 nm) upon continuous excitation of the sensitizer. The rate constant of 1O2 total quenching by HPT was determined (kt=3.1⋅106 M−1 s−1), indicating that this compound was able to quench 1O2. However, 1O2 did not participate in the photooxidation of HPT to FPT.
Angustilodine, an Unusual Pentacyclic Indole Alkaloid from Alstonia
Authors: Kam Toh‐Seok , Choo Yeun‐Mun
Published: February 2004

Two new indole alkaloids, angustilodine (1), with an unprecedented pentacyclic carbon skeleton, and angustilocine (2), belonging to the seco‐angustilobine‐B group of alkaloids, were obtained from the leaf extract of the Malayan species Alstonia angustiloba, and their structures were established by spectroscopic analysis.
Novel Synthesis of 2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones and Their S‐Oxides
Authors: Siegemund Anja , Hartung Christine , Baumann Sven , Schulze Bärbel
Published: February 2004

2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones 1a–e were synthesized by cyclocondensation of 2‐(thiocyanato)cyclohexene‐1‐carboxanilides 9 as a convenient new method. Their S‐oxides 10 were prepared by two routes, either by oxidation of 1 or dehydration of rac‐cis‐3‐hydroperoxysultims 11. Furthermore, compounds 1 have been identified by HPLCAPI‐MS‐MS as intermediates in the oxidation process of the salts 6. The hydroperoxides 12b and rac‐trans‐11b have been unambiguously detected by HPLCMS investigations and in the reaction of rac‐cis‐13b with H2O2 to the hydroperoxides rac‐trans‐11b and rac‐cis‐11b.
Two New Compounds from Dendrobium chrysotoxum
Authors: Yang Hong , Chou Gui‐Xin , Wang Zheng‐Tao , Guo Yue‐Wei , Hu Zhi‐Bi , Xu Luo‐Shan
Published: February 2004

Two novel compounds, (9R)‐4‐methoxy‐9H‐fluorene‐2,5,9‐triol (1a) and 2,7‐dihydroxy‐8‐methoxyphenanthro[4,5‐bcd]pyran‐5(5H)‐one (2) were isolated from the stems of the orchid Dendrobium chrysotoxum Lindl. Their structures were established spectroscopically, by chemical derivatization, and by single‐crystal X‐ray diffraction analysis. The absolute configuration of 1a was determined by Mosher's method. Neither compound showed antitumoral activity.
Parameter Study for the Pre‐Irradiation Grafting of Styrene/Divinylbenzene onto Poly(tetrafluoroethylene‐co‐hexafluoropropylene) from Isopropanol Solution
Authors: Rager Timo
Published: February 2004

Pre‐irradiation grafting of styrene/divinylbenzene (DVB) onto poly(tetrafluoroethylene‐co‐hexafluoropropylene) (FEP) films from isopropanol (iPrOH) solution was investigated with respect to the effect of irradiation dose, film thickness, cross‐linker concentration, and reaction temperature. A mathematical model was applied to the kinetic curves to extract information on the polymerization rate, the radical‐recombination rate, and the grafting through time. It turned out that the two closely correlated reaction rates for polymerization and radical recombination can be varied over a wide range by changing the irradiation dose, the cross‐linker concentration, and the reaction temperature. On the other hand, the time until the grafting front has progressed to the center of the film is mainly affected by the film thickness and the reaction temperature. The formation of homopolymer in the grafting solution increases steeply with temperature and cross‐linker concentration.
Reactions of α,β‐Enones with Diazo Compounds. Part 4
Authors: Anaç Olcay , Güngör Füsun Seyma , Kahveci Çiĝdem , Cansever M. Şerif
Published: February 2004

In this study, (E)‐ and (Z)‐enones carrying only a phenyl substituent at their C(β) atom were treaced with dimethyl diazomalonate in the presence of (acetylacetonato)copper(II). According to the configuration of the starting enones, the products were dioxole or dihydrofuran derivatives, significant heterocycles in natural products.
Pakistolides A and B, Novel Enzyme Inhibitory and Antioxidant Dimeric 4‐(Glucosyloxy)Benzoates from Berchemia pakistanica
Authors: Mukhtar Naveen , Malik Abdul , Riaz Naheed , Iqbal Kiran , Tareen Rasool Bakhsh , Khan Shamsun Nahar , Nawaz Sarfraz Ahmad , Siddiqui Juveria , Choudhary M. Iqbal
Published: February 2004

Pakistolides A and B, novel dimeric β‐(glucosyloxy)benzoates were isolated from Berchemia pakistanica and assigned structures 1 and 2 on the basis of extensive NMR studies. In addition, the known compounds 7,5′‐dimethoxy‐3,5,2′‐trihydroxyflavone (=3,5‐dihydroxy‐2‐(2‐hydroxy‐5‐methoxyphenyl)‐7‐methoxy‐4H‐1‐benzopyran‐4‐one), 4′,5‐dihydroxy‐3,6,7‐trimethoxyflavone (=5‐hydroxy‐2‐(4‐hydroxyphenyl)‐3,6,7‐trimethoxy‐4H‐1‐benzopyran‐4‐one), 5,6‐dihydroxy‐4,7‐dimethoxy‐2‐methylanthracene‐9,10‐dione, and 1,3,4‐trihydroxy‐6,7,8‐trimethoxy‐2‐methylanthracene‐9,10‐dione were reported for the first time from the genus Berchemia. Both 1 and 2 showed significant α‐glucosidase and lipoxygenase inhibitory activities, while 2 also showed antioxidant potential.
New Cholinesterase‐Inhibiting Steroidal Alkaloids from Sarcococca saligna
Authors: Atta‐ur‐Rahman  , Zaheer‐ul‐Haq  , Feroz Fareeda , Khalid Asaad , Nawaz Sarfraz Ahmad , Khan M. Riaz , Choudhary M. Iqbal
Published: February 2004

Seven new steroidal alkaloids, 2‐hydroxysalignarine‐E (=(2′E,20S)‐20‐(dimethylamino)‐2β‐hydroxy‐3β‐(tigloylamino)pregn‐4‐ene; 1), 5,6‐dihydrosarconidine (=(20S)‐20‐(dimethylamino)‐3β‐(methylamino)‐5α‐pregn‐16‐ene; 2), salignamine (=(20S)‐20‐(methylamino)‐3β‐methoxypregna‐5,16‐diene; 3), 2‐hydroxysalignamine (=(20S)‐20‐(dimethylamino)‐2β‐hydroxy‐3β‐methoxypregna‐5,16‐diene; 4), salignarine‐F (=(2′E, 20S)‐20‐(dimethylamino)‐4β‐hydroxy‐3β‐(tigloylamino)pregn‐5‐ene; 5), salonine‐C (=(2′E,20S)‐20‐(dimethylamino)‐3β‐(tigloylamino)pregna‐4,14‐diene; 6), and N‐[formyl(methyl)amino]salonine‐B (=(20S)‐20‐[formyl(methyl)amino]‐3β‐methoxypregna‐5,16‐diene; 7) have been isolated from the MeOH extract of Sarcococca saligna, along with the six known alkaloids dictyophlebine (8), epipachysamine‐D (9), saracosine (10), iso‐N‐formylchonemorphine (11), sarcodinine (12), and alkaloid‐C (13). The structures of 1–7 were deduced from spectral data. Compounds 1–13 demonstrated significant activity against acetyl‐ and butyrylcholinesterase.
NMR Investigations into the Vase‐Kite Conformational Switching of Resorcin[4]arene Cavitands
Authors: Azov Vladimir A. , Jaun Bernhard , Diederich François
Published: February 2004

We report the detailed investigation of temperature‐ and pH‐triggered conformational switching of resorcin[4]arene cavitands 1–10 (Figs. 1, 8, and 9). Depending on the experimental conditions, these macrocycles adopt a vase conformation, featuring a deep cavity for potential guest inclusion, or two kite conformations (kite 1 and kite 2) with flat, extended surfaces (Schemes 1 and 2). The thermodynamic and kinetic parameters for the interconversion between these structures were determined by variable‐temperature NMR (VT‐NMR) spectroscopy (Figs. 2–7 and 10, and Tables 1 and 2). It was discovered that vase→kite switching of cavitands is strongly solvent‐dependent: it is controlled not only by solvent polarity but also by solvent size. Conformational interconversions similar to those of the parent structure 1 with four quinoxaline flaps are also observed when the octol base skeleton is differentially or incompletely bridged. Only octanitro derivative 2 was found to exist exclusively in the kite conformation under all experimental conditions. The detailed insight into the vase⇌kite conformational equilibrium gained in this investigation provides the basis for the design and construction of new, dynamic resorcin[4]arene cavitands that are switchable between bistable states featuring strongly different structures and functions.
Cyclobutanoid Amides from Piper arborescens
Authors: Lee Fan‐Pin , Chen Yu‐Chang , Chen Jih‐Jung , Tsai Ian‐Lih , Chen Ih‐Sheng
Published: February 2004

Two new cyclobutanoid amides, piperarborenine A (=1,1′‐{[(1α,2α,3β,4β)‐2,4‐bis(3,4‐dimethoxyphenyl)cyclobutane‐1,3‐diyl]dicarbonyl}bis[5,6‐dihydropyridin‐2(1H)‐one]; 1) and piperarborenine B (=1,1′‐{[(1α,2α,3β,4β)‐2‐(3,4‐dimethoxyphenyl)‐4‐(3,4,5‐trimethoxyphenyl)cyclobutane‐1,3‐diyl]dicarbonyl}bis[5,6‐dihydropyridin‐2(1H)‐one]; 2) were isolated from the stem of Piper arborescens, besides two known cyclobutanoid amides, piperarboresine (=1,1′‐{[(1α,2α,3β,4β)‐2‐(7‐methoxy‐1,3‐benzodioxol‐5‐yl)‐4‐(3,4,5‐trimethoxyphenyl)cyclobutane‐1,3‐diyl]dicarbonyl}bis[5,6‐dihydropyridin‐2(1H)‐one]; 3) and piplartine‐dimer A (=1,1′‐{[(1α,2α,3β,4β)‐2,4‐bis(3,4,5‐trimethoxyphenyl)cyclobutane‐1,3‐diyl]dicarbonyl}bis[5,6‐dihydropyridin‐2(1H)‐one]; 4). The structures of the two new compounds were determined by spectral analyses.
Synthesis of Acyclic Nitroazole Nucleosides and Their Incorporation into Oligonucleotides, and Their Duplex and Triplex Formation
Authors: Walczak Krzysztof , Wamberg Michael , Pedersen Erik B.
Published: February 2004

Acyclic nucleosides of 4‐nitro‐1H‐imidazole and 4‐nitropyrazole have been synthesized by nucleophilic addition of the appropriate 4‐nitroazole to (−)‐(S)‐(hydroxymethyl)oxirane in the presence of a catalytic amount of potassium carbonate. (+)‐(R)‐3‐(4‐nitro‐1H‐imidazol‐1‐yl)propane‐1,2‐diol and (+)‐(R)‐3‐(2‐methyl‐4‐nitro‐1H‐imidazol‐1‐yl)propane‐1,2‐diol were also obtained in an independent reaction starting from appropriate 1,4‐dinitro‐1H‐imidazole and (+)‐(R)‐3‐aminopropane‐1,2‐diol. (+)‐(R)‐3‐(4‐Nitropyrazol‐1‐yl)propane‐1,2‐diol was also obtained by direct noncatalyzed addition of 4‐nitropyrazole to (−)‐(S)‐(hydroxymethyl)oxirane, whereas the (S)‐enantiomer was obtained by reaction of 4‐nitropyrazole with (+)‐(S)‐1,2‐O‐isopropylideneglycerol under Mitsunobu reaction conditions, followed by a cleavage of the isopropylidene group with 80% AcOH. Racemization during any of these syntheses has not been observed. 3‐(4‐Nitroazol‐1‐yl)propane‐1,2‐diols were incorporated into a 26‐mer oligonucleotide. UV Thermal melting studies of duplexes of the oligonucleotides with 4‐nitropyrazole or 4‐nitro‐1H‐imidazole paired with four natural bases showed moderately decreased stabilities of the duplexes. A narrow range of melting temperatures, typically being within 2° for each acyclic nucleoside, fulfill one of the requirements of using acyclic 4‐nitroazoles as general bases. Single incorporation of 4‐nitroazoles into a 14‐mer triplex forming oligonucleotide resulted in considerably decreased triplex stabilities.
Two New Resveratrol (=5‐[(1E)‐2‐(4‐Hydroxyphenyl)ethenyl]benzene‐1,3‐diol) Tetramers with a Tetrahydrofuran Ring from Dipterocarpus grandiflorus
Authors: Ito Tetsuro , Tanaka Toshiyuki , Iinuma Munekazu , Nakaya Ken‐ichi , Takahashi Yoshikazu , Sawa Ryuichi , Murata Jin , Darnaedi Dedy
Published: February 2004

Two new stilbene tetramers, grandiphenols A (1) and B (2), along with ten known stilbene oligomers and bergenin were isolated from the stem of Dipterocarpus grandiflorus. The structures of 1 and 2 composed of four resveratrol (=5‐[(1E)‐2‐(4‐hydroxyphenyl)ethenyl]benzene‐1,3‐diol) units had eight asymmetric C‐atoms in the partial structures of a tetrahydrofuran and two dihydrobenzofuran moieties. Detailed spectroscopic analyses, especially HMBC and NOESY experiments, allowed to differentiate the configurations of 1 and 2.
New Studies on [2+3] Cycloadditions of Thermally Generated N‐Isopropyl‐ and N‐(4‐Methoxyphenyl)‐Substituted Azomethine Ylides
Authors: Urbaniak Katarzyna , Szymański Radosław , Romański Jarosław , Mlostoń Grzegorz , Domagała Małgorzata , Linden Anthony , Heimgartner Heinz
Published: February 2004

The thermal reaction of 1‐substituted 2,3‐diphenylaziridines 2 with thiobenzophenone (6a) and 9H‐fluorene‐9‐thione (6b) led to the corresponding 1,3‐thiazolidines (Scheme 2). Whereas the cis‐disubstituted aziridines and 6a yielded only trans‐2,4,5,5‐tetraphenyl‐1,3‐thiazolidines of type 7, the analogous reaction with 6b gave a mixture of trans‐ and cis‐2,4‐diphenyl‐1,3‐thiazolidines 7 and 8. During chromatography on SiO2, the trans‐configured spiro[9H‐fluorene‐9,5′‐[1,3]thiazolidines] 7c and 7d isomerized to the cis‐isomers. The substituent at N(1) of the aziridine influences the reaction rate significantly, i.e., the more sterically demanding the substituent the slower the reaction. The reaction of cis‐2,3‐diphenylaziridines 2 with dimethyl azodicarboxylate (9) and dimethyl acetylenedicarboxylate (11) gave the trans‐cycloadducts 10 and 12, respectively (Schemes 3 and 4). In the latter case, a partial dehydrogenation led to the corresponding pyrroles. Two stereoisomeric cycloadducts, 15 and 16, with a trans‐relationship of the Ph groups were obtained from the reaction with dimethyl fumarate (14; Scheme 5); with dimethyl maleate (17), the expected cycloadduct 18 together with the 2,3‐dihydropyrrole 19 was obtained (Scheme 6). The structures of the cycloadducts 7b, 8a, 15b, and 16b were established by X‐ray crystallography.
Theoretical Elucidation of the Radical‐Scavenging‐Activity Difference of Hydroxycinnamic Acid Derivatives
Authors: Kong Ling , Sun Zhen‐Ling , Wang Lan‐Fen , Zhang Hong‐Yu , Yao Si‐De
Published: February 2004

To elucidate the nitrogen dioxide radical‐scavenging‐activity difference of three hydroxycinnamic acid derivatives (HCAs), i.e., caffeic acid (=3‐(3,4‐dihydroxyphenyl)prop‐2‐enoic acid; 1), ferulic acid (=3‐(4‐hydroxy‐3‐methoxyphenyl)prop‐2‐enoic acid; 2), and sinapic acid (=3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)prop‐2‐enoic acid; 3), a combined density‐functional‐theory (DFT) method, labeled as B3LYP/6‐31G(d)//AM1, was employed to calculate adiabatic ionization potentials (IPs) for parent molecules and anions derived by proton dissociation. It was found that not the IPs of the parent HCAs but those of the anions account well for the experimentally observed higher activity of caffeic acid as compared to those of the other two HCAs, suggesting that the antioxidant anion should be taken into consideration in the selection or rational design of novel antioxidants; this, however, was neglected in previous studies.
Six Novel 5α‐Adynerin‐Type Cardenolides from Parepigynum funingense
Authors: Hua Yan , Han Li Da , Chen Chang Xiang
Published: February 2004

Six novel 5α‐adynerin‐type cardenolides, funingenosides K (1), L (2), M (3), N (4), O (5), and P (6), have been isolated from the roots of Parepigynum funingense. Their structures were elucidated on the basis of 1D‐ and 2D‐NMR techniques.
Atom Economy and Yield of Synthesis Sequences
Authors: Eissen Marco , Mazur Radoslaw , Quebbemann Heinz‐Georg , Pennemann Karl‐Heinz
Published: February 2004

Atom economy (AE) or atom utilization was one of the first defining terms in the sustainable chemistry movement. In contrast to the often‐cited twelve (qualitative) principles of green chemistry, AE represents a metric for quantification purposes. The theoretical efficiency of a reaction expressed by its stoichiometric equation can be determined by AE=Product [g/mol]/(Substrate 1+Substrate 2+…︁) [g/mol] and compared with synthetic alternatives. Of course, the atom economy will be of limited use, if starting materials differ much in complexity, i.e., in the degree of refinement. In these cases, their syntheses have to be taken in consideration, too. But, the further the retrospect goes and the more preceding synthesis steps ramify, the more complex the calculation gets. To overcome this limitation, we introduce a stepwise approach that is enabled by a simple modification of the above formula (P=product; S=substrate; Syn.=synthesis): AE=P [g/mol]/((S1/AE(Syn. of S1))+(S2/AE(Syn. of S2))+…︁) [g/mol]. To illustrate this equation, which is derived mathematically, the convergent multistep synthesis of the natural product trans‐chrysanthemic acid is subjected to a stepwise method of calculation. The equation can be understood as a general expression for related ratios, i.e., there are corresponding modified equations for yield, selectivity, etc. In terms of the yield, it is no longer necessary to decide between the chains of the convergent synthesis, when possibly forced to ignore significant parts of the sequence. For demonstration purposes, the yield of the convergent synthesis of the natural product peridinin has been determined with a correspondingly modified equation.
Single‐Stranded DNA: Replacement of Canonical by Base‐Modified Nucleosides in the Minihairpin 5′‐d(GCGAAGC)‐3′ and Constructs with the Aptamer 5′‐d(GGTTGGTGTGGTTGG)‐3′
Authors: Rosemeyer Helmut , Mokrosch Verena , Jawalekar Anup , Becker Eva‐Maria , Seela Frank
Published: February 2004

The minihairpin 5′‐d(GCGAAGC)‐3′ (1) was modified either in the loop region, in the base‐paired stem, or at the 5′‐terminus by incorporation of base‐modified nucleosides. The thermal melting was correlated to the structural changes induced by the various donor‐acceptor properties of the nucleosides. Overhanging nonpaired nucleosides at the 5′‐terminus stabilized the hairpin, while a reverse of the dG3⋅dA5 sheared base pair to dA3⋅dG5 severely affected the stability. The combination of the minihairpin 5′‐d(GCGAAGC)‐3′ (1) and the thrombin‐binding aptamer 5′‐d(GGTTGGTGTGGTTGG)‐3′ (2 (=46)) resulted in the new construct 5′‐d(GGTTGGGCGAAGCGGTTGG)‐3′ (43) arising by replacement of the 5′‐d(TGT)‐3′ loop of 2 by the minihairpin. The fused oligonucleotide 43 exhibits a two‐phase thermal transition indicating the presence of the two unaltered moieties. According to slight changes of the Tm values of the construct 43 as compared to the separate units 1 and 2, cooperative distorsions are discussed.
Donor participatory governance evaluation: initial trends, implications, opportunities, constraints
Authors: Kapoor Ilan
Published: February 2004

The article examines the current trend within international development agencies towards adopting participatory approaches to governance evaluation (GE). It argues that, while this trend is to be welcomed, there are important political, institutional and methodological implications and constraints worth considering. Donors appear not to have addressed as yet such questions as the institutional changes required for participatory GEs to be meaningful, the relationship between conventional and participatory GEs, issues of quality and power in participatory GEs, and relationships to broader governance structures in developing countries. Copyright © 2004 John Wiley & Sons, Ltd.
Foreign aid: is it all consumed?
Authors: Durbarry Ramesh
Published: February 2004

Recent studies have found evidence to suggest that aid's effectiveness on growth has improved. Yet the debate on aid and domestic savings is still inconclusive and aid fungibility continues to be particularly contentious. One of the problems with much of the earlier literature examining the relationship between aid and savings (or aid‐consumption) is that the relationship is not well embedded in a convincing theoretical framework. Although recent developments in fiscal response models have been made, the methodology applied when testing the model empirically is still not convincing. In this paper we use an alternative theoretical setting and start from a ‘normal income’ perspective that consumption and savings are driven by life cycle/permanent income factors. Using a panel setting, the model is tested on a sample of developing countries. We found limited support for life cycle/permanent income drivers but did find that changes in the policy environment, for instance stabilisation programmes, may have been influential. The hypothesis that aid has been fungible in the pre‐1980 era could not be rejected. However, for the post 1980 period, where policy reforms were common, aid inflows did not seem to have leaked to finance consumption contrary to the views of both the right and the left questioning the utility of foreign aid. Copyright © 2004 John Wiley & Sons, Ltd.
Recipient country's ‘policies’ and the effect of foreign aid on economic growth in developing countries: additional evidence
Authors: Ram Rati
Published: February 2004

This note adds to the research which questions the recent influential view that recipient country's ‘policies’ play an important role in the effect of foreign aid on economic growth in developing countries. In the first step, the almost universal practice of imposing the constraint of equality on parameters of bilateral and multilateral aid is relaxed and it is shown that ‘policy’ has no role in the effect of aid even in those cases where the usual constrained models do show such an effect. In addition, many cases are noted where there is no indication of recipient country's policies having any role in the effect of aid on growth even in the usual constrained specifications. These cases employ not merely the Burnside–Dollar ‘policy’ index, which almost all scholars have used, but also two other broader measures. It is thus concluded that there is little empirical evidence to support the widely‐disseminated view that redirecting aid toward countries with ‘good’ policies leads to more growth and greater poverty reduction in developing countries. Copyright © 2004 John Wiley & Sons, Ltd.
Japan's official development assistance: recent issues and future directions
Authors: Kawai Masahiro , Takagi Shinji
Published: February 2004

The paper discusses recent issues and possible future directions of Japan's official development assistance (ODA). While Japan remains one of the world's largest donor nations, given its prolonged economic stagnation and mounting public sector debt, the Japanese government is under increasing public pressure to reduce ODA budgets and to use ODA in more explicit pursuit of Japan's own economic and political interests. Internationally, Japan continues to attract criticism for its emphasis on infrastructure‐related projects and for its restrained willingness to participate in multilateral partnerships. This paper argues that Japan can meet these domestic and international challenges by developing a coherent national strategy for ODA, broadly designed to enhance effectiveness, accountability and transparency. Copyright © 2004 John Wiley & Sons, Ltd.
Does saving really matter for growth? Mexico (1970–2000)
Authors: Alguacil Maite , Cuadros Ana , Orts Vicente
Published: February 2004

This paper uses the Granger non‐causality test procedure developed by Toda and Yamamoto (1995) and Dolado and Lütkepohl (1996) to analyse the saving‐growth nexus in Mexico. Contrary to the reverse causation between national saving and domestic income found in recent empirical studies, evidence is presented in favour of Solow's model prediction that higher saving leads to higher economic growth. The confirmation of a saving‐growth nexus in this country seems to be related to the inclusion of foreign direct investment (FDI) in the model, as the most relevant component of foreign saving. As this study will try to show, this last variable enhances economic growth and reinforces the connection between the two focus variables in the analysed country. Copyright © 2004 John Wiley & Sons, Ltd.
T2 and T1ρ MRI in articular cartilage systems
Authors: Menezes Nina M. , Gray Martha L. , Hartke James R. , Burstein Deborah
Published: February 2004

T2 and T1ρ have potential to nondestructively detect cartilage degeneration. However, reports in the literature regarding their diagnostic interpretation are conflicting. In this study, T2 and T1ρ were measured at 8.5 T in several systems: 1) Molecular suspensions of collagen and GAG (pure concentration effects): T2 and T1ρ demonstrated an exponential decrease with increasing [collagen] and [GAG], with [collagen] dominating. T2 varied from 90 to 35 ms and T1ρ from 125 to 55 ms in the range of 15–20% [collagen], indicating that hydration may be a more important contributor to these parameters than previously appreciated. 2) Macromolecules in an unoriented matrix (young bovine cartilage): In collagen matrices (trypsinized cartilage) T2 and T1ρ values were consistent with the expected [collagen], suggesting that the matrix per se does not dominate relaxation effects. Collagen/GAG matrices (native cartilage) had 13% lower T2 and 17% lower T1ρ than collagen matrices, consistent with their higher macromolecular concentration. Complex matrix degradation (interleukin‐1 treatment) showed lower T2 and unchanged T1ρ relative to native tissue, consistent with competing effects of concentration and molecular‐level changes. In addition, the heterogeneous GAG profile in these samples was not reflected in T2 or T1ρ. 3) Macromolecules in an oriented matrix (mature human tissue): An oriented collagen matrix (GAG‐depleted human cartilage) showed T2 and T1ρ variation with depth consistent with 16–21% [collagen] and/or fibril orientation (magic angle effects) seen on polarized light microscopy, suggesting that both hydration and structure comprise important factors. In other human cartilage regions, T2 and T1ρ abnormalities were observed unrelated to GAG or collagen orientation differences, demonstrating that hydration and/or molecular‐level changes are important. Overall, these studies illustrate that T2 and T1ρ are sensitive to biologically meaningful changes in cartilage. However, contrary to some previous reports, they are not specific to any one inherent tissue parameter. Magn Reson Med 51:503–509, 2004. © 2004 Wiley‐Liss, Inc.