bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoparticle formulation enhances the delivery and activity of a vascular endothelial growth factor antisense oligonucleotide in human retinal pigment epithelial cells
Authors: Aukunuru Jithan V , Ayalasomayajula Surya P , Kompella Uday B 
Published: September 2003

Abstract
The objective of this study was to investigate the delivery and activity of a vascular endothelial growth factor (VEGF) antisense oligonucleotide in a human retinal pigment epithelial cell line (ARPE-19) using a biodegradable nanoparticulate delivery system. A 19-mer antisense phosphorothioate oligonucleotide (PS-ODN) complementary to bases 6–24 relative to the translational start site of the VEGF mRNA, a sense PS-ODN and a mismatch PS-ODN were examined for the inhibition of secretion and mRNA expression of VEGF using an enzyme-linked immunosorbent assay and reverse transcription–polymerase chain reaction, respectively. Nanoparticles of the antisense oligonucleotides were formulated using a poly(lactide-co-glycolide) (50:50) copolymer using a double emulsion solvent evaporation method. After preparing nanoparticles, drug loading, encapsulation efficiency and particle size were determined. The cells were exposed to either plain solution of oligonucleotide or nanoparticles of oligonucleotide from Day 3 through Day 6. Alternatively, the cells were incubated with PS-ODNs and lipofectin for 4h on Day 4. In all studies, VEGF secretion and mRNA expression were determined on Day 6. The particle size, drug loading and encapsulation efficiency were 252 nm, 5.5% and 16.5%, respectively. The antisense PS-ODN inhibited VEGF mRNA and protein secretion when delivered using nanoparticles or lipofectin but not in its free form. This was consistent with the ability of nanoparticles and lipofectin to elevate the cellular uptake of the oligonucleotide by 4-fold and 13-fold, respectively. Neither mismatch nor sense oligonucleotides inhibited VEGF secretion. In conclusion, biodegradable nanoparticles enhance cellular delivery of a VEGF antisense oligonucleotide and inhibit VEGF secretion and mRNA expression in a human retinal pigment epithelial cell line.
Therapeutic effect of Semecarpus anacardium Linn. nut milk extract on carbohydrate metabolizing and mitochondrial TCA cycle and respiratory chain enzymes in mammary carcinoma rats
Authors: Arathi G , Sachdanandam P 
Published: September 2003

Abstract
Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have evaluated the effect of S. anacardium nut milk extract on carbohydrate metabolizing enzymes and mitochondrial tricarboxylic acid cycle and respiratory enzymes in liver and kidney mitochondria of dimethyl benzanthracene-induced mammary carcinoma in Sprague–Dawley rats. Mammary carcinoma-bearing rats showed a significant rise in glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase) and a simultaneous fall in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase). The activities of mitochondrial enzymes isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome C oxidase were significantly lowered in mammary carcinoma-bearing rats when compared with control rats. S. anacardium nut extract administration to tumour-induced animals significantly lowered the glycolytic enzyme activities (hexokinase, phosphoglucoisomerase and aldolase) and there was a rise in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase), which indicated an antitumour and anticancer effect. Comparison of normal control rats and rats administered S. anacardium only as drug control animals showed no significant variations in enzyme activities. S. anacardium nut extract administration to dimethyl benzanthracene-tumour-induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.
Synthesis and evaluation of 5-arylated 2(5H)-furanones and 2-arylated pyridazin-3(2H)-ones as anti-cancer agents
Authors: Lattmann Eric , Ayuko Washington O , Kinchinaton Derek , Langley Christopher A , Singh Harjit , Karimi Leila , Tisdale Michael J 
Published: September 2003

Abstract
Bis-cyclic butenolides, 5-arylated 2(5H)-furanones 6a–c, 7a, b and the 3(2H)-pyridazones 9a–d were prepared by using the aldehyde form of muco halogen acids in electrophilic substitution reactions and in an aldol-like condensation reaction. The cytotoxicity of these simple and bis-cyclic butenolides have been evaluated in tissue culture studies on MAC 13 and MAC 16 murine colon cancer cell lines. The butyl furanone 3 displayed the highest cytotoxicity of 3 μM, as one selected example of a series of dichlorinated pseudoesters. The 5-arylated 2(5H)-furanones 6 and 7 did not show a structure–activity relationship (SAR) depending on the substitution pattern of the aromatic system. An IC50 (concentration inhibiting growth by 50%) was found within a range of 30–50 and 40–50 μM for the MAC 13 and MAC 16 cell lines, respectively. The pyridazine series 9 showed a maximum in-vitro activity for the p-methoxydrivative 9b, having an IC50 of 17 in MAC 13 and 11 μM in MAC 16 cell lines. Selected examples of each series and further novel 2(5H)-furanones such as the hydrazone 5 and the hydantoin 8 have been screened in-vivo in mice and the data are presented. For the pyridazines 9a–d, the in-vitro cytotoxicity correlated with an in-vivo inhibition of tumour growth. The ring expansion of the 5-membered 2(5H)-furanone ring system such as 6a into the 6-membered 3(2H)-pyridazone 9b led to an agent with improved antineoplastic properties. On the resistant MAC 16 cell line the pyridazone 9b displayed 52% tumour inhibition in mice at a dose of 50 mg kg−1 compared with 27% for the 5-FU standard.
Analgesic effects of intra-nasal enkephalins
Authors: Gwak H S , Cho Y M , Chun I K 
Published: September 2003

Abstract
The analgesic effects of intranasal delivery of leucine enkephalin (Leu-Enk) and its synthetic analogue [D-ala2]-leucine enkephalinamide (YAGFL) with or without enzyme inhibitors and/or absorption enhancers were investigated using the acetic acid-induced writhing test in mice. The analgesic activity was significantly affected by the time delay after the administration of Leu-Enk; the inhibition rates for the groups administered with acetic acid 5 min and 30 min after the administration of Leu-Enk were 56.40 + 8.54 and 17.98 + 7.07%, respectively. The addition of enzyme inhibitors and absorption enhancers markedly increased the inhibition rate of Leu-Enk and YAGFL; their inhibition rates were about four times and twice those without any enzyme inhibitor or absorption enhancer, respectively. The enzyme inhibitors and absorption enhancers that produced the highest inhibition rates of Leu-Enk and YAGFL were azelaic acid (1%), thimerosal (0.5% mM, TM), ethylenediamine-tetraacetic acid (5 mM, EDTA) and L-α-lysophosphatidylcholine (0.5%, LPC), and TM (0.5 mM), EDTA (5 mM), LPC (0.5%) and povidone (5%), respectively. The ED50 value of both enkephalins was also determined and found to be about 13 μg kg−1, which is 850 and 60 times more potent than literature values for ketoprofen and morphine, respectively. Based on these results it was concluded that Leu-Enk or YAGFL could exert very high analgesic activity when administered nasally with a combination of inhibitors and absorption enhancers as compared with other analgesics.
Hepatocyte hollow-fibre bioreactors: design, set-up, validation and applications
Authors: Planchamp Corinne , Vu Thanh L , Mayer Joachim M , Reist Marianne , Testa Bernard 
Published: September 2003

Abstract
Hepatocytes carry out many vital biological functions, such as synthetic and catabolic reactions, detoxification and excretion. Due to their ability to restore a tissue-like environment, hollow-fibre bioreactors (HFBs) show great potential among the different systems used to culture hepatocytes. Several designs of HFBs have been proposed in which hepatocytes or hepatocyte-derived cell lines can be cultured in suspensions or on a solid support. Currently the major use of hepatocyte HFBs is as bioartificial livers to sustain patients suffering from acute liver failure, but they can also be used to synthesize cell products and as cellular models for drug metabolism and transport studies. Here, we present an overview of the set-up of hepatocyte HFBs and aim to provide potential users with the basic knowledge necessary to develop their own system. First, general information on HFBs is given, including basic principles, transport phenomena, designs and cell culture conditions. The importance of the tests necessary to assess the performance of the HFBs, i.e. the viability and functionality of hepatocytes, is underlined. Special attention is paid to drug metabolism studies and to adequate analytical methods. Finally, the potential uses of hepatocyte HFBs are described.
Including a 'no active intervention' arm in surgical trials is possible: evidence from the CLasP randomised trial
Authors: Brookes Sara , Peters Tim , Campbell Rona , Featherstone Katie , Neal David , Abrams Paul , Donovan Jenny 
Published: September 2003

Objectives: To examine the impact of including a 'no active intervention' arm (called 'conservative management') in a randomised controlled trial comparing treatments (including surgery) for men with lower urinary tract symptoms related to benign prostatic enlargement. Methods: Outcomes 7.5 months after randomisation were acceptability of randomisation, overall acceptability of and satisfaction with conservative management, impact on quality of life, perceived need for further treatment and treatment failure (defined a priori). Results: In total, 177 (out of 755) patients refused randomisation, including 31% who did not want surgery and 22% who wanted surgery. Most men randomised to conservative management were willing to undertake it as part of a trial but at the end of the trial they were divided between those who wanted to continue with it and those who expected surgery. At follow-up, 39% of conservative management patients requested surgery, and interference of symptoms with life and an unsuccessful outcome were more commonly reported in this arm. There were no appreciable differences between treatment groups in terms of treatment failures. Conclusions: Including a 'no active intervention' arm did not appear to have a detrimental effect on patient recruitment or the completion of this trial in the short-term; overall, conservative management was successfully completed by the majority of patients during the trial period, suggesting that researchers need not avoid including a no-intervention arm in surgical trials as long as they take care with its presentation.
Carbamazepine-Induced Pseudo Mycosis Fungoides
Authors: Gül Ülker , Kiliç Arzu , Dursun Ayşe 
Published: September 2003

Objective To report a case of pseudo mycosis fungoides due to carbamazepine. Case Summary A 54-year-old man experienced a skin lesion resembling mycosis fungoides without any systemic symptoms or signs 2 months after he had begun carbamazepine treatment for his seizures. Skin-punch biopsy specimens revealed mycosis fungoides–like histopathologic appearance. After drug discontinuation, the patient experienced complete remission of the clinical and pathologic findings. This suggests a diagnosis of pseudo mycosis fungoides due to carbamazepine. Discussion Mycosis fungoides is the cutaneous T-cell lymphoma of the skin that needs aggressive chemotherapy and radiation treatment. Pseudo mycosis fungoides is a condition caused by certain drugs that has a similar clinical and histopathologic appearance to mycosis fungoides. When the causative drug is discontinued, the lesions resolve completely. Conclusions An objective causality assessment revealed that carbamazepine was highly probable as the cause of the adverse reaction. Patients who are diagnosed with mycosis fungoides should be asked about any drug use, and clinicians should recognize signs of pseudo mycosis fungoides.
Oxidation and Degradation Products of Papaverine, Part II[1]: Investigations on the Photochemical Degradation of Papaverine Solutions
Authors: Girreser Ulrich , Hermann Tadeusz W. , Piotrowska Karolina 
Published: September 2003

AbstractThe structure of the final degradation product formed in papaverine solutions in either water or chloroform was found to be a 2, 3, 9, 10‐tetramethoxy‐12‐oxo‐12H‐indolo [2, 1‐a] isoquinolinylium salt (a dibenzo [b, g] pyrrocolonium derivative). Its formation from papaverine oxidation products that is papaverinol, papaveraldine, and papaverine‐N‐oxide chloroformsolutions under the influence of UV light, was investigated and possible reaction pathways are discussed.
Synthesis and Effects on the COX‐1 and COX‐2 Activity in Human Whole Blood ex vivo of Derivatives Containing the [1]Benzothienol‐[3, 2‐d]pyrimidin‐4‐one Heterocyclic System
Authors: Santagati Andrea , Granata Giuseppe , Marrazzo Agostino , Santagati Maria 
Published: September 2003

AbstractMethyl and phenyl derivatives containing the [1]Benzothieno [3, 2‐d]pyrimidin‐4‐one system have been synthesized and tested as inhibitors of COX‐1 and COX‐2 activities in human whole blood (HWB) ex vivo; all compounds turned out to be weak inhibitors of COX‐1 activity, as deduced from the TXB2 (thromboxane B) generation; the acid phenyl derivative 11 b was an interesting inhibitor of COX‐2 activity, as deduced from the PGE2 (prostaglandine E) generation.
Synthesis and Evaluation of Pharmacological Activities of 3, 5‐Dialkyl 1, 4‐Dihydro‐2, 6‐Dimethyl‐4‐Nitroimidazole‐3, 5‐Pyridine Dicarboxylates
Authors: Miri Ramin , Javidnia K. , Kebriaie‐Zadeh A. , Niknahad H. , Shaygani N. , Semnanian S. , Shafiee A. 
Published: September 2003

AbstractNew analogues of nifedipine, in which the 2‐nitrophenyl group at position 4 is replaced by a 1‐methyl‐5‐nitro‐2‐imidazolyl substituent, were synthesized. The symmetrical dialkyl 1, 4‐dihydro‐2, 6‐dimethyl‐4‐(1‐methyl‐5‐nitro‐2‐imidazolyl)‐3, 5‐pyridinedicarboxylates were prepared by a classical Hantzsch condensation. The asymmetrical analogues were synthesized using a procedure reported by Iwanami that involved the condensation of alkylacetoacetate with methyl‐, ethyl‐ or isopropyl3‐aminocrotonate and 1‐methyl‐5‐nitroimidazole‐2‐carboxaldehyde. Calcium channel antagonist activities were determined in vitro using a guinea pig ileum longitudinal smooth muscle (GPILSM)assay. Many compounds exhibited superior, or equipotent, calcium antagonist activity (IC50 = 10—10 to 10—13 M range) relative to the reference drug nifedipine (IC50 = 1.09 ± 0.12 × 10—11 M). Antinociceptive effects of some compounds were evaluated by the mouse tail‐flick assay in vivo. Results demonstrate that some of the compounds were active as an antinociceptive.
Investigations of New Pyridazinone Derivatives for the Synthesis of Potent Analgesic and Anti‐Inflammatory Compounds with Cyclooxygenase Inhibitory Activity
Authors: Ökçelik Berna , Ünlü Serdar , Banoglu Erden , Küpeli Esra , Yeşilada Erdem , Şahin M. Fethi 
Published: September 2003

AbstractIn this study we describe the synthesis of two novel 4‐phenyl‐and 4‐(2‐chlorophenyl)‐6‐(5‐chloro‐2‐oxo‐3H‐benzoxazol‐7‐yl)‐3(2H)‐pyridazinone derivatives (compounds 8a and b) and their testing as inhibitors of cyclooxygenases (COX‐1 and COX‐2). Both compounds inhibited COX‐1 (by 59 % and 61 % for compounds 8a and 8b respectively and COX‐2 (by 37 % and 28 % for compounds 8a and 8b spectively) at a concentration of 10 μM. Furthermore, we tested the analgesic and anti‐inflammatory activities of the synthesized compounds in vivo by using the pbenzoquinone‐induced writhing test and the carrageenan‐induced hind paw edema model, respectively. Compounds 8a and 8b showed potent analgesic and anti‐inflammatory activities without causing gastric lesions in the tested animals.
Geometrically Constrained Analogues of N‐Benzylindolylglyoxylylamides: [1, 2, 4]Triazino[4, 3‐a]benzimidazol‐4(10H)‐one Derivatives as Potential New Ligands at the Benzodiazepine Receptor
Authors: Primofiore Giampaolo , Da Settimo Federico , Taliani Sabrina , Marini Anna Maria , Simorini Francesca , Novellino Ettore , Greco Giovanni , Trincavelli Letizia , Martini Claudia 
Published: September 2003

AbstractA series of 3‐benzylamino‐and 3‐arylalkylaminocarbonyl [1, 2, 4]triazino [4, 3‐a]benzimidazoles 1—12 were synthesized and biologically assayed as geometrically constrained analogues of N‐benzylindolylglyoxylylamides II, which are high affinity ligands at the benzodiazepine receptor (BzR). The intermediate 3‐ethoxycarbonyl [1, 2, 4]triazino [4, 3‐a]benzimidazol‐4(10H)‐one 14 and its N(10)‐methyl analogue 15 closely related to 3‐alkoxycarbonyl‐β‐carbolines I were also investigated. The title compounds exhibited a lower affinity compared with the corresponding indolylglyoxylylamide derivatives II. Attempts were made to rationalize these results taking into account the possible tautomeric equilibria involving these ligands.
Completeness of state administrative databases for surveillance of congenital heart disease
Authors: Cronk Christine E. , Malloy Marsha E. , Pelech Andrew N. , Miller Richard E. , Meyer Sally A. , Cowell Melissa , McCarver D. Gail 
Published: September 2003

AbstractBACKGROUNDTracking birth prevalence of cardiac defects is essential to determining time and space clusters, and identifying potential associated factors. Resource limitations on state birth defects surveillance programs sometimes require that databases already available be used for ascertaining such defects. This study evaluated the data quality of state administrative databases for ascertaining congenital heart defects (CHD) and specific diagnoses of CHD.METHODSChildren's Hospital of Wisconsin (CHW) medical records for infants born 1997–1999 and treated for CHD (n = 373) were abstracted and each case assigned CHD diagnoses based on definitive diagnostic reports (echocardiograms, catheterizations, surgical or autopsy reports). These data were linked to state birth and death records, and birth and postnatal (<1 year of age) hospital discharge summaries at the Wisconsin Bureau of Health Information (WBHI). Presence of any code/checkbox indicating CHD (generic CHD) and exact matches to abstracted diagnoses were evaluated.RESULTSFifty‐eight percent of cases with generic CHD were identified by state databases. Postnatal hospital discharge summaries identified 48%, birth hospital discharge summaries 27%, birth certificates 9% and death records 4% of these cases. Exact matches were found for 52% of 633 specific diagnoses. Postnatal hospital discharge summaries provided most matches.CONCLUSIONState databases identified 60% of generic CHD and exactly matched about half of specific CHD diagnoses. The postnatal hospital discharge summaries performed best in both in identifying generic CHD and matching specific CHD diagnoses. Vital records had limited value in ascertaining CHD. Birth Defects Research (Part A) 67:597–603, 2003. © 2003 Wiley‐Liss, Inc.
Estimating prevalence of fetal alcohol syndrome (FAS): Effectiveness of a passive birth defects registry system
Authors: Fox Deborah J. , Druschel Charlotte M. 
Published: September 2003

AbstractBACKGROUNDFetal alcohol syndrome (FAS) is a preventable birth defect, easiest to recognize in children two through eleven years and more difficult to recognize in newborns. In New York State, two systems ascertain FAS cases, the statewide birth defects registry and the Fetal Alcohol Syndrome Surveillance Network (FASSNet) system. The accuracy of FAS reports to the birth defects registry was assessed through a comparison with the FASSNet system.METHODSThe birth defects registry mandates reporting up to age two, including FAS with an ICD‐9 code of 760.71. FASSNet is a population‐based, multi‐source surveillance and uses a standard definition to determine FAS case status.RESULTSAmong 33 children reported to the registry with FAS, 19 (58%) met FASSNet criteria for FAS. FASSNet identified 24 additional children with FAS facial features documented before the child's second birthday that should have been reported to the birth defects registry. FAS prevalence rate for the birth defects registry was 0.28 per 1,000 live births but would have been 0.37 if all children diagnosed before age two were included.CONCLUSIONSAlmost 60% of children reported to a birth defects registry with FAS from 1995 to 1998 were confirmed as FAS based on a more intensive surveillance. Additional children with FAS were not reported to the CMR. FAS prevalence calculated from birth defects registries, relying on the ICD‐9 code 760.71, include false positives and underestimate the true prevalence. Age limits for reporting FAS to registries further contribute to under ascertainment. Birth Defects Research (Part A) 67:604–608, 2003. © 2003 Wiley‐Liss, Inc.
Random error and undercounting in birth defects surveillance data: Implications for inference
Authors: Correa‐Villaseñor Adolfo , Satten Glen A. , Rolka Henry , Langlois Peter , Devine Owen 
Published: September 2003

AbstractBACKGROUNDThere has been an ongoing debate among birth defects investigators about whether or not to publish estimates of rates of birth defects with confidence intervals to allow for comparisons of rates across regions and time. A major impediment in resolving this debate has been the lack of a framework for quantifying uncertainties in the data that can be applied uniformly to birth defects surveillance programs. This report presents an overview of random error and ascertainment bias in birth defects surveillance data, and of the implications of these errors for estimation and comparisons of birth defects rates.METHODSWe consider when confidence intervals can be used as part of a strategy to make inference on rates, as well as ratios of or differences between two rates. Worth noting is that confidence intervals only address random error in the data. In the presence of undercounting of cases, estimation of rates and confidence intervals requires knowledge or an estimate of the extent of underascertainment. Rate estimates and confidence intervals that ignore such bias can be misleading. However, if it is reasonable to assume that the ascertainment bias is constant over time (or across regions), then it is possible to make valid comparisons of rates over time (or across regions) using ratio or difference estimators, even when lack of knowledge of the extent of undercounting makes estimating the absolute rate and its confidence interval problematic. Finally, sensitivity analyses can use confidence limits to determine the difference in ascertainment bias necessary to explain an apparent difference in rates.CONCLUSIONBecause birth defects surveillance systems have evolved in the absence of agreed upon standards to guide the process, it is difficult to determine the extent to which the variability in rates of birth defects across programs or over time is real or due to differences in surveillance methods. Efforts to develop standards for birth defects surveillance may help to minimize the variability in prevalence of birth defects due to differences in case ascertainment methods and allow for evaluations of real temporal and spatial variations in environmental effects. In the meantime, if comparisons of rates need to be made to address public health concerns, it would be prudent to conduct only such comparisons between regions or across time when the degree of case ascertainment can be assumed to be relatively constant across regions and time. Birth Defects Research (Part A) 67:610–616, 2003. Published 2003 Wiley‐Liss, Inc.