bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacogenetic interactions of three candidate gene polymorphisms with ACE‐inhibitors or β‐blockers and the risk of atherosclerosis
Authors: Schelleman H. , Klungel O. H. , Witteman J. C. M. , Hofman A. , Van Duijn C. M. , De Boer A. , Stricker B. H. CH.
Published: February 2007

What is already known about this subject

• To our knowledge, there are no prior studies which investigate whether there is a drug–gene interaction between the three genes involved in the renin–angiotensin system and ACE‐inhibitor therapy or β‐blocker therapy with these subclinical measurements of atherosclerosis.

• Some studies have found an effect on blood pressure or stroke/myocardial infarction, although the results are not conclusive.

What this study adds

• The results do not indicate the presence of a strong drug–gene interaction between the use of ACE‐inhibitors or β‐blockers and the ACE insertion/deletion, AGT M235T or AGTR1573C/T polymorphism on the overall risk of atherosclerosis.

Aims To investigate whether the angiotensin‐converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen M235T or angiotensin II receptor type 1 573C/T polymorphism modify the risk of atherosclerosis associated with β‐blocker or ACE‐inhibitor therapy.

Methods Data were used from the Rotterdam Study, a population‐based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects of ≥ 55 years. In this study, 2216 subjects with hypertension were included. Three subclinical measurements were used for atherosclerosis, i.e. peripheral arterial disease, carotid atherosclerosis and aortic atherosclerosis. The interaction between antihypertensive drugs and genetic polymorphisms on the risk of atherosclerosis was determined with binary logistic regression analysis.

Results The risk of aortic atherosclerosis associated with long‐term (≥4 years) β‐blocker treatment compared with no use of β‐blockers was higher in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene [synergy index (SI) = 3.36; 95% confidence interval (CI) 1.14, 9.97]. The risk of carotid atherosclerosis associated with long‐term ACE‐inhibitor treatment compared with no use of ACE‐inhibitors was lower in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene (SI = 0.20; 95% CI 0.04, 0.95).

Conclusion Overall, the risk of atherosclerosis in hypertensives taking a β‐blocker or ACE‐inhibitor‐based regimen was not strongly modified by any of the three candidate gene polymorphisms.
The use of mechanistic DM‐PK‐PD modelling to assess the power of pharmacogenetic studies –CYP2C9and warfarin as an example
Authors: Dickinson Gemma L. , Lennard Martin S. , Tucker Geoffrey T. , Rostami‐Hodjegan Amin
Published: February 2007

What is already known about this subject

• Many studies have shown that genetic polymorphisms of theCYP2C9gene contribute to some of the variability (around 20%) in warfarin dose requirements and therapeutic response to the drug.

• It is also clear that this effect must be elicited through differences in the plasma (S)‐warfarin concentration between individuals of different genotypes, although assessing the effects of any single genotype ofCYP2C9on the kinetics of (S)‐warfarin has generally failed.

What this study adds

• The study aims to simulate the impact of genetic polymorphism in CYP2C9 on both the pharmacokinetics (PK) and pharmacodynamics (PD) of (S)‐warfarin using a mechanistic, population approach to modelling.

• The outcomes with respect to the design of studies and their statistical power are compared against those of actual reported studies.

• The exercise with warfarin is offered as an example of how prior information on thein vitroPK and PD of new drugs might be used in association with knowledge of relevant genetic polymorphisms and their frequencies to carry out virtual clinical studies as an aid to the design, optimization and powering of subsequent real clinical trials assessing the impact of specific genetic differences.

AimTo assess the power ofin vivostudies needed to discern the effect of genotype on pharmacokinetics (PK) and pharmacodynamics (PD) usingCYP2C9and (S)‐warfarin as an example.

MethodsInformation on thein vitrometabolism of (S)‐warfarin and genetic variation in CYP2C9 was incorporated into a mechanistic population‐based PK–PD model. The influence of study design on the ability to detect significant differences in PK (AUC0−12 h) and PD (AUEC0−12 hINR) betweenCYP2C9genotypes was investigated.

ResultsA study size of 90 (based on the natural abundance of genotypes and uniform dosage) was required to achieve 80% power to discriminate the PK of (S)‐warfarin between wild type (*1/*1) and the combination of all other genotypes. About 250 subjects were needed to detect a difference in anticoagulant response. The power to detect differences between specific genotypes was much lower. Analysis of experimental comparisons of the PK or PD between wild‐type and other individual genotypes indicated that only 21% of cases (20 of 95 comparisons within 11 PD and four PK–PD studies) reported statistically significant differences. This was similar to the percentage expected from our simulations (20%, χ2test,P = 0.80). Simulations of studies enriched with specific genotypes indicated that only three and five subjects were required to detect differences in PK and PD between wild type and the *3/*3 genotype, respectively.

ConclusionThe utilization of prior information (includingin vivoenzymology) in clinical trial simulations can guide the design of subsequentin vivostudies of the impact of genetic polymorphisms, and may help to avoid costly, inconclusive outcomes.
Do calcium antagonists contribute to gastro‐oesophageal reflux disease and concomitant noncardiac chest pain?
Authors: Hughes Jeff , Lockhart Judith , Joyce Andrew
Published: February 2007

What is already known about this subject

• Calcium antagonists (CA) are listed in textbooks as potential causes of gastro‐oesophageal reflux disease (GORD).

• There have been two studies which have documented increased use of acid suppressant therapy amongst patients taking CAs.

What this study adds

• This study provides the first data on the frequency of exacerbation and precipitation of gastro‐oesophageal reflux symptoms amongst users of CAs.

• It also provides evidence of the likely potential of the different CAs to cause such symptoms and highlights the need for a prospective study into CA therapy.

• The data from the study should heighten prescribers' awareness of the potential of these agents to exacerbate/precipitate GORD, and to consider avoiding CAs in patients with GORD or withdrawing them in patients in whom GORD symptoms develop or worsen.

Aims A cohort retrospective observational study was undertaken to determine the relationship between calcium antagonist (CA) use and gastro‐oesophageal reflux disease (GORD), as well the ability of CAs to precipitate or exacerbate noncardiac chest pain, an atypical symptom of GORD.

Methods Eligible patients were those prescribed CAs for hypertension without a history of ischaemic heart disease or nitrate use. Patients were recruited through 15 pharmacies (hospital 1, community 14). Patients giving informed consent were administered a standard questionnaire to obtain information including history of reflux symptoms before and during treatment with CAs, and the management of these symptoms.

Results Three hundred and seventy‐one participants were enrolled. Their mean age was 64 years (SD ± 12.7 years), 51.2% were females and 48.8% males. Of the 130 patients with pre‐existing gastrointestinal (GI) symptoms, 59 (45.4%) reported a worsening of reflux symptoms during CA therapy. Increases in both frequency and severity of symptoms were most common amongst patients on amlodipine (61.3%; P ≤ 0.0001) and least common amongst those taking diltiazem (12.5%). Reflux‐related symptoms developed in 85 (35.3%) of the 241 previously asymptomatic patients during CA therapy, with verapamil having the greatest number of reports (39.1%; P = 0.001) and diltiazem the least (30.7%).

Conclusions Diltiazem appears the least likely of the CAs to precipitate or exacerbate reflux symptoms. Further research using a prospective design could test whether it may be more appropriate to use diltiazem in patients with ischaemic heart disease and could assess the appropriateness of CA therapy in patients with moderate to severe GORD. Increasing prescriber and pharmacist awareness of these adverse effects may result in better patient outcomes and potentially reduce treatment costs.
Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia
Authors: Tang Yi‐lang , Mao Peixian , Li Feng‐Min , Li Wenbiao , Chen Qi , Jiang Feng , Cai Zhuo‐ji , Mitchell Philip B.
Published: February 2007

What is already known about this subject

• Plasma concentrations of clozapine (CLZ) and its active metabolite vary considerably at a given dosage.

• A number of patient‐related factors have been reported to increase the variability of plasma CLZ concentrations, with gender, age and smoking behaviour representing some of the more important contributing variables

• However, results of previous studies concerning these factors have been inconsistent and most studies were conducted in western populations.

What this study adds

• Using this ethnically unique, relatively large sample, we replicated some findings in western populations, including large interindividual variability of plasma CLZ concentrations, significant effects of gender on plasma CLZ concentrations.

• Female patients had significantly higher levels than males and no significant differences in plasma CLZ concentrations were observed between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher.

Aim To study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia.

Methods Data from a therapeutic drug monitoring programme were analysed retrospectively. One hundred and ninety‐three Chinese inpatients with schizophrenia were assessed using clinical data forms. Steady‐state plasma concentrations of CLZ and NCLZ were assayed using high‐performance liquid chromatography. Comparisons of dosage and plasma CLZ concentrations were undertaken between males (n = 116) and females (n = 77), younger (≤40 years, n = 82) and older patients (>40 years, n = 111) and current male smokers (n = 50) and nonsmokers (n = 66).

Results (i) Plasma CLZ concentrations demonstrated large interindividual variability, up to eightfold at a given dose; (ii) there were significant effects of gender on plasma CLZ concentrations (relative to dose per kg of body weight) with female patients having significantly higher concentrations than males (30.09 ± 24.86 vs. 19.87 ± 3.55 ng ml−1 mg−1 day−1 kg−1; P < 0.001); (iii) there were no significant differences in plasma CLZ concentrations between those patients ≤40 years old and those >40 years; and (iv) there were no significant differences in plasma CLZ concentrations between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher.

Conclusions Plasma CLZ concentrations vary up to eightfold in Chinese patients. Among the patient‐related factors investigated, only gender was significant in affecting CLZ concentrations in Chinese patients with schizophrenia, with female patients having higher levels.
Trends over 5 years in cardiovascular medicine use in Australian veterans with diabetes
Authors: Roughead Elizabeth E. , Pratt Nicole , Gilbert Andrew L.
Published: February 2007

What is already known about this subject

• Previous cross‐sectional studies have demonstrated underuse of cardiovascular medicines in the population with diabetes.

What this study adds

• Trends are changing over 5 years with increasing use of medicines affecting the angiotensin–renin system, lipid‐lowering medicines and antiplatelets in the Australian veteran population, in line with recommended practice.

Aim To determine trends over 5 years in cardiovascular medicine use in the Australian veteran population with diabetes

Methods An observational study. All veterans dispensed medicines indicative of diabetes between 2000 and 2005 were identified from the Veterans Affairs pharmacy claims dataset. Concurrent dispensings of angiotensin‐converting enzyme inhibitor (ACEI), lipid‐lowering medicines and antiplatelets were assessed.

Results ACEI/angiotensin II receptor blocker use has risen from 46% to 67% in the veteran population dispensed medicines indicative of diabetes. Lipid‐lowering medicines have increased from 33% to 58% and antiplatelets from 28% to 50%.

Conclusion The increasing use of cardiovascular medicines in the diabetes population is suggestive of improved treatment practices over time, consistent with guidelines and quality use of medicines initiatives.
The BPS Diploma in Advanced Pharmacology: a training opportunity for clinical pharmacologists
Authors: Hall Judith M
Published: February 2007

Coinciding with its 75th anniversary, the British Pharmacological Society (BPS) has launched a Diploma in Advanced Pharmacology (BPS Dip Pharmacol). This award is open to clinical and non‐clinical scientists and those in related occupations. The Diploma is designed to appeal to those who want to further their pharmacological knowledge or gain an appreciation of basic and clinical aspects of the subject through participation in an advanced programme of non‐clinical and clinical pharmacological study. The Diploma is unique in the UK. It provides not only a mechanism for continuing and updating education in basic pharmacology, clinical pharmacology, and therapeutics, but also a range of networking opportunities for non‐clinical and clinical scientists in industry and academia.
Iron‐bearing phases in a peat‐derived duricrust from Brazil
Authors: Varajão A. F. D. C. , Da Costa G. M. , Varajão C. A. C. , Meunier J. D. , Colin F.
Published: February 2007

The formation of aluminium‐substituted iron‐minerals is still subject to debate. We report a case study in a Humic Gleysol soil profile, developed on a sedimentary saprolite, from a basin floor on the Uberaba Plateau (Minas Gerais State, Brazil) where iron‐phases are crystallized by a ferruginization process. The mineralogical and chemical properties were investigated by X‐ray diffraction, thermogravimetric analysis, differential scanning calorimetry and Mössbauer spectroscopy. The specific surface area (BET method) and cation exchange capacity (CEC) were also determined. The soil profile is mainly composed of gibbsite, kaolinite and amorphous alumino‐silicate phases, the latter being more frequent in the H horizon where the organic carbon content is greater. The surface area and CEC values are also greater in the H horizon (58.6 m2g−1 and 4.65 molckg−1, respectively) which indicates an increase in porosity caused by the presence of 20.8% of organic matter and amorphous materials. Goethite occurs as a secondary mineral in the H horizon and as the main mineral in the duricrust in association with haematite. The omnipresence of aluminium in the environment (24.6–46.2% of Al2O3) resulted in Al‐substitution in all iron‐bearing phases but the goethite from the H horizon has the greatest Al‐for‐Fe substitution, with at least 20 mole per cent of aluminium. In spite of the greater microporosity and wetness of the H horizon, the immediate contact with the richest Al‐source (gibbsite) favours the precipitation of unusually greatly Al‐substituted goethite instead of haematite in this horizon.
Inter‐annual variation in responses of water chemistry and epilithon to Pacific salmon spawners in an Alaskan stream
Authors: CHALONER D. T. , LAMBERTI G. A. , CAK A. D. , BLAIR N. L. , EDWARDS R. T.
Published: February 2007

1. Pacific salmon (Oncorhynchus spp.) deliver salmon‐derived nutrients (SDN) to the streams in which they spawn. However, many stream parameters, such as discharge and spawner abundance, can vary from year to year, which could alter the quantity and flux of SDN.

2. Over six consecutive years, we studied responses in streamwater chemistry and epilithon (i.e. the microbial community on submerged rocks) to salmon spawners in Fish Creek, southeastern Alaska, U.S.A. The lower reach of Fish Creek receives spawners of several salmon species, while the upper reach does not receive spawners because of an intervening waterfall.

3. We estimated salmon spawner biomass, analysed water chemistry [ammonium, nitrate, soluble reactive phosphorus (SRP) and dissolved organic carbon (DOC)], and measured epilithon abundance [as chlorophyll a (chl a) and ash‐free dry mass (AFDM)] in Fish Creek. Measurements were made in both the upper and lower reaches, before, during and after the major salmon runs.

4. Absolute values and relative differences indicated that the presence of salmon spawners consistently increased dissolved ammonium (by 58 μg L−1 on average, 41× over background), SRP (by 6 μg L−1, 14×), epilithon chl a (by 35 mg m−2, 16×), and epilithon AFDM (by 3 g m−2, 8×). Salmon spawners did not increase nitrate or DOC in either absolute or relative amounts. The persistence and magnitude of spawner effects varied among years and appeared to reflect weather‐driven hydrology as well as spawner biomass.

5. Salmon‐derived nutrients can stimulate the growth of primary producers by increasing streamwater nutrient concentrations, but this positive influence may be modulated by other factors, such as water temperature and discharge. To better assess the ecological influence of SDN on stream biota, future studies should explicitly consider the role of key environmental factors and their temporal and spatial dynamics in stream ecosystems.
Sub‐lethal effects of disturbance on a predatory net‐spinning caddisfly
Authors: BEVERIDGE OLIVER S. , LANCASTER JILL
Published: February 2007

1. The sub‐lethal effects of hydrologic disturbances on stream invertebrates are poorly understood, but integral to some models of how disturbances influence population and community dynamics. Carnivorous larvae of a net‐spinning caddisfly, Plectrocnemia conspersa, have a strong predatory impact in some streams. Their silken nets, however, are vulnerable to high flow disturbance and the consequent destruction of nets could reduce predatory impacts and have life history consequences.

2. In a laboratory experiment, we manipulated the frequency of disturbances that destroyed the nets of P. conspersa, in the presence and absence of potential prey. Animals were housed individually and each trial lasted 8 days. We estimated net size, cumulative mass of silk produced, net allocation (net mass expressed as a proportion of body mass), per capita prey consumption and growth or mass loss of larvae.

3. In the absence of prey, increased disturbance frequency was accompanied by increased loss of body mass, a reduction of net size and an increase in the cumulative mass of silk produced. At the highest disturbance frequency, larvae eventually gave up producing nets. The ratio of net mass to body mass decreased with increasing disturbance, suggesting a trade‐off in the allocation of resources, with a decreasing proportion of resources available for foraging. In the presence of prey, increased disturbance frequency was accompanied by a reduction in per capita prey consumption. Although foraging success offset the costs of silk production, growth rate decreased with increasing disturbance and could eventually lead to reduced body size and fecundity of adults.

4. These sub‐lethal effects suggest that hydrologic disturbances could impose metabolic costs and reduce foraging efficiency of this predator. Thus, disturbances may reduce predator impact on prey populations and reduce predator population size without any direct mortality or loss of individuals.
Variation in body size and trophic morphology within and among genetically differentiated populations of the cichlid fish, Metriaclima zebra, from Lake Malawi
Authors: TODD STREELMAN J. , ALBERTSON R. C. , KOCHER T. D.
Published: February 2007

1. The cichlid fish Metriaclima zebra, common in Lake Malawi, feeds by filtering plankton from the water and by brushing items from sediment covered substrata. It inhabits isolated rocky reefs among which community structure, resource availability and gene pools are likely to differ. We speculated that body size and trophic morphology of M. zebra might vary concomitantly.

2. We quantified the extent of genetic, body size and trophic variation within and between populations of M. zebra from southern Lake Malawi. Specifically, we tested the hypotheses that: (i) local populations are genetically differentiated, (ii) local populations differ in jaw morphology, dentition and standard length (SL), and (iii) variation in size is correlated with variation in trophic morphology.

3. Local populations of M. zebra differed in mean SL and were genetically differentiated. Moreover, populations exhibited dissimilar oral jaw morphologies and dentitions, perhaps related to differences in feeding biology. Variation in jaw shape was largely restricted to the curvature of the distal tip of the dentary. Populations were characterised by individuals with oblique, upward or downward directed gapes. Dental patterns differed in the proportion of unicuspid teeth in all rows of each jaw (dentaries and premaxillae) and the spacing of teeth in affected rows.

4. Within populations, jaw and tooth shapes were correlated with body size. Smaller individuals possessed upward curving jaws and closely packed multicusped teeth, while larger individuals exhibited relatively downward‐directed jaws with increasing numbers of widely spaced unicuspid teeth.

5. Metriaclima zebra populations have increased in mean SL over the last decade, in contrast to a decline among Lake Malawi pelagic cichlids. Differences in size may contribute to variation in trophic morphology and may track local environmental dynamics in this lacustrine system.
Spatio‐temporal genetic variability in sea trout (Salmo trutta) populations from north‐western Spain
Authors: CAMPOS JOSÉ L. , POSADA DAVID , CABALLERO PABLO , MORÁN PALOMA
Published: February 2007

1. Genetic variation at five microsatellite loci was investigated in six sea trout (Salmo trutta) populations to describe their spatio‐temporal genetic variation in north‐western Spain. We observed significant genetic variation between river basins, and isolation by distance with restricted gene flow between neighbouring rivers, which suggests an important homing behaviour.

2. Despite these populations suffering a serious demographic decline during 1998, we did not detect any reduction in their genetic variation, suggesting a reasonably high effective population size and temporal stability.

3. Genetic differences among rivers should be taken into account in future management activities. Given the high genetic variability and the temporal stability observed, we believe that no supportive breeding programmes are presently needed in these populations.
Alewife planktivory controls the abundance of two invasive predatory cladocerans in Lake Michigan
Authors: POTHOVEN STEVEN A. , VANDERPLOEG HENRY A. , CAVALETTO JOANN F. , KRUEGER DAMON M. , MASON DORAN M. , BRANDT STEPHEN B.
Published: February 2007

1. We sampled along a nearshore transect (10‐m bathymetric contour) in Lake Michigan to determine diet, 24‐h feeding periodicity, daily ration and food requirements of an invasive fish, the alewife, Alosa pseudoharengus, relative to zooplankton abundance and production. Our objective was to determine whether the alewife controls the abundance of two invasive, predatory cladocerans, Bythotrephes longimanus and Cercopagis pengoi.

2. Bosminidae was the most abundant prey taxon and Chydoridae, Leptodora, Chironomidae and Bythotrephes were the least abundant. Neither Bythotrephes nor Cercopagis were important prey for small alewives (≤100 mm). Bythotrephes was eaten by over 50% of large alewives (>100 mm) and accounted for 10–27% of the diet weight. Cercopagis was eaten by about 30% of the large alewives but only accounted 1% of the diet weight.

3. Food weight in stomachs was highest early in the night for small alewives and lowest at night for large alewives. Chironomidae and large Chydoridae were the preferred prey of small alewives. Bythotrephes and large Chydoridae were the preferred prey for large alewives.

4. Food requirements of alewife were much less than production for most prey taxa, although the consumption of Bythotrephes greatly exceeded production on both dates. Alewives consumed only 3% of Cercopagis production. High selectivity and food requirements of alewife for Bythotrephes, and low selectivity and food requirements for Cercopagis, probably explain the difference in abundance between these two invasive cladocerans at our nearshore site in Lake Michigan.
Fourier reconstruction with sparse inversion
Authors: Zwartjes P. , Gisolf A.
Published: February 2007

The problem of seismic data reconstruction is posed as an inverse problem where the objective is to obtain the Fourier coefficients that synthesize the signal. Once the coefficients have been found, they are used to reconstruct the data on a uniformly spaced grid. A non‐quadratic model weight function is included to stabilize the inversion and to provide the additional information required to interpolate through gaps. In the reconstruction of a non‐uniformly sampled trace, an image and a marine 3D VSP shot‐record, the method shows improved reconstruction in large gaps and is less sensitive to the spatial bandwidth used in the inversion compared to Fourier reconstruction without the non‐quadratic model weight function.
Non‐minimum phase wavelet estimation by non‐linear optimization of all‐pass operators
Authors: Misra Somanath , Sacchi Mauricio D.
Published: February 2007

Convolution of a minimum‐phase wavelet with an all‐pass wavelet provides a means of varying the phase of the minimum‐phase wavelet without affecting its amplitude spectrum. This observation leads to a parametrization of a mixed‐phase wavelet being obtained in terms of a minimum‐phase wavelet and an all‐pass operator. The Wiener–Levinson algorithm allows the minimum‐phase wavelet to be estimated from the data. It is known that the fourth‐order cumulant preserves the phase information of the wavelet, provided that the underlying reflectivity sequence is a non‐Gaussian, independent and identically distributed process. This property is used to estimate the all‐pass operator from the data that have been whitened by the deconvolution of the estimated minimum‐phase wavelet. Wavelet estimation based on a cumulant‐matching technique is dependent on the bandwidth‐to‐central‐frequency ratio of the data. For the cumulants to be sensitive to the phase signatures, it is imperative that the ratio of bandwidth to central frequency is at least greater than one, and preferably close to two. Pre‐whitening of the data with the estimated minimum‐phase wavelet helps to increase the bandwidth, resulting in a more favourable bandwidth‐to‐central‐frequency ratio. The proposed technique makes use of this property to estimate the all‐pass wavelet from the prewhitened data. The paper also compares the results obtained from both prewhitened and non‐whitened data. The results show that the use of prewhitened data leads to a significant improvement in the estimation of the mixed‐phase wavelet when the data are severely band‐limited. The proposed algorithm was further tested on real data, followed by a test involving the introduction of a 90°‐phase‐rotated wavelet and then recovery of the wavelet. The test was successful.
Estimation of clay content in soil based on resistivity modelling and laboratory measurements
Authors: Shevnin Vladimir , Mousatov Aleksandr , Ryjov Albert , Delgado‐Rodriquez Omar
Published: February 2007

The determination of clay content in near‐surface formations is crucial for geotechnical, hydrogeological and oil‐contamination studies. We have developed a technique for estimating clay content that consists of the minimization of the difference between the theoretically calculated and measured soil resistivities as a function of water salinity. To calculate the resistivity, we used a model that takes into account the electrochemical processes in the clay micropores. The experimental measurements of soil resistivity were performed on soil samples, completely saturated by brines at different concentrations of NaCl salt in the range 0.6–100 g/l, to obtain the resistivity versus salinity curve. The parameters obtained with this curve inversion are the clay content, the total porosity and the cation exchange capacity. To verify the new technique, we determined clay concentrations of artificial mixtures of calibrated sand and clay. The relative mean error in the clay content does not exceed 20% for a 5% fitting error of the resistivity versus salinity curves. Such evaluations allow the correct separation of the main lithological groups (sand, sandy loam, loam, and light, medium and heavy clay).

We applied this technique to estimate the petrophysical parameters of soils (clay content, porosity and cation exchange capacity) at various sites in Mexico. The results improved the interpretation of the vertical electrical soundings, the lithological soil characterization and the delineation of oil‐contaminated areas.
Quantitative detection of fluid distribution using time‐lapse seismic
Authors: Tsuneyama Futoshi , Mavko Gary
Published: February 2007

Although previous seismic monitoring studies have revealed several relationships between seismic responses and changes in reservoir rock properties, the quantitative evaluation of time‐lapse seismic data remains a challenge. In most cases of time‐lapse seismic analysis, fluid and/or pressure changes are detected qualitatively by changes in amplitude strength, traveltime and/or Poisson's ratio.

We present the steps for time‐lapse seismic analysis, considering the pressure effect and the saturation scale of fluids. We then demonstrate a deterministic workflow for computing the fluid saturation in a reservoir in order to evaluate time‐lapse seismic data. In this approach, we derive the physical properties of the water‐saturated sandstone reservoir, based on the following inputs: VP, VS, ρ and the shale volume from seismic analysis, the average properties of sand grains, and formation‐water properties. Next, by comparing the in‐situ fluid‐saturated properties with the 100% formation‐water‐saturated reservoir properties, we determine the bulk modulus and density of the in‐situ fluid. Solving three simultaneous equations (relating the saturations of water, oil and gas in terms of the bulk modulus, density and the total saturation), we compute the saturation of each fluid. We use a real time‐lapse seismic data set from an oilfield in the North Sea for a case study.
Single nucleotide polymorphisms in succinate dehydrogenase subunits and citrate synthase genes: association results for impaired spermatogenesis
Authors: Bonache Sandra , Martínez Juanjo , Fernández Marlin , Bassas Lluís , Larriba Sara
Published: February 2007

Evaluation of the possible implication of the SDHA, SDHB, SDHC, SDHD and CS genes in non‐obstructive male infertility was performed on the basis that sperm concentration in the ejaculate has been previously correlated with nuclear‐encoded mitochondrial enzyme activities (the four subunits of succinate dehydrogenase/complex II of the respiratory chain and citrate synthase). We performed an exhaustive analysis of the five genes for the presence of sequence variants that could be associated with impairment of sperm production. blastn searches in the genomic sequence NCBI database evidenced the presence of highly homologous sequences elsewhere on the genome that can interfere with polymerase chain reaction experiments. Therefore, a careful design of the analytical strategy to search for sequence variants was performed. In this report, we provide primer sequences that allowed selective amplification of coding and immediate flanking regions of the five genes. Fifty‐five sequence variations in the five genes were identified in infertile and normozoospermic fertile individuals as controls and only one of them (SDHA c.456+32G>A) showed significant genotype association with impairment of sperm production. Moreover, new single nucleotide polymorphisms identified should be useful in future association studies for other human diseases related to nuclear‐encoded genes, leading to mitochondrial respiratory chain activity impairment revealing the physiological role of these genes.
Measuring gonadotropins is of limited value in detecting hypogonadism in ageing men: the Tromsø study
Authors: Svartberg Johan , Jorde Rolf
Published: February 2007

Testosterone levels decrease with age. The mechanisms responsible for the age‐related decrease in testosterone concentration are still being debated, and probably involve all three levels of the hypothalamo‐pituitary‐testicular axis. Luteinizing hormone (LH) concentration is often measured in combination with testosterone, but its value is questionable when considering the testosterone levels of older men. The objective of the present study was to examine the associations of endogenous gonadotropin and testosterone levels both in a cross‐sectional cohort of 3447 men participating in the fifth Tromsø study and longitudinally in a cohort of 1352 men participating in both the fourth and the fifth Tromsø study. Total testosterone, LH, follicle‐stimulating hormone and sex hormone‐binding globulin levels were measured with immunoassay while free testosterone levels were calculated. Total testosterone and LH were independently and positively associated in the cross‐sectional analyses (p < 0.001). In the longitudinal study, however, LH levels did not predict changes in total and free testosterone levels. Thus, in clinical practice, measuring gonadotropins seems to be of limited value in detecting hypogonadism in ageing men.
Prostatic massage: a simple method of semen retrieval in men with spinal cord injury
Authors: Arafa Mohamed Mostafa , Zohdy Wael Ahmed , Shamloul Rany
Published: February 2007

The aim of this study was to evaluate the efficacy of prostatic massage (PM) as a method for obtaining semen in men with spinal cord injury (SCI) and to evaluate the semen parameters in the semen samples obtained by this method. Sixty‐nine patients with SCI underwent PM as a trial for semen retrieval. History taking, examination and hormonal assay analysis (follicle‐stimulating hormone, luteinizing hormone, prolactin and testosterone) were performed in all patients. Patients were grouped as follows: group ‘A’ where sperm could be successfully retrieved by PM and group ‘B’ where no sperm could be retrieved. PM resulted in the production of prostatic secretion in 51 patients (73.9%) and no secretion was obtained in 18 patients. Spermatozoa were successfully retrieved in only 22 patients (31.9%). The semen analysis of the sperm‐positive samples showed asthenoteratozoospermia with decreased vitality and increased number of leucocytes. Semen collection by PM was significantly higher in patients with an SCI level above T10. PM is a safe and simple outpatient clinic procedure that can be easily used to retrieve semen in men with SCI.
Assessment of nuclear DNA integrity of epididymal spermatozoa following experimental chronic spinal cord injury in the rat
Authors: Talebi Ali Reza , Khalili Mohammad Ali , Hossaini Ahmad
Published: February 2007

Infertility is considered as one of the major problems associated with spinal cord injury (SCI). However, the exact underlying mechanism is still unknown. Therefore, the main objective of this experimental study was to evaluate the effect of chronic SCI on sperm parameters as well as chromatin integrity and DNA of spermatozoa aspirated from cauda epididymis of rats. Forty‐five adult Wistar rats were divided into three groups – SCI, sham, and control. Following laminectomy, SCI was induced onto exposed dura matter (T10). The sham group underwent laminectomy of T10 only, while the control rats were not exposed to any type of injury or medication. The cauda epididymal sperms were aspirated after 8 weeks for analysis of sperm parameters and sperm chromatin integrity with aniline blue (AB), chromomycin A3 (CMA3), sodium dodecyl sulphate (SDS), and acridine orange (AO) tests. The sperm progressive motility and normal morphology of SCI rats were significantly changed when compared with other groups (p < 0.05). In addition, AB as well as CMA3 tests were insignificantly increased in the SCI group when compared with the sham and control groups. However, SDS and AO tests were significantly changed in SCI samples when compared with the sham and control groups (p < 0.001). The results showed that chronic SCI in rat disturbs sperm parameters as well as nuclear maturity and DNA integrity of sperms. Therefore, sperm chromatin structure is compromised in SCI animals as revealed by chromatin structural probes. These alterations may reduce the fertility potential of the male gamete following SCI.
The mouse as a model for the study of penile erection: moving towards a smaller animal
Authors: Piao Shuguang , Ryu Ji‐Kan , Shin Hwa‐Yean , Han Jee‐Young , Lee Hong‐Sik , Suh Jun‐Kyu
Published: February 2007

We evaluated erectile haemodynamics in mice and characterized the corpus cavernosum morphologically. Four‐month‐old male BALB/c mice and Sprague–Dawley rats were used. The following stimulation parameters were tested to achieve maximal erectile responses: voltage, 1–6 V; frequency, 6–24 Hz; pulse width, 1 msec; duration, 1 min (n = 7 per group). In a separate group of mice and rats (n = 10 per group), we measured systemic arterial pressure by use of either a 24‐gauge angiocatheter or smaller calibre PE‐10 tubing. Cavernous tissues from mice, rats or patients with psychogenic erectile dysfunction were stained for factor VIII, α‐actin and Masson trichrome. Electrical stimulation of the cavernous nerve in mice produced voltage‐dependent erectile responses of up to 5 V, with the highest response at a frequency of 12 Hz. The maximal intracavernous pressure recorded at this stimulation parameter was comparable with that in rats. A PE‐10 catheter was more reliable for measuring systemic arterial pressure in mice than was a 24‐gauge angiocatheter, and the values recorded were similar between mice and rats. The content of endothelial cells, smooth muscle cells and collagen was similar between mice and rats. However, the cavernous tissue of both animals contained lesser amounts of smooth muscle cells and greater amounts of collagen than that of humans (p < 0.01). These results suggest that the mouse is a useful and technically feasible model for the study of penile erection and has functional and structural properties similar to those of rats.
Comprehensive analysis of gene expression in testes producing haploid germ cells using DNA microarray analysis
Authors: Ike Akiko , Tokuhiro Keizo , Hirose Mika , Nozaki Masami , Nishimune Yoshitake , Tanaka Hiromitsu
Published: February 2007

The comprehensive changes in testicular gene expression before and after haploid germ cell differentiation were examined using microarray analysis. Approximately 14 000 expressed sequence tag (EST) clones of Mouse FANTOM Array ver.1 were hybridized with probes generated from mRNA of adult and juvenile (17 days postpartum) testes before the onset of spermiogenesis. Of 1315 genes that exhibited reproducible changes in expression (p < 0.05), 46% exhibited an increase of twofold or more in adults compared to juveniles, and 22% a decrease of twofold or more. The analysis not only confirmed the reported haploid‐specific expression of several known genes, but also provided new information on the differential expression of various other genes, including upregulated genes such as Allc and Skd3 and downregulated genes such as hbb b1, before or after the onset of spermiogenesis. Based on the fundamental difference in expression profiles, and molecular functions of the encoded products, the genes were classified into several groups: postmeiotically upregulated genes encoding various enzymes, structural and regulatory proteins, and chaperones, and downregulated genes encoding haemoglobins and oxidation/reduction‐related proteins or the machinery associated with protein synthesis, such as ribosomal proteins.
The equilibrium of XIAP and Smac/DIABLO expression is gradually deranged during the development and progression of testicular germ cell tumours
Authors: Kempkensteffen Carsten , Jäger Tobias , Bub Johannes , Weikert Steffen , Hinz Stefan , Christoph Frank , Krause Hans , Schostak Martin , Miller Kurt , Schrader Mark
Published: February 2007

Overexpression of the inhibitor of apoptosis protein (IAP) XIAP (BIRC4) and downregulation of its antagonist Smac/DIABLO (DIABLO) are associated with the onset and progression of various malignancies. In this study, real‐time RT‐PCR was used to quantify the mRNA expression of XIAP and Smac/DIABLO in normal testicular tissue (n = 19), testicular carcinoma in situ (CIS; n = 4), testicular seminomas (n = 64) and non‐seminomatous germ cell tumours (NSGCT; n = 35). XIAP and Smac/DIABLO were commonly expressed in normal and malignant testicular tissue with no apparent differences in XIAP mRNA levels among the histologic subgroups. Smac/DIABLO levels, on the other hand, gradually decreased from normal testicular tissue to CIS and seminomas and finally to NSGCT (p < 0.001). An inverse trend was observed when calculating the XIAP‐to‐Smac/DIABLO ratio (p < 0.001). This ratio differed when comparing normal testicular tissue with CIS (p = 0.014), seminomas (p < 0.001) and NSGCT (p < 0.001) and when comparing seminomas with NSGCT (p = 0.002), whereas no such difference was observed between CIS and seminomas (p = 0.302). TGCT patients dichotomized by the overall median XIAP‐to‐Smac/DIABLO ratio were more likely to present with a high ratio in clinical stage (CS) III than in CS I or II (p = 0.034). These data indicate that the balance of mRNA expression between XIAP and Smac/DIABLO is altered in favour of antiapoptotic XIAP during the development and progression of TGCT. Thus the expression of proapoptotic Smac/DIABLO is lowest in NSGCT and stage III tumours.
c‐Myc partially mediates IFNγ‐induced apoptosis in the primary hepatocyte
Authors: McCullough C. T. , Tura B. J. , Harrison D. J.
Published: February 2007

Interferon‐gamma (IFNγ) is a central component of the complex cytokine and inflammatory response that contributes to liver cell injury in hepatitis. We report that in the primary hepatocyte IFNγ synergizes with the mechanistically distinct apoptotic stimuli CD95, tumour necrosis factor‐alpha (TNFα) and UV‐irradiation. For the first time in primary hepatocytes, we show that IFNγ‐mediated apoptotic signalling requires the cell surface interaction of CD95 and its ligand, and we demonstrate that IFNγ induces soluble CD95 ligand release from hepatocyte monolayers. Utilizing c‐myc phosphorothioate antisense fragments, we suppresses hepatocyte apoptosis induced by IFNγ. In summary, we identify apoptotic pathways that contribute to IFNγ‐mediated cell death. The hepatocellular response to IFNγ signalling can be modulated by cytokines and by the interruption of CD95 interaction with its ligand. We present evidence to suggest that c‐myc contributes to IFNγ signalling.
How two different host species influence the performance of a gregarious parasitoid: host size is not equal to host quality
Authors: HÄCKERMANN JOHANNA , ROTT ANJA S. , DORN SILVIA
Published: February 2007

Hyssopus pallidus Askew (Hymenoptera, Eulophidae) is a gregarious ectoparasitoid of the two tortricid moths species Cydia molesta Busck and C. pomonella L. (Lepidoptera, Tortricidae). It paralyses and parasitizes different larval instars of both species inside the apple fruit, which leads to the death of the caterpillar.

We assessed the influence of host species characteristics and host food on the performance of the parasitoid female in terms of clutch size decisions and fitness of the F1 generation.

A comparison of clutch size revealed that female parasitoids deposited similar numbers of eggs on the comparatively smaller C. molesta hosts as on the larger C. pomonella hosts. The number of parasitoid offspring produced per weight unit of host larva was significantly higher in C. molesta than in C. pomonella, which is contrary to the general prediction that smaller hosts yield less parasitoid offspring. However, the sex ratio was not influenced by host species that differed considerably in size.

Despite the fact that less host resources were available per parasitoid larva feeding on C. molesta caterpillars, the mean weight of emerging female wasps was higher in the parasitoids reared on C. molesta. Furthermore, longevity of these female wasps was neither influenced by host species nor by the food their host had consumed. In addition we did not find a positive relationship between adult female weight and longevity.

Parasitoid females proved to be able to assess accurately the nutritional quality of an encountered host and adjust clutch size accordingly. These findings indicate that host size is not equal to host quality. Thus host size is not the only parameter to explain the nutritional quality of a given host and to predict fitness gain in the subsequent generation.
Interactions between habitat heterogeneity and food affect reproductive output in a top predator
Authors: BYHOLM PATRIK , NIKULA ARI , KENTTA JUSSI , TAIVALMÄKI JUKKA‐PEKKA
Published: February 2007

Habitat heterogeneity has important repercussions for species abundance, demography and life‐history patterns. While habitat effects have been more thoroughly studied in top‐down situations (e.g. in association with predation), their role in bottom‐up situations (e.g. in association with food abundance) has been less explored and the underlying mechanism(s) behind the ecological patterns have not commonly been identified.

With material from 1993 to 2003, we test the hypothesis that the reproduction of Finnish northern goshawks Accipiter gentilis (L.) is bottom‐up limited by habitat composition, especially in situations where the density of their main prey (grouse) is low. Special emphasis was placed on identifying the mechanism(s) behind potential habitat effects.

While laying date and large‐scale variation in the main prey density (but not habitat composition) were related to the number of eggs goshawks laid, small‐scale differences in alternative prey density between different territories later influenced how many young were fledged via the mechanism of habitat‐dependent partial‐brood loss. As a result of this mechanism, a difference in nestling condition also arose between goshawk territories with differing habitat compositions.

As the relative proportions of different landscape elements in a given landscape is a function of large‐scale differences in geomorphology and land use, this means that the reproductive performance of goshawks as averaged over larger scales can be understood correctly only in respect to the fact that habitat gradients differ across landscapes.

In addition to being one of the first papers identifying the mechanism of partial brood loss as being primarily responsible for the habitat‐specific differences in the production of young, this study further illustrates the need to identify small‐scale mechanisms to correctly understand the large‐scale patterns of reproductive performance in territorial species. The repercussions of the observed habitat effect for local population development are discussed.