bluuebunny/crossref_metadata_2025 huggingface dataset:
Geochemical evidence for Holocene palaeodischarge variations in lacustrine records from the Westeifel Volcanic Field, Germany: Schalkenmehrener Maar and Meerfelder Maar
Authors: Schettler Georg , Rein Bert , Negendank Jörg F.W.
Published: January 2003

Various chemical elements (Fe, Mn, U, Mo) can be transported in both dissolved and solid form and then deposited into lakes. Geochemical profiles of these elements in lacustrine records are therefore potential palaeoclimatic proxies since there should be a positive correlation between discharge from the catchment and dissolved element input. Flux rates for the dissolved input of uranium Ul(t) and the total allochthonous minerog enic deposit were calculated for an annually laminated sediment record from the Lake Schalkenmehrener Maar (SMM). Calculated Ul(t) values were critically examined with the help of monitoring data (hydrochemistry, soil chemistry) from the modern Meerfelder Maar (MFM) catchment. The calculated Ul(t)-profile and the variation of varve thickness show a corresponding pattern. The palaeoproductivity of Lake SMM with respect to diatomaceous matter was clearly controlled by the discharge from the catchment. The deposition rate of allochthonous minerogenic matter, which received significant aeolian contributions from a remote source during the early Holocene, has been found to correlate with the Ul(t) values. The deposit of dust on the lake surface is undoubtedly influenced by rainfall events during which fine particles are washed out from the atmosphere. A higher discharge of groundwater from the lake's catchment is indicated at around 10 200 (D1), 8500 (D2), 7150 (D3), 6000 (D4) and between about 4050 and 3300 varve years BP (D5), Significantly lower discharge was obtained for periods around 11 000, 9500, 5000 and after about 3050 varve years BP. There are several indications of a lowering of the SMM lake level between 8100 and 7300 varve years BP. A drier climate can, therefore, be suggested as likely for this period. In addition to three early Holocene periods, which display an increase in element input into Lake MFM (thus supporting the positive discharge indications D1, D2, D3 from the SMM sediment profile), a general increase of discharge since the Neolithic period due to anthropogenic forest clearance can be inferred from the MFM sediment record.
Radiocarbon chronology andδ13C analysis of mid-to late-Holocene aeolian environments, Guadalupe Mountains National Park, Texas, USA
Authors: Wilkins David E. , Currey Donald R.
Published: January 2003

The Red Dunes of Guadalupe Mountains National Park are quartzose sand sheets and dunes stabilized by sparse plant cover. Stratigraphy, radiocarbon dating, and δ13C analysis were examined in two of the larger arroyos for correlating evidence of aeolian deposition, which in this basin is taken as an indication of arid conditions. Four quartz-sand lithostratigraphic units, representing intervals of aeolian activity, are identified. Radiocarbon dates provide constraint on the timing of the three youngest quartz-sand units. A mid-Holocene aeolian interval, represented by a single radiocarbon date of 6350± 70 BP, is interpreted as transitional to an altithermal regime. A neopluvial period, dated at 3370± 70 BP, separates mid-and late-Holocene aeolian activity. Late-Holocene time is characterized by generally drier conditions than present and almost continuous aeolian activity from 1690± 80 BP to 350± 0 BP. Stable carbon isotope analysis suggests an abrupt shift to generally cooler summer temperatures during this late-Holocene arid interval. While climate changes identified in the stratigraphic record broadly agree with changes reported elsewhere in the southwestern United States, differences in the timing of climate onset between this and adjacent regions suggest that climate change was time transgressive, and supports the recognition of the spatial and temporal variability of climates in response to local and regional controls.
A high-resolution proxy record of rainfall and ENSO since AD 1550 from layering in stalagmites from Anjohibe Cave, Madagascar
Authors: Brook George A. , Rafter Margaret A. , Railsback L. Bruce , Sheen Shaw-Wen , Lundberg Joyce
Published: January 2003

Two stalagmites from Anjohibe Cave have annual layers made up of inclusion-rich calcite over inclusion-free calcite or of darker aragonite over clear aragonite. Geochemical evidence indicates that the basal units are deposited slowly in the wet season and the upper units more rapidly in the dry season. For the period with rainfall and temperature data (ad 1951–1992), layer thickness correlates well with the Southern Oscillation Index (SOI), as well as rainfall, water surplus, and actual evapotranspiration (AET) at nearby Majunga. Com parison of the layer record for one stalagmite with 1866–1994 SOI data indicates that layer thickness correlates best with the frequency and intensity of warm, low-phase SO (El Niño) events, not with average SOI conditions. In addition, the 415-year layer thickness time-series from that speleothem agrees remarkably well with historical records of El Niño frequency, with Galápagos (Ecuador) coral records of sea-surface temperature in the eastern Pacific, and with accumulation rates on the Quelccaya Ice Cap of Peru, which are lower at times of high El Niño frequency.
Climatic information from tree-rings of Pinus sylvestris L. and a reconstruction of summer temperatures back to AD 1500 in Femundsmarka, eastern Norway, using partial least squares regression (PLS) analysis
Authors: Kalela-Brundin Maarit
Published: January 2003

Chronologies of tree-ring width (RW), earlywood width (EW) and latewood width (LW) were costructed back to AD 1500 (AD 1360 with small sample size) using Scots pine, Pinus sylvestris L. in the Femundsmarka area, eastern Norway. The influence of 17 monthly temperature, 17 monthly precipitation and three prior growth variables on RW, EW and LW indices were studied for different periods since AD 1872 using partial least squares regression (PLS). The most important variable for explaining radial growth was the current July temperature with regard to RW, EW and LW. Other important variables were the temperatures in the preceding December and the current August and June, and the tree-ring index of the previous year. No common and consistent pattern was found for monthly precipitation and previous summer temperatures. The climate-growth responses from the different standard 30-year periods varied considerably, indicating that the radial growth is very sensitive to even minor climatic changes. Estimates of July and July-August temperatures were made back to AD 1500 using PLS with RW, EW and LW chronologies as predictors. Best reconstructions were achieved with a six- or eight-variable model in which July and July-August temperatures in year t are estimated as functions of RW, EW and LW from two, three or four succeeding years (Q 1, t, t + 1, t + 2). The best reconstruction equations of July and July-August temperature accounted for 61%, and 56% of the temperature variance over a 61-year calibration period and 53%, and 34%/ of the variance over an independent 61-year verification period. The reconstructions indicate that, since AD 1500, warm summers clustered around AD 1510, 1770 and 1940, and the cool summers around AD 1600, 1710 and 1800. Summer temperatures have increased since AD 1860 even though there was a short cold period centred around AD 1910. It is concluded that the PLS method is well suited to the analysis of climate-growth relationships and creating models for reconstructing past climate variables.
The influence of simultaneous whole body exposure to cigarette smoke and low-protein diet feeding on fertility, reproduction, and progeny of rats
Authors: Florek E , Szymanowski K , Wrzosek J , Piekoszewski W , Biczysko W , Marszaek A
Published: January 2003

The aim of the present study was to evaluate the toxicological influence of different concentrations of tobacco smoke and low-protein diet on fertility, reproduction, and survival of offspring of Wistar female rats. We studied three generations, two litters in each. There were 192 animals in parent generation. Animals were exposed to three different concentrations of tobacco smoke that were reflected by the carbon monoxide (CO) concentration (500, 1000, and 1500 mg CO/m3 air) during 11 weeks (six before and two weeks during mating, and three weeks of pregnancy). Additionally, animals were divided into two subgroups that were fed normal or low-protein diet. In the present study, we concentrated on the indices describing the reproduction ability, fertility, and rearing of pups of mothers exposed to tobacco smoke. The parameters of newborns survival were estimated also. We concluded that neither tobacco smoke exposure nor the low-protein diet changed the duration of pregnancy. The tobacco smoke in all doses and low-protein diet had a negative influence on fertility, reproduction, and survival of newborns from exposed mothers. This influence was mainly attributed to the tobacco smoke exposure. The levels of carboxyhaemoglobin were increasing with increasing tobacco smoke concentration.
Biointerventional cardiology: the future interface of interventional cardiovascular medicine and bioengineering
Authors: Thompson Craig A , Oesterle Stephen N
Published: January 2003

Major advances in cardiovascular intervention for chronic disease are underway. These innovations lie at the interface of minimally invasive catheter-based technologies and biologic approaches for the management of complex cardiovasculardiseases. This review highlights key areas where such ‘biointerventional’ cardiovascular therapies are envisioned to occur: cardiac cell transplantation, myocardial gene therapy, genetic and photodynamic endovascular interventions, and vascular tissue engineering.
Physical training for intermittent claudication: a comparison of structured rehabilitation versus home-based training
Authors: Degischer Steve , Labs Karl-Heinz , Hochstrasser Jacques , Aschwanden Markus , Tschoepl Martin , Jaeger Kurt A
Published: January 2003

In a non-randomized, open-label study results after a structured institution-based peripheral arterial occlusive disease (PAD) rehabilitation program were compared with the results of training at home. Three groups were compared: group 1 (n = 19) PAD rehabilitation; group 2 (n = 19) PAD rehabilitation + clopidogrel 75 mg once daily; group 3 (n = 21) home-based training. The training period was 3 months for all groups, which was followed by a 3-month observation phase (without prescribed training). The rehabilitation program consisted of 3 training hours per week. Background variables, demographics, and baseline claudication distances were comparable between groups. After 3 months of training the absolute claudication distances (ACD) improved by 82.7%, 131.4%, and 5.4% for groups 1, 2 and 3. The initial claudication distances (ICD) changed by 163.8%, 200.6%, and 44.4%, respectively. All changes, except the ACD result for group 3, were statistically significant (p 0.05).

Structured training groups (1 and 2) performed significantly better than group 3 (p 0.05). When results from groups 1 and 2 were pooled, ACDs changed from 493.3 218.1 to 1026.0 468.9 m, 546.0 378.8 m [95% CI 417.8 - 674.2 m]; p 0.05. ICDs improved from 175.3 110.8 m to 493.1 326.7 m, 320.8 315.9 m [95% CI 213.9 - 427.7 m]; p 0.05. The difference between the pooled mean results of the structured training groups and the results of group 3 amounted to 474.3 m [95% CI 270.2 - 678.4 m] and 242.4 m [95% CI 99.0 - 385.7 m], for ACD and ICD, respectively.

Structured, supervised PAD rehabilitation is a highly efficacious treatment for intermittent claudication and may be regarded as the present gold standard among conservative treatment options.
Poly(L-lysine) as a model drug macromolecule with which to investigate secondary structure and microporous membrane transport, part 2: diffusion studies
Authors: Chittchang Montakarn , Salamat-Miller Nazila , Alur Hemant H , Velde David G Vander , Mitra Ashim K , Johnston Thomas P
Published: January 2003

Peptide drugs are hydrophilic in nature and so their preferred pathway of membrane transport is by the paracellular route, which primarily involves passive diffusion across intercellular pores. The objective of the present study was to investigate the effect of secondary structure on the aqueous diffusion of a model polypeptide, poly(l-lysine), through a microporous membrane. The primary aim was to systematically evaluate the variables (e.g. viscosity and/or hydrodynamic radius) that may contribute to the difference, if any, in the calculated values of the aqueous diffusion coefficient (Daq) for each conformer of poly(l-lysine). Variations in pH and temperature of the medium were used to induce secondary structural changes in poly(l-lysine). Transport studies were conducted for 3 h at 25 or 37°C using side-by-side diffusion cells. Hydrophilic microporous polyester membranes with a 1-μm pore diameter were used to measure the free diffusion of each conformer. The values for the apparent permeability (Papp) and Daq were calculated using standard equations. The viscosity of each conformer solution was determined and the hydrodynamic radius of each conformer was then estimated. At 25°C, both Papp and Daq of the α-helix conformer were approximately the same as those of the random coil conformer. In contrast, at 37°C, the Papp and the Daq of the β-sheet conformer were significantly (P < 0.05) less than those of the random coil conformer. At 25°C, the solutions containing primarily either the random coil or the α-helix conformers had approximately the same viscosity. On the other hand, at 37°C, the solutions containing the β-sheet conformer had a significantly (P < 0.05) higher viscosity than when this conformer was absent. The random coil and the α-helix conformers appeared to have comparable sizes, whereas the hydrodynamic radius estimated for the β-sheet conformer was significantly (P < 0.05) larger than those for the other two conformers. In summary, changing the secondary structure of poly(l-lysine) from the random coil to the α-helix did not affect its Papp and intrinsic Daq. On the other hand, appearance of the β-sheet conformer significantly decreased the values of Papp and Daq. The differences appeared to result from the significantly higher solution viscosity as well as the extended structure associated with the β-sheet conformer of poly(l-lysine). This strategy may represent a potential mechanism to sustain the delivery of therapeutic peptide drugs from a controlled drug delivery device.
Effects of histamine H2-receptor antagonists on human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal peptide
Authors: Itoh Hiroki , Naito Takafumi , Takeyama Masaharu
Published: January 2003

The effects of the histamine H2-receptor antagonists (H2-antagonists), ranitidine, nizatidine, cimetidine and famotidine, on plasma levels of gastrointestinal peptides, calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP) was investigated with respect to regulation of gastric mucosal blood flow, in healthy volunteers. H2-Antagonists or placebo was orally administered to five healthy male volunteers. Venous blood samples were taken before and after drug administration. The levels of plasma gastrointestinal peptides were determined by enzyme immunoassay. The administration of ranitidine and nizatidine caused significant increases in plasma CGRP and SP levels at 30 to 120 min compared with the placebo group. Peak plasma CGRP levels (39.8 ± 3.1 and 40.6 ± 3.6 pg mL−1) were achieved 60 min after administration of ranitidine and nizatidine, respectively. Maximum plasma SP levels (21.3 ± 5.2 and 22.8 ± 4.2 pg mL−1) were reached 60 min after administration of ranitidine and nizatidine, respectively. However, all H2-antagonists did not alter the levels of VIP. The released CGRP and SP by ranitidine and nizatidine administration may produce a gastroprotective effect, increase mucosal blood flow, and inhibit acid secretion in the gastrointestinal tract.
Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract
Authors: de Moura R Soares , Viana F S Costa , Souza M A V , Kovary K , Guedes D C , Oliveira E P B , Rubenich L M S , Carvalho L C R M , Oliveira R M , Tano T , Correia M L Gusmão
Published: January 2003

Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol-free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g−1) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate-salt and NG- nitro-L-arginine methyl ester (L-NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre-contracted with norepinephrine, bolus injections of GSE induced endothelium-dependent vasodilatation that was substantially inhibited by L-NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration-dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.
Inhibition and possible induction of rat CYP2D after short- and long-term treatment with antidepressants
Authors: Daniel Wladysława A , Haduch A , Wójcikowski J
Published: January 2003

The aim of this study was to investigate the influence of tricyclic antidepressants (imipramine, amitriptyline, clomipramine, desipramine), selective serotonin reuptake inhibitors (SSRIs: fluoxetine, sertraline) and novel antidepressant drugs (mirtazapine, nefazodone) on the activity of CYP2D, measured as a rate of ethylmorphine O-deethylation. The reaction was studied in control liver microsomes in the presence of the antidepressants, as well as in microsomes of rats treated intraperitoneally for one day or two weeks (twice a day) with pharmacological doses of the drugs (imipramine, amitriptyline, clomipramine, nefazodone 10 mg kg−1 i.p.; desipramine, fluoxetine, sertraline 5 mg kg−1 i.p.; mirtazapine 3 mg kg−1 i.p.), in the absence of the antidepressants in-vitro. Antidepressants decreased the activity of the rat CYP2D by competitive inhibition of the enzyme, the potency of their inhibitory effect being as follows: clomipramine (Ki = 14 μM) > sertraline ≈ fluoxetine (Ki = 17 and 16 μM, respectively) > imipramine ≈ amitriptyline (Ki = 26 and 25 μM, respectively) > desipramine (Ki = 44 μM) > nefazodone (Ki = 55 μM) > mirtazapine (Ki = 107 μM). A one-day treatment with antidepressants caused a significant decrease in the CYP2D activity after imipramine, fluoxetine and sertraline. After prolonged administration of antidepressants, the decreased CYP2D activity produced by imipramine, fluoxetine and sertraline was still maintained. Moreover, amitriptyline and nefazodone significantly decreased, while mirtazapine increased the activity of the enzyme. Desipramine and clomipramine did not produce any effect when administered in-vivo. The obtained results indicate three different mechanisms of the antidepressants-CYP2D interaction: firstly, competitive inhibition of CYP2D shown in-vitro, the inhibitory effects of tricyclic antidepressants and SSRIs being stronger than those of novel drugs; secondly, in-vivo inhibition of CYP2D produced by both one-day and chronic treatment with tricyclic antidepressants (except for desipramine and clomipramine) and SSRIs, which suggests inactivation of the enzyme apoprotein by reactive metabolites; and thirdly, in-vivo inhibition by nefazodone and induction by mirtazapine of CYP2D produced only by chronic treatment with the drugs, which suggests their influence on the enzyme regulation.
Influence of pharmaceutical quality on the bioavailability of active components from Ginkgo biloba preparations
Authors: Kressmann S , Biber A , Wonnemann M , Schug B , Blume H H , Müller W E
Published: January 2003

To be effective, herbal medicinal products are expected to meet comparable standards concerning the assessment of efficacy, safety and biopharmaceutical quality as chemically defined synthetic drugs as food supplements. However, these requirements are often not fulfilled, particularly regarding the characterization of biopharmaceutical properties such as in-vitro dissolution and in-vivo bioavailability. With respect to the relevance of biopharmaceutical quality of herbal medicinal products, two different Ginkgo biloba brands (test product: Ginkgo biloba capsules; reference product: Ginkgold) were analysed for dissolution rates and bioavailability of the most relevant active ingredients. Dissolution rates at pH 1 and 4.5 were determined according to the USP 23. The relative bioavailability of ginkgolide A, ginkgolide B and bilobalide was investigated after single oral administration of 120 mg Ginkgo biloba extract as tablets or capsules. Bioavailability data (area under the curve and peak concentration in plasma) were clearly different and did not show bioequivalence of test and reference products. The slow in-vitro dissolution of the test product resulted in a large decrease in bioavailability. These results indicate for the first time that the pharmaceutical properties of a herbal medicinal product have a significant impact on the rate and extent of drug absorption, and very likely on efficacy in humans.
Influence of hydroxypropyl-β-cyclodextrin on photo-induced free radical production by the sunscreen agent, butyl-methoxydibenzoylmethane
Authors: Scalia Santo , Simeoni Silvia , Barbieri Andrea , Sostero Silvana
Published: January 2003

The aim of the study was to investigate the effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) on the photo-induced production of free radicals by the sunscreen agent, butyl-methoxydibenzoylmethane (BMDBM). Spin-trapping/electron paramagnetic resonance spectroscopy was used to evaluate the formation of radicals and the extent of BMDBM photodegradation was measured by high-performance liquid chromatography. The stable 2,2,6,6-tetramethylpiperidine-1-oxyl, nitroxide radical (TEMPO) was used as spin-trap. Any free radicals generated during irradiation of the sunscreen agent will couple with the TEMPO radicals giving diamagnetic species and thus a decrease of the signal intensity in the electron paramagnetic resonance spectrum. Following 2-h illumination with simulated sunlight, the solution containing free BMDBM exhibited a 93.9% decrease of the intensity of the TEMPO signal. Under the same irradiation conditions, only a 12.2% reduction of the TEMPO concentration was measured in the sample containing BMDBM complexed with HP-β-CD. Moreover, the decrease of the spin-trap level observed for the HP-β-CD/BMDBM complex was not significantly different from that produced when solutions containing TEMPO only or TEMPO in the presence of HP- β-CD alone were subjected to irradiation. In addition, the photodegradation of the sunscreen agent was reduced by complexation with HP-β-CD (the extent of degradation was 27.6% for the complex compared with 63.1% for free BMDBM). The results obtained indicate that the free radicals generated by BMDBM when exposed to simulated sunlight are effectively scavenged by inclusion complexation of the sunscreen agent with HP-β-CD.
Solubilization of the lichen metabolite (+)-usnic acid for testing in tissue culture
Authors: Kristmundsdóttir Thórdís , Aradóttir Halldóra Aesa , Ingólfsdóttir Kristín , Ögmundsdóttir Helga M
Published: January 2003

The pharmacological testing of natural products can often be hampered by the poor solubility of such compounds in non-toxic solvents. There is thus a need for a suitable agent for solubilization of natural substances to allow testing on a variety of cell lines in-vitro. Such an agent should ideally have no direct effects on any of the commonly used cell lines from a variety of tissues and mammalian species to allow proper comparison. In this study, the lichen metabolite (+)-usnic acid, a dibenzofuran derivative, was used as a prototype for an insoluble natural product with the aim of finding a solvent that was both capable of solubilizing usnic acid and was free of direct activity against a test cell line. Solubilization was measured at different pH values in various concentrations of co-solvents (glycofurol 75, propylene glycol, polyethylene glycol 400), surfactants (polysorbate 20 and Cremophor RH40), and the complexing agent 2-hydroxypropyl-β-cyclodextrin. The solubility achieved in a 20% aqueous solution was 0.11 mg mL−1 for propylene glycol, 0.19 for PEG 400, 0.27 for glycofurol 75, 0.57 for Cremophor RH40, 0.68 for 2-hydroxypropyl-β-cyclodextrin and 0.84 for polysorbate 20. The direct effects of the various solvent systems were tested on the human leukaemia cell line K-562 in a standard proliferation assay. Most of the solvents proved toxic with the exception of propylene glycol, PEG 400 and 2-hydroxypropyl-β-cyclodextrin. Anti-proliferative activity of usnic acid could be demonstrated with an ED50 (amount of substance required to reduce thymidine uptake to 50% of uptake by untreated control culture) of 4.7μg mL−1 using PEG 400 and 2-hydroxypropyl-β-cyclodextrin but only the latter gave satisfactory solubility. 2-Hydroxypropyl-β-cyclodextrin was thus identified as a solubilizing agent that fulfilled both set criteria of solubility and lack of toxicity against the test cells.
Radioprotection: the non-steroidal anti-inflammatory drugs (NSAIDs) and prostaglandins
Authors: Lee Tat Khuen , Stupans Ieva
Published: January 2003

Clinical and experimental studies of the acute and late effects of radiation on cells have enhanced our knowledge of radiotherapy and have led to the optimisation of radiation treatment schedules and to more precise modes of radiation delivery. However, as both normal and cancerous tissues have similar response to radiation exposure, radiation-induced injury on normal tissues may present either during, or after the completion of, the radiotherapy treatment. Studies on both NSAIDs and prostaglandins have indeed shown some evidence of radioprotection. Both have the potential to increase the survival of cells but by entirely different mechanisms. Studies of cell kinetics reveal that cells in the mitotic (M) and late G2 phases of the cell cycle are generally most sensitive to radiation compared with cells in the early S and G1/G0 phases. Furthermore, radiation leads to a mitotic delay in the cell cycle. Thus, chemical agents that either limit the proportion of cells in the M and G2 phases of the cell cycle or enhance rapid cell growth could in principle be exploited for their potential use as radioprotectors to normal tissue during irradiation. NSAIDs have been shown to exert anti-cancer effects by causing cell-cycle arrest, shifting cells towards a quiescence state (G0/G1). The same mechanism of action was observed in radioprotection of normal tissues. An increase in arachidonic acid concentrations after exposure to NSAIDs also leads to the production of an apoptosis-inducer ceramide. NSAIDs also elevate the level of superoxide dismutase in cells. Activation of heat shock proteins by NSAIDs increases cell survival by alteration of cytokine expression. A role for NSAIDs with respect to inhibition of cellular proliferation possibly by an anti-angiogenesis mechanism has also been suggested. Several in-vivo studies have provided evidence suggesting that NSAIDs may protect normal tissues from radiation injury. Prostaglandins do not regulate the cell cycle, but they do have a variety of effects on cell growth and differentiation. PGE2 mediates angiogenesis, increasing the supply of oxygen and nutrients, essential for cellular survival and growth. Accordingly, PGE2 at sufficiently high plasma concentrations enhances cellular survival by inhibiting pro-inflammatory cytokines such as TNF-α and IL-1β. Thus, PGE2 acts as a modulator, rather than a mediator, of inflammation. Prospective studies have suggested the potential use of misoprostol, a PGE1 analogue, before irradiation, in prevention of radiation-induced side effects. The current understanding of the pharmacology of NSAIDs and prostaglandins shows great potential to minimise the adverse effects of radiotherapy on normal tissue.
Effect of gentamicin on pharmacokinetics of lysozyme in rats: interaction between megalin substrates in the kidney
Authors: Nagai Junya , Katsube Takayuki , Murakami Teruo , Takano Mikihisa
Published: January 2003

To investigate the pharmacokinetic interaction between substrates of megalin, a 600-kDa endocytic receptor abundantly expressed in the renal proximal tubules, we examined the effect of gentamicin infusion on the pharmacokinetics of fluorescein isothiocyanate (FITC)-lysozyme in rats. Infusion of gentamicin did not affect the plasma concentration-time profile of FITC-lysozyme. On the other hand, gentamicin significantly decreased the accumulation of FITC-lysozyme in the renal cortex and medulla, whereas the accumulation in the renal papilla, liver, brain and lung was not changed. Urinary excretion of FITC-lysozyme was increased by gentamicin, whereas there was no change in the biliary excretion of FITC-lysozyme or its degradation products. Gentamicin infusion had little influence on the ATP content in the renal cortex and urinary excretion of glucose, indicating that nephrotoxicity is not induced by short-term infusion of gentamicin. These findings suggest that lysozyme and gentamicin interact with each other in their reabsorption processes in the renal proximal tubules, probably by competing for their binding to megalin expressed in the apical membrane of the renal proximal tubules.
Physically cross-linked chitosan hydrogels as topical vehicles for hydrophilic drugs
Authors: Cerchiara T , Luppi B , Bigucci F , Orienti I , Zecchi V
Published: January 2003

Physically cross-linked chitosan hydrogels with lauric, myristic, palmitic or stearic acid were prepared by freeze-drying and have been studied for topical use. This study selected propranolol hydrochloride as a hydrophilic model drug to design a transdermal delivery system. We evaluated the effect of the nature of the cross-linker on drug permeation through porcine skin and the main permeation parameters (diffusion coefficient, flux and lag time) were calculated. All the chitosan hydrogels analysed provided more transcutaneous permeation of propranolol hydrochloride than the corresponding solution of the commercial drug. Among the different chitosan vehicles, chitosan-laurate and chitosan-myristate hydrogels enhanced lyophilised drug diffusion through the skin with respect to chitosan-palmitate and chitosan-stearate hydrogels. This can been explained by the interaction of the hydrogels with the stratum corneum, increasing the solubility of the drug in the skin.
Novel natural ligands for Drosophila olfactory receptor neurones
Authors: Stensmyr Marcus C. , Giordano Elena , Balloi Annalisa , Angioy Anna-Maria , Hansson Bill S.
Published: January 2003

Due to its well-defined genome, the fruitfly Drosophila melanogaster has become a very important model organism in olfactory research. Despite all the research invested, few natural odour ligands have been identified. By using a combined gas chromatographic—single receptor neurone recording technique (GC—SC), we set out to identify active odour molecules in head space-collected volatiles from preferred food sources, i.e. different overripe or rotting fruit. In total, we performed 101 GC—SC experiments on 85 contacted sensilla. Using GC—mass spectrometry, we identified 24 active compounds. Synthetic samples of these compounds were used to establish dose—response curves for several of the receptor neurone types encountered. The response patterns of individual neurones were repeatable, and neurones were found to reside in stereotyped pairs. In total,we identified eight distinct sensillum types based on response profiles of 12 olfactory receptor neurone types. In most recordings, a single GC peak would produce a strong response, whereas a few other, often chemically related,compounds would produce weaker responses. The GC—SC recordings revealed that the olfactory receptor neurones investigated were often selective and could be divided into distinct functional types with discrete characteristics. Dose—response investigations revealed very low response thresholds to the tested compounds. Six of the novel ligands were also tested for their behavioural effect in a T-maze set up. Of these, five elicited attraction and one elicited repulsion.
On stress concentration on nearly flat contacts
Authors: Ciavarella M , Macina G , Demelio G. P
Published: January 2003

Fretting fatigue can severely damage components subjected to oscillatory tangential loads, leading to a dramatic reduction in fatigue life and causing catastrophic ruptures. A conservative approach that can be used when considering the effect of stress concentration induced by fretting is to ensure that the peak stress is smaller than the fatigue limit of the material. However, this depends on details of the geometry as well as loading conditions. In the present work, the contact problem of a flat rounded punch in contact with a half-plane is considered, where a dovetail joint contact geometry is approximated and the classical Hertzian contact is retrieved in the limit. Developing the analytical results given by Ciavarella, Hills and Monno, an approximate Hertzian equivalent solution using Cattaneo superposition is obtained, leading to a simple formula to estimate the maximum tangential stress as a function of the load parameter Q/(f P) and geometric parameter a/b. The accuracy of the formula is checked numerically. The proposed formula gives a maximum error as low as 4 per cent in the case of zero bulk loads. For non-zero bulk loads an analytical solution is possible for the Hertzian case for moderate bulk. This leads to a second general formula containing the three dependencies (geometry, tangential load and bulk stress), which also gives a very good approximation for rounded flat and larger bulk loads, the error being generally well below 10 per cent.
Cracking under fretting fatigue: Damage prediction under multiaxial fatigue
Authors: Dubourg M-C , Berthier Y , Vincent L
Published: January 2003

Fretting is one of the plagues of modern industry. It occurs whenever a junction between components is subjected to cyclic sliding, with small relative displacements at the interface of the contacting surfaces. Further cyclic bulk stresses may be superimposed on to one or both components. The investigation of fretting wear and fretting fatigue started in the early 1970s. It is responsible for premature fatigue failures and often limits the life of a component.

Crack initiation and growth under fretting contact conditions have been investigated. The fretting map concepts allow the first degradation responses of the material—no degradation, cracking and wear—to be related to a fretting regime with its corresponding local contact conditions during fretting tests.

The fretting fatigue prediction models have been developed and compared to experiments conducted either on metallic or photoelastic materials. A special emphasis has been directed towards crack nucleation and early growth during stage I, the stage I-stage II transition and stage II crack growth (crack initiation sites, orientation, growth path, formation of a branch, growth mechanism). The analysis of the different stages that comprise the crack lifetime has been carried out in order to understand the effects of diverse parameters that are thought to influence the fretting damage.
An investigation of the fatigue and fretting performance of a representative aero-engine spline coupling
Authors: Leen S. B , Hyde T. H , Ratsimba C. H. H , Williams E. J , McColl I. R
Published: January 2003

The fatigue behaviour of a representative high-performance aero-engine spline coupling is investigated under test conditions designed to simulate in-service conditions. The test load cycles consist of major cycle torque and axial load, simulating maximum thrust, combined with minor cycle rotating bending moment and fluctuating torque, simulating life-limiting conditions at take-off. The objective of the study is to develop understanding of the fatigue behaviour of the coupling over a range of loading conditions, including interaction between low-cycle fatigue, fretting fatigue and fretting wear. This information is necessary for the development of fatigue and fretting-fatigue life prediction techniques. The test results are interpreted with the help of three-dimensional finite element models, which include the frictional contact between the spline teeth.
An overview of progress in the study of fretting fatigue
Authors: Hills D A , Mugadu A
Published: January 2003

This paper attempts to review some of the developments in the study of fretting fatigue. It is not comprehensive, but focuses on issues relating to the mechanics of the problem, the current state of understanding and the contributions from this laboratory. Work in progress and the likely directions research will follow are discussed.
Die design by a void index in multi-pass drawing
Authors: Kuboki T , Furuta H , Yoshikawa H , Neishi Y , Akiyama M
Published: January 2003

Die design was optimized for suppressing the void growth in multi-pass drawing. The void index to evaluate the void fraction in multi-pass drawing was first proposed, based on the well-known equation to predict the fracture limit in cold working. Using finite element analysis, the influence of die geometries on the void index was investigated and dies were designed to have the effect of suppressing void with the least minimum die length. A series of experiments was then carried out to verify the validity of the numerical analysis. The densities of drawn bars were measured and voids in microstructures were observed to verify the validity of the proposed void index.
The variation of the reflection coefficient of extensional guided waves in pipes from defects as a function of defect depth, axial extent, circumferential extent and frequency
Authors: Cawley P , Lowe M J S , Simonetti F , Chevalier C , Roosenbrand A G
Published: January 2003

The reflection coefficients of extensional guided modes from notches of different axial, circumferential and through-thickness extent in pipes of different diameters have been studied using finite element analysis. A selection of the predictions has also been validated by experiments. For part-thickness notches of a given circumferential extent and minimal axial extent, the reflection coefficient increases monotonically with depth at all frequencies, and increases with frequency at a given depth. When the wavelength is long compared to the pipe wall thickness, the reflection coefficient from part-thickness notches of a given circumferential extent is a strong function of the defect axial extent, the reflection being a maximum at an axial extent of about 25 per cent of the wavelength and a minimum at 0 and 50 per cent. The reflection coefficient is a linear function of the defect circumferential extent at higher frequencies (with frequency-diameter products greater than about 3000 kHz mm) where a ray theory analysis explains the behaviour, while at low frequencies the reflection coefficient at a given circumferential extent is reduced. In the high-frequency regime, the axial extent of a through-thickness defect has little influence on the reflection coefficient, while it is important at lower frequencies. Three-dimensional, finite element predictions in the high-frequency regime have shown that the reflection coefficient from a part-thickness, part-circumferential defect can be predicted by multiplying the reflection coefficient for an axisymmetric defect of the same depth and axial extent by that for a through-thickness defect of the same circumferential extent.
Effects of target curvature on the impact characteristics of simulated hailstones
Authors: Pan H , Render P M
Published: January 2003

As hail ingestion tests are introduced into aero-engine certification procedures, there is an increasing need for an understanding of ice particle behaviour within an engine. In this paper, the possible effects that ingested ice may have on a turbofan engine are briefly discussed. The objective of this paper is to study the effect of target curvature on ice-ball (simulated hailstone) impact characteristics. The target curvature effect was studied on the concave side of two curved plates using the experimental techniques of patternator and still photography. The results are compared with those from a flat plate. The comparison shows that the curvature has a small effect on post-impact particle sizes, and significantly decelerates the movement of the particles after an impact.
Trimming of flight simulation ground models
Authors: Mallock B , Harris C J , Hogg C R , Jones D
Published: January 2003

A number of research programmes are being undertaken in the field of flight simulation. This paper accounts for a component of the research being performed under one of those programmes. The specific aim of the work presented in the paper was to establish a means whereby an aircraft and its associated undercarriage could be ‘trimmed’. The equilibrium condition is found without the need to run the full simulation model. This results in time saving without loss of accuracy. The trimming algorithm is detailed in terms of the method of solution and the range of shock strut and tyre models that can be employed. Sample results are presented in the paper.
Riveted single lap joints Part 2: Fatigue life prediction
Authors: Fung C-P , Smart J
Published: January 2003

Fatigue lives of snap and countersunk riveted single lap joints with either one-row or two- rows of rivets have been predicted with fatigue laws using either local total strain range or effective stress obtained from finite element analyses and data obtained from fatigue testing of plates with holes. The finite element models of the joints were subjected to an alternating cyclic load; plasticity and nonlinear geometry are considered. The failures have also been metallurgically examined and gave evidence of fretting damage.

It was found that all the data points lie within a narrow band using the strain-life law although the band is wider when using the effective stress-life law, but it is impossible to predict the fatigue life from one kind of specimen to another using the conventional stress-life law.
Pitfalls of the substitution of sophistication for common sense
Authors: Howe D
Published: January 2003

Aviation history is littered with the debris of sophisticated projects that failed, at least in part, because inadequate initial thought was given to fundamental airworthiness considerations. The paper reviews a number of such projects with the intention of using past experience to derive lessons for the future and as an introduction to a consideration of the airworthiness of new technologies.
Night vision goggles—integration and operation in fast jet aircraft: An airworthiness perspective
Authors: Knowles S J
Published: January 2003

The use of night vision goggles on fast jets is becoming increasingly common; indeed, in certain theatres their use is operationally imperative. Novel systems such as these introduce new integration and safety problems. This paper provides an airworthiness perspective on the problems and presents some thoughts on the service release of such systems.
Optimum exciter placement for normal mode force appropriation
Authors: Wright J R , Holmes P S , Desforges M J , Cooper J E
Published: January 2003

A method of predicting optimum exciter placement for normal mode testing using an a priori mathematical dynamic model of the test structure is presented and compared to other approaches. A genetic algorithm is used to perform the search for an optimum where the number of possible combinations is too large for an exhaustive search. The proposed methodology is also shown to provide an estimate of the effective number of modes in a given frequency range. The technique is demonstrated using a mathematical model of a benchmark rectangular perspex plate and the results validated experimentally. The technique is also applied to a model of a representative aircraft structure. Finally, an extension of this methodology, suitable for mid-test exciter optimization, is described.
Evaluation of steam and water injection effects on gas turbine operation using explicit analytical relations
Authors: Mathioudakis K
Published: January 2003

The changes in performance of a gas turbine resulting from the injection of steam or water into the combustion chamber are evaluated using explicit analytic relations. From the values of performance parameters at an operating point without injection, the changes in fuel amount, power output, and efficiency are evaluated. The difference in behaviour of the case of water and steam injection are highlighted and explained. It is shown that the movement of the operating point on the compressor map, for single and twin shaft turbines, can also be predicted. Comparison with predictions of computer models show that the deviations are predicted accurately. Design data from a large number of commercial gas turbines are used to show the range of variation of parameter deviations and provide some general guidelines as to the size of expected parameter deviations for any gas turbine, when water or steam are injected between the compressor exit and the turbine inlet.
Performance analysis of directly coupled photovoltaic electro-mechanical systems
Authors: Kolhe M , Joshi J C
Published: January 2003

The application of stand-alone directly coupled photovoltaic (PV) electro-mechanical systems for water pumping has been the increase in remote rural areas of developing countries. The performance of directly coupled PV electro-mechanical systems has here been analysed for DC motors (that is, permanent magnet, series, and shunt motor) coupled to centrifugal and constant loads. It has been observed that for a good match between the characteristics of the PV array and the electro-mechanical system, the load should have torque-speed characteristics that increase as rapidly as possible in the operating region. The analysis has been carried out at different solar intensities with corresponding solar cell temperatures. It has been observed that the operating characteristics of the DC permanent magnet motor coupled with a centrifugal load are best situated relative to the maximum power point locus of a PV array, indicating the quality of matching between the system components. It operates most of the day time and because of its higher starting torque even at low solar intensities as compared with the DC shunt and series motors. The DC series motor coupled with a centrifugal load operates better compared to the DC shunt motor, but operates poorer than the DC permanent magnet motor.