bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential oils of Lippia grandis Schau.
Authors: Maia José Guilherme S. , Taveira Francisca Socorro N. , Andrade Eloisa Helena A. , da Silva Milton Helio L. , Zoghbi Maria das Graças B.
Published: September 2003

The essential oils of leaves and ﬁne stems of ﬁve specimens of Lippia grandis collected at different places in the Amazon were analysed by GC–MS. These oils presented two distint chemical proﬁles. The percentage of the main identiﬁed compounds varied with the plant part, season time and collection site: thymol (19.3–69.7%), 1,8‐cineole (22.2–56.0%), carvacrol (0.2–21.2%), (E)‐nerolidol (0.8–21.1%), α‐pinene (0.1–17.4%), p‐cymene (4.0–14.0%), thymol methyl ether (1.0–14.0%) and β‐caryophyllene (0.7–12.1%). Based on the results, we believe to have at least two chemical varieties for Lippia grandis in the Amazon: the thymol and 1,8‐cineole types. Copyright © 2003 John Wiley & Sons, Ltd.
Chemical variability of Artemisia vulgaris L. essential oils originated from the Mediterranean area of France and Croatia
Authors: Jerkovic I. , Mastelic J. , Milos M. , Juteau F. , Masotti V. , Viano J.
Published: September 2003

The essential oils of Artemisia vulgaris L. originating from France and Croatia were subjected to detailed GC–MS analysis in order to determine possible similarities and differences between them and their chemical compositions, depending on the stage of development. Plant materials were collected in Provence (France) and Dalmatia (Croatia) at four different stages of development: vegetative (June), buds (July), ﬂowering (August) and seeding (September). Comparison of the chemical composition and content, depending on phenological stages in both localities, shows qualitative similarity, but also the noticeable difference in the amounts of most components. First, the chemical composition of main compounds is very different; Croatian oils are rich in hydrocarbons, which are absent or present in low amounts in French oils. Also, with regard to the yield of essential oils, the yields from Croatian oils were higher (0.09–0.61%) than these from French oil (0.04–0.15%) at each development stage, respectively. Copyright © 2003 John Wiley & Sons, Ltd.
Composition of the essential oil of Medicago marina L. from the coastal dunes of Tuscany, Italy
Authors: Flamini Guido , Luigi Cioni Pier , Morelli Ivano , Ceccarini Lucia , Andolfi Laura , Macchia Mario
Published: September 2003

This paper discusses essential oil composition of the dried aerial parts of Medicago marina harvested before and during blossom, in Vada (Livorno, Italy). In the two essential oils, rich in carbonylic compounds, 54 components were identified. Linalool (5.8%) and α‐terpineol (3.3%) were the main monoterpenes in the vegetative phase sample, while linalool (1.2%) and p‐mentha‐4‐en‐3‐one (0.4%) in the was the main constituent flowering stage. Sesquiterpenes were present only during the flowering stage, when the main constituents were non‐terpenic substances. 1‐Octen‐3‐ol and the (E)‐β‐ionone were the two constituents which showed the greater differences between the two samples (9.3% and 0.7% for the first component and 14.4% and 5.6% for the second component in the two different phases). Furthermore, phenyl propanoids were also identified in these oils, particularly methyl eugenol during the reproductive phase and eugenol during the vegetative phase. Copyright © 2003 John Wiley & Sons, Ltd.
Broad expression of fructose‐1,6‐bisphosphatase and phosphoenolpyruvate carboxykinase provide evidence for gluconeogenesis in human tissues other than liver and kidney
Authors: Yánez Alejandro J. , Nualart Francisco , Droppelmann Cristian , Bertinat Romina , Brito Mónica , Concha Ilona I. , Slebe Juan C.
Published: September 2003

The importance of renal and hepatic gluconeogenesis in glucose homeostasis is well established, but the cellular localization of the key gluconeogenic enzymes liver fructose‐1,6‐bisphosphatase (FBPase) and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in these organs and the potential contribution of other tissues in this process has not been investigated in detail. Therefore, we analyzed the human tissue localization and cellular distribution of FBPase and PEPCK immunohistochemically. The localization analysis demonstrated that FBPase was expressed in many tissues that had not been previously reported to contain FBPase activity (e.g., prostate, ovary, suprarenal cortex, stomach, and heart). In some multicellular tissues, this enzyme was detected in specialized areas such as epithelial cells of the small intestine and prostate or lung pneumocytes II. Interestingly, FBPase was also present in pancreas and cortex cells of the adrenal gland, organs that are involved in the control of carbohydrate and lipid metabolism. Although similar results were obtained for PEPCK localization, different expression of this enzyme was observed in pancreas, adrenal gland, and pneumocytes type I. These results show that co‐expression of FBPase and PEPCK occurs not only in kidney and liver, but also in a variety of organs such as the small intestine, stomach, adrenal gland, testis, and prostate which might also contribute to gluconeogenesis. Our results are consistent with published data on the expression of glucose‐6‐phosphatase in the human small intestine, providing evidence that this organ may play an important role in the human glucose homeostasis.
J. Cell. Physiol. 197: 189–197, 2003© 2003 Wiley‐Liss, Inc.
Intracellular dynamics of Smad‐mediated TGFβ signaling
Authors: Greene Robert M. , Nugent Paul , Mukhopadhyay Partha , Warner Dennis R. , Pisano M. Michele
Published: September 2003

The transforming growth factor‐β (TGFβ) family represents a class of signaling molecules that plays a central role in morphogenesis, growth, and cell differentiation during normal embryonic development. Members of this growth factor family are particularly vital to development of the mammalian secondary palate where they regulate palate mesenchymal cell proliferation and extracellular matrix synthesis. Such regulation is particularly critical since perturbation of either cellular process results in a cleft of the palate. While the cellular and phenotypic effects of TGFβ on embryonic craniofacial tissue have been extensively catalogued, the specific genes that function as downstream mediators of TGFβ action in the embryo during palatal ontogenesis are poorly defined. Embryonic palatal tissue in vivo and murine embryonic palate mesenchymal (MEPM) cells in vitro secrete and respond to TGFβ. In the current study, elements of the Smad component of the TGFβ intracellular signaling system were identified and characterized in cells of the embryonic palate and functional activation of the Smad pathway by TGFβ1, TGFβ2, and TGFβ3 was demonstrated. TGFβ‐initiated Smad signaling in cells of the embryonic palate was found to result in: (1) phosphorylation of Smad 2; (2) nuclear translocation of the Smads 2, 3, and 4 protein complex; (3) binding of Smads 3 and 4 to a consensus Smad binding element (SBE) oligonucleotide; (4) transactivation of transfected reporter constructs, containing TGFβ‐inducible Smad response elements; and (4) increased expression of gelatinases A and B (endogenous genes containing Smad response elements) whose expression is critical to matrix remodeling during palatal ontogenesis. Collectively, these data point to the presence of a functional Smad‐mediated TGFβ signaling system in cells of the developing murine palate. J. Cell. Physiol. 197: 261–271, 2003. © 2003 Wiley‐Liss, Inc.
Cyclic AMP and cyclic GMP independent stimulation of ventricular calcium current by peroxynitrite donors in guinea pig myocytes
Authors: Malan Daniela , Levi Renzo Cesare , Alloatti Giuseppe , Marcantoni Andrea , Bedendi Ivano , Gallo Maria Pia
Published: September 2003

We investigated the potential involvement of peroxynitrite (ONOO−) in the modulation of calcium current (ICa) in guinea pig ventricular myocytes with the whole‐cell patch clamp technique and with cyclic AMP (cAMP) measurements. Because of the short half‐life of ONOO− at physiological pH, we induced an increase in its intracellular levels by using donors of the precursors, nitric oxide (NO) and superoxide anion (O2−). High concentrations of NO donors, SpermineNONOate (sp/NO, 300 μM) or SNAP (300 μM) increased basal ICa (50.3 ± 4.6%, n = 7 and 46.2 ± 5.0%, n = 13). The superoxide anion donor Pyrogallol (100 μM) also stimulated basal ICa (44.6 ± 2.8%, n = 11). At lower concentration sp/NO (10 nM) and Pyrogallol (1 μM), although separately ineffective on ICa, enhanced the current if applied together (33.5 ± 0.7%, n = 7). The simultaneous donor of O2− and NO, SIN‐1 (500 μM), also stimulated basal ICa (22.8 ± 2.1%, n = 13). In the presence of saturating cyclic GMP (cGMP, 50 μM) in the patch pipette or of extracellular dibutyryl cGMP (dbcGMP, 100 μM), ICa was still increased by SIN‐1 (32.0 ± 6.1%, n = 4 and 30.0 ± 5.4%, n = 8). Both Manganese(III)tetrakis(4‐benzoic acid) porphyrin chloride (MnTBAP, 100 μM) a ONOO− scavenger, and superoxide dismutase (SOD) (150 U/ml) reversed the stimulatory effect of SIN‐1 on ICa (respectively −0.6 ± 4.1%, n = 4 and 3.6 ± 4.3%, n = 4). Intracellular cAMP level was unaltered by SIN‐1, while it was enhanced by blocking the NO–cGMP pathway with the NO synthase inhibitor L‐NMMA. These results suggest that peroxynitrite donors increase cardiac calcium current without the involvement of cAMP and cGMP. J. Cell. Physiol. 197: 284–296, 2003© 2003 Wiley‐Liss, Inc.
Moyamoya‐induced paroxysmal dyskinesia
Authors: Gonzalez‐Alegre Pedro , Ammache Zakaria , Davis Patricia H. , Rodnitzky Robert L.
Published: September 2003

Moyamoya disease (MMD) is an uncommon intracranial vasculopathy that typically presents with ischemic or hemorrhagic stroke. Persistent choreoathetosis has been identified as a rare early manifestation of MMD. We present 2 patients with paroxysmal dyskinesia as the initial symptom of MMD, one resembling paroxysmal kinesigenic dyskinesia (PKD) and the other paroxysmal non‐kinesigenic dyskinesia (PNKD). We also review the cases of moyamoya‐induced chorea reported previously, none of which resembled PKD or PNKD. We hypothesize that both hormonal and ischemic factors may be implicated in the pathogenesis of these abnormal involuntary movements. These cases suggest that MMD should be included in the differential diagnosis of PKD and PNKD. © 2003 Movement Disorder Society
Sensory training as treatment for focal hand dystonia: A 1‐year follow‐up
Authors: Zeuner Kirsten E. , Hallett Mark
Published: September 2003

In a prior study, 10 patients with focal hand dystonia learned braille reading as sensory training for 8 weeks. Practice time was 30 to 60 minutes daily. They improved both their spatial acuity using the Grating Orientation Discrimination Task (GOT) and their dystonia using the Fahn scale. Three patients continued training for 1 year. Patients showed further improvement in the GOT, writing a standard paragraph, and self‐rating scales. Sensory training lasting longer than 8 weeks may lead to continued improvement. © 2003 Movement Disorder Society
Regional and racial differences in the prevalence of physician‐diagnosed essential tremor in the United States
Authors: Louis Elan D. , Fried Linda P. , Fitzpatrick Annette L. , Longstreth William T. , Newman Anne B.
Published: September 2003

For reasons that are unclear, prevalence estimates of essential tremor (ET) differ considerably across the United States. Separate communities have never been sampled within the framework of the same study to substantiate these differences. We estimated the prevalence of physician‐diagnosed ET in the elderly in four communities in the United States in whom the same screening questions were used, and examined whether this prevalence differed between Caucasians and African Americans. The Cardiovascular Health Study recruited a sample of Medicare beneficiaries ≥65 years of age from four communities in different regions of the United States. In 1998 to 1999, 3,494 participants (mean age, 80.0 years; range, 70–103 years) answered a 12‐question screen for ET, including the question, “has a doctor diagnosed you as having familial tremor or benign essential tremor?” Fifty‐four participants reported that a doctor had diagnosed them as having ET (1.5%; 95% confidence interval, [CI], 1.1–2.0%). Prevalence was similar across the four communities (1.1–2.0%). A larger proportion of Caucasians than African Americans reported a diagnosis of ET (1.7% vs. 0.4%; odds ratio = 4.9; 95% CI, 1.2–20.2; P = 0.028). In a logistic regression analysis, physician‐diagnosed ET was associated with Caucasian ethnicity (P = 0.038) but not with age, gender, education, mental status or depression scores, income, smoking status, or alcohol consumption. When a standardized screening question was used, the proportion of participants with physician‐diagnosed ET was similar across four communities, suggesting that the prevalence of this condition may be less variable than is often reported. Caucasians were five times more likely to have physician‐diagnosed ET than were African Americans. This study does not provide an explanation for this difference, which deserves further study. © 2003 Movement Disorder Society
Different effects of unilateral versus bilateral subthalamic nucleus stimulation on walking and reaching in Parkinson's disease
Authors: Bastian Amy J. , Kelly Valerie E. , Revilla Fredy J. , Perlmutter Joel S. , Mink Jonathan W.
Published: September 2003

The purpose of this study was to determine the effects of unilateral versus bilateral subthalamic nucleus (STN) stimulation on quantitative measures of walking and reaching in Parkinson's disease (PD). We used kinematic measures and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale (subscale III) to evaluate the movement of 6 people with PD who had bilateral STN stimulators implanted for at least 6 months and withheld their anti‐parkinson medication for at least 8 hours. Subjects were studied with both stimulators off, one on, and both on. Kinematic data were collected as subjects walked, reached to a target, and were rated using the UPDRS motor subscale. STN stimulation improved walking speed and stride length, with the greatest benefit from bilateral stimulation. Reaching speed was improved by unilateral STN stimulation alone, with no additive effect of bilateral stimulation. UPDRS motor subscale ratings paralleled the kinematic findings. STN stimulation did not restore PD subjects' movements to the level of age‐matched controls. Overall, these results provide further evidence that the basal ganglia pathways involved in control of walking and reaching may be distinct. We speculate that basal ganglia may influence walking through bilateral pedunculopontine projections and reaching through ipsilateral thalamocortical projections. Our findings also suggest that maximal improvement of walking requires bilateral rather than unilateral STN stimulation. © 2003 Movement Disorder Society
Fast real‐time convolution algorithm for transients of nonlinearly‐terminated microwave multiport circuits
Authors: Chiang I‐Ting , Chew Weng Cho
Published: September 2003

In this work, a fast real‐time convolution algorithm is proposed. By using this approach, the cost for real‐time convolution in the presence of nonlinear terminations is reduced from O(N2) to O(N log2N). It is important to reduce the cost for the convolution operation because it usually dominates the computation time in a nonlinear circuit simulation. A nonlinearly‐terminated microwave 3‐port circuit, characterized by S parameters, is employed to demonstrate the efficiency of this fast algorithm. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 280–282, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11190
High‐power dual‐wavelength loop‐mirror cavity fiber laser
Authors: Abdullah F. , Mahdi M. A. , Bouzid B. , Abdullah M. K.
Published: September 2003

A high‐power dual‐wavelength laser is constructed in two fiber‐loop mirror cavities by utilizing a common‐gain medium. The output power and side‐mode suppression ratio (SMSR) of the lasers were investigated for a bidirectionally pumped system. The outcome of the experiment shows that two lasing signals can be obtained at the wavelengths of 1546.04 and 1550.64 nm at a less than 1‐dB peak power difference, at peak powers of 7.30 and 6.57 dBm, respectively. This result was obtained without any intracavity attenuators. The side‐mode suppression ratio of both signals is around 46 dB. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 286–287, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11192
Large signal model of quantum‐well lasers for spice
Authors: Jianjun Gao , Baoxin Gao , Chunguang Liang
Published: September 2003

A large‐signal equivalent‐circuit model of quantum‐well lasers is developed in this paper. This model is based on three‐level rate equations, including carrier transport effects and the role of the gateway state at the quantum well. The experiential formula of the optical peak gain variation with carrier density is given. Turn‐on delay and modulation frequency response of QW lasers are obtained using a SPICE simulator. The simulation results of the frequency response show excellent agreement with experimentally obtained data. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 295–298, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11195
L‐band erbium‐doped fiber ring laser with a wide tuning range
Authors: Mao Qinghe , Lit John W. Y.
Published: September 2003

A ring erbium‐doped fiber (EDF) laser with an additional EDF saturable absorber operating in the L‐band can produce dual‐wavelength optical bistability. The bistabilities of the two wavelengths evolves in antiphase; the dual‐wavelength bistable behavior can be controlled by the cavity loss and adjusted by varying the EDF length. This property is used to switch the laser between the two wavelengths by triggering the pump source. The typical switching time is about 4–15 ms. By making use of the bistability, the laser may be tuned across the entire L‐band by using only ordinary commercial tunable fiber Bragg gratings (FBGs). An output dynamic range of 7.5 dB and an optical signal‐to‐noise ratio of 70 dB have been achieved. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 304–307, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11198
Bias‐dependence of FET intrinsic noise sources, determined with a quasi‐2D model
Authors: Lázaro A. , Maya M. C. , Pradell L.
Published: September 2003

The bias‐dependence of microwave‐FET intrinsic noise sources in their hybrid configuration is theoretically determined, using a new quasi‐2D (Q‐2D) physical model based on Thornber's current equation 8. It is shown that the correlation coefficient cannot be neglected, in agreement with empirical work in the literature. Experimental verification using noise‐parameter measurements up to 26 GHz is presented. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 317–319, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11202
Optical random‐bit generator employing quantum and chaotic dynamics
Authors: Ramos Rubens Viana , Giraudo Elvio César
Published: September 2003

Random‐bit generators, working as noise generators and producing keys for cryptography's algorithms are very useful in tests of communication links. However, a truly random sequence can be obtained only if a certain physical variable that obeys a certain statistical rule is used. In this paper we show two possible optical setups for a random‐bit generator. They are based on nonlinear quantum dynamics. Their main properties are shown analytically by using numerical simulations. We then use randomness tests to infer the quality of the bit sequences generated by the nonlinear system. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 338–342, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11208
Direct extraction technique for a small‐signal MOSFET equivalent circuit with substrate parameters
Authors: Lee Seonghearn
Published: September 2003

A simple and efficient method to extract model parameters of a small‐signal MOSFET equivalent circuit, including substrate resistance and capacitance, is proposed. Unlike previous methods, substrate parameters, resistances, and inductances are directly determined without any curve‐fitting optimization. Good agreement between the measured and modeled S parameters is observed up to 40 GHz, thus verifying the accuracy of the model and its extraction method. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 39: 344–347, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11210
9‐cis‐retinoic acid during in vitro maturation improves development of the bovine oocyte and increases midkine but not IGF‐I expression in cumulus‐granulosa cells
Authors: Gómez Enrique , Royo Luis‐José , Duque Paloma , Carneiro Gustavo , Hidalgo Carlos , Goyache Félix , Lorenzo Pedro L. , Alvarez Isabel , Facal Nieves , Díez Carmen
Published: September 2003

The isomer 9‐cis of retinoic acid (9‐cis‐RA) exerts a beneficial effect on bovine in vitro development when added to in vitro maturation (IVM) culture. In the present work, 9‐cis‐RA 5 nM was found to be stimulatory as opposed to 500 nM (toxic). Cumulus–oocyte complexes (COCs) were treated with the found physiological dose 9‐cis‐RA 5 nM, and the next determinations performed: (1) relative expression of midkine (MK) and IGF‐I, by reverse transcriptase‐polymerase chain reaction (RT‐PCR), in cumulus‐granulosa cells detached from oocytes; (2) cytoplasmic granular migration, by labeling of oocytes with fluoroscein isothiocyanate lectins; and (3) in vitro survival of blastocysts after vitrification and warming. Gene expression of MK was enhanced by 9‐cis‐RA, but not by 1% ethanol (vehicle). However, we did not detect IGF‐I expression, both in dependence on or in the absence of 9‐cis‐RA acting on cumulus‐granulosa cells. The ability of vitrified blastocysts to survive in vitro was not improved by 9‐cis‐RA. Nevertheless, since only blastocysts obtained from oocytes matured with serum survived, more factors should be considered when evaluating cryopreservation survival. The complete granular migration observed in oocytes matured with 9‐cis‐RA anticipates the gain in developmental competence of the oocyte, being MK probably involved in this beneficial effect. Mol. Reprod. Dev. 66: 247–255, 2003. © 2003 Wiley‐Liss, Inc.
Role of substrate on larval development of the freshwater teleost Pelvicachromis pulcher
Authors: Maradonna Francesca , Bavestrello Giorgio , Cardinali Marco , Olivotto Ike , Cerrano Carlo , Giovine Marco , Carnevali Oliana
Published: September 2003

It is known that, in an aquatic environment, the mineralogical composition of the substrate can affect the structure of settled communities. In marine environments, the presence of quartz negatively influences the formation of biofilm, as well as the selection and the colonization of the substrate by benthic organisms. Direct laboratory observation revealed that the freshwater teleost Pelivicachromis pulcher selects, when available, nonquartzitic brooding substrate. To monitor the effects of substrate on larvae development, ten lots of embryos were distributed in grid nurseries; carbonatic gravel was laid in five of the nurseries, while freshly fractured quartz gravel was used in the remaining ones. All the embryos laid in the two nurseries hatched, and 90% of the carbonate developing larvae reached adulthood, while 100% of those reared on quartz grain died 120 hr post hatching. Examination was made, both in larvae developed on carbonatic substrates and in those developed on quartz substrates, of the expression of the fetal growth factor, the insulin growth factor‐II (IGF‐II), of the molecular chaperone, the heat shock protein 70 (HSP70), which is involved in the folding of the nascent polypeptide chain, of the key enzyme of the glycolytic pathway, the glyceraldehyde‐3‐phosphate dehydrogenase (GADPH), and of the housekeeping gene, the β‐actin. All the data were normalized against 18S RNA expression. In larvae reared on quartz substrate, the genes IGF‐II and the β‐actin showed a lower expression, while the GADPH was totally suppressed and the expression of HSP70 increased. In conclusion, the data presented in this article demonstrated, for the first time, that the presence of quarzitic substrates is sufficient to stop larvae development through the inhibition of gene transcription in this African cichlid, leading to its death. Mol. Reprod. Dev. 66: 256–263, 2003. © 2003 Wiley‐Liss, Inc.
Epidermal growth factor induces Bcl‐xL gene expression and reduces apoptosis in porcine parthenotes developing in vitro
Authors: Cui Xiang‐Shun , Kim Nam‐Hyung
Published: September 2003

The aim of this study was to determine the interactive effects of bovine serum albumin (BSA) and epidermal growth factor (EGF) on the viability and development of porcine presumptive diploid parthenotes developing in vitro. The addition of 0.1 and 0.4% BSA to the culture medium enhanced the development of 4‐cell parthenotes to the blastocyst stage but EGF had no effect. However, while BSA also increased cell numbers, it did so only when EGF was also present. Either agent on its own had no effect. Similarly, apoptosis in the blastocysts was not influenced by either agent on its own but was reduced when both BSA and EGF were present. Furthermore, semi‐quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) revealed that EGF enhanced the mRNA expression of Bcl‐xL in the presence of 0.4% BSA but BSA and EGF alone had no effect. EGF and/or BSA did not influence Bak gene expression in the blastocyst stage parthenotes. These results suggest that EGF and BSA synergistically enhance Bcl‐xL gene expression, which may result in a net increase in cell number in porcine presumptive diploid parthenotes developing in vitro. Mol. Reprod. Dev. 66: 273–278, 2003. © 2003 Wiley‐Liss, Inc.
Quantitative determination of anti‐fungal and insecticide amides in adult plants, plantlets and callus from Piper tuberculatum by reverse‐phase high‐performance liquid chromatography
Authors: Debonsi Navickiene Hosana M. , Bolzani Vanderlan da S. , Kato Massuo J. , Pereira Ana Maria S. , Bertoni Bianca Waléria , França Suzelei Castro , Furlan Maysa
Published: September 2003

A rapid, sensitive and reliable reverse‐phase HPLC method was used for the quantitative determination of the anti‐fungal and insecticide amides, dihydropiplartine (1), piplartine (2), Δα,β‐dihydropiperine (3) and pellitorine (4) in plants in natura, in plantlets in vitro and ex vitro, and in callus of Piper tuberculatum. Well‐resolved peaks were obtained with good detection response and linearity in the range of 15.0–3000 µg/mL. The plants in natura contained compounds 1–4, the plantlets ex vitro and in vitro accumulated compounds 1–2 and 1–4, respectively, while only amide 4 was found in callus. Copyright © 2003 John Wiley & Sons, Ltd.
The risk of liver disorders in women prescribed cyproterone acetate in combination with ethinyloestradiol (Dianette): a nested case‐control study using the GPRD
Authors: Seaman H. E. , de Vries C. S. , Farmer R. D. T.
Published: September 2003

Purpose

To explore the risk of liver disorders associated with cyproterone acetate combined with ethinyloestradiol (CPA/EE). CPA/EE is licensed in the UK for the treatment of women with acne and hirsutism and is a treatment option for polycystic ovary syndrome (PCOS). It acts as a contraceptive also.

Methods

Using the General Practice Research Database, we conducted a cohort analysis and case‐control study in women aged 15–39 with acne, hirsutism or PCOS to estimate the risk of liver disorders associated with CPA/EE.

Results

Compared with cases exposed to conventional combined oral contraceptives (COCs), the age‐adjusted incidence rate ratio for liver disorders in women using CPA/EE was 1.7 (95%CI: 0.9,3.4) and compared with no use it was 1.5 (95%CI: 0.8, 2.8). In the case‐control study, the adjusted odds ratio (OR) for liver disorders in women exposed to CPA/EE was 1.6 (95%CI: 0.7, 3.5) and 0.8 (95%CI: 0.5, 1.3) for exposure to conventional COCs, compared with no use. The risk of liver disorders in women prescribed CPA/EE was not significantly greater than that in women prescribed conventional COCs (OR: 2.1 [95%CI: 0.9, 4.8]).

Conclusion

Our results do not indicate an increased risk for liver disorders associated with CPA/EE use in women with acne, hirsutism or PCOS after adjusting for potential confounding. This may be due to lack of statistical power. Copyright © 2003 John Wiley & Sons, Ltd.
Hemicyanine n‐butyltriphenylborate salts as effective initiators of free‐radical polymerization photoinitiated via photoinduced electron‐transfer process
Authors: Kabatc Janina , Jędrzejewska Beata , Pączkowski Jerzy
Published: September 2003

Two different groups of hemicyanine n‐butyltriphenylborate salts (HCBo) were synthesized and examined to verify the possibility of the Marcus equation application for the description of the kinetics of free‐radical polymerization photoinitiated via the photoinduced electron‐transfer process. The free‐energy change (ΔGel) of the electron‐transfer process between an excited acceptor and a donor were experimentally determined for 14 new organic photoredox pairs. The relationship between the rate of polymerization and the free‐energy change for the electron‐transfer process displayed typical Marcus kinetic behavior. The photoreduction of the HCBo produced colorless products. The experimental results indicated that the rate of the light‐absorber bleaching process does not compete with the photoinitiation of polymerization. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3017–3026, 2003
Self‐organized liquid‐crystalline polyethers obtained by grafting tapered mesogenic groups onto poly(epichlorohydrin): Toward biomimetic ion channels
Authors: Ronda Joan Carles , Reina José Antonio , Cádiz Virginia , Giamberini Marta , Nicolais Luigi
Published: September 2003

A set of high‐molecular‐weight new side‐chain liquid‐crystalline polyethers was obtained by chemical modification of poly(epichlorohydrin) with potassium 3,4,5‐tris(dodecyloxy)benzoate. The degree of modification ranged from 48 to 70% depending on the reaction conditions, and the upper value was an apparent modification plateau. NMR characterization indicated that no side reactions of any kind occurred (e.g., deshydrohalogenation). All copolymers had a nematic columnar mesophase whose range of stability depended on the modification degree. X‐ray diffraction experiments performed on mechanically oriented samples showed that tapered groups were tilted with respect to the column axes. Also X‐ray experiments and density measurements demonstrated that the number of disks per unit cell decreased as the modification degree increased. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2918–2929, 2003
Synthesis and monomer reactivity ratios of methyl methacrylate and 2‐vinyl‐4,4′‐dimethylazlactone copolymers
Authors: Stanek Lee G. , Heilmann Steven M. , Gleason William B.
Published: September 2003

We report the monomer reactivity ratios for copolymers of methyl methacrylate (MMA) and a reactive monomer, 2‐vinyl‐4,4′‐dimethylazlactone (VDMA), using the Fineman–Ross, inverted Fineman–Ross, Kelen–Tudos, extended Kelen–Tudos, and Tidwell–Mortimer methods at low and high polymer conversions. Copolymers were obtained by radical polymerization initiated by 2,2′‐azobisisobutyronitrile in methyl ethyl ketone solutions and were analyzed by NMR, gas chromatography (GC), and gel permeation chromatography. 1H NMR analysis was used to determine the molar fractions of MMA and VDMA in the copolymers at both low and high conversions. GC analysis determined the molar fractions of the monomers at conversions of less than 27% and greater than 65% for the low‐ and high‐conversion copolymers, respectively. The reactivity ratios indicated a tendency toward random copolymerization, with a higher rate of consumption of VDMA at high conversions. For both low‐ and high‐conversion copolymers, the molecular weights increased with increasing molar fractions of VDMA, and this was consistent with the faster consumption of VDMA (compared with that of MMA). © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3027–3037, 2003
On estimation of frequency data with censored observations
Authors: Menjoge Shailendra S.
Published: September 2003

The problem of the estimation of mean frequency of events in the presence of censoring is important in assessing the efficacy, safety and cost of therapies. The mean frequency is typically estimated by dividing the total number of events by the total number of patients under study. This method, referred to in this paper as the ‘naïve estimator’, ignores the censoring. Other approaches available for this problem require many assumptions that are rarely acceptable. These include the assumption of independence, constant hazard rate over time and other similar distributional assumptions. In this paper a simple non‐parametric estimator based on the sum of the products of Kaplan–Meier estimators is proposed as an estimator of mean frequency, and its approximate variance and standard error are derived. An illustration is provided to show the derivation of the proposed estimator. Although the clinical trial setting is used in this paper, the problem has applications in other areas where survival analysis is used and recurrent events are studied. Copyright © 2003 John Wiley & Sons, Ltd.
Repeated‐measures models in the analysis of QT interval
Authors: Dmitrienko Alex , Smith Brian
Published: September 2003

Because of the recent regulatory emphasis on issues related to drug‐induced cardiac repolarization that can potentially lead to sudden death, QT interval analysis has received much attention in the clinical trial literature. The analysis of QT data is complicated by the fact that the QT interval is correlated with heart rate and other prognostic factors. Several attempts have been made in the literature to derive an optimal method for correcting the QT interval for heart rate; however the QT correction formulae obtained are not universal because of substantial variability observed across different patient populations. It is demonstrated in this paper that the widely used fixed QT correction formulae do not provide an adequate fit to QT and RR data and bias estimates of treatment effect. It is also shown that QT correction formulae derived from baseline data in clinical trials are likely to lead to Type I error rate inflation. This paper develops a QT interval analysis framework based on repeated‐measures models accomodating the correlation between QT interval and heart rate and the correlation among QT measurements collected over time. The proposed method of QT analysis controls the Type I error rate and is at least as powerful as traditional QT correction methods with respect to detecting drug‐related QT interval prolongation. Copyright © 2003 John Wiley & Sons, Ltd.
A constraint‐based approach for the optimum redesign of a packaging operation
Authors: Hicks B. J. , Medland A. J. , Mullineux G.
Published: September 2003

The task of the design engineer is to configure a design such that a predetermined functional requirement is fulfilled, and that it is achieved within a given set of performance criteria. As a design evolves, so these performance criteria change, driven by the ever‐increasing needs of the customer and the inherent competition between manufacturers. It is during this evolutionary process that the engineer demands a CAD system which can represent knowledge about the design and explore solutions regarding the relationship between geometry and behaviour. This is necessary in order to realize the full potential of an existing design, or to examine modifications to an existing design that may achieve the desired performance characteristics. The work described in this paper uses a constraint‐based modelling environment to represent and analyse a high‐speed packaging operation. The goal of the modelling work is to produce an optimal design solution for the given performance requirements, as well as to satisfy the constraints imposed by the existing machine system and packaging process. The construction of the model is described and the identification and representation of the design constraints are discussed. These constraints are then applied to a possible machine modification or redesign and an optimized configuration is developed in the modelling environment. Copyright © 2003 John Wiley & Sons, Ltd.
Decreased enzyme activity of hepatic thioredoxin reductase and glutathione reductase in rabbits by prolonged exposure to inorganic arsenate
Authors: Nikaido Masatoshi , Pi Jingbo , Kumagai Yoshito , Yamauchi Hiroshi , Taguchi Keiko , Horiguchi Satomi , Sun Yang , Sun Guifan , Shimojo Nobuhiro
Published: September 2003

Chronic exposure of humans to inorganic arsenic, mainly pentavalent arsenate (iAsV), results in drinking water–induced oxidative stress (Pi et al., 2002). Thioredoxin reductase (TR) and glutathione reductase (GR) are the two critical enzymes in the response to oxidative stress in vivo. In the present study we examined alterations in enzyme activities of hepatic TR and GR from prolonged exposure of male New Zealand white rabbits to iAsV. Exposure of rabbits to iAsV in drinking water (5 mg/L) for 18 weeks caused a significant suppression of hepatic TR and GR activities, of approximately 30% and 20%, respectively, below controls. In vitro experiments suggested that trivalent inorganic arsenic (iAsIII) but not pentavalent arsenicals including iAsV, monomethylarsonic acid (MMAsV), and dimethylarsinic acid (DMAsV) affected the hepatic TR activity of rabbit. So it was suggested that in the present study iAsV ingested via drinking water was metabolized to reactive trivalent arsenicals, such as iAsIII, which may play an important role in the decreased TR and GR activities from prolonged exposure to iAsV observed in vivo. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 306–311, 2003.
The fungicide benomyl inhibits differentiation of neural tissue in the Xenopus embryo and animal cap explants
Authors: Yoon Chun‐Sik , Jin Jung‐Hyo , Park Joo‐Hung , Youn Hyun‐Joo , Cheong Seon‐Woo
Published: September 2003

The toxic effect of benomyl on the embryogenesis of Xenopus laevis was investigated, and the tissues most affected by benomyl were identified. The toxicity of benomyl at various concentrations (5–20 μM) was tested with the Xenopus frog embryo teratogenesis assay (FETAX), used with slight modification. All test embryos subjected to 20 μM of benomyl died, and exposure to 10 and 15 μM benomyl produced growth inhibition and 11 types of severe external malformations. Histological examination of the test embryos showed dysplasia of the brain, eyes, intestine, otic vesicle, and muscle and swelling of the pronephric ducts and integuments. Among the tissues and organs affected, malformation of neural tissue was the most severe. The presumptive ectoderm isolated from st. 9 embryo was cultured in 10 ng/mL of activin A to induce neural tissue and mesoderm. When it was cultured with 10 ng/mL of activin A in the presence of 1 and 10 μM of benomyl, neural tissue induction was inhibited more severely than that of any other tissue. The gene expression of cultivated explants was investigated by reverse transcription–polymerase chain reaction (RT‐PCR) assay in order to study the inhibition of neural tissue by benomyl. The results showed that with increasing benomyl concentration, the expression of the neural‐specific marker NCAM (neural cell adhesion molecule), was more strongly inhibited than the muscle‐specific marker muscle actin. Electron micrographs of test explants showed many residual yolk platelets and mitochondrial degeneration. In the present investigation the most severe toxic effects of benomyl were seen in the nerve tissues of the Xenopus embryo. This inhibition of neural development may have been caused by the inhibition of the assembly of neural microtubules and by the effect of benomyl on neuronal proliferation and migration. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 327–337, 2003.
Cell alterations but no DNA strand breaks induced in vitro by cylindrospermopsin in CHO K1 cells
Authors: Fessard Valérie , Bernard Cécile
Published: September 2003

Cylindrospermopsin has been involved in some cyanobacterial blooms associated with animal and human intoxications in different countries. Liver is the main target organ even though thymus and kidney are also affected. Its toxic effect has been shown to be induced by protein synthesis inhibition. However, further research about its toxicological potential is required, as revealed by the U.S. Unregulated Contaminant Monitoring Regulation (US UCMR) meeting in 2001. Induction of DNA damage by cylindrospermopsin has been reported by some authors either by a direct effect on DNA or by an indirect effect on associated macromolecules. This study focused on evaluating its in vitro genotoxic potential using the comet assay coupled to various cell alteration measurements. No DNA damage was detected by the alkaline comet assay on Chinese hamster ovary (CHO) K1 cells after 24 h of treatment with cylindrospermopsin concentrations of 0.5 and 1 μg mL−1. However, inhibition of cell growth was noticed as well as cell blebbing and rounding. These morphological effects were linked to cytoskeletal reorganization (mainly microfilaments) but not to apoptosis. This study concluded that cylindrospermopsin does not obviously react directly with DNA in CHO K1 cells. But the hypothesis of its metabolization into a genotoxic product must be explored further. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 353–359, 2003.
Ghrelin, a widespread hormone: insights into molecular and cellular regulation of its expression and mechanism of action
Authors: Gualillo Oreste , Lago Francisca , Gómez-Reino Juan , Casanueva Felipe F , Dieguez Carlos
Published: September 2003

The recent discovery of ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, is the result of almost 25 years of research by many groups all around the world, and represents a milestone in our understanding of growth hormone secretion and energy homeostasis. This minireview is focused on recent studies on ghrelin, pointing out the cellular and molecular mechanisms involved in the gene expression of ghrelin since recent studies have unequivocally shown that ghrelin biological activity is dependent on a peculiar post‐translational processing. Major interest in this peptide derived from the fact that, in addition to other effects, it is involved in the regulation of energy balance by inducing weight gain and reducing fat utilization. These activities are likely mediated by a CNS network of cells that is also modulated by other hormones such as leptin. Ghrelin has emerged as a premeal initiation factor that informs CNS about the status of the energy balance. The development of ghrelin analogs, agonists and antagonists, appears as a suitable approach for possible therapeutic intervention in a variety of disease states linked to alterations in body weight homeostasis.
Nitric oxide‐dependent cytoskeletal changes and inhibition of endothelial cell migration contribute to the suppression of angiogenesis by RAD50 gene transfer
Authors: Kook Hyun , Ahn Kyu Youn , Lee Song Eun , Na Hee Sam , Kim Kyung Keun
Published: September 2003

Previous reports showed that human RAD50 (hRAD50) gene delivery induced regression of an experimental rat tumor and porcine neointimal hyperplasia. In this study, we examined the effects of hRAD50 on the morphological changes and migration of endothelial cells (EC) as possible mechanisms by which hRAD50 might block angiogenesis. Quantitative image analysis revealed significant inhibition of the number and total area of blood vessels in rat tumor tissues following hRAD50 gene delivery. hRAD50 distorted actin and tubulin arrangements, and significantly reduced the F/G‐actin ratio and increased the nitric oxide (NO) production in the primary cultured human EC. These effects were blocked by pretreatment with L‐NAME (NG‐nitro‐L‐arginine‐methyl ester), a NO synthase inhibitor. FACScan analysis showed that NO was involved in the necrosis and apoptosis of EC by hRAD50. hRAD50 also inhibited EC migration in an in vitro wound‐healing model. These results indicate that NO‐dependent cytoskeletal changes and inhibition of EC migration contribute to the suppression of angiogenesis by hRAD50 delivery in vivo.
A study of metabolic compartmentation in the rat heart and cardiac mitochondria using high‐resolution magic angle spinning 1H NMR spectroscopy
Authors: Bollard M.E , Murray A.J , Clarke K , Nicholson J.K , Griffin J.L
Published: September 2003

High‐resolution magic angle spinning (MAS) 1H nuclear magnetic resonance (NMR) spectroscopy is increasingly being used to monitor metabolic abnormalities within cells and intact tissues. Many toxicological insults and metabolic diseases affect subcellular organelles, particularly mitochondria. In this study high‐resolution 1H NMR spectroscopy was used to examine metabolic compartmentation between the cytosol and mitochondria in the rat heart to investigate whether biomarkers of mitochondrial dysfunction could be identified and further define the mitochondrial environment. High‐resolution MAS spectra of mitochondria revealed NMR signals from lactate, alanine, taurine, choline, phosphocholine, creatine, glycine and lipids. However, spectra from mitochondrial extracts contained additional well‐resolved resonances from valine, methionine, glutamine, acetoacetate, succinate, and aspartate, suggesting that a number of metabolites bound within the mitochondrial membranes occur in ‘NMR invisible’ environments. This effect was further investigated using diffusion‐weighted measurements of water and NMR spectroscopy during state 2 and state 3 respiration. State 3 respiration caused a decrease in the resonance intensity of endogenous succinate compared with state 2 respiration, suggesting that coupled respiration may also modulate the NMR detection of metabolites within mitochondria.
Photophysical properties ofProchlorococcus marinusSS120 divinyl chlorophylls and phycoerythrin in vitro and in vivo
Authors: Steglich Claudia , Mullineaux Conrad W , Teuchner Klaus , Hess Wolfgang R , Lokstein Heiko
Published: September 2003

Prochlorococcus marinusSS120 is an ecologically important and biochemically intriguing marine cyanobacterium. In addition to divinyl chlorophylls (DV‐Chls)aandbit possesses a particular form of phycoerythrin (PE), but no other phycobilins and therefore no complete phycobilisomes. Here, a spectroscopic characterisation of these DV‐Chls and PE is provided. Comparison of fluorescence quantum yields, excited state lifetimes and absorption characteristics indicate similar light‐harvesting properties of the DV‐Chls as their monovinyl counterparts. PE, which is present only in tiny amounts, was purified and considerably enriched. A phycourobilin to phycoerythrobilin ratio of 3:1 chromophores per (αβ) PE monomer is suggested. The in vitro fluorescence lifetime of PE is 1.74 ns. In vivo time‐resolved fluorescence measurements with synchrotron radiation were used to investigate the possible role of PE in light‐harvesting. The fluorescence decay time for PE is about 550 ps, indicating an unusually slow excitation energy transfer. The decay time slowed to 1 ns after addition of glycerol to cell cultures. The contribution of PE to total light‐harvesting capacity was estimated to be about one (αβ) PE monomer per 330 DV‐Chlbmolecules. Thus, the capacity of PE to function primarily as a photosynthetic light‐harvesting pigment inP. marinusSS120 is low.