bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mitogen-activated Protein Kinase p38 Links Shiga Toxin-dependent Signaling and Trafficking
Authors: Wälchli Sébastien , Skånland Sigrid S. , Gregers Tone F. , Lauvrak Silje U. , Torgersen Maria L. , Ying Ming , Kuroda Shun'ichi , Maturana Andrés , Sandvig Kirsten
Published: October 2007

Shiga toxin (Stx) binds to the cell, and it is transported via endosomes and the Golgi apparatus to the endoplasmic reticulum and cytosol, where it exerts its toxic effect. We have recently shown that Stx activates the tyrosine kinase Syk, which in turn induces clathrin phosphorylation and up-regulates Stx uptake. Here, we show that toxin-induced signaling can also regulate another step in intracellular Stx transport. We demonstrate that transport of Stx to the Golgi apparatus is dependent on the mitogen-activated protein kinase p38. Treatment of cells with chemical inhibitors or small interfering RNA targeting p38 inhibited Stx transport to the Golgi and reduced Stx toxicity. This p38 dependence is specific to Stx, because transport of the related toxin ricin was not affected by p38 inhibition. Stx rapidly activated p38, and recruited it to early endosomes in a Ca2+-dependent manner. Furthermore, agonist-induced oscillations in cytosolic Ca2+levels were inhibited upon Stx stimulation, possibly reflecting Stx-dependent local alterations in cytosolic Ca2+levels. Intracellular transport of Stx is Ca2+dependent, and we provide evidence that Stx activates a signaling cascade involving cross talk between Ca2+and p38, to regulate its trafficking to the Golgi apparatus.
Differential Growth Suppression of Human Melanoma Cells by Tea (Camellia sinensis) Epicatechins (ECG, EGC and EGCG)
Authors: Ravindranath Mepur H. , Ramasamy Vaishali , Moon Songeun , Ruiz Carlos , Muthugounder Sakunthala
Published: October 2007

We previously reported that catechins of green tea have different antiproliferative effects on cell lines derived from gender‐dependent cancers; epicatechin 3‐gallate (ECG) had the strongest inhibitory effect. In the present study, we examined the effects of epigallocatechin (EGC), epicatechin‐gallate (ECG) and EGC 3‐gallate (EGCG) on the viability, density, doubling time and cycle number of cell lines derived from melanoma metastasized to lymph nodes (MB‐1133 and SE‐0154) or distant organs (CH‐0356, JK‐0346, SA‐1171, GE‐0208, NS‐1176 and LF‐0023). These catechins have been documented to have no growth suppressive or apoptotic effects on normal melanocytes (Nihal et al., Int J Cancer 2005;114:513–21). EGCG (50 μM) showed greater inhibitory potency than EGC (50 μM) in SE‐0154, NS‐1176, GE‐0208 and LF‐0023 cell lines but the two catechins produced similar inhibitory effects in CH‐0356, JK‐0346 and SA‐1171 cell lines. The IC50 (50% inhibitory concentration) was lower for EGC than EGCG in MB‐1133 and CH‐0356 cells, higher for EGC than EGCG in GE‐0208 cells and comparable (11–12 μM) for both the catechins in LF‐0023 cells. When compared with EGC, the cytotoxic effect (% dead cell counts) and the suppression of the growth (change in cell number) of all melanoma cell lines tested were pronounced with EGCG. This investigation validates the hypothesis that anticancer action of the various catechins may vary with the type of malignancy and provides a model for tumor cell heterogeneity based on susceptibility and resistance of tumor cells to different green tea catechins. Therefore, this information is critical for undertaking chemopreventive or chemotherapeutic trials against melanoma and gender‐based cancers.
In Vitro Cytotoxic Effect of Brazilian Green Propolis on Human Laryngeal Epidermoid Carcinoma (HEp‐2) Cells
Authors: Búfalo Michelle C. , Candeias João M. G. , Sforcin José Maurício
Published: October 2007

Propolis is a sticky dark‐colored material showing a very complex chemical composition that honeybees collect from plants. It has been used in folk medicine since ancient times, due to several biological properties, such as antimicrobial, anti‐inflammatory, antioxidant and immunomodulatory activities, among others. Its antitumor action in vivo and in vitro has also been reported, using propolis extracts or its isolated compounds. The goal of this work was to evaluate propolis′s cytotoxic action in vitro on human laryngeal epidermoid carcinoma (Hep‐2) cells. These cells were incubated with different concentrations of this bee product for different time periods, and morphology and the number of viable HEp‐2 cells analyzed. Data showed that propolis exhibited a cytotoxic effect in vitro against HEp‐2 cells, in a dose‐ and time‐dependent way. Propolis solvent had no effects on morphology and number of viable cells, proving that the cytotoxic effects were exclusively due to propolis components. Since humans have been using propolis for a long time, further assays will provide a better comprehension of propolis′s antitumor action.
Acori graminei rhizoma Ameliorated Ibotenic Acid‐Induced Amnesia in Rats
Authors: Kim Ji Hyun , Hahm Dae-Hyun , Lee Hye-Jung , Pyun Kwang Ho , Shim Insop
Published: October 2007

In the present study, we investigated the effects of Acori graminei rhizoma (AGR) on learning and memory for the Morris water maze task and on the central cholinergic system of the rats with excitotoxic medial septum (MS) lesion. On the water maze test, the rats were trained to find a platform that was in a fixed position during 6 days and then they received a 60 s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesioning of the MS impaired the performance on the maze test and it caused degeneration of choline acetyltransferase and acetylcholine esterase in the hippocampus, which are markers of the central cholinergic system. Daily administrations of AGR (100 mg kg−1, i.p.) for 21 consecutive days produced reversals of the ibotenic acid‐induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus that was induced by ibotenic acid. These results demonstrated that AGR ameliorated learning and memory deficits through their effects on the central nervous system, and neuroprotection was partly evaluated through the effect of AGR on the cholinergic system. Our studies suggest that AGR can possibly be used as treatment for Alzheimer′s disease.
The obstacle problem for a class of hypoelliptic ultraparabolic equations
Authors: Francesco Marco Di , Pascucci Andrea , Polidoro Sergio
Published: October 2007

We study the obstacle problem for a class of degenerate parabolic operators with continuous coefficients. This problem arises in the Black–Scholes framework when considering path-dependent American options. We prove the existence of a unique strong solutionuto the Cauchy and Cauchy–Dirichlet problems, under rather general assumptions on the obstacle function. We also show thatuis a solution in the viscosity sense.
Electromagnetic diffraction by arbitrary-angle impedance wedges
Authors: Osipov Andrey V , Senior Thomas B.A
Published: October 2007

The problem of the diffraction of a plane electromagnetic wave incident at an oblique angle on a wedge of arbitrary angle with general tensor impedance boundary conditions is solved using a semi-analytical approach. Application of Maliuzhinets' method transforms the boundary-value problem into coupled functional difference equations (FDEs) for two unknown Sommerfeld integral spectra in a basic strip. By explicitly separating out the singular parts of the spectra in the strip, followed by a partial inversion of the FDEs, we obtain integral representations of the regular parts of the spectra. The regular parts are then expanded in a Taylor series in terms of a new variable that conformally maps the strip on to a disc. This expansion reduces the integral representations to algebraic equations for the series coefficients and these are solved numerically. We examine the convergence of the procedure, compare the numerical solution with an available reference solution and present solutions of new problems.
The 1 : 2 spatial resonance on a hexagonal lattice in two-layered Rayleigh–Bénard problems
Authors: Fujimura K
Published: October 2007

This paper investigates pattern formation resulting from the interaction between steady modes with wavenumbers in the ratio 1 : 2. A two-layered Rayleigh–Bénard problem with infinite extent is examined; two layers are separated by a non-deformable and thin dividing plate. This physical set-up is known to provide an exact 1 : 2 resonance between critical modes. Restricting the wavevectors of interacting modes on a hexagonal lattice, we derive 12-dimensional amplitude equations up to cubic order. Among steady solutions of the equations, the stable ones are hexagons and mixed hexagons. Travelling waves corresponding to relative equilibria are also found to be stable depending on parameter values.
Gene expression underlying adaptive variation inHeliconiuswing patterns: non-modular regulation of overlappingcinnabarandvermilionprepatterns
Authors: Reed Robert D , McMillan W. Owen , Nagy Lisa M
Published: October 2007

Geographical variation in the mimetic wing patterns of the butterflyHeliconius eratois a textbook example of adaptive polymorphism; however, little is known about how this variation is controlled developmentally. Using microarrays and qPCR, we identified and compared expression of candidate genes potentially involved with a red/yellow forewing band polymorphism inH. erato. We found that transcripts encoding the pigment synthesis enzymescinnabarandvermilionshowed pattern- and polymorphism-related expression patterns, respectively.cinnabarexpression was associated with the forewing band regardless of pigment colour, providing the first gene expression pattern known to be correlated with a majorHeliconiuscolour pattern. In contrast,vermilionexpression changed spatially over time in red-banded butterflies, but was not expressed at detectable levels in yellow-banded butterflies, suggesting that regulation of this gene may be involved with the red/yellow polymorphism. Furthermore, we found that the yellow pigment, 3-hydroxykynurenine, is incorporated into wing scales from the haemolymph rather than being synthesizedin situ.We propose that some aspects ofHeliconiuscolour patterns are determined by spatio-temporal overlap of pigment gene transcription prepatterns and speculate that evolutionary changes invermilionregulation may in part underlie an adaptive colour pattern polymorphism.
A catfish of the genus Trichomycterus from a thermal stream in southern South America (Teleostei, Siluriformes, Trichomycteridae), with comments on relationships within the genus
Authors: Fernández L. , Miranda G.
Published: October 2007

The first record of two trichomycterid species from the thermal waters of a small stream in Miraflores, north of Potosí, Bolivia is given. The reported species are Trichomycterus therma n. sp. and Trichomycterus tiraquae. The new species differ from all congeners in the possession of thickened transverse skin on the ventral surface of the head. They are further distinguished from all congeners by the following combination of characteristics: presence of spatulate incisiform premaxillary teeth; presence of large and rounded papilla‐like structures on trunk of body; continuous segment of the laterosensory canal within the frontal with the presence of a segment between pores 2 and 6; long laterosensory canal with four to six pores; maxilla with a short anterior process that is smaller than the main axis of the bone, and has an anterior orientation; mesethmoid shaft narrower than the width of the lateral cornua; prepelvic length 58·7–61·0% of standard length (LS); head width 19·1–22·8% of LS; submaxillary barbel length 23·9–37·5% of head length (LH). Two derived characters, namely the presence of spatulate incisiform premaxillary teeth and large and rounded papilla‐like structures, define a monophyletic group within Trichomycterus, comprising T. therma, T. corduvensis and T. tiraquae.
Determining patterns of use by black bream Acanthopagrus butcheri (Munro, 1949) of re‐established habitat in a south‐eastern Australian estuary
Authors: Hindell J. S.
Published: October 2007

Acoustic telemetry was used to assess patterns of utilization by black bream Acanthopagrus butcheri of regions with and without re‐introduced large woody debris (LWD) in two estuaries of south‐eastern Australia, the Mitchell and Tambo Rivers. The fish (n = 46) were implanted with acoustic transmitters in December 2004 and March 2005 and monitored for c. 12 months. The two principal metrics from the telemetry data, number of visits per day (N day−1) and residency (amount of time, s) were highly correlated (r > 0·948), and subsequent analyses were based on N day−1. Rates of N day−1 varied inconsistently among estuarine regions across diel periods and times of year for each river. In the Tambo River during autumn, winter and spring, the N day−1 was greatest in the middle and upper estuarine regions during the day, and often greater in the lower region at dawn and dusk, but varied little among regions in summer. The provision of LWD had little effect on N day−1 in the Tambo River. In the Mitchell River, N day−1 varied little among estuarine regions without LWD, regardless of the time of day, and these patterns were consistent across seasons, but N day−1 was significantly greater to the LWD during the day in winter and spring. Freshwater flows had little effect on monthly patterns of N day−1 among regions in either estuary. The perceived ‘benefits’ to A. butcheri of re‐establishing LWD within estuarine systems of south‐eastern Australia depended strongly on the time of year, time of day and river system, but acoustic telemetry was a useful method of evaluating the use by fish of these artificial structures.
Reproductive biology of the endangered Oxleyan pygmy perch Nannoperca oxleyana Whitley
Authors: Knight J. T. , Butler G. L. , Smith P. S. , Wager R. N. E.
Published: October 2007

The reproductive biology of the Oxleyan pygmy perch Nannoperca oxleyana is described from simultaneous studies of wild populations in north‐eastern New South Wales and mature fish held in aquaria. In the wild, 50% of males and females matured at total lengths of 24·0–25·9 and 28·0–29·9 mm, respectively. The species displays sexual dichromatism during the spawning season, with males developing more intense red and brown fin and body colouration, and black pelvic fins. Captive male broodfish displayed territoriality during the breeding season, closely guarding sites within artificial, plant‐like substrata in which pairs of fish spawned adhesive eggs. Protracted serial spawning of wild and captive fish occurred from September to April and May at mean water temperatures ≥16·6° C and day length ≥10·7 h. Captive broodfish spawned on an average of 57% of days during the 256 day spawning period. Gonado‐somatic indices averaged 0·7% for all ripe males and 4·1–4·2% for all ripe females collected. Mean total and batch fecundities of captive females were 1323 eggs per fish and 7·8 eggs per fish per day, respectively, and relative fecundity was 587 eggs g−1 of body mass. Batch fecundity of wild females was estimated at 7·8 eggs per fish. The adaptive significance of this reproductive strategy in a harsh, variable environment is discussed.
Age and size compositions, growth and reproductive biology of the breaksea cod Epinephelides armatus, a gonochoristic serranid
Authors: Moore S. E , Hesp S. A. , Hall N. G. , Potter I. C.
Published: October 2007

Details of the reproductive biology, size and age compositions and growth of the breaksea cod Epinephelides armatus, the sole representative of Epinephelides, were obtained by collecting monthly samples of a wide total length (LT) range of individuals from coastal marine waters at 31–32° S on the lower west coast of Australia. Although the modal LT class of females (250–299 mm) was markedly less than that of males (400–449 mm), the modal ages of the two sexes were similar, i.e. 4 v. 5 years, respectively. The similarity in the age compositions and the histological demonstration that the gonads of all E. armatus consist solely of either ovarian or testicular tissues demonstrate that this species is gonochoristic, which is highly unusual for an anthiinine serranid. The absence of a central, membrane‐lined ‘ovarian’ lumen in the testes of juveniles would account for adult testes containing neither this ovarian remnant nor the peripherally located sperm sinuses that are found in the mature testes of almost all other serranids. The results demonstrate that E. armatus exhibits a very unusual pattern of sexual development for a serranid. The spawning period of E. armatus lasts for c. 9 months, which is long for a species in temperate Western Australian waters, but comparable with that of many other relatively small serranids elsewhere. Females grow slower than males, attaining LT at 3, 5 and 10 years of c. 200, 285 and 420 mm, respectively, compared with c. 215, 315 and 450 mm, respectively. Females, however, attain maturity at a greater LT and older age than males.
Growth rate differences between resident native brook trout and non‐native brown trout
Authors: Carlson S. M. , Hendry A. P. , Letcher B. H.
Published: October 2007

Between species and across season variation in growth was examined by tagging and recapturing individual brook troutSalvelinus fontinalisand brown troutSalmo truttaacross seasons in a small stream (West Brook, Massachusetts, U.S.A.). Detailed information on body size and growth are presented to (1) test whether the two species differed in growth within seasons and (2) characterize the seasonal growth patterns for two age classes of each species. Growth differed between species in nearly half of the season‐ and age‐specific comparisons. When growth differed, non‐native brown trout grew faster than native brook trout in all but one comparison. Moreover, species differences were most pronounced when overall growth was high during the spring and early summer. These growth differences resulted in size asymmetries that were sustained over the duration of the study. A literature survey also indicated that non‐native salmonids typically grow faster than native salmonids when the two occur in sympatry. Taken together, these results suggest that differences in growth are not uncommon for coexisting native and non‐native salmonids.
Geographic divergence in the relationship between Paragobiodon echinocephalus and its obligate coral host
Authors: Belmaker J. , Polak O. , Shashar N. , Ziv Y.
Published: October 2007

The redhead goby Paragobiodon echinocephalus lives exclusively within the branching coral Stylophora pistillata. While in the Great Barrier Reef fish occupation rate of large coral is higher than that of small coral, an opposite pattern exists in the northern Red Sea. It is suggested that this pattern is caused by a limitation on the adult body size of fish in the northern Red Sea.
Hypoxia‐inducible factor‐1α contributes to hypoxia‐induced chemoresistance in gastric cancer
Authors: Liu Lili , Ning Xiaoxuan , Sun Li , Zhang Hongbo , Shi Yongquan , Guo Changcun , Han Shuang , Liu Jie , Sun Shiren , Han Zheyi , Wu Kaichun , Fan Daiming
Published: October 2007

Hypoxia induced drug resistance is a major obstacle in the development of effective cancer therapy. Our previous study revealed that hypoxia‐inducible factor‐1 (HIF‐1), the major transcriptional factor significantly activated by hypoxia, was overexpressed in gastric vincristine‐resistant cells SGC7901/vincristine (VCR) under normoxic conditions, which suggested that it was associated with drug resistance in gastric cancer cells. In the present study, a colony‐forming assay revealed that hypoxia and forced HIF‐1α expression increased maximal –8.9‐fold or –14.8‐fold of IC50 toward vincristine in gastric cancer cell lines SGC7901 and SGC7901/VCR, respectively (P < 0.01). Annexin‐V/propidium iodide staining analysis revealed hypoxia or forced HIF‐1α expression reduced apoptosis by 24% or 18% in SGC7901 cells (P < 0.05). Flow cytometry analysis of intracellular adriamycin revealed that hypoxia and forced expression of HIF‐1α increased –1.79‐fold or –2.36‐fold of the adriamycin releasing index, respectively (P < 0.05). However, resistance acquisition subject to hypoxia in vitro and in vivo was suppressed by blocking HIF‐1α expression with siRNA. We further demonstrated that HIF‐1 α overexpression showed a 1.85‐fold increased expression of Bcl‐2 and a 2.16‐fold decreased expression of Bax, and also showed significantly induced expression of p‐gp and MRP1, which indicated that HIF‐1α may confer hypoxia‐induced drug resistance via inhibition of drug‐induced apoptosis and decreases in intracellular drug accumulation. (Cancer Sci 2008; 99: 121–128)
Clinical relevance of the homologous recombination machinery in cancer therapy
Authors: Miyagawa Kiyoshi
Published: October 2007

Cancer chemotherapy and radiotherapy kill cancer cells by inducing DNA damage, unless the lesions are repaired by intrinsic repair pathways. DNA double‐strand breaks (DSB) are the most deleterious type of damage caused by cancer therapy. Homologous recombination (HR) is one of the major repair pathways for DSB and is thus a potential target of cancer therapy. Cells with a defect in HR have been shown to be sensitive to a variety of DNA‐damaging agents, particularly interstrand crosslink (ICL)‐inducing agents such as mitomycin C and cisplatin. These findings have recently been applied to clinical studies of cancer therapy. ERCC1, a structure‐specific endonuclease involved in nucleotide excision repair (NER) and HR, confers resistance to cisplatin. Patients with ERCC1‐negative non‐small‐cell lung cancer were shown to benefit from adjuvant cisplatin‐based chemotherapy. Imatinib, an inhibitor of the c‐Abl kinase, has been investigated as a sensitizer in DNA‐damaging therapy, because c‐Abl activates Rad51, which plays a key role in HR. Furthermore, proteins involved in HR have been shown to repair DNA damage induced by a variety of other chemotherapeutic agents, including camptothecin and gemcitabine. These findings highlight the importance of HR machinery in cancer therapy. (Cancer Sci 2008; 99: 187–194)
Comparative and physical mapping of 111 previously reported and 105 new porcine microsatellites
Authors: Alexander L. J. , Juneja B. , Shiroma D. , Nonneman D. , Snelling W. , Fahrenkrug S. C.
Published: October 2007

Here we report radiation hybrid mapping of 105 new porcine microsatellite markers on the IMpRH7000 radiation hybrid panel. In addition, we searched flanking sequences of these markers, as well as 673 previously reported RH‐mapped microsatellite markers, for orthology to human sequences. Eighty‐seven new and 111 previously mapped sequences exhibited orthology to human sequences. Using a stringent sequence alignment, 25 microsatellite‐flanking sequences were found to be highly similar to genic sequences, whereas 173 were similar to non‐genic sequences in the human genome. Five markers were located near known breakpoints of synteny between human and swine.
Issues concerning the use of hormone replacement therapy and risk of fracture: a population‐based, nested case‐control study
Authors: Corrao Giovanni , Zambon Antonella , Nicotra Federica , Conti Valentino , Nappi Rossella E. , Merlino Luca
Published: October 2007

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Several studies have consistently shown that hormone replacement therapy (HRT) can reduce the risk of fracture.

• The questions that are still controversial include the duration of treatment needed, the duration of the protective effect after treatment is stopped, and the influence of age at which treatment is initiated.

WHAT THIS STUDY ADDS

• Our findings suggest that HRT should be continued for long periods to achieve optimal protection from fracture.

• The fracture reducing potential of HRT seems to disappear after a few months without treatment and might mainly act in women who begin therapy at an older age.

AIMS

To investigate the effect of duration, how recently it has been used, and age at start of hormone replacement therapy (HRT) and the risk of bone fracture.

METHODS

A population‐based, nested case‐control study was conducted in Lombardia, Northern Italy. The 78 294 women aged 45–75 years who received at least one HRT prescription during 1998–2000 were followed until 2005. Cases were women who experienced bone fracture during follow‐up. Up to six controls were randomly selected for each case from the cohort after matching for age and date of cohort entry. The odds ratio of fracture associated with the use of HRT was estimated by conditional logistic regression.

RESULTS

One thousand one hundred and seventy‐four cases and 6760 controls were included. Compared with women who took HRT for less than 2 months, those who were treated for more than 20 months had an odds ratio (OR) of 0.80 (95% confidence interval 0.65, 0.99). This risk reduction was still significant among current HRT users (OR 0.71, 95% CI 0.55, 0.90) and in women who began therapy at the age of 55–65 years (OR 0.63, 95% CI 0.42, 0.94) or 65–75 years (OR 0.56, 95% CI 0.32, 0.99). There was no statistical evidence of a protective effect for women who had stopped treatment more than 6 months previously or those who began HRT at the age of 45–55 years.

CONCLUSIONS

HRT should be continued for long periods to achieve an optimal protection from fracture. The fracture reducing potential of HRT seems to disappear after a few months without treatment and might mainly act in women who begin therapy at older age.
Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population‐based cohort study from the Netherlands
Authors: Bakker Marian K. , Kölling Pieternel , Van Den Berg Paul B. , De Walle Hermien E. K. , De Jong van den Berg Lolkje T. W.
Published: October 2007

What is already known about this subject

• Recently, the use of selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, in pregnancy has been associated with an increased risk on specific birth defects or other adverse pregnancy outcomes.

• However, the extent of SSRI use in pregnancy is largely unknown.

What this study adds

• In the last decade the use of SSRIs in the year preceding delivery has increased twofold.

• This increase runs parallel with the increase in use of SSRIs among women of fertile age.

• Paroxetine is one of the most commonly used SSRIs.

• Only recently have sufficient data become available on the use of paroxetine to detect moderate increased risks for specific malformations.

• The safety of SSRIs which are less frequently used is not yet established.

• Case–control birth defect‐monitoring systems may be helpful in providing safety and risk estimates that become more precise as data accumulate for these drugs.

Aims

Recent case–control studies suggest a relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and the occurrence of birth defects and other adverse pregnancy outcomes. The aim was to determine the extent of the use of SSRIs before and during pregnancy and its trend over the years 1995–2004 in the Netherlands.

Methods

The study was performed with data from a population‐based prescription database. Within this database, women giving birth to a child between 1995 and 2004 were identified. The exposure rate and 95% confidence interval (CI) were calculated as the number of pregnancies per 1000 that were exposed to an SSRI in a defined period (per trimester or in the year preceding delivery). Exposure rates were calculated for 2‐year periods: 1995/1996, 1997/1998, 1999/2000, 2001/2002 and 2003/2004. Trends in exposure rates were analysed using the χ2 test for trend.

Results

Included were 14 902 pregnancies for which complete pharmacy records were available from 3 months before pregnancy until delivery. A total of 310 pregnancies were exposed to an SSRI in the year preceding delivery. The exposure rate increased from 12.2 (95% CI 7.0, 19.8) in 1995/1996 to 28.5 (95% CI 23.0, 34.9) in 2003/2004.

Conclusion

There has been a significant increase in the use of SSRIs among pregnant women in the Netherlands over the last 10 years, parallel with the increase in exposure in women of fertile age. In light of the recent warnings about the use of SSRIs in pregnancy, healthcare professionals should be careful in prescribing SSRIs to women planning a pregnancy.
Characterization of glycans in the developmental stages of Myxobolus cerebralis (Myxozoa), the causative agent of whirling disease
Authors: Kaltner H , Stippl M , Knaus M , El‐Matbouli M
Published: October 2007

Glycans and sugar‐binding molecules (lectins) form an interactive recognition system, which may enable parasitic organisms to adhere to host cells and migrate into target tissues. The aim of the present study was to analyse surface‐associated glycans in the developmental stages of Myxobolus cerebralis (Hofer), the causative agent of whirling disease. A panel of biotin‐labelled plant lectins was used to detect a broad spectrum of glycan motifs with high specificity. Binding sites were detected histochemically in the tissue sections of infected rainbow trout, Oncorhynchus mykiss (Walbaum), and infected Tubifex tubifex (Müller), and were characterized by light, fluorescence and transmission electron microscopy. With mannose‐specific lectins [Lens culinaris agglutinin, Pisum sativum agglutinin, Canavalia ensiformis agglutinin (LCA, PSA, CanA)] mannose‐containing glycans were detected in all the developmental stages and host tissues. No binding sites for galactose‐specific lectins were present in M. cerebralis spores but reactivity with host tissues occurred. Diversity in glycans was detected by N‐acetyl‐D‐galactosamine‐specific lectins in sporoplasm cells of M. cerebralis and triactinomyxon spores. In the group of lectins with monosaccharide‐specificity for N‐acetyl‐D‐glucosamine (GlcNAc), the reactivity of Datura stramonium agglutinin (DSA), Lycopersicon esculentum agglutinin (LEA) and Solanum tuberosum agglutinin (STA) was restricted to polar capsules whereas Griffonia simplicifolia agglutinin II (GSA II) also bound to sporoplasm cells of stages in the fish host but not in those present in infected T. tubifex. Moreover, Triticum vulgaris (wheat germ) agglutinin (WGA) and succinylated WGA indicated the presence of N‐acetyl‐D‐glucosamine polymers in polar capsules. No specificity for spores was observed concerning ‘bisected’N‐glycans and no reactivity in parasitic stages was observed with the fucose‐binding lectin Ulex europaeus agglutinin (UEA) I, Sambucus nigra agglutinin (SNA) (specific for α2,6‐sialylated glycans) and Maackia amurensis agglutinin (MAAI) (specific for α2,3‐sialylated glycans). Arachis hypogaea (peanut) agglutinin (PNA), Erythrina cristagalli agglutinin (ECA), GSA I, Sophora japonica agglutinin (SJA), Dolichos biflorus agglutinin (DBA) and GSA II detected reactive sites solely confined to the developmental stages of M. cerebralis and were not reactive in the fish host. These parasite‐specific glycans may play a role in the adhesion process of the parasite to fish epidermis prior to infection, but may provide protection to the host by activating the complement system, or stimulating an adaptive immune response as putative antigens.
Isolation of a cyprinid herpesvirus 2 from goldfish, Carassius auratus (L.), in the UK
Authors: Jeffery K R , Bateman K , Bayley A , Feist S W , Hulland J , Longshaw C , Stone D , Woolford G , Way K
Published: October 2007

Haematopoietic necrosis virus [cyprinid herpesvirus 2 (CyHV‐2)] was isolated during disease outbreaks in goldfish, Carassius auratus, at an ornamental fish retail site in southern England in 2004. Signs of disease included lethargy and inappetence and were first seen after water temperatures increased from 14–15 to 19–21 °C. External gross pathology included pale patches on the gills and skin and internally the spleen was enlarged, often with distinctive white nodules. The most prominent histopathological changes observed were necrotic lesions in the spleen and kidney and focal patches of necrosis in the gill lamellae. Necrotic cells often contained nuclei with marginated chromatin and pale intranuclear inclusions. Ultrastructural examination of the spleen tissue revealed typical herpesvirus‐like particles measuring 100 nm in diameter. The virus was isolated from extracts of gill tissue in KF‐1 cells at 20 °C and oligonucleotide primer sets were designed based on conserved gene sequences and used to amplify viral DNA by polymerase chain reaction (PCR). The PCR assays were then used to detect the virus in DNA extracted from tissues sampled during earlier disease investigations at the retail site owner’s holding facility in 2002 and 2003 and stored at −70 °C since then. Polymerase gene‐specific PCR amplification products obtained from tissue samples and from the virus isolated in cell culture shared 100% nucleotide sequence identity with the published sequence for CyHV‐2.
Phenotypic, serological and genetic characterization of Pseudomonas anguilliseptica strains isolated from cod, Gadus morhua L., in northern Europe
Authors: Balboa S , Ferguson H W , Romalde J L
Published: October 2007

The biochemical, serological and genetic characteristics of six strains of Pseudomonas anguilliseptica isolated from cod, Gadus morhua, in Scotland were compared to well characterized isolates of this same bacterial species but of different origin. Biochemical and physiological analyses showed that this group of isolates was highly homogeneous, their characteristics matching previous descriptions of the pathogen. Similar results were obtained for the six cod isolates in the serological assays, all of them belonging to the serotype O1. Marked homogeneity was observed also in the genetic study, analysed by means of RAPD, ERIC‐PCR and REP‐PCR procedures, showing that they were similar to isolates from gilthead seabream, Sparus aurata, black spot seabream, Pagellus bogaraveo, and turbot, Psetta maxima. Virulence assays demonstrated that the cod isolates were highly pathogenic for turbot and sole, Solea senegalensis, with LD50 between 7.6 × 104 and 5 × 107 bacterial cells per fish.
Cloning and characterization of Photobacterium damselae ssp. piscicida phospholipase: an enzyme that shows haemolytic activity
Authors: Naka H , Hirono I , Aoki T
Published: October 2007

A phospholipase gene of Photobacterium damselae ssp. piscicida (ppp) was cloned from a genomic library and its nucleotide sequence was determined. The open reading frame consisted of 1218 bp encoding a protein of 405 amino acids with a predicted molecular mass of 46 kDa. The PPP had identities (53–55%) with phospholipase and haemolysin of Vibrio spp., while it showed low identities (23–26%) with glycerophospholipid cholesterol acyltransferase of Aeromonas spp. A recombinant PPP (rPPP) with a His tag at the C‐terminus expressed in Escherichia coli and purified showed phospholipase activity. The rPPP also showed lecithin‐dependent haemolytic activity against mammalian erythrocytes and direct haemolytic activity against fish erythrocytes. The culture supernatant of wild‐type P. damselae ssp. piscicida showed phospholipase activity, while that of a PPP gene knockout mutant did not.
Adoptive T‐cell therapy as a therapeutic option for chronic hepatitis B
Authors: Bohne F. , Protzer U.
Published: October 2007

Summary.  The human hepatitis B virus is a small, enveloped and non‐cytopathic virus, with a very narrow host range and a strong liver tropism causing acute and chronic liver disease. Although a well‐tolerated vaccine is available, more than 350 million people are chronically infected worldwide. Available therapies for chronic hepatitis B only rarely eliminate the virus. Although new antivirals are being developed, long‐term treatment is required, which may be limited by the selection of resistant viruses. Therefore, immunotherapies are investigated as an approach to eliminate persistently infected cells. Besides therapeutic vaccination, adoptive T‐cell therapy is an interesting option, which is discussed in this review.
Management of hepatitis B in liver transplant recipients
Authors: Coffin Carla S. , Terrault Norah A.
Published: October 2007

Summary.  Advances in hepatitis B virus (HBV) antiviral prophylaxis have dramatically improved graft and patient survival for patients undergoing liver transplantation for hepatitis B related end‐stage liver disease. In particular, the availability of hepatitis B immune globulin (HBIg) in combination with nucleos(t)ide analogues such as lamivudine and adefovir, have transformed outcomes. The availability of newer antivirals such as adefovir, tenofovir and entecavir either as monotherapy or in combination offer an increasing number of antiviral options. Despite these advances, significant challenges remain. Factors that affect the efficacy of anti‐viral therapy include detectable HBV viraemia at the time of transplant and emergence of HBV mutants (especially in patients with prior exposure to lamivudine). HBV prophylaxis protocols are expensive especially with use of high‐dose HBIg and newer nucleos(t)ide analogues. This review summarizes current HBV prophylaxis protocols and management of recurrent disease post‐transplantation. There is an increasing need for individualization of therapy based on prior drug exposures, level of HBV DNA at time of transplantation and type of prophylaxis used.
Treatment of chronic hepatitis D
Authors: Farci P. , Chessa L. , Balestrieri C. , Serra G. , Lai M. E.
Published: October 2007

Summary.  Despite recent advances in the treatment of chronic viral hepatitis, therapy of chronic hepatitis D is not yet satisfactory. The only option currently available is interferon‐α (IFN), whose efficacy is related to the dose and duration of treatment. However, the rate of sustained hepatitis D virus (HDV) clearance after a 1‐year course with high doses of standard IFN is low. Better results have recently been reported with pegylated IFN both in IFN‐naïve and in previous nonresponders to standard IFN, suggesting the use of pegylated IFN as a first‐line therapy in chronic hepatitis D. Nucleoside analogues that inhibit hepatitis B virus (HBV) are ineffective against HDV and combination therapy with lamivudine or ribavirin has not shown significant advantages over monotherapy with either standard or pegylated IFN. Because the ultimate goal of treatment is eradication of both HDV and HBV, in responders IFN therapy should be continued as long as possible until the loss of hepatitis B surface antigen, adjusting the dose to patient tolerance. However, because side‐effects are common, continuous monitoring is mandatory. Although the first results obtained with pegylated IFN have been encouraging, the rate of sustained virological response is still low and the rate of relapse high, emphasizing the need for developing novel classes of antivirals specifically interfering with the life cycle of this unique virus.
Hepatitis C virus infection: in vivo and in vitro models
Authors: Brass V. , Moradpour D. , Blum H. E.
Published: October 2007

Summary.  Major advances in the understanding of the molecular biology of hepatitis C virus (HCV) have been made recently. While the chimpanzee is the only established animal model of HCV infection, several in vivo and in vitro models have been established that allow us to study various aspects of the viral life cycle. In particular, the replicon system and the production of recombinant infectious virions revolutionized the investigation of HCV‐RNA replication and rendered all steps of the viral life cycle, including entry and release of viral particles, amenable to systematic analysis. In the following we will review the different in vivo and in vitro models of HCV infection.
Antiviral therapy: chronic hepatitis C
Authors: Jenny Heathcote E.
Published: October 2007

Summary.  The combination of pegylated interferon (IFN) with ribavirin is the standard of care for chronic hepatitis C. Response rates range from 50 to 90% for genotype 1 and 2/3 which also differ in the duration of treatment (48 vs 24 weeks, respectively). Therapy if given with weight‐based dosing may be shortened from 24 to 12, 14 or 16 weeks (genotypes 2 and 3), and from 48 to 24 weeks (genotype 1) in case of hepatitis C virus (HCV) clearance at week 4, without reducing sustained virologic response (SVR). Conversely, prolonging treatment for 72 weeks in those with only a decrease of viral load at week 4, i.e. “slow responders” increases SVR rates by preventing relapse. In spite of such progress, over half of patients are relapsers or nonresponders. If the previous treatment was suboptimal, retreatment with higher doses or longer duration may be beneficial unless an individual was a ‘null responder’ previously. New promising anti‐HCV molecules (antiproteases and antipolymerases), some with potent antiviral activity, are in phase II trials but appear to require the addition of IFN and ribavirin to maintain viral suppression. Other immunomodulatory agents such as new IFN or therapeutic vaccines and alternatives to ribavirin are also under development. Future regimens should improve efficacy and provide shorter and better‐tolerated combination therapy.
A new role for P2 receptors: talking with calcium‐activated potassium channels
Authors: Bertrand P. P.
Published: October 2007

Abstract  Purinergic fast synaptic transmission may play a very subtle role in regulating the excitability of enteric circuits. That is one of the important findings in a new paper by Ren and Galligan in the current issue of this Journal. They first provide compelling evidence that P2X3 receptors (ionotropic purine receptors) are expressed by guinea‐pig motor and interneurons and that these subtypes mediate the purinergic fast excitatory postsynaptic potential (EPSP). They also found that the P2X3‐mediated depolarization was often followed by a hyperpolarization. This is an intriguing finding because if the purinergic fast EPSPs are also followed by a hyperpolarization, then it could play a role in truncating bursts of synaptic potentials or in shaping periodic synaptic input. The hyperpolarization is caused by calcium entry through the P2X3 receptor which then activates a calcium‐activated potassium (KCa) channel. Surprisingly, the hyperpolarization was not affected by any of the standard blockers of calcium‐ or voltage‐activated K+ channels suggesting that a novel KCa channel is present in the enteric neurons. Such a wide‐spread channel could well have an important physiological role and could be an important new drug target for regulating reflex activity in the enteric nervous system.
Oral amoxicillin vs. oral erythromycin in the treatment of pyoderma in Bamako, Mali: an open randomized trial
Authors: Faye Ousmane , Hay Roderick J. , Diawara Ismaila , Mahé Antoine
Published: October 2007

Background  Pyoderma (bacterial superficial skin infection) is an extremely common disorder in tropical developing countries. In these settings, Streptococcus pyogenes is considered to be the main etiological agent. Apart from epidemics of poststreptococcal glomerulonephritis where mass treatment with intramuscular benzathine‐penicillin is recommended, no recommendation exists for the treatment of pyoderma in this setting. The aim of this study was to evaluate the efficacy of oral amoxicillin in the treatment of pyoderma in Mali, by comparison with oral erythromycin.

Methods  In Bamako, 132 patients with pyoderma, diagnosed and graded as “severe” on clinical grounds, were randomly assigned to an oral treatment by either amoxicillin (50 mg/kg per day) or erythromycin; infections of the follicular appendage were excluded. Both drugs were associated with the topical application of povidone iodine. The patients were evaluated openly at the seventh day of treatment for cure or marked improvement of the clinical features, indicating successful treatment.

Results  Three patients were lost to follow‐up. Treatment was successful in 57 of 64 patients treated with amoxicillin vs. 58 of 65 patients treated with erythromycin (P = 0.00).

Conclusions  Amoxicillin was as efficacious as erythromycin in the treatment of severe pyoderma in Mali. Owing to its efficacy, added to high availability and low cost, this compound should be considered a first‐line treatment of this disorder in this country, and perhaps in other countries where this condition presents in a similar way.
Poverty, health and development in dermatology
Authors: Morrone Aldo
Published: October 2007

The WHO Constitution states that “The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political, economic or social condition.”

The right to health means that governments must generate conditions in which everyone can be as healthy as possible. Such conditions range from ensuring availability of health services, healthy and safe working conditions, adequate housing and nutritious food.

In this report the author analyzes the relationship among health, dermatology and development and tries to find out what the scientific world, including dermatologists, could do for the improvement of health systems.
Nonclinical challenges of Indian dermatology – cities vs. villages, poverty, and lack of awareness
Authors: Verma Shyam
Published: October 2007

As India shines in its enviable achievements, one after the other in rapid succession, it also invites criticism from visitors for what they witness. It is imperative to delve deeper to fathom the realities of the predominantly rural India with its poverty and lack of awareness which are stumbling blocks and are major pitfalls in the practice of dermatology. The urban–rural divide, the phenomenon of migration, poverty, lack of awareness all affect practice of dermatology in this country. These are battles that have no ready answers. However a deeper understanding of the ground reality is a worthwhile exercise for the increasing tribe of international dermatologists who like to explore “cross cultural dermatology”.
Effects of the Reproductive Status on Morphological Oocyte Quality and Developmental Competence of Oocytes after In Vitro Fertilization and Somatic Cell Nuclear Transfer in Cat
Authors: Naoi H , Agung B , Karja NWK , Wongsrikeao P , Shimizu R , Taniguchi M , Otoi T
Published: October 2007

Contents

This study was conducted to examine the effects of the reproductive cycle of donor cat on the quality of oocytes at recovery and developmental competence of oocytes after in vitro fertilization (IVF) and somatic cell nuclear transfer (NT). Based on the presence or absence of follicles and corpora lutea, the ovarian pairs collected were classified into inactive, follicular or luteal stages. After collection of oocytes, the oocytes were classified into four grades according to the morphological condition of oocyte cytoplasm and cumulus cells. A total of 16 558 oocytes were obtained from 198 ovarian pairs. The total mean numbers of oocytes and the mean numbers of oocytes with high quality (grade I) were significantly higher in ovarian pairs at the inactive stage (111.1 and 19.0 oocytes, respectively) than in ovarian pairs at the follicular stage (67.1 and 11.4 oocytes, respectively). A significant difference in the proportions of oocytes with grade I out of the total examined oocytes was observed between the follicular and luteal stages of ovaries (14.9% vs 20.2%, p < 0.05). The proportions of IVF embryos cleaved and developed to blastocysts significantly decreased with decreased quality of oocytes at recovery, irrespective of the reproductive status of ovaries. Moreover, there were no significant differences in the proportions of cleavage and development to the blastocyst stage of IVF and NT embryos among three oestrous stages of ovaries. These results indicate that the reproductive cycle stage of donor cat ovaries has no apparent effects on the in vitro development of oocytes after IVF and NT, but the quality of oocytes at recovery influences the development of IVF embryos.