bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Effects of Bangladeshi Medicinal Plant Extracts on Interactions between Transcription Factors and Target DNA Sequences
Authors: Lampronti Ilaria , Khan Mahmud T. H. , Borgatti Monica , Bianchi Nicoletta , Gambari Roberto
Published: May 2007

Several transcription factors (TFs) play crucial roles in governing the expression of different genes involved in the immune response, embryo or cell lineage development, cell apoptosis, cell cycle progression, oncogenesis, repair and fibrosis processes and inflammation. As far as inflammation, TFs playing pivotal roles are nuclear factor kappa B (NF‐kB), activator protein (AP‐1), signal transducer and activator of transcription (STATs), cAMP response element binding protein (CREB) and GATA‐1 factors. All these TFs regulate the expression of pro‐inflammatory cytokines and are involved in the pathogenesis of a number of human disorders, particularly those with an inflammatory component. Since several medicinal plants can be employed to produce extracts exhibiting biological effects and because alteration of gene transcription represents a very interesting approach to control the expression of selected genes, this study sought to verify the ability of several extracts derived from Bangladeshi medicinal plants in interfering with molecular interactions between different TFs and specific DNA sequences. We first analyzed the antiproliferative activity of 19 medicinal plants on different human cell lines, including erythroleukemia K562, B lymphoid Raji and T lymphoid Jurkat cell lines. Secondly, we employed the electrophoretic mobility shift assay as a suitable technique for a fast screening of plant extracts altering the binding between NF‐kB, AP‐1, GATA‐1, STAT‐3, CREB and the relative target DNA elements.
Evidence‐Based Critical Evaluation of Glycemic Potential of Cynodon dactylon
Authors: Singh Santosh Kumar , Rai Prashant Kumar , Jaiswal Dolly , Watal Geeta
Published: May 2007

The present study is an extension of our previous work carried out on Cynodon dactylon. This study deals with the critical evaluation of glycemic potential of ethanolic extract of defatted C. dactylon. The doses of 250, 500 and 750 mg kg−1 bw of the extract were administered orally to normal as well as Streptozotocin‐induced diabetic rats to study its glycemic potential. The effect of repeated oral administration of the same doses of ethanolic extract was also studied on serum lipid profile of severely diabetic (SD) rats. The dose of 500 mg kg−1 bw was identified as the most effective dose as it lowered the blood glucose levels of normal by 42.12% and of diabetic by 43.42% during fasting blood glucose (FBG) and glucose tolerance test respectively. The SD rats were also treated daily with this identified dose of 500 mg kg−1 bw for 2 weeks and a significant reduction of 56.34% was observed in FBG level. Total cholesterol, low density lipoprotein and triglyceride levels were also decreased by 32.94, 64.06 and 48.46% respectively in SD rats whereas, cardioprotective high density lipoprotein increased by 16.45%. The reduced urine sugar level and increased body weight are additional advantages. These evidences clearly indicate that the ethanolic extract of defatted C. dactylon has high antidiabetic potential along with good hypolipidemic profile.
Maintaining a Physiological Blood Glucose Level with ‘Glucolevel’, a Combination of Four Anti‐Diabetes Plants Used in the Traditional Arab Herbal Medicine
Authors: Said Omar , Fulder Stephen , Khalil Khaled , Azaizeh Hassan , Kassis Eli , Saad Bashar
Published: May 2007

Safety and anti‐diabetic effects of Glucolevel, a mixture of dry extract of leaves of the Juglans regia L, Olea europea L, Urtica dioica L and Atriplex halimus L were evaluated using in vivo and in vitro test systems. No sign of toxic effects (using LDH assay) were seen in cultured human fibroblasts treated with increasing concentrations of Glucolevel. Similar observations were seen in vivo studies using rats (LD50: 25 g/kg). Anti‐diabetic effects were evidenced by the augmentation of glucose uptake by yeast cells (2‐folds higher) and by inhibition of glucose intestinal absorption (∼49%) in a rat gut‐segment. Furthermore, treatment with Glucolevel of Streptozotocin‐induced diabetic rats for 2–3 weeks showed a significant reduction in glucose levels [above 400 ± 50 mg/dl to 210 ± 22 mg/dl (P < 0.001)] and significantly improved sugar uptake during the glucose tolerance test, compared with positive control. In addition, glucose levels were tested in sixteen human volunteers, with the recent onset of type 2 diabetes mellitus, who received Glucolevel tablets 1 × 3 daily for a period of 4 weeks. Within the first week of Glucolevel consumption, baseline glucose levels were significantly reduced from 290 ± 40 to 210 ± 20 mg/dl. At baseline, a subgroup of eleven of these subjects had glucose levels below 300 mg% and the other subgroup had levels ≥ 300 mg%. Clinically acceptable glucose levels were achieved during the 2–3 weeks of therapy in the former subgroup and during the 4th week of therapy in the latter subgroup. No side effect was reported. In addition, a significant reduction in hemoglobin A1C values (8.2 ± 1.03 to 6.9 ± 0.94) was found in six patients treated with Glucolevel. Results demonstrate safety, tolerability and efficacy of herbal combinations of four plants that seem to act differently but synergistically to regulate glucose‐homeostasis.
Abnormal Sensorimotor Integrative Function of the Larynx in Congenital Laryngomalacia: A New Theory of Etiology
Authors: Thompson Dana Mara
Published: May 2007

Objectives/Hypothesis: Laryngomalacia is an enigmatic disease in which laryngeal tone is weak, resulting in dynamic prolapse of tissue into the larynx. Sensorimotor integrative function of the brainstem and peripheral reflexes are responsible for laryngeal tone and airway patency. The goal of this study was to elucidate the etiology of decreased laryngeal tone through evaluating the sensorimotor integrative function of the larynx. The secondary goal was to evaluate factors and medical comorbidities that contribute to the wide spectrum of symptoms and outcomes.

Study Design: Prospective and retrospective collection of evaluative data on infants with congenital laryngomalacia at two tertiary care pediatric referral centers.

Methods: Two hundred one infants with laryngomalacia were divided into three groups on the basis of disease severity (mild, moderate, severe). Patients were followed prospectively every 8 to 12 weeks until symptom resolution or loss to follow‐up. Sensorimotor integrative function of the larynx was evaluated in 134 infants by laryngopharyngeal sensory testing (LPST) of the laryngeal adductor reflex (LAR) by delivering a duration‐ (50 ms) and intensity‐ (2.5–10 mm Hg) controlled air pulse to the aryepiglottic fold to induce the LAR. Medical records were retrospectively reviewed for medical comorbidities.

Results: The initial LPST was higher (P < .001) in infants with moderate (6.8 mm Hg) and severe disease (7.4 mm Hg) compared with those with mild disease (4.1 mm Hg). At 1, 3, and 6 months, infants with moderate and severe disease continued to have a higher LPST compared with those with mild disease. At 9 months, the LPST decreased in all subjects (3.1–3.5 mm Hg, P = .14), which also correlated with symptom resolution. Neurologic, genetic, and cardiac diseases were more common in infants with severe disease (P < .001). Gastroesophageal reflux disease (GERD) and feeding problems more common in those with moderate and severe disease (P < .001). Apgar scores were lower in those with severe disease (P < .001). Most symptoms resolved within 12 months of presentation. Those with GERD benefited from treatment. Supraglottoplasty resulted in few complications. Multiple comorbidities (>3) influenced the need for tracheotomy.

Conclusions: Laryngeal tone and sensorimotor integrative function of the larynx is altered. The degree of alteration correlated with disease severity, indicating that factors that alter the peripheral and central reflexes of the LAR have a role in the etiology of signs and symptoms of laryngomalacia. GERD, neurologic disease, and low Apgar scores influenced disease severity and clinical course, explaining the spectrum of disease symptoms and outcomes. Sensorimotor integrative function improved as symptoms resolved.
The mechanical power requirements of avian flight
Authors: Askew G.N , Ellerby D.J
Published: May 2007

A major goal of flight research has been to establish the relationship between the mechanical power requirements of flight and flight speed. This relationship is central to our understanding of the ecology and evolution of bird flight behaviour. Current approaches to determining flight power have relied on a variety of indirect measurements and led to a controversy over the shape of the power–speed relationship and a lack of quantitative agreement between the different techniques. We have used a new approach to determine flight power at a range of speeds based on the performance of the pectoralis muscles. As such, our measurements provide a unique dataset for comparison with other methods. Here we show that in budgerigars (Melopsittacus undulatus) and zebra finches (Taenopygia guttata) power is modulated with flight speed, resulting in U-shaped power–speed relationship. Our measured muscle powers agreed well with a range of powers predicted using an aerodynamic model. Assessing the accuracy of mechanical power calculated using such models is essential as they are the basis for determining flight efficiency when compared to measurements of flight metabolic rate and for predicting minimum power and maximum range speeds, key determinants of optimal flight behaviour in the field.
An extended Reynolds analogy for excited wavy instabilities of developing streamwise vortices with applications to scalar mixing intensification
Authors: Liu J.T.C
Published: May 2007

Studies are presented to elucidate the role of steady streamwise vortex structures, initiated upstream from weak Görtler vortices in the absence of explicit vortex generators, and their excited nonlinear wavy instabilities in the intensification of scalar mixing in a spatially developing mixing region. While steady streamwise vortex flow gives rise to significant mixing enhancement, the excited nonlinear wavy instabilities, which in turn modify the basic three-dimensional streamwise vortices, give rise to further mixing intensification which is quantitatively assessed by a mixedness parameter. Possibility of similarity between the dimensionless streamwise momentum and scalar transport problems leading to an extended Reynolds analogy is sought. This similarity is shown earlier to hold for the steady streamwise vortex flow in the absence of nonlinear wavy instabilities (Liu & Sabry 1991
Proc. R. Soc. A
432
, 1–12). In this paper, the momentum conservation equations for the nonlinear wavy or secondary instabilities together with the advected fluctuation scalar problems are examined in detail. The presence of the streamwise fluctuation pressure gradient, which prevents the similarity, is estimated in terms of the fluctuation dynamical pressure and its relative importance to advective transport. It is found from scaling that the fluctuating streamwise pressure gradient, though not completely negligible, is sufficiently unimportant so as to render similarity between fluctuation streamwise velocity and fluctuation temperature and concentration a distinct possibility. The scalar fluctuations are then inferable from the fluctuation streamwise velocity and that the Reynolds stresses of the nonlinear fluctuations and the scalar fluxes are also similar. The nonlinear instability-modified mean streamwise momentum and the modified mean heat and mass transport problems are also similar, thus providing a complete ‘Reynolds analogy’, rendering possible the interpretation of the scalar mixedness for a gaseous medium for which the Prandtl and Schmidt numbers are near unity. It is found that the nonlinearity of the wavy instability, which induces scalar fluxes modifying the mean scalar transport, further intensifies scalar mixedness over a significant streamwise region which is well above that achieved by the steady, unmodified streamwise vortices alone for the numerical example corresponding to the most amplified wavy-sinuous mode.
Higher order weak linearizations of stochastically driven nonlinear oscillators
Authors: Saha Nilanjan , Roy D
Published: May 2007

We present derivative-free weak and strong solutions of stochastically driven nonlinear oscillators of engineering interest using higher order forms of the locally transversal linearization (LTL) method. Unlike strong solutions, weak stochastic solutions attempt to predict only mathematical expectations of functions of the true solution and are obtainable with much less computational effort. The linearized equations corresponding to the higher order implicit LTL schemes are arrived at using backward Euler–Maruyama and Newmark expansions in order to conditionally replace nonlinear drift and multiplicative diffusion vector fields. We also briefly describe alterations through which explicit forms of such higher order linearizations are obtained. In the weak forms, the Gaussian stochastic integrals, appearing in the linearized solutions, are replaced by random variables with simpler and discrete probability distributions. The resulting local approximations to the true solution are of significantly higher formal order of accuracy, as reflected through local error estimates. Numerical illustrations are presently provided for the Duffing and Van der Pol oscillators driven by additive and multiplicative noises, which are indicative of the numerical accuracy, computational speed and algorithmic simplicity.
Temporal order and the evolution of complex acoustic signals
Authors: Gerhardt H. Carl , Humfeld Sarah C , Marshall Vincent T
Published: May 2007

The evolution of complex signals may be favoured by hidden preferences or pre-existing sensory biases. Females of two species of grey treefrogs (Hyla chrysoscelisandHyla versicolor) were tested with combinations of a conspecific advertisement call and acoustic appendages. Appendages consisted of aggressive calls and segments of advertisement calls from conspecific males and males of three other species and bursts of filtered noise. When a wide variety of these acoustic appendages followed the advertisement call, the resulting compound signal was often more attractive than the same advertisement call alone. When the same appendages led advertisement calls, however, the compound signal was never more attractive and sometimes less attractive. The order effect was especially strong in tests ofH. versicolorin which advertisement-call duration was decreased. These results cannot be explained by a general pre-existing bias for extra stimulationper se. Rather, order and other effects may constrain the evolution and subsequent modification of complex and extravagant signals, examples of which have been reported for a wide range of taxa.
Effects of RAS on the genesis of embryonal rhabdomyosarcoma
Authors: Langenau David M. , Keefe Matthew D. , Storer Narie Y. , Guyon Jeffrey R. , Kutok Jeffery L. , Le Xiuning , Goessling Wolfram , Neuberg Donna S. , Kunkel Louis M. , Zon Leonard I.
Published: May 2007

Embryonal rhabdomyosarcoma (ERMS) is a devastating cancer with specific features of muscle differentiation that can result from mutational activation of RAS family members. However, to date, RAS pathway activation has not been reported in a majority of ERMS patients. Here, we have created a zebrafish model of RAS-induced ERMS, in which animals develop externally visible tumors by 10 d of life. Microarray analysis and cross-species comparisons identified two conserved gene signatures found in both zebrafish and human ERMS, one associated with tumor-specific and tissue-restricted gene expression in rhabdomyosarcoma and a second comprising a novel RAS-induced gene signature. Remarkably, our analysis uncovered that RAS pathway activation is exceedingly common in human RMS. We also created a new transgenic coinjection methodology to fluorescently label distinct subpopulations of tumor cells based on muscle differentiation status. In conjunction with fluorescent activated cell sorting, cell transplantation, and limiting dilution analysis, we were able to identify the cancer stem cell in zebrafish ERMS. When coupled with gene expression studies of this cell population, we propose that the zebrafish RMS cancer stem cell shares similar self-renewal programs as those found in activated satellite cells.
An ortholog of the Ro autoantigen functions in 23S rRNA maturation in D. radiodurans
Authors: Chen Xinguo , Wurtmann Elisabeth J. , Van Batavia Jason , Zybailov Boris , Washburn Michael P. , Wolin Sandra L.
Published: May 2007

In both animal cells and the eubacterium Deinococcus radiodurans, the Ro autoantigen, a ring-shaped RNA-binding protein, associates with small RNAs called Y RNAs. In vertebrates, Ro also binds the 3′ ends of misfolded RNAs and is proposed to function in quality control. However, little is known about the function of Ro and the Y RNAs in vivo. Here, we report that the D. radiodurans ortholog Rsr (Ro sixty related) functions with exoribonucleases in 23S rRNA maturation. During normal growth, 23S rRNA maturation is inefficient, resulting in accumulation of precursors containing 5′ and 3′ extensions. During growth at elevated temperature, maturation is efficient and requires Rsr and the exoribonucleases RNase PH and RNase II. Consistent with the hypothesis that Y RNAs inhibit Ro activity, maturation is efficient at all temperatures in cells lacking the Y RNA. In the absence of Rsr, 23S rRNA maturation halts at positions of potential secondary structure. As Rsr exhibits genetic and biochemical interactions with the exoribonuclease polynucleotide phosphorylase, Rsr likely functions in an additional process with this nuclease. We propose that Rsr functions as a processivity factor to assist RNA maturation by exoribonucleases. This is the first demonstration of a role for Ro and a Y RNA in vivo.
Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate
Authors: Tayab Zia R. , Fardon Tom C. , Lee Daniel K. C. , Haggart Kay , McFarlane Lesley C. , Lipworth Brian J. , Hochhaus Günther
Published: May 2007

What is already known about this subject

• Mometasone furoate (MF) is a new inhaled glucocorticoid for which the first reports suggested a low degree of systemic side‐effects and low systemic availability.

• Recent studies of Fardon and colleagues have shown that MF's cortisol suppression is similar to that of fluticasone.

• Pharmacokinetic/dynamic evaluations of MF's systemic side‐effects, probing whether systemic side‐effects can be explained by systemic availability, plasma protein binding and receptor binding affinity, are lacking in the literature.

What this study adds

• This study shows that the systemic availability of MF and fluticasone propionate (FP) are similar and that systemic availability is directly related to the dose.

• It also shows that the metabolites of MF are present only in very low concentrations at most, contrary to results in rats.

• The observed cortisol suppression of FP and MF is related to the trough plasma concentrations and seems to be in agreement with its observed systemic availability, plasma protein binding and receptor binding affinity.

Aim

Fluticasone propionate (FP) and mometasone furoate (MF) are inhaled corticosteroids that possess a high ratio of topical to systemic activity. The systemic bioavailability of MF has been claimed to be minimal (1%). FP has been shown to exhibit the same degree of systemic effects, but its systemic availability is between 13 and 17%. We hypothesize that FP and MF have comparable systemic availabilities that can explain their potential to cause systemic effects.

Methods

Steady‐state FP and MF trough plasma samples were determined from a clinical study by Fardon et al. in patients with persistent asthma (forced expiratory volume in 1 s = 91%). The percent plasma protein binding of FP and MF was measured using ultracentrifugation. Free FP plasma concentrations were normalized for their differences in receptor binding affinity compared with MF and linked to overnight urinary cortisol/creatinine with an inhibitory Emax.

Results

A plot of steady‐state FP and MF total trough plasma concentrations vs. dose showed that both drugs exhibit dose linearity. MF has comparable bioavailability to FP based on the steady‐state concentrations observed for the different doses. The free plasma concentration producing 50% of urinary cortisol suppression (IC50) for MF was not statistically different from the free, normalized IC50 for FP.

Conclusion

FP and MF have similar pulmonary deposition and the same potential to cause systemic side‐effects due to their similar IC50 values. The observed urinary cortisol suppression of FP and MF is in agreement with their systemic availability, their differences in plasma protein binding and receptor binding affinity.
Anti‐factor Xa activity of enoxaparin administered at prophylactic dosage to patients over 75 years old
Authors: Berges A. , Laporte S. , Epinat M. , Zufferey P. , Alamartine E. , Tranchand B. , Decousus H. , Mismetti P. ,   for the PROPHRE.75 study group
Published: May 2007

What is already known about this subject

• Major bleeds with low‐molecular‐weight heparin have been reported at curative and prophylactic dosages.

• Enoxaparin clearance depends on body weight, and therefore weight‐adjusted dosing is recommended to minimize interindividual variability in drug exposure and the risk of haemorrhage in patients treated at curative doses.

• Monitoring of this treatment is recommended in curative indications in patients at risk.

• The need for monitoring of patients at risk receiving prophylactic doses of enoxaparin, in this case the elderly, remains unclear.

What this study adds

• Clearance of enoxaparin at prophylactic doses is predictably related to body weight and creatinine clearance in the elderly.

• The simplified Modification of Diet in Renal Disease formula seems to be most discriminating and powerful in detecting any influence of glomerular filtration rate in the elderly.

• The influence of these covariates does not seem to be sufficiently clinically relevant to support routine assessment in the elderly.

Aims

Major bleeding complications with low‐molecular‐weight heparin (LMWH) treatment have been reported both in clinical studies and during postmarketing surveillance. Monitoring of antifactor Xa (anti‐Xa) activities is therefore recommended in special populations often predisposed to renal impairment. The PROPHRE.75 study was conducted to estimate the distribution parameters of anti‐Xa activity in the elderly.

Methods

PROPHRE.75 was a prospective study of a cohort of consecutive patients aged >75 years and treated with 4000 IU of enoxaparin once daily for venous thromboembolism prophylaxis. Dosing history and measurements of anti‐Xa activity in sparse samples were recorded throughout treatment. The covariates included weight, gender, age, renal function, medical history and concomitant medication. Population parameters and interindividual variability were estimated using NONMEM® V software.

Results

Anti‐Xa activity was studied in 189 patients (mean age 82 ± 5 years, 22% weighing <50 kg, 50% presenting renal impairment according to the Cockcroft and Gault formula). A first‐order input two‐compartment model best fitted the data. Clearance was significantly related to body weight and creatinine clearance based on the simplified Modification of Diet in Renal Disease formula, central volume being related to body weight. According to individual Bayesian estimations, 4% of patients presented with a peak anti‐Xa activity >1.0 IU ml−1, but this group did not include the sole patient experiencing a major bleed (0.53%).

Conclusions

Systematic monitoring of anti‐Xa activity in elderly patients treated with enoxaparin at prophylactic doses does not seem to be necessary to prevent the occurrence of major bleeding.
When a placebo is not a ‘placebo’: a placebo effect on postprandial glycaemia
Authors: Sievenpiper John L. , Ezatagha Adish , Dascalu Anamaria , Vuksan Vladimir
Published: May 2007

What is already known about this subject

• Although placebo effects have been shown on subjective continuous variables such as pain, placebo effects on objective continuous variables remain uncertain.

• The present, pilot, follow‐up investigation represents the first to assess a placebo effect on the objective continuous measurement of acute postprandial plasma glucose.

What this study adds

• Placebo effects may be operating on postprandial plasma glucose outcomes.

• Cornstarch sources of placebo may decrease the plasma glucose response to a 75‐g oral glucose tolerance test, rendering them as positive controls when assessing postprandial outcomes.

• Other carbohydrate sources used as placebos in research may show similar effects.

Aims

Placebo effects in clinical trials remain uncertain. To investigate a placebo effect on acute postprandial plasma glucose, we conducted a follow‐up investigation on a previous study.

Methods

The effect of placebo (9 g encapsulated cornstarch +500 ml water, taken at −40 min) on the plasma glucose response to a 75‐g oral glucose tolerance test (OGTT) was assessed in a previous study in 12 healthy subjects (gender, five male, seven female; age 27 ± 6 years; body mass index 24 ± 3.4 kg m−2). This was compared with the effect of a water control (500 ml water taken alone at −40 min) on the same outcome in the same subjects in a follow‐up study.

Results

Cornstarch placebo decreased plasma glucose area under the curve during the 75‐g OGTT by 28% [Δ (95% confidence interval) −63.3 min mmol−1 l−1 (−218.33, 91.66), P < 0.02] compared with the water control (P < 0.05).

Conclusions

Postprandial plasma glucose outcomes may be vulnerable to placebo effects.
Diclofenac and acute myocardial infarction in patients with no major risk factors
Authors: Jick Susan S. , Kaye James A. , Jick Hershel
Published: May 2007

What is already known about this subject

• We recently published the results of a study on the risk of acute myocardial infarction (AMI) in users of five nonsteroidal anti‐inflammatory drugs during the years 2001 to 2005.

• The results demonstrated, as has been reported in randomized trials, that rofecoxib and celecoxib increase the risk of AMI when taken for at least 10 months.

• As expected, ibuprofen and naproxen did not materially increase the risk.

• However, long‐term users of diclofenac were at an increased risk of AMI similar to that of users of rofecoxib and celecoxib.

What this study adds

• Extensive use of diclofenac, similarly to rofecoxib and celecoxib, substantially increases the risk of AMI.

• There is little suggestion of such an effect in users of ibuprofen and naproxen.

Aims

To explore further a recent finding that long‐term users of diclofenac are at increased risk of acute myocardial infarction (AMI) similar to users of rofecoxib and celecoxib.

Methods

Using the General Practice Research Database, we conducted three separate nested case–control studies of three nonsteroidal anti‐inflammatory drugs (NSAIDs) where use started after 1 January 1993 — diclofenac, ibuprofen and naproxen. Cases of AMI were identified between 1 January 1993 and 31 December 2000. Relative risk (RR) estimates for AMI in patients with no major clinical risk factors were determined for each NSAID according to number of prescriptions received compared with one prescription. Results were adjusted for variables possibly related to risk of AMI.

Results

There was no material elevation of AMI risk according to the number of prescriptions for ibuprofen [RRs and 95% confidence intervals (CIs) 1.0 (0.6, 1.6) and 1.7 (0.9, 3.1) for use of 10–19 and 20+ prescriptions, respectively, compared with one prescription] or naproxen [RRs 1.0 (0.5, 2.2) and 2.0 (0.9, 4.5) for use of 10–19 and 20+ prescriptions, respectively]. However, a substantial increased risk similar to that obtained in our prior study was found in patients who received ≥10 prescriptions for diclofenac [RRs 1.9 (1.3, 2.7) and 2.0 (1.3, 3.0) for use of 10–19 and 20+ prescriptions, respectively].

Conclusions

Extensive use of diclofenac substantially increases the risk of AMI. There is little suggestion of such an effect in users of ibuprofen and naproxen.
The effect of ABCG2 V12M, Q141K and Q126X, known functional variantsin vitro, on the disposition of lamivudine
Authors: Kim Ho‐Sook , Sunwoo Yu Eun , Ryu Ji Young , Kang Ho‐Jin , Jung Hye‐Eun , Song Im‐Sook , Kim Eun‐Young , Shim Joo‐Cheol , Shon Ji‐Hong , Shin Jae‐Gook
Published: May 2007

Aims

To evaluate the effects of three ABCG2 variants (Q141K, V12M and Q126X), which are known to have altered transport propertiesin vitro, on the disposition of lamivudine in healthy subjects.

Methods

To evaluate whether lamivudine is a substrate of ABCG2, intracellular accumulation and vectorial transport of3H‐lamivudine were determined in MDCK‐ABCG2 cells. The pharmacokinetic parameters of lamivudine were compared among subjects with four different ABCG2 genotypes, including wild type (seven subjects), K141/K141 (six subjects), Q126/Stop126 (four subjects) and M12/M12 (five subjects) after a single oral dose of 100 mg lamivudine.

Results

The intracellular accumulation of lamivudine in MDCK‐ABCG2 cells was significantly lower than that in MDCK‐mock cells, but fumitremorgin C reversed the intracellular lamivudine concentration to that of MDCK‐mock cells. The ABCG2‐mediated transport of lamivudine was saturable and the values ofKmandVmaxwere 216.5 ± 58 µmand 20.42 ± 2.9 nmol h−1per 106cells, respectively. After lamivudine administration to healthy subjects, the AUC of lamivudine showed no difference among subjects with different ABCG2 genotypes; 2480 ± 502, 2207 ± 1019, 2422 ± 239, 2552 ± 698 ng h−1 ml−1for wild type, K141/K141, Q126/Stop126 and M12/M12 genotype, respectively (P = 0.85). The estimated 95% confidence intervals for the mean difference between K141/K141, Q126/Stop126, M12/M12 and wild as reference were (−1053, 507), (−555, 439) and (−552, 696), respectively. No other pharmacokinetic parameters were estimated to be significantly different among four different ABCG2 genotypes tested.

Conclusions

Lamivudine appeared to be a substrate of ABCG2in vitro, but the disposition of lamivudine was not significantly influenced by knownin vitrofunctional variants of ABCG2, Q141K, V12M and Q126X in healthy subjects.
Effects of rain forest logging on species richness and assemblage composition of small mammals in Southeast Asia
Authors: Wells Konstans , Kalko Elisabeth K. V. , Lakim Maklarin B. , Pfeiffer Martin
Published: May 2007

Aim  The effects of logging and habitat degradation on the richness and abundance of small mammals in Asian rain forests are largely unknown. This work compares the species richness, dominance and evenness of small non‐volant mammals between logged and unlogged forests, and assesses whether assemblage variability (β‐diversity) is similar between forest types.

Location  Southeast Asia, northern Borneo (Sabah, Malaysia), Sunda‐shelf.

Methods  We surveyed species‐rich assemblages of small non‐volant mammals in three unlogged and three logged forests for 2 years. At each forest site, we sampled a permanently marked transect and two additional sites in three trapping sessions. All analyses were performed at both levels to include the effects of local abundances and point estimates, separately from the relative abundances of species on a more regional scale.

Results  We trapped a total of 1218 individuals of 28 species. Eleven common species accounted for 95% of all captures. Species richness and diversity were significantly higher in unlogged forest (27 species) than in logged forest (17 species). This was mainly attributable to the smaller number of rarely recorded species in logged forest (five compared with 16 in unlogged forest, with a total of fewer than 10 captures). However, all common species were present in both logged and unlogged forests, and our analyses revealed similar patterns of dominance, evenness and fluctuations in abundance. Hence overall assemblage composition in multivariate space did not differ greatly between forest types. Assemblages of Muridae and Tupaiidae showed similar population fluctuations in space and time, indicating that the ecology of these taxa may be partially driven by the same environmental factors.

Main conclusions  Although species were distributed patchily within sites, analyses at local and regional scales revealed similar patterns in diversity and assemblage variability, suggesting that effects of forest modification did not differ extensively locally and regionally, but had a profound effect on rare species. Our results emphasize the importance and conservation value of logged forest stands that are able to hold a large proportion of the small mammals also found in unlogged forests. Rare and more specialized species are more vulnerable to forest degradation than commonly caught species, resulting in the complete loss, or a decrease in numbers, of certain groups, such as arboreal small mammals and Viverridae.
Levels of endemism are not necessarily biased by the co‐presence of species with different range sizes: a case study of Vilenkin and Chikatunov's models
Authors: Fattorini Simone
Published: May 2007

Aim To illustrate problems in the methods proposed by B. Vilenkin and V. Chikatunov to study levels of endemism and species–area relationships.

Location The study used data on the distribution of tenebrionid beetles (Coleoptera, Tenebrionidae) on the Aegean Islands (Greece).

Methods A total of 32 islands and 170 taxa (species and subspecies) were included in this study. Levels of endemism were evaluated both as the proportion of endemic taxa, and according to the methods proposed by Vilenkin and Chikatunov, which are based on the number of non‐endemic taxa and various relationships with area. A model of the species–area relationship proposed by these authors was also analysed.

Results The number of endemic taxa was positively correlated with the number of taxa with different distribution types, but this positive correlation did not influence the estimation of the level of endemism. In fact, the commonly used estimate of endemicity as a percentage was strongly correlated with the endemism values calculated according to the method of Vilenkin and Chikatunov. The usual power function fitted the species–area relationship as well as the most complicated method of Vilenkin and Chikatunov.

Main conclusions As hypothesized by Vilenkin and Chikatunov, the number of endemic taxa was influenced both by the number of taxa of other biogeographical ranks, and by an island's area. However, explanations for the positive relationship between the number of endemic taxa and taxa of different biogeographical ranks are equivocal. Importantly, this relationship did not necessarily influence the level of endemism, which could be expressed adequately by percentages. The method proposed by Vilenkin and Chikatunov to estimate the species–area relationship cannot be clearly justified on theoretical grounds and is of questionable practical utility.
Predicting habitat distribution and frequency from plant species co‐occurrence data
Authors: Römermann Christine , Tackenberg Oliver , Scheuerer Martin , May Rudolf , Poschlod Peter
Published: May 2007

Aim  Species frequency data have been widely used in nature conservation to aid management decisions. To determine species frequencies, information on habitat occurrence is important: a species with a low frequency is not necessarily rare if it occupies all suitable habitats. Often, information on habitat distribution is available for small geographic areas only. We aim to predict grid‐based habitat occurrence from grid‐based plant species distribution data in a meso‐scale analysis.

Location  The study was carried out over two spatial extents: Germany and Bavaria.

Methods  Two simple models were set up to examine the number of characteristic plant species needed per grid cell to predict the occurrence of four selected habitats (species data from FlorKart, http://www.floraweb.de). Both models were calibrated in Bavaria using available information on habitat distribution, validated for other federal states, and applied to Germany. First, a spatially explicit regression model (generalized linear model (GLM) with assumed binomial error distribution of response variable) was obtained. Second, a spatially independent optimization model was derived that estimated species numbers without using spatial information on habitat distribution. Finally, an additional uncalibrated model was derived that calculated the frequencies of 24 habitats. It was validated using NATURA2000 habitat maps.

Results  Using the Bavarian models it was possible to predict habitat distribution and frequency from the co‐occurrence of habitat‐specific species per grid cell. As the model validations for other German federal states were successful, the models were applied to all of Germany, and habitat distribution and frequencies could be retrieved for the national scale on the basis of habitat‐specific species co‐occurrences per grid cell. Using the third, uncalibrated model, which includes species distribution data only, it was possible to predict the frequencies of 24 habitats based on the co‐occurrence of 24% of formation‐specific species per grid cell. Predicted habitat frequencies deduced from this third model were strongly related to frequencies of NATURA2000 habitat maps.

Main conclusions  It was concluded that it is possible to deduce habitat distributions and frequencies from the co‐occurrence of habitat‐specific species. For areas partly covered by habitat mappings, calibrated models can be developed and extrapolated to larger areas. If information on habitat distribution is completely lacking, uncalibrated models can still be applied, providing coarse information on habitat frequencies. Predicted habitat distributions and frequencies can be used as a tool in nature conservation, for example as correction factors for species frequencies, as long as the species of interest is not included in the model set‐up.
Detection of Strawberry RNA and DNA Viruses by RT‐PCR Using Total Nucleic Acid as a Template
Authors: Chang L. , Zhang Z. , Yang H. , Li H. , Dai H.
Published: May 2007

Strawberry mild yellow edge virus (SMYEV), Strawberry mottle virus (SMoV) and Strawberry vein banding virus (SVBV), three of strawberry viruses can cause a severe loss in commercial strawberry worldwide. In this paper, total nucleic acid from strawberry leaves was compared with total RNA as the template for detection of the above viruses both by single and multiplex reverse transcription polymerase chain reaction (RT‐PCR). Total nucleic acid extract with the modified CTAB method and total RNA extracts with both the modified RNeasy method and the modified CTAB method examined by electrophoresis resulted in a high quality ribosomal 28S and 18S RNA when loaded on an agarose gel. When total RNA and total nucleic acid were used as templates, detection results of SMYEV and SMoV were identical and the amplified band intensity was nearly the same whether by single or duplex RT‐PCR. Using total nucleic acid as the template, the detection results of SMYEV and SMoV by multiplex RT‐PCR were in a good concord with that amplified by single and duplex RT‐PCR, and for SVBV this was similar to the result of detection that amplified by direct PCR using pure DNA as the template. This study demonstrates that total nucleic acid extracted from strawberry leaves by a modified CTAB method is suitable as a template for virus detection by RT‐PCR. This makes investigation of the epidemiology of strawberry viruses much easier.
Pathogenic Fungi in Garlic Seed Cloves from the United States and China, and Efficacy of Fungicides Against Pathogens in Garlic Germplasm in Washington State
Authors: Dugan F. M. , Hellier B. C. , Lupien S. L.
Published: May 2007

Commercially distributed garlic (Allium sativum) seed cloves from six states of the United States and mainland China were surveyed for the presence of fungi recorded as pathogenic to garlic in the literature.Aspergillus niger, A. ochraceus, Botrytis porri, Embellisia allii, Fusarium oxysporumf. sp.cepae, F. proliferatumandPenicillium hirsutum, were each recovered from one or more of these commercial sources, as wasF. verticillioides, not previously reported as pathogenic to garlic, but here demonstrated to be a pathogen. Seed garlic distributed from public germplasm collections may also contain fungal pathogens:E. allii, F. oxysporumf. sp.cepaeand/orF. proliferatumcaused severe losses in 2002–2003 and 2005–2006 during germplasm regeneration and storage for the National Plant Germplasm System in Pullman, Washington. Use of fludioxonil, thiophanate methyl and/or benomyl (the latter withdrawn from the market, but used here as a standard) at label rates againstE. alliiandFusariumspecies promoted plant health, but not when infections were located deep within tissues nor under some situations involving high disease pressure.
Phylogenetic Diversities of Dominant Culturable Bacillus, Pseudomonas and Pantoea Species on Tomato Leaves and Their Possibility as Biological Control Agents
Authors: Enya J. , Koitabashi M. , Shinohara H. , Yoshida S. , Tsukiboshi T. , Negishi H. , Suyama K. , Tsushima S.
Published: May 2007

We have demonstrated the phylogenetic diversity and antagonistic activities of three genera of dominant culturable bacteria (Bacillus, Pseudomonas and Pantoea) on tomato leaves. A total of 133 Bacillus isolates that were dominant on greenhouse plants and 109 Pseudomonas and 48 Pantoea isolates that were dominant on field‐grown plants were analyzed based on their 16S rRNA gene sequences. Bacillus pumilus (38%), Pseudomonas monteilii (76%) and Pantoea agglomerans (90%) were the most predominant of their genera, respectively. In the genus Bacillus, effective biological control agents (BCAs) against tomato leaf mould were interspersed among its phylogenetic tree as minority groups, while the effective BCAs of Pseudomonas and Pantoea were in majority groups that showed consistent suppressive activities. The results suggest that isolating Pseudomonas and Pantoea species from field‐grown tomato plants may be preferable for BCA‐candidate screening than isolating species of Bacillus from greenhouse.
Peroxidase Activity, Isozyme Patterns and Electrolyte Leakage in Roots of Cocoyam Infected with Pythium myriotylum
Authors: Nyochembeng L. M. , Beyl C. A. , Pacumbaba R. P.
Published: May 2007

Knowledge of host defence response in cocoyam against Pythium myriotylum is essential in understanding disease resistance and the development of effective control measures for the cocoyam root rot disease. Four cocoyam accessions were assessed for root rot disease reaction by inoculating the roots of intact plants in the greenhouse and detached roots in the laboratory with P. myriotylum isolate ‘Mamu’ from Cameroon. Electrolyte leakage in detached infected roots and peroxidase activities and isozyme expressions in crude protein extracts collected from healthy roots of inoculated and non‐inoculated plants at 0, 2, 4, 6 and 8 days post inoculation (dpi) were used independently to assess resistance/tolerance. Based on the results, cocoyam accessions RO1054 and RO3015 were rated tolerant/moderately resistant while accessions RO2063 and ‘Local White’ (LW) were rated susceptible to P. myriotylum isolate ‘Mamu’. The time‐course spectrophotometric analysis of peroxidase activity showed an increase in activity in the roots of the tolerant RO1054, 8 days after inoculation. One peroxidase isoform (Rf 0.66) was induced only in roots of the susceptible inoculated accessions ‘Local White’ and R02063 at 4 and 6 dpi. One acidic peroxidase isozyme (pI 4.5) and one basic isozyme (pI 7.4) were detected only in roots of inoculated plants. Our results suggest that electrolyte leakage in infected roots can be used to assess tolerance/susceptibility in cocoyam and that tolerance to the root rot disease in cocoyam may be associated in part with an increased generation of peroxidase activity in the roots.
A Real‐time PCR Assay for Quantitative and Accurate Assessment of Fungicide Effects on Mycosphaerella graminicola Leaf Blotch
Authors: Guo J.‐R. , Schnieder F. , Verreet J.‐A.
Published: May 2007

A real‐time PCR assay was applied to evaluate the effects of two fungicide treatments on Mycosphaerella graminicola leaf blotch in the field and compared with two usual visual methods. The three fungicides Fandango, Input and Prosaro used in the two treatments showed high inhibitions against germ tube growth and conidial germination in vitro, suggesting that they had high curative and protective activities. In the field, the fungicide effect was assessed for two times on 17 May and 14 June, 2004. M. graminicola DNA, disease index and pycnidial number per leaf reduced obviously on most leaf layers after both treatments. According to the real‐time PCR data, significant effects were still observed on leaf 3, 4 and 5 even after 25 days of treatment (17 May). And on 14 June, treatment A significantly decreased the DNA amount by 99.42, 87.68, 24.12 and 68.87% on leaf 1, 2, 3 and 4 and treatment B by 98.83, 98.12, 70.79 and 64.15% respectively. In contrast, effects could neither be assessed by disease classification on leaf 5 of treatment B on 17 May and leaf 3 and 4 of treatment A on 14 June and nor by pycnidia‐counting method on leaf 3 and 5 of treatment B on 17 May and leaf 4 of both treatments on 14 June. The band intensity of final real‐time PCR products could be hardly distinguished on agarose gel amongst those samples with disease index >2.7, although their initial DNA amounts quantified by real‐time PCR were different, indicating the superiority of the real‐time PCR assay over those PCR assays estimating initial DNA input with end‐point measurement. All this shows that the real‐time PCR assay may serve as an alternative method for accurate assessment of the fungicide effects on M. graminicola leaf blotch.
Influence of Fusarium Crown Rot Disease on Semiochemical Production by Wheat Plants
Authors: Piesik D. , Wenda‐Piesik A. , Weaver D. K. , Morrill W. L.
Published: May 2007

Plants infected by Fusarium spp. can emit volatile chemicals that differ both quantitatively and qualitatively from undamaged plants. In this experiment, pathogen infection increased the release of the secondary metabolites linalool, linalool oxide and β‐farnesene by wheat plants. The amounts of released metabolites varied significantly with Fusarium species. The time interval for the volatile collections within photophase also influenced the amount collected for each day. The increased emission of these compounds, as a result of infection, may be explained as a defence mechanism.