bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold
Authors: Koutsopoulos Sotirios , Unsworth Larry D. , Nagai Yusuke , Zhang Shuguang
Published: March 2009

The release kinetics for a variety of proteins of a wide range of molecular mass, hydrodynamic radii, and isoelectric points through a nanofiber hydrogel scaffold consisting of designer self-assembling peptides were studied by using single-molecule fluorescence correlation spectroscopy (FCS). In contrast to classical diffusion experiments, the single-molecule approach allowed for the direct determination of diffusion coefficients for lysozyme, trypsin inhibitor, BSA, and IgG both inside the hydrogel and after being released into the solution. The results of the FCS analyses and the calculated pristine in-gel diffusion coefficients were compared with the values obtained from the Stokes–Einstein equation, Fickian diffusion models, and the literature. The release kinetics suggested that protein diffusion through nanofiber hydrogels depended primarily on the size of the protein. Protein diffusivities decreased, with increasing hydrogel nanofiber density providing a means of controlling the release kinetics. Secondary and tertiary structure analyses and biological assays of the released proteins showed that encapsulation and release did not affect the protein conformation and functionality. Our results show that this biocompatible and injectable designer self-assembling peptide hydrogel system may be useful as a carrier for therapeutic proteins for sustained release applications.
A family of
Salmonella
virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases
Authors: Quezada Cindy M. , Hicks Stuart W. , Galán Jorge E. , Stebbins C. Erec
Published: March 2009

Processes as diverse as receptor binding and signaling, cytoskeletal dynamics, and programmed cell death are manipulated by mimics of host proteins encoded by pathogenic bacteria. We show here that the
Salmonella
virulence factor SspH2 belongs to a growing class of bacterial effector proteins that harness and subvert the eukaryotic ubiquitination pathway. This virulence protein possesses ubiquitination activity that depends on a conserved cysteine residue. A crystal structure of SspH2 reveals a canonical leucine-rich repeat (LRR) domain that interacts with a unique E3 ligase [which we have termed NEL for
Novel E3 Ligase
] C-terminal fold unrelated to previously observed HECT or RING-finger E3 ligases. Moreover, the LRR domain sequesters the catalytic cysteine residue contained in the NEL domain, and we suggest a mechanism for activation of the ligase requiring a substantial conformational change to release the catalytic domain for function. We also show that the N-terminal domain targets SspH2 to the apical plasma membrane of polarized epithelial cells and propose a model whereby binding of the LRR to proteins at the target site releases the ligase domain for site-specific function.
Relative CO
2
/NH
3
selectivities of AQP1, AQP4, AQP5, AmtB, and RhAG
Authors: Musa-Aziz Raif , Chen Li-Ming , Pelletier Marc F. , Boron Walter F.
Published: March 2009

The water channel aquaporin 1 (AQP1) and certain Rh-family members are permeable to CO
2
and NH
3
. Here, we use changes in surface pH (pH
S
) to assess relative CO
2
vs. NH
3
permeability of
Xenopus
oocytes expressing members of the AQP or Rh family. Exposed to CO
2
or NH
3
, AQP1 oocytes exhibit a greater maximal magnitude of pH
S
change (ΔpH
S
) compared with day-matched controls injected with H
2
O or with RNA encoding SGLT1, NKCC2, or PepT1. With CO
2
, AQP1 oocytes also have faster time constants for pH
S
relaxation (τ
pHs
). Thus, AQP1, but not the other proteins, conduct CO
2
and NH
3
. Oocytes expressing rat AQP4, rat AQP5, human RhAG, or the bacterial Rh homolog AmtB also exhibit greater ΔpH
S
(CO
2
) and faster τ
pHs
compared with controls. Oocytes expressing AmtB and RhAG, but not AQP4 or AQP5, exhibit greater ΔpH
S
(NH
3
) values. Only AQPs exhibited significant osmotic water permeability (P
f
). We computed channel-dependent (*) ΔpH
S
or P
f
by subtracting values for H
2
O oocytes from those of channel-expressing oocytes. For the ratio ΔpH
S
(CO
2
)*/P
f
*, the sequence was AQP5 > AQP1 ≅ AQP4. For ΔpH
S
(CO
2
)*/ΔpH
S
(NH
3
)*, the sequence was AQP4 ≅ AQP5 > AQP1 > AmtB > RhAG. Thus, each channel exhibits a characteristic ratio for indices of CO
2
vs. NH
3
permeability, demonstrating that, like ion channels, gas channels can exhibit selectivity.
Birth complications, overweight, and physical inactivity
Authors: VOLDNER NANNA , FRØSLIE KATHRINE FREY , HAAKSTAD LENE ANETTE HAGEN , BØ KARI , HENRIKSEN TORE
Published: March 2009

Objective. Maternal lifestyle factors are potential predictors of pregnancy complications. We examined relations between modifiable factors and delivery complications. Design. Prospective cohort. Setting. University hospital antenatal clinic, Oslo, Norway. Sample. A cohort of 553 women followed through pregnancy and delivery. Main outcome measures. Pre‐specified birth complications: cesarean section (CS), operative vaginal deliveries (VDs), third and fourth degree of perineal lacerations and hemorrhage (≥1,000 ml). Methods. Univariate and multiple logistic regression analyses were performed. Besides high birthweight (≥4,200 g), modifiable predictors (high body mass index (BMI), fasting glucose and physical inactivity) and non‐modifiable predictors (parity, maternal age, gestational age, and gender) were considered. Results. Significant predictors for induction of labor were parity (odds ratio (OR): 2.1; 95% CI 1.3–3.5), maternal age (OR: 2.0; 1.2–3.4), gestational age (OR: 1.9; 1.1–3.1), and BMI ≥30 (OR: 4.2; 2.2–7.8, p<0.01). High birthweight and high BMI were overrepresented among CSs. Emergency CS was associated with birthweight (OR: 3.7; 1.7–8.1), parity (OR: 3.5; 1.7–7.2), maternal age (OR: 2.6; 1.3–5.3), and induction of labor (OR: 4.8; 2.6–9.1). After excluding CS, operative VD was associated with parity (OR: 8.7; 3.8–20) and gender (OR: 2.2; 1.2–14.1). Perineal laceration was associated with pre‐gestational physical inactivity (OR: 6.1; 1.6–22.9) and operative VD (OR: 5.1; 1.5–17.6). Hemorrhage was associated with high birthweight (OR: 4.2; 1.2–4.7) and BMI ≥30 (OR: 4.6; 1.2–17.7). Conclusions. Pre‐gestational physical inactivity increased the risk of perineal lacerations and male infants were associated with higher risk of vaginal operative delivery.
Human cytomegalovirus infection downregulates the expression of glial fibrillary acidic protein in human glioblastoma U373MG cells: identification of viral genes and protein domains involved
Authors: Koh Kyungmi , Lee Karim , Ahn Jin-Hyun , Kim Sunyoung
Published: March 2009

Human cytomegalovirus (HCMV) has tropism for glial cells, among many other cell types. It was reported previously that the stable expression of HCMV immediate-early protein 1 (IE1) could dramatically reduce the RNA level of glial fibrillary acidic protein (GFAP), an astroglial cell-specific intermediate filament protein, which is progressively lost with an increase in glioma malignancy. To understand this phenomenon in the context of virus infection, a human glioblastoma cell line, U373MG, was infected with HCMV (strain AD169 or Towne). The RNA level of GFAP was reduced by more than 10-fold at an m.o.i. of 3 at 48 h post-infection, whilst virus treated with neutralizing antibody C23 or with UV light had a much-reduced effect. Treatment of infected cells with ganciclovir did not prevent HCMV-mediated downregulation of GFAP. Although the expression of GFAP RNA is downregulated in IE1-expressing cells, a mutant HCMV strain lacking IE1 still suppressed GFAP, indicating that other IE proteins may be involved. IE2 is also proposed to be involved in GFAP downregulation, as an adenoviral vector expressing IE2 could also reduce the RNA level of GFAP. Data from the mutational analysis indicated that HCMV infection might affect the expression of this structural protein significantly, primarily through the C-terminal acidic region of the IE1 protein.
Sequence analysis and comparison of avian hepatitis E viruses from Australia and Europe indicate the existence of different genotypes
Authors: Bilic Ivana , Jaskulska Barbara , Basic Ana , Morrow Chris J. , Hess Michael
Published: March 2009

Avian hepevirus infections were detected in chickens suffering from big liver and spleen disease or hepatitis–splenomegaly syndrome in Australia, the USA and Europe. Available data indicate their genetic relationship to mammalian hepatitis E virus (HEV). In the present study, the near-complete genomic sequences of an Australian and a European isolate of avian hepatitis E virus (avian HEV) are reported for the first time. Furthermore, the phylogenetic relationship to other avian HEVs is determined. Sequence analyses of these isolates identified major genetic differences among avian HEVs. Most of them are located within the open reading frame (ORF)1 region, although only a few lie within conserved motifs of predicted domains. Non-silent mutations in the ORF2 region suggest the presence of potentially different epitopes among avian HEV isolates. Finally, phylogenetic analysis confirmed the distant relationship to mammalian HEV and additionally suggested that the avian HEVs can be separated into three different genotypes: 1 (Australia), 2 (USA) and 3 (Europe), indicating a geographical distribution pattern.
Transmission of scrapie and sheep-passaged bovine spongiform encephalopathy prions to transgenic mice expressing elk prion protein
Authors: Tamgüney Gültekin , Miller Michael W. , Giles Kurt , Lemus Azucena , Glidden David V. , DeArmond Stephen J. , Prusiner Stanley B.
Published: March 2009

Chronic wasting disease (CWD) is a transmissible, fatal prion disease of cervids and is largely confined to North America. The origin of CWD continues to pose a conundrum: does the disease arise spontaneously or result from some other naturally occurring reservoir? To address whether prions from sheep might be able to cause disease in cervids, we inoculated mice expressing the elk prion protein (PrP) transgene [Tg(ElkPrP) mice] with two scrapie prion isolates. The SSBP/1 scrapie isolate transmitted disease to Tg(ElkPrP) mice with a median incubation time of 270 days, but a second isolate failed to produce neurological dysfunction in these mice. Although prions from cattle with bovine spongiform encephalopathy (BSE) did not transmit to the Tg(ElkPrP) mice, they did transmit after being passaged through sheep. In Tg(ElkPrP) mice, the sheep-passaged BSE prions exhibited an incubation time of approximately 300 days. SSBP/1 prions produced abundant deposits of the disease-causing PrP isoform, denoted PrPSc, in the cerebellum and pons of Tg(ElkPrP) mice, whereas PrPScaccumulation in Tg mice inoculated with sheep-passaged BSE prions was confined to the deep cerebellar nuclei, habenula and the brainstem. The susceptibility of ‘cervidized’ mice to ‘ovinized’ prions raises the question about why CWD has not been reported in other parts of the world where cervids and scrapie-infected sheep coexist.
Diversity of the G3 genes of human rotaviruses in isolates from Spain from 2004 to 2006: cross-species transmission and inter-genotype recombination generates alleles
Authors: Martínez-Laso Jorge , Román Angela , Rodriguez Miriam , Cervera Isabel , Head Jacqueline , Rodríguez-Avial Iciar , Picazo Juan J.
Published: March 2009

Rotavirus evolves by using multiple genetic mechanisms which are an accumulation of spontaneous point mutations and reassortment events. Other mechanisms, such as cross-species transmission and inter-genotype recombination, may be also involved. One of the most interesting genotypes in the accumulation of these events is the G3 genotype. In this work, six new Spanish G3 sequences belonging to 0–2-year-old patients from Madrid were analysed and compared with 160 others of the same genotype obtained from humans and other host species to establish the evolutionary pathways of the G3 genotype. The following results were obtained: (i) there are four different lineages of the G3 genotype which have evolved in different species; (ii) Spanish G3 rotavirus sequences are most similar to the described sequences that belong to lineage I; (iii) several G3 genotype alleles were reassigned as other G genotypes; and (iv) inter-genotype recombination events in G3 viruses involving G1 and G2 were described. These findings strongly suggest multiple inter-species transmission events between different non-human mammalian species and humans.
Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships
Authors: Olson Victoria A. , Karem Kevin L. , Smith Scott K. , Hughes Christine M. , Damon Inger K.
Published: March 2009

Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to ∼40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.
DC-SIGN (CD209) gene promoter polymorphisms in a Brazilian population and their association with human T-cell lymphotropic virus type 1 infection
Authors: Kashima Simone , Rodrigues Evandra Strazza , Azevedo Rochele , da Cruz Castelli Erick , Mendes-Junior Celso Teixeira , Yoshioka France Keiko Nascimento , da Silva Israel Tojal , Takayanagui Osvaldo Massaiti , Covas Dimas Tadeu
Published: March 2009

This study evaluated four polymorphisms located in the DC-SIGN (CD209) gene promoter region (positions −336, −332 −201 and −139) in DNA samples from four Brazilian ethnic groups (Caucasians, Afro-Brazilian, Asians and Amerindians) to establish the population distribution of these single-nucleotide polymorphisms (SNPs) and correlated DC-SIGN polymorphisms and infection in samples from human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals. To identifyCD209SNPs, 452 bp of theCD209promoter region were sequenced and the genotype and allelic frequencies were evaluated. This is the first study to show genetic polymorphism in theCD209gene in distinct Brazilian ethnic groups with the distribution of allelic and genotypic frequency. The results showed that −336A and −139A SNPs were quite common in Asians and that the −201T allele was not observed in Caucasians, Asians or Amerindians. No significant differences were observed between individuals with HTLV-1 disease and asymptomatic patients. However, the −336A variant was more frequent in HTLV-1-infected patients [HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 80 %; healthy asymptomatic HTLV-1 carriers, 90 %] than in the control group (70 %) [P=0.0197, odds ratio (OR)=2.511, 95 % confidence interval (CI)=1.218–5.179). In addition, the −139A allele was found to be associated with protection against HTLV-1 infection (P=0.0037, OR=0.3758, 95 % CI=0.1954–0.7229) when the HTLV-1-infected patients as a whole were compared with the healthy-control group. These observations suggest that the −139A allele may be associated with HTLV-1 infection, although no significant association was observed among asymptomatic and HAM/TSP patients. In conclusion, the variation observed in SNPs −336 and −139 indicates that this lectin may be of crucial importance in the susceptibility/transmission of HTLV-1 infections.
Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase
Authors: Potier A. , Lavigne C. , Chappard D. , Verret J. L. , Chevailler A. , Nicolie B. , Drouet M.
Published: March 2009

Objectives
To compare the clinical presentation of systemic anaphylaxis to Hymenoptera and Diptera with regard to basal serum tryptase (BT) and to evaluate mastocytosis in patients with elevated tryptase.

Patients and Methods
The medical records of 140 patients with a history of a systemic reaction to venom were retrospectively reviewed. Symptoms and severity of anaphylaxis and BT were recorded. Most patients with elevated tryptase were screened for mastocytosis: a dermatological examination with a skin biopsy was performed in 19 cases and a bone marrow biopsy in 14 cases.

Results
Tryptase was elevated in 23 patients. These patients reported fewer usual skin reactions (urticaria in 26.1% of cases with raised tryptase vs. 76.1% of cases with normal tryptase), more flushing (52.2% vs. 4.3%) and frequently did not present skin reaction (26.1% vs. 9.4%). They presented a more severe reaction (mean grade of severity: 3.48 vs. 2.69). Mastocytosis was diagnosed in seven patients with elevated tryptase: indolent systemic mastocytosis in six cases and cutaneous mastocytosis without systemic involvement in one case. In five cases, mastocytosis was previously undiagnosed. Lesions of cutaneous mastocytosis, diagnosed in five patients, consisted of urticaria pigmentosa in all cases and were often inconspicuous.

Conclusion
These results demonstrate particular clinical features of the allergic reaction in patients with elevated BT and the higher frequency of mastocytosis in this population. In patients with a severe anaphylactic reaction without urticaria, but with flushing, tryptase should be assayed and an underlying mastocytosis should be considered.
The Nordic Volcanological Institute: understanding volcanoes at spreading centres
Authors: Brooks Kent
Published: March 2009

The Nordic countries (known as ‘Norden’) are not immediately associated with volcanoes: Norway with folded mountains cut by fjords and its offshore oil and gas deposits, Sweden and Finland by the western part of the Baltic shield, a huge area of Precambrian rocks, of which gneisses form a large part, and Denmark, a country of Mesozoic and Cenozoic rocks, where glacial, superficial deposits are of major importance. But Norden also includes Iceland, where everyone immediately thinks of volcanoes and glaciers. Clearly volcanological research would be expected to be a major priority for the Icelandic nation. However, in the other Nordic countries old volcanic and other igneous rocks play a significant role, comprising a large part of the Precambrian and Caledonian terrains and being a key to many of the commercial mineral deposits which play a major role in the economies of Norway, Sweden and Finland. Even Denmark, a country of sedimentary rocks has an impressive sequence of Paleogene volcanic ashes and the Faeroe Islands, made up almost entirely of basalts, are part of Denmark.
Genetic effect of the NPHS2 gene variants on proteinuria in minimal change disease and immunoglobulin A nephropathy
Authors: ZHU LI , YU LEI , WANG CHEN‐DAN , LV JI‐CHENG , LI GUI‐SEN , ZHANG HONG , WANG HAI‐YAN
Published: March 2009

Background:  Proteinuria varies in different glomerular diseases and even the same one. Podocin, encoded by gene NPHS2, is important in maintaining the integrity of slit diaphragm structure and avoiding proteinuria. Presently, case–control association studies were performed to investigate the genetic effect of variants in NPHS2 in a mass proteinuric glomerulopathy, minimal change disease (MCD) at first, followed by further investigation in immunoglobulin A nephropathy (IgAN).

Methods:  At first, 214 northern Chinese patients with MCD and 493 geographically‐matched healthy controls were enrolled. Variants of the NPHS2 were screened. SNP‐2 (rs3829795:C>T, c.‐670C>T) and SNP‐5 (rs3738423:C>T, c.288C>T) were selected as tagging single nucleotide polymorphisms (SNP) and haplotypes were reconstructed. Association was analyzed in MCD patients. Then, the identified SNP site was analyzed in IgAN patients with mild histological changes (Haas subclass I and II).

Results:  The C allele and CC genotype frequencies at the SNP‐2 site, as well as the frequency of haplotype CC, were significantly lower in MCD patients than in healthy controls. Furthermore, they were also associated with the degree of proteinuria in MCD patients. But in IgAN patients, no such association was identified.

Conclusion:  The study suggested the polymorphism and haplotype of NPHS2 gene were associated with the genetic susceptibility and also the degree of proteinuria to MCD. Proteinuria in MCD and IgAN might occur through different mechanisms.
Review article: Biomarkers of clinical outcomes in advanced chronic kidney disease
Authors: KOVESDY CSABA P , KALANTAR‐ZADEH KAMYAR
Published: March 2009

Chronic kidney disease (CKD) is a complex condition, where the decrease in kidney function is accompanied by numerous metabolic changes affecting virtually all the organ systems of the human body. Many of the biomarkers characteristic of the individually affected organ systems have been associated with adverse outcomes including higher mortality in advanced CKD, whereas in persons without CKD these biomarkers may have no bearing on survival. It is believed that the high mortality seen in CKD is a result of several abnormalities conspiring to induce or aggravate a heightened degree of cardiovascular morbidity and predisposition to wasting syndrome. Not all the biomarkers may, however, be causally responsible for the adverse outcomes associated with them. We review various biomarkers of protein‐energy wasting, inflammation, oxidative stress, potassium disarrays, acid‐base disorders, bone and mineral disorders, glycemic status, and anemia. Although all of these biomarkers have shown associations with worsened outcomes in CKD, markers of protein‐energy wasting, especially serum albumin, remain the strongest predictor of survival in CKD patients, especially those undergoing maintenance dialysis treatment. We also review the putative pathophysiologic mechanisms behind these associations, and present potential therapeutic interventions that could result in remedies to improve poor clinical outcomes in CKD, pending the results of current and future controlled trials.
Could exercise be a new strategy to revert some patients with atrial fibrillation?
Authors: Gates P. , Al‐Daher S. , Ridley D. , Black A.
Published: March 2009

Background: This study is the result of the anecdotal observation that a number of patients with atrial fibrillation (AF) had noted reversion to sinus rhythm (SR) with exercise. We aimed to evaluate the potential role of exercise stress test (EST) for the reversion of AF.

Methods: Patients with AF who were scheduled to undergo electrical cardioversion (DCR) underwent EST using a modified Bruce protocol.

Results: Eighteen patients (16 male); aged 36–74 years (mean 58 years) were studied. Five patients (27.7%) had successful reversion with exercise (group 1). Thirteen patients remained in AF (group 2). No patient who failed to revert with exercise did so spontaneously before DCR 3 h to 7 months later (median 20 days). Comparison between group 1 and group 2 did not reveal any significant difference

Conclusion: This small preliminary study suggests that in some patients it may be possible to revert AF to SR with exercise and avoid DCR and concomitant general anaesthesia. The authors suggest that a larger multicentre randomized trial is warranted to confirm or refute these initial results and if correct identify those who might benefit.
A novel method for identifying behavioural changes in animal movement data
Authors: Gurarie Eliezer , Andrews Russel D. , Laidre Kristin L.
Published: March 2009

A goal of animal movement analysis is to reveal behavioural mechanisms by which organisms utilize complex and variable environments. Statistical analysis of movement data is complicated by the fact that the data are multidimensional, autocorrelated and often marked by error and irregular measurement intervals or gappiness. Furthermore, movement data reflect behaviours that are themselves heterogeneous. Here, we model movement data as a subsampling of a continuous stochastic processes, and introduce the behavioural change point analysis (BCPA), a likelihood‐based method that allows for the identification of significant structural changes. The BCPA is robust to gappiness and measurement error, computationally efficient, easy to implement and reveals structure that is otherwise difficult to discern. We apply the analysis to a GPS movement track of a northern fur seal (Callorhinus ursinus), revealing an unexpectedly complex diurnal behavioural profile, and demonstrate its robustness to the greater errors associated with the ARGOS tracking system. By informing empirical interpretation of movement data, we suggest that the BCPA can eventually motivate the development of mechanistic behavioural models.
Technical Improvements and Welfare under International Duopoly
Authors: Okawa Masayuki
Published: March 2009

It is now common wisdom that a free‐trading country with perfectly competitive markets might be hurt by its own technical improvement of that country's export industry, and that an improvement in the import‐competing industry never impoverishes the country if no commodity is inferior for that country. This paper examines the welfare effects of technical progress in a perfectly competitive industry and in an internationally duopolistic market in a two‐country, two‐good, one‐factor trading model. It will be shown that the above propositions are severely qualified in our setting with duopolistic industry.
Self‐esteem and interpersonal functioning in psychiatric outpatients
Authors: BJØRKVIK JOFRID , BIRINGER EVA , EIKELAND OLE‐JOHAN , NIELSEN GEIR HØSTMARK
Published: March 2009

This study explored associations between self‐esteem and interpersonal functioning in a one‐year clinic cohort of psychiatric outpatients (n= 338). At intake, patients completed questionnaires measuring self‐esteem, interpersonal problems, interpersonal style, and general symptomatic distress. They were also diagnosed according to the ICD‐10. Interpersonal behaviour was measured along the agency and communion dimensions of the Inventory of Interpersonal Problems – Circumplex [IIP‐C]. The results show that lower self‐esteem was associated with higher levels of interpersonal problems in general. Further, lower self‐esteem was first and foremost linked to frustrated agentic motives, as measured by the IIP‐C. Hence, the study concludes that fostering patient agency should be considered as an important goal in psychotherapy. Furthermore, the analyses revealed an interaction effect of agency and communion on self‐esteem, indicating a need for balancing the two motive dimensions. Finally, some questions are raised concerning the interpretation of the IIP‐C subscales in general.
Y27632, a Rho‐activated kinase inhibitor, normalizes dysregulation in alpha1‐adrenergic receptor‐induced contraction of Lyon hypertensive rat artery smooth muscle
Authors: Freitas Maria Regina , Eto Masumi , Kirkbride Jason A. , Schott Christa , Sassard Jean , Stoclet Jean‐Claude
Published: March 2009

RhoA‐activated kinase (ROK) is involved in the disorders of smooth muscle contraction found in hypertension model animals and patients. We examined whether the α1‐adrenergic receptor agonist‐induced ROK signal is perturbed in resistance small mesentery artery (SMA) of Lyon genetically hypertensive (LH) rats, using a ROK antagonist, Y27632. Smooth muscle strips of SMA and aorta were isolated from LH and Lyon normotensive (LN) rats. After Ca2+‐depletion and pre‐treatment with phenylephrine (PE), smooth muscle contraction was induced by serial additions of CaCl2. In LH SMA Ca2+ permeated cells to a lesser extent as compared with LN SMA, while CaCl2‐induced contraction of LH SMA was greater than that of LN SMA, indicating a higher ratio of force to Ca2+ in LH SMA contraction (Ca2+ sensitization). No hyper‐contraction was observed in LH aorta tissues. Treatment of LH SMA with Y27632 restored both Ca2+ permeability and Ca2+‐force relationship to levels seen for LN SMA. In response to PE stimulation, phosphorylation of CPI‐17, a phosphorylation‐dependent myosin phosphatase inhibitor protein, and MYPT1 at Thr853, the inhibitory phosphorylation site of the myosin phosphatase regulatory subunit, was increased in LN SMA, but remained unchanged in LH SMA. These results suggest that the disorder in ROK‐dependent Ca2+ permeability and Ca2+‐force relationship is responsible for LH SMA hyper‐contraction. Unlike other hypertensive models, the ROK‐induced hyper‐contractility of LH SMA is independent of MYPT1 and CPI‐17 phosphorylation, which suggests that ROK‐mediated inhibition of myosin phosphatase does not affect SMA hyper‐contractility in LH SMA cells.
Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumption
Authors: Gaubert Sabine , Vié Martine , Damase‐Michel Christine , Pathak Atul , Montastruc Jean‐Louis
Published: March 2009

Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half‐lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization‐days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (−8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital‐based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene.
Cell Types Obtained from the Epidural Space of Patients with Low Back Pain/Radiculopathy
Authors: Heavner James E. , Bosscher Hemmo A. , Wachtel Mitchell S.
Published: March 2009

Background:  We investigated if correlations exist between medical history, tissue abnormalities, and cell types retrieved from the epidural space of patients with chronic low back pain (LBP) and chronic radicular pain (RP).

Methods:  Approval was obtained from the Institutional Review Board for the Protection of Human Subjects to study 191 patients undergoing epiduroscopy. Visual inspection was performed and abnormal areas were identified. A specimen obtained from the area using a cytology brush was processed by the Thin Prep technique. Patients were divided into four groups based on the presence or absence and intensity of LBP and RP. The gender and age of the patients were recorded, as was any history of prior back surgery. Areas of tissue abnormalities were rated according to changes in vascularity and amount of fat, fibrosis, and inflammation. Stenosis was assessed from magnetic resonance imaging or computerized tomography scan images. Cytologic assessments included notations of the presence or absence of erythrocytes, leukocytes, cell groups, lipocytes, spindled cells, and large round cells.

Results:  There was a significant difference in the number of patients from whom big round cells were obtained who had a high degree of LBP compared with the number of patients who had a high degree of both LBP and RP.

Conclusions:  The findings provide a foundation for future studies of cells obtained from similar patients with the goal of furthering the understanding of the pathogenesis of LBP/RP.
Estimation of LV End‐Diastolic Pressure Using Color‐TDI and Its Application to Noninvasive Quantification of Myocardial Wall Stress
Authors: Moladoust Hassan , Mokhtari‐Dizaji Manijhe , Ojaghi‐Haghighi Zahra , Khaledifar Arsalan , Khajavi Amir
Published: March 2009

Background: This study was undertaken to evaluate early‐diastolic annular velocity (Ea) by color‐TDI, combined with the early transmitral filling velocity (E) by pulsed Doppler echocardiography for estimation of left ventricular end diastolic pressure (LVEDP). We applied LVEDP to noninvasive quantification of myocardial wall stress in end‐diastole. Forty‐one coronary artery disease (CAD) patients with sinus rhythm underwent echocardiography and cardiac catheterization evaluated in the study. Methods: First linear regression analysis was performed to assess the relationships between E/Ea and LVEDP. Second LVEDP estimation with these two methods was tested prospectively in 59 additional CAD patients, and average end‐diastolic wall stress was calculated at rest by measuring the principal radii, the thickness of the LV segments, and the estimated LVEDP. The results were compared to the wall stress that was calculated using catheter‐measured LVEDP. Linear regression analysis was performed to assess the relationships between calculated wall stress using Doppler‐estimated LVEDP (WSEP) and calculated wall stress using catheter‐measured LVEDP (WSMP). Results: The results showed that LVEDP had a strong correlation to the lateral E/Ea (r = 0.85; P < 0.001) and medial E/Ea ratios (r = 0.73; P < 0.001). No significant differences were found between the WSEP and WSMP. There were highly significant correlations (at least r = 0.85, P < 0.001) between the WSMP and WSEP at all the myocardial sites. Conclusions: The current data demonstrate that the lateral E/Ea ratio obtained by Doppler echocardiography and color‐TDI is a powerful estimator of LVEDP in CAD patients and provides pressure information required for noninvasive quantification of LV myocardial wall stress with reasonable accuracy in diastole.
Extrinsic Compression of the Left Atrium by a Mediastinal Hematoma Secondary to Inadvertent Carotid Puncture
Authors: Bouzas‐Mosquera Alberto , Mosquera Victor X. , Portela Francisco , Cuenca José J. , Álvarez‐García Nemesio , Castro‐Beiras Alfonso
Published: March 2009

We present the case of a 63‐year‐old man who underwent surgical closure of a paravalvular mitral leak. Immediately after surgery, transesophageal echocardiography revealed the appearance of a mediastinal hematoma encroaching on the left atrium and separating the esophageal probe from the posterior left atrial wall. The cause was an inadvertent puncture of the carotid artery, presumably during central venous line insertion prior to surgery.
Cellulose Pads (Hydrotin‐C): A New Solid Coupling Agent
Authors: Bail Dorothee H.L. , Gruler Miriam , Walker Tobias , Haefner Anja , Wendel H.P. , Ziemer Gerhard
Published: March 2009

Objectives: Hydrotin‐C is a bacterial cellulose consisting of 90% of physiological solution. The cellulose pad is smooth and elastic and cannot be torn, and is therefore suitable for use on any local skin condition. The aim of this study was to evaluate the image quality (IQ) and transducer pressure of Hydrotin‐C‐Pads as a solid coupling agent compared with standard coupling gel. Methods: To date, transthoracic echocardiography has been performed in 51 patients (ongoing study) using standard coupling gel and Hydrotin‐C‐Pads. The IQ was categorized as follows: 1 = excellent, 2 = good, 3 = poor, 4 = inadequate. All patients were questioned about the transducer pressure, which was categorized as: 0 = less, 1 = equal, 2 = more. The body mass index (BMI) was documented for all patients. Results: The IQ was very good with Hydrotin‐C‐Pads. The IQ was better in 84% of all patients. In patients with a BMI of over 25 and in patients with a BMI of over 30, Hydrotin‐C‐Pads was also better compared with standard gel. The transducer pressure was lower in 33 patients. Conclusions: Hydrotin‐C‐Pads can be used as a solid ultrasonic coupling agent. Because of the consistent thickness of the coupling zone, the IQ seems to be better for Hydrotin‐C‐Pads compared with standard coupling gel. The transducer presser is lower, and these pads are easy to apply and are reusable and reduce the burden of clean‐up after treatment.
Imaging of Ventricular Septal Tumor in an Asymptomatic Adolescent using Multiple Modalities
Authors: Chamsi‐Pasha Mohammed A.R. , Anwar Ashraf M. , Al‐Nasser Ibrahim , Nosir Youssef F. M. , Ajam Aref , Chamsi‐Pasha Hassan
Published: March 2009

Primary cardiac tumors are rare at all ages, and especially so in childhood, where the most prevalent type of benign cardiac masses are rhabdomyomas followed by fibromas, both of which have a predilection for ventricular septum. We report an unusual case of a tumor involving the ventricular septum in an asymptomatic 17‐year‐old adolescent who has been known to have this tumor for 10 years. The use of multiple imaging included myocardial contrast two‐dimensional echocardiography, real time three‐dimensional echocardiography (with and without myocardial contrast), and magnetic resonance imaging supported the diagnosis of cardiac rhabdomyoma.
Left Ventricular Outflow Tract Gradient Provoked by Upright Position or Exercise in Treated Patients with Hypertrophic Cardiomyopathy without Obstruction at Rest
Authors: Dimitrow Pawel Petkow , Bober Maria , Michałowska Joanna , Sorysz Danuta
Published: March 2009

Objectives: The aim of the study was to assess inducibility of left ventricular outflow tract (LVOT) gradient by change of position from supine to upright and by treadmill exercise in treated patients with hypertrophic cardiomyopathy (HCM) without obstruction at rest. Methods: We studied 37 treated HCM patients (21 men and 16 women, mean age 44 ± 12 years) with LVOT gradient <30 mmHg at rest in supine position. The patients were then placed in upright position and the gradient was reexamined. The patients who developed LVOT gradient ≥30 mmHg during this maneuver were not exercised, whereas the remaining patients (nonobstructive in orthostatic position) performed moderate‐intensity exercise on a treadmill, with continuous monitoring of the LVOT gradient. For comparison with resting measurements, gradients at peak exercise (in upright position) and at recovery (in supine position) were used. The resting minimal distance between the mitral valve and ventricular septum at systole was used to assess the degree of narrowing of LVOT. Results: The orthostatic position provoked LVOT gradient ≥30 mmHg in 8 of 37 patients. At peak exercise, 10 of the remaining 29 patients developed significant LVOT gradient. At recovery in supine position, this significant gradient disappeared in 6 of 10 patients, despite only a short delay in measurement. Of resting echocardiographic parameters, only systolic mitral–septal distance differentiated between the provocable and nonprovocable subgroups. Patients with provocable gradient (either by changing position or by exercise) presented with lower values of this parameter than the nonprovacable subgroup. Conclusions: In nonobstructive HCM patients under treatment, the LVOT gradient was inducible by upright position in 21.6% and by upright moderate exercise in 34.5%. The minimal septal–mitral distance may be useful to identify patients with provocable obstruction.
Effects of antisense oligodeoxynucleotide to type I collagen gene on hypertrophic scars in the transplanted nude mouse model
Authors: Xie Julin , Qi Shaohai , Yuan Jishan , Xu Yinbing , Li Tianzeng , Li Houdong , Liu Xusheng , Shu Bin , Liang Huizeng
Published: March 2009

Background:  Antisense nucleic acids are effective in inhibiting harmful or uncontrolled gene expression. We had previously proved that the antisense DNA to type I collagen could effectively inhibit the synthesis of collagen type I in cultured hypertrophic scar fibroblasts, suggesting a potential role in anti‐scarring, but there are no published reports of its effect on scar in the transplanted nude mouse model.

Aims:  To investigate the effects of antisense oligodeoxynucleotide (ASODN) to type I collagen gene on hypertrophic scars in the transplanted nude mouse model and clarify the potential of ASODN for the treatment of scars.

Methods:  The nude mouse model of hypertrophic scar was created and subjected to daily injections with ASODN and Lipofectamine™ for 2 ,4 or 6 weeks. We then examined the scars for changes in histopathological characteristics. The effects of ASODN on type I collagen gene expression were examined by reverse transcription‐polymerase chain reaction and Western blots.

Results:  The ASODN could remarkably alleviate the scar in the nude mouse model and consistently inhibit type I collagen gene expression at both the mRNA and protein levels.

Conclusion:  ASODN was effective in downregulating type I collagen gene expression and could prove to be useful in the treatment of scars.
Dermal contributions to UVA‐induced oxidative stress in skin
Authors: Ou‐Yang Hao , Stamatas Georgios , Kollias Nikiforos
Published: March 2009

Background: When the skin is exposed to solar irradiation, UVA photons interact with skin tissues and induce excessive reactive oxygen species, resulting in oxidative stress. We have shown in a previous study that in vivo chemiluminescence's measurement can be used to evaluate the overall level of UVA‐induced oxidative stress in human skin. However, the origin of the observed chemiluminescence signals remains unclear.

Methods: UVA‐induced chemiluminescence measurements were conducted: (a) in vitro on collagen solutions and solid collagen sheet preparations, (b) ex vivo on human and mouse skin biopsies, and (c) in vivo on human skin of various constitutive pigmentation levels. Fluorescence was measured on collagen in vitro as well as on skin for the in vivo experiments.

Results: We found in the in vitro experiments that UVA‐induced chemiluminescence increases with the presence of collagen cross‐links. When dermal sides were exposed to UVA irradiation, both mouse and human skin biopsies demonstrated significantly higher chemiluminescence levels than when epidermal sides were exposed to UVA. The amount of collagen cross‐links decreases slightly following UVA exposure, as shown both by in vivo fluorescence and by UVA‐induced chemiluminescence. Finally, there was less measurable UVA‐induced chemiluminescence in dark skin compared with light pigmented skin in vivo.

Conclusions: The dermis is very sensitive to UVA photons. Dermal cross‐links are potential UVA sensitizers. The oxidative stress induced by UVA and measured by chemiluminescence may largely be attributed to the breakdown of dermal collagen cross‐links.
Spectrophotometric intracutaneous analysis as an early non‐invasive predictor of efficacy in the phototherapy of psoriasis
Authors: Novaković Ljubomir , Cotton Symon , Hawk John L. M.
Published: March 2009

Background: Phototherapy is generally effective for psoriasis but individual responsiveness and optimal treatment duration for disease clearance are unpredictable. However, easy, rapid and non‐invasive plaque assessment by spectrophotometric intracutaneous analysis (SIAscopy), a novel multispectral skin imaging technique, may now make prediction feasible.

Objectives: The early prediction of psoriatic plaque clearance during phototherapy by SIAscopy.

Methods: Sixteen psoriatic plaques in 10 psoriasis patients were serially assessed SIAscopically during phototherapy for punctate dots representing the dilated papillary dermal blood vessels characteristic of active psoriasis, and the results compared with the clinical findings.

Results: All plaques showing full SIAscopic clearance at early follow‐up also showed complete or almost complete clinical clearance, and remained the same thereafter. All showing no SIAscopic clearance at early follow‐up showed at most partial clinical clearance, and also remained the same thereafter. All showing only partial SIAscopic clearance at early follow‐up also showed just partial clinical clearance, but then generally progressed to full SIAscopic and clinical clearance.

Conclusions: SIAscopy of psoriatic plaques at early follow‐up during patient phototherapy enables good prediction of likely later clinical clearance, thereby potentially avoiding unnecessary further treatment. A larger confirmatory study is now needed.
Oral vs. bath PUVA using 8‐methoxypsoralen for chronic palmoplantar eczema
Authors: Tzaneva Stanislava , Kittler Harald , Thallinger Christiane , Hönigsmann Herbert , Tanew Adrian
Published: March 2009

Background: Both oral and bath PUVA with 8‐methoxypsoralen (8‐MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema. However, most studies were retrospective and did not include longer follow‐up periods.

Aim: To compare the therapeutic efficacy, tolerability and duration of remission after oral vs. bath PUVA using 8‐MOP in patients with chronic palmoplantar eczema.

Methods: Twenty‐nine patients were randomly allocated to treatment with oral or bath PUVA. Treatment was given thrice weekly for a maximum of 20 weeks. The primary outcome measure was the improvement in eczema score at the end of treatment. After clearing patients were followed up until relapse or up to 40 months.

Results: Overall, both PUVA modalities appeared comparably effective. However, after stratifying according to eczema type, significant differences in therapeutic outcome in general as well as in response to the two regimes were found. Dyshidrotic eczema responded better to both treatments (P=0.048) and remained longer in remission than hyperkeratotic eczema. Hyperkeratotic eczema cleared significantly better with oral than with bath PUVA (P=0.03).

Conclusion: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.