bluuebunny/crossref_metadata_2025 huggingface dataset:
Neprilysin activity and expression are controlled by nicastrin
Authors: Pardossi‐Piquard R. , Dunys J. , Yu G. , St. George‐Hyslop P. , Alves da Costa C. , Checler F.
Published: April 2006

We recently demonstrated that the presenilin‐dependent γ‐secretase complex regulates the expression and activity of neprilysin, one of the main enzymes that degrade the amyloid β‐peptide (Aβ) which accumulates in Alzheimer's disease. Here, we examined the influence of endogenous nicastrin (NCT), a member of the γ‐secretase complex, on neprilysin physiology. We show that nicastrin deficiency drastically lowers neprilysin expression, membrane‐bound activity and mRNA levels, but it did not modulate the expression of two other putative Aβ‐cleaving enzymes, endothelin‐converting enzyme and insulin‐degrading enzyme. Furthermore, we show that nicastrin restores neprilysin activity and expression in nicastrin‐deficient, but not presenilin‐deficient fibroblasts, indicating that the control of neprilysin necessitates the complete γ‐secretase complex harbouring its four reported components. Finally, we show that NCT expression peaked 24 h after NCT cDNA transfection of wild‐type and NCT–/– fibroblasts, while neprilysin expression drastically increased only after 36 h and was maximal at 48 h. This delayed effect on neprilysin expression correlates well with our demonstration of an indirect γ‐secretase‐dependent modulation of neprilysin at its transcriptional level.
Binding characteristics and sensitivity to endogenous dopamine of [11C]‐(+)‐PHNO, a new agonist radiotracer for imaging the high‐affinity state of D2 receptors in vivo using positron emission tomography
Authors: Ginovart Nathalie , Galineau Laurent , Willeit Matthaeus , Mizrahi Romina , Bloomfield Peter M. , Seeman Philip , Houle Sylvain , Kapur Shitij , Wilson Alan A.
Published: April 2006

[11C]‐(+)‐PHNO (4‐propyl‐9‐hydroxynaphthoxazine) is a new agonist radioligand that provides a unique opportunity to measure the high‐affinity states of the D2 receptors (D2‐high) using positron emission tomography (PET). Here we report on the distribution, displaceablity, specificity and modeling of [11C]‐(+)‐PHNO and compare it with the well characterized antagonist D2 radioligand, [11C]raclopride, in cat. [11C]‐(+)‐PHNO displayed high uptake in striatum with a mean striatal binding potential (BP) of 3.95 ± 0.85. Pre‐treatment with specific D1 (SCH23390), D2 (raclopride, haloperidol) and D3 receptor (SB‐277011) antagonists indicated that [11C]‐(+)‐PHNO binding in striatum is specific to D2 receptors. Within‐subject comparisons showed that [11C]‐(+)‐PHNO BP in striatum was almost 2.5‐fold higher than that measured with [11C]‐(–)‐NPA ([11C]‐(–)‐N‐propyl‐norapomorphine). Comparison of the dose‐effect of amphetamine (0.1, 0.5 and 2 mg/kg; i.v.) showed that [11C]‐(+)‐PHNO was more sensitive to the dopamine releasing effect of amphetamine than [11C]raclopride. Amphetamine induced up to 83 ± 4% inhibition of [11C]‐(+)‐PHNO BP and only up to 56 ± 8% inhibition of [11C]raclopride BP. Scatchard analyses of [11C]‐(+)‐PHNO and [11C]raclopride bindings in two cats showed that the Bmax obtained with the agonist (29.6 and 32.9 pmol/mL) equalled that obtained with the antagonist (30.6 and 33.4 pmol/mL). The high penetration of [11C]‐(+)‐PHNO in brain, its high signal‐to‐noise ratio, its favorable in vivo kinetics and its high sensitivity to amphetamine shows that [11C]‐(+)‐PHNO has highly suitable characteristics for probing the D2‐high with PET.
Functional analysis of a mammalian odorant receptor subfamily
Authors: Abaffy Tatjana , Matsunami Hiroaki , Luetje Charles W.
Published: April 2006

Phylogenetic analysis groups mammalian odorant receptors into two broad classes and numerous subfamilies. These subfamilies are proposed to reflect functional organization. Testing this idea requires an assay allowing detailed functional characterization of odorant receptors. Here we show that a variety of Class I and Class II mouse odorant receptors can be functionally expressed in Xenopus laevis oocytes. Receptor constructs included the N‐terminal 20 residues of human rhodopsin and were co‐expressed with Gαolf and the cystic fibrosis transmembrane regulator to allow electrophysiological measurement of receptor responses. For most mouse odorant receptors tested, these conditions were sufficient for functional expression. Co‐expression of accessory proteins was required to allow functional surface expression of some mouse odorant receptors. We used this assay to examine the receptive ranges of all members of the mouse odorant receptor 42 (MOR42) subfamily. MOR42‐1 responded to dicarboxylic acids, preferring a 10–12 carbon chain length. MOR42‐2 responded to monocarboxylic acids (7–10 carbons). MOR42‐3 responded to dicarboxylic acids (8–10 carbons) and monocarboxylic acids (10–12 carbons). Thus, the receptive range of each receptor was unique. However, overlap between the individual receptive ranges suggests that the members of this subfamily form one contiguous subfamily receptive range, suggesting that odorant receptor subfamilies do constitute functional units.
Interpopulation differences exhibited by Spotted Bowerbirds Chlamydera maculata across a suite of male traits and female preferences
Authors: MADDEN JOAH R.
Published: April 2006

Male Spotted Bowerbirds Chlamydera maculata build and decorate structures, bowers, that act as targets for female choice. Bower construction, orientation and distribution all differed between two populations, as did rates of intrasexual aggression. Although there was a broad similarity in classes of decorations used on bowers, the exact types and positioning varied between populations. For two intensively studied populations, different decorations appeared to be the best predictors of mating success. In both populations, male owners of high‐quality bowers obtained higher mating success. Male display intensity differed dramatically between populations, and females appeared to differ in the attention that they paid to the male's own display movements. Females also differed in the position that they took to observe a male's display. These variations suggest that differing selective forces may be acting on the elaboration of extreme male display traits across populations. I comment on how this variation can be used to illuminate current hypotheses for the evolution of bowers.
Monthly survival of African Sylvia warblers in a seasonally arid tropical environment
Authors: SCHAEFER HANS‐CHRISTIAN , ESHIAMWATA GEORGE W. , MUNYEKENYE FRED B. , GRIEBELER EVA MARIA , BÖHNING‐GAESE KATRIN
Published: April 2006

Latitudinal gradients of life‐history traits in animals are thought to be shaped by environmental variables. For example, it has been suggested that the increase in avian clutch size from the tropics towards the northern temperate regions is caused by a reduced survival of adult birds in the north due to increasing environmental seasonality. However, the tropical savannahs of East Africa show pronounced seasonality in resources caused by distinct rainy and dry seasons. This raises the question of whether survival and other life‐history traits of birds living in these tropical savannahs are influenced by this seasonality, making them more similar to northern temperate species. We used 2‐year monthly resighting data, a multistate modelling approach and the program MARK to test whether survival, transition probabilities between breeding states and other life‐history traits of two resident Kenyan Sylvia species (Aves: Passeriformes: Sylviidae) are shaped by seasonality of rainfall in their environment. Contradicting our hypotheses, the two species showed only very slight influence of seasonality of rainfall on their survival. Survival in the dry months was hardly lower than in the rainy months. The species in the more seasonal environment (S. boehmi, annual survival 71%) survived as well as the one in the more constant environment (S. lugens, 56%). The observed survival rates correspond well to other life‐history traits of the two species and are of similar magnitude to survival rates of other tropical passerines. This implies that either seasonality is not the driving force behind the life‐history traits of the two species or the birds do not experience their environment as seasonal, as might be suggested by fluctuations in rainfall.
Endogenous anti‐oxidants in pregnancy and preeclampsia
Authors: PERKINS Anthony V.
Published: April 2006

Oxidative stress has been implicated in a wide variety of diseases and degenerative states including cancer, rheumatoid arthritis, cardiovascular disease and ageing. There is now considerable evidence to suggest that pregnancy leads to the generation of an increased oxidative burden, but whether this overwhelms the anti‐oxidant capacity within the placenta and/or the peripheral circulation remains a point of conjecture. There is little doubt that oxidative stress is a significant contributor in the pathogenesis of preeclampsia. The use of exogenous anti‐oxidants such as vitamins C and E in the prevention of preeclampsia is the subject of several large clinical trials currently being conducted in many countries around the world. The results of these studies are eagerly awaited, but what of the endogenous anti‐oxidant systems that have evolved to combat the oxidative burden associated with living in an aerobic environment? This review will focus on several important anti‐oxidant enzyme systems, their role in pregnancy and the evidence to suggest that endogenous anti‐oxidants are important in the development of complications of pregnancy such as preeclampsia.
Hormone therapy in the WHI era
Authors: BURGER Henry G.
Published: April 2006

The announcement in July 2002 in the media of the results of the combined continuous hormone treatment arm of the Women's Health Initiative (WHI) had a profound effect on perceptions about hormone therapy among the lay public and the medical profession. Careful scrutiny of the announcement and the subsequent publications leads to the conclusion that the widespread fear of hormone therapy that was generated was not supported by the facts. WHI was not designed to be, nor can it be, interpreted as a randomised controlled trial of menopausal hormone therapy – rather, it was a trial of chronic disease prevention, particularly aimed at the possible cardiovascular benefits of a specific combination hormone therapy in postmenopausal women. The results, which were consistent with existing data, did not and do not warrant any major change in the previously established guidelines for the use of hormone therapy. Tibolone has emerged as an alternative treatment for menopausal symptoms, but its long‐term benefits and risks have yet to be documented.
Subcutaneous sterile water injection for labour pain: A randomised controlled trial
Authors: BAHASADRI Shohreh , AHMADI‐ABHARI Sara , DEHGHANI‐NIK Mojghan , HABIBI Gholam Reza
Published: April 2006

Background:  About 30% of women experience severe continuous low‐back pain in labour, but limited options are available to reduce this pain especially in developing countries and remote areas.

Aims:  To evaluate the efficacy of subcutaneous sterile water injection in reduction of labour pain compared with placebo.

Methods:  One hundred (100) consecutive patients were enrolled in a double‐blind randomised controlled trial. During the first stage of labour with planned normal vaginal delivery, the intervention group (n = 50) received 0.5 mL sterile water injected subcutaneously and the control group (n = 50) received normal saline as a placebo. Pain score was measured before and 10 and 45 min after the injection, using the faces rating scale.

Main outcome measure:  Low‐back labour pain.

Results:  The two groups were not significantly different regarding maternal age and weight, gestational age, parity and gravidity and degree of effacement. The median pain score was equal in both groups prior to the injection. Pain severity was reduced in both groups after the injection. However, the median pain score in the sterile water group was significantly lower than the placebo group 10 min (P < 0.01), as well as 45 min, after the injection (P < 0.01).

Conclusion:  Administering one subcutaneous injection of sterile water in a painful point of the lumbosacral area is effective in reducing low‐back pain during labour.
A medical management of interstitial ectopic pregnancy: A 5‐year clinical study
Authors: TANG Amy , BAARTZ David , KHOO Soo Keat
Published: April 2006

Background:  Medical treatment of the rare interstitial ectopic pregnancy with methotrexate has been considered an alternative to surgical resection.

Aim:  To determine the treatment success rate with a single‐dose intravenous methotrexate/folinic acid regimen and to identify predictors of treatment outcome.

Methods:  A 5‐year audit (April 2000–August 2005) was carried out, collecting clinical imaging data and serum beta‐human chorionic gonadotrophin (β‐hCG). Time taken for complete β‐hCG resolution was recorded, and a negative β‐hCG result was used as an endpoint of successful outcome.

Results:  Of the 13 cases, two required urgent surgery for rupture on presentation. In the remaining 11 cases, intravenous methotrexate (300 mg) was used, with oral folinic acid rescue (15 mg × 4 doses). There were no side‐effects. Complete β‐hCG resolution was achieved in 10 of the 11 medically treated cases (91% success rate), requiring 21–129 days. Successful outcome was seen with initial β‐hCG level as high as 106 634 IU/L and gestation sac as large as 6 cm and a live fetus.

Conclusion:  The methotrexate/folinic acid regimen used as a one‐dose treatment is safe and effective for unruptured interstitial pregnancy, with no side‐effects and the advantage of avoiding invasive surgery. Subsequent tubal patency and reproductive function are yet to be ascertained.
Guidelines following hydatidiform mole: A reappraisal
Authors: WIESMA Sabien , KERKMEIJER Linda , BEKKERS Ruud , PYMAN Jan , TAN Jeffrey , QUINN Michael
Published: April 2006

Objective:  The aim of this study was to determine how often patients with complete hydatidiform mole (CHM) who spontaneously achieve normal human chorionic gonadotrophin (hCG) levels subsequently develop persistent or recurrent gestational trophoblast disease.

Methods:  Four hundred and fourteen cases of CHM registered at the Hydatidiform Mole Registry of Victoria were reviewed retrospectively after molar evacuation. Maternal age, gestational age, gravidity and parity were determined for each patient, as well as the need for chemotherapy.

Results:  Among the 414 patients, 55 (13.3%) required chemotherapy for persistent trophoblastic disease. None of the patients whose hCG levels spontaneously fell to normal subsequently developed persistent molar disease.

Conclusion:  Weekly hCG measurements are recommended for all patients until normal levels are achieved. For patients who attain normal hCG levels within 2 months after evacuation, it seems safe to discontinue monitoring once normal levels are achieved. Patients who fail to achieve normal hCG levels by 2 months after evacuation should be monitored with monthly hCG measurements for 1 year after normalisation to assure sustained remission.
Persistent trophoblast disease following partial molar pregnancy
Authors: WIESMA Sabien , KERKMEIJER Linda , BEKKERS Ruud , PYMAN Jan , TAN Jeffrey , QUINN Michael
Published: April 2006

Objective:  Human chorionic gonadotrophin (hCG) follow‐up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow‐up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM).

Methods:  Demographic factors were determined for all 344 cases with a review diagnosis of PHM, included age, history of previous hydatidiform mole, gestation length, hCG levels and compliance with follow‐up.

Findings:  Six of the 344 patients diagnosed with PHM required treatment with single‐agent methotrexate and folinic acid rescue. All six patients achieved and maintained a complete biochemical remission after chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients had at least one normal hCG measurement during follow‐up, of whom 152 (64.7%) patients obtained normal values within 2 months after evacuation. All patients obtained normal levels within 32 weeks after evacuation of the partial hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow‐up program. No patient who achieved normal hCG levels required chemotherapy because of a recurrent gestational trophoblastic tumour.

Recommendations:  This study indicates that 1.7% of all partial mole pregnancy patients needed treatment for malignant sequelae. In contrast, no patient diagnosed with partial mole had a biochemical or clinical relapse after achieving normal levels of hCG, consistent with previous studies. Patients who have had a partial hydatidiform mole should be followed by hCG assays until normal levels are achieved and then follow‐up can be safely discontinued.
Vacuum‐assisted delivery: An analysis of traction force and maternal and neonatal outcomes
Authors: VACCA Aldo
Published: April 2006

Safety recommendations for vacuum‐assisted delivery focus on limiting the number of pulls and the duration of the procedure. With the introduction of the Kiwi OmniCup vacuum extractor incorporating a Traction Force IndicatorTM, it is now possible to reliably monitor and control the amount of traction force exerted on the fetal scalp. The OmniCup was used in a prospective observational study of 119 vacuum‐assisted deliveries in nulliparous women to establish practical guidelines for safe practice in typical clinical settings.
Do women with polycystic ovary syndrome really have predisposition to atherosclerosis?
Authors: TOPCU Semra , CALISKAN Mustafa , GULLU Hakan , OZCIMEN Emel Ebru , ERDOGAN Dogan , UCKUYU Ayla , ZEYNELOGLU Hulusi , MUDERRISOGLU Haldun
Published: April 2006

The elastic properties of the aorta were studied in 28 women with polycystic ovary syndrome (PCOS) and in 26 regularly menstruating healthy women. In PCOS and control groups, systolic and diastolic blood pressure, aortic systolic diameter, aortic diastolic diameter, aortic distensibility, aortic stiffness index, and aortic elastic modulus were similar. It is likely that PCOS does not have any innate adverse effects on the cardiovascular system if its undesirable metabolic consequences are successfully controlled.
Postmenopausal hormone therapy: Who now takes it and do they differ from non‐users?
Authors: TAYLOR Anne W. , MACLENNAN Alastair H. , AVERY Jodie C.
Published: April 2006

Background:  Considerable changes in hormone therapy use have taken place in the last few years.

Aims:  To determine current usage of postmenopausal hormone therapy and assess the trend and rate of change in hormone therapy usage over the last 13 years. Additionally, to assess differences between current users and non‐users for health‐related and risk factor variables.

Methods:  Questions regarding hormone therapy use have been included in an annual face to face population health survey of South Australians eight times since 1991. In 2004, additional questions on health status and quality of life were included.

Results:  In 2004, current use of hormone therapy was 15.4, 19.8 and 31.2% in all women over 40, 50 and 50–59 years, respectively. Ever use of hormone therapy among all women over 50 years was 46.5% with a mean duration of use of 7.46 years. Hormone therapy users did not differ from non‐users in chronic disease indicators, body mass index, complementary medicine or therapist use, other health service use, socioeconomic status or quality of life. Increased hormone therapy use was associated with higher income, better educated, employed and married women in their sixth decade. Current use has varied over the years, with an increase to 2000, but a drop in 2003 and 2004.

Conclusion:  Apart from menopausal symptoms, there is no evidence to support differences between users and non‐users in terms of quality of life or health characteristics, requiring more appropriate selection of women for hormone therapy.
Effect of inhaled glucocorticoid treatment on placental 11β‐hydroxysteroid dehydrogenase type 2 activity and neonatal birthweight in pregnancies complicated by asthma
Authors: CLIFTON Vicki L. , RENNIE Natascha , MURPHY Vanessa E.
Published: April 2006

Background:  Asthma is a common disease affecting 12% of Australian women with 55% of women experiencing at least one exacerbation during pregnancy. Exacerbations during pregnancy are associated with low birthweight neonates and stillbirth. One of the main reasons for maternal exacerbations during pregnancy is non‐compliance with inhaled glucocorticoid treatment due to the misconception that inhaled glucocorticoids are harmful to the fetus.

Aims and methods:  We have therefore assessed whether the commonly used inhaled glucocorticoids reduce placental glucocorticoid metabolising capacity, by measuring 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD‐2) activity. As these treatments potentially increase the exposure of the fetus to the growth‐inhibiting effects of glucocorticoids, we also examined the question of whether inhaled glucocorticoid use was associated with reduced birthweight. Pregnant women using budesonide (n = 18), fluticasone propionate alone (n = 14) and fluticasone propionate in combination with the long‐acting β2 agonist salmeterol (n = 9) were compared to a non‐asthmatic control group (n = 20).

Results:  The use of inhaled budesonide was associated with significantly increased placental 11β‐HSD‐2 activity relative to the control group. Inhaled glucocorticoid use for the treatment of asthma was associated with normal birthweight. In the small number of women using combination therapy (fluticasone and salmeterol), there was reduced birthweight compared to the control group.

Conclusion:  Inhaled glucocorticoids alone do not adversely affect fetal growth and placental function.
No more surrogate end‐points in randomised trials: The PCOSMIC trial protocol for women with polycystic ovary syndrome using metformin for infertility with clomiphene
Authors: JOHNSON Neil Philip
Published: April 2006

Current data supporting the effectiveness of metformin as a fertility treatment for women with polycystic ovary syndrome have been misinterpreted. Still unproven for women with polycystic ovary syndrome is, first, whether metformin adds to the standard first‐line fertility management in all women, second, whether metformin is an effective fertility treatment for overweight women, and third, the relative fertility efficacy of metformin and clomiphene citrate as a first‐line treatment in women with a lower body weight. The PCOSMIC (polycystic ovary syndrome: metformin for infertility with clomiphene) trial is an ongoing New Zealand multicentre double‐blind placebo‐controlled parallel randomised trial assessing these questions.
Activin A, hypoxia and the prediction of obstetric outcomes
Authors: TONG Stephen
Published: April 2006

On the back of sheep experiments showing that uterine hypoxia induces a rapid and sustained elevation of fetal activin A levels, we undertook two prospective studies to explore whether this novel observation could be exploited clinically. The first was a prospective labour ward study investigating whether umbilical arterial activin A levels at delivery correlated with either neonatal hypoxic ischaemic encephalopathy or pH. Unfortunately, we were unable to demonstrate a link with either, but found that levels were significantly depressed among those who had an emergency Caesarean section, suggesting a possible role in active labour. Second, we investigated the link between activin A and intrauterine growth restriction (IUGR), a condition of fetoplacental hypoxia, by measuring levels in women presenting for antenatal ultrasound biometry with clinical suspicion of a small baby. We found that, compared to pregnancies with a baby that was small for gestational age (SGA) but otherwise healthy, levels were 2.4 and 8 times higher, respectively, in pregnancies complicated by IUGR, and those complicated by both IUGR and preeclampsia. However, a single blood sample of activin A was unable to distinguish between IUGR and SGA pregnancies with sufficient sensitivity to be clinically useful. Our studies were unable to demonstrate clinical utility for the experimental observation linking activin A and hypoxia.
Molecular profiling of human endometrium during the menstrual cycle
Authors: PONNAMPALAM Anna P. , WESTON Gareth C. , SUSIL Beatrice , ROGERS Peter A. W.
Published: April 2006

This summary of the findings of investigations of the changing transcriptional profile of human endometrium during the menstrual cycle shows that it is possible to classify the menstrual cycle based on the global gene expression profile, and identifies groups of known and novel genes that may be associated with different biological processes that occur in the endometrium such as implantation and menstruation.
A possible role for progesterone metabolites in human parturition
Authors: SHEEHAN Penelope M.
Published: April 2006

There has been a recent resurgence of interest in the role of progesterone in the maintenance of human pregnancy and the onset of labour, following recent reports of its use to prevent preterm labour in high‐risk patients. One possible mechanism by which progesterone might contribute to uterine quiescence is through the actions of its metabolites. This article provides a brief overview of progesterone in human pregnancy and an outline of progesterone metabolism in the various reproductive tract tissues as well as the evidence for actions of progesterone metabolites in pregnancy.
Time‐dependent Modulation of Alignment and Differentiation of Smooth Muscle Cells Seeded on a Porous Substrate Undergoing Cyclic Mechanical Strain
Authors: Cha Jae Min , Park Si‐Nae , Noh Sung Hoon , Suh Hwal
Published: April 2006

Abstract:  The orientation of cellular alignment in smooth muscle tissue engineering is directly related to optimal movement of engineered tissue when it is transplanted in vivo. Cyclic mechanical strain has been applied to modulate the alignment, proliferation, and differentiation of smooth muscle cells. This study was conducted to investigate the effects of cyclic mechanical strain on primary cultured myofibroblasts seeded onto three‐dimensional polymeric scaffolds, and to determine the optimal mechanical treatment time required to produce artificial smooth muscle. The cells were primary cultured from rabbit esophageal smooth muscle layer, and a self‐designed stretching chamber was used to modulate the cells on porous polyurethane (PU) scaffolds with 10% strain at a frequency of 1 Hz. The applied cyclic strain induced cellular alignment. In particular, cellular alignment perpendicular to the direction of strain was generated in the condition strained over 18 h. In terms of proliferation, the strained groups differed significantly from the statically cultured group, but no difference was observed between groups that were subjected to straining for different lengths of time. Quantitative analysis of α‐smooth muscle actin (SMA) showed that differentiation was significantly promoted at 18 h of strain. Penetration of primary cultured cells into the pores of PU scaffolds was shown after cyclic strain application, especially in 18 and 24 h of strain. Consequently, it is expected that myofibroblast/scaffold hybrids, cyclically strained in the defined time course, could be practically applied to organize functional smooth muscle tissues having consistent cell alignment and up‐regulated SMA.
Effect of Cryopreservation Techniques on Aortic Valve Glycosaminoglycans
Authors: Dainese Luca , Barili Fabio , Topkara Veli K. , Cheema Faisal H. , Formato Marilena , Aljaber Emad , Fusari Melissa , Micheli Barbara , Guarino Anna , Biglioli Paolo , Polvani Gianluca
Published: April 2006

Abstract:  This study was designed to evaluate the effect of cryopreservation on the glycosaminoglycan (GAG) content of the aortic allografts. Twenty‐one porcine aortic valves were obtained. Five aortic roots were immediately analyzed without cryopreservation, eight were cryopreserved in closed leaflet position, and eight in open leaflet position. The groups were compared in terms of GAG concentration and subclass proportion in three different zones including the aortic root wall, the commissures, and the leaflets. GAG content at the commissures was significantly lower in the closed leaflet group than in the other groups (P = 0.001). The electrophoretic analysis did not show any significant difference in the zonal distribution of GAG classes between groups. Quantitative analysis in various aortic valve zones suggests that cryopreservation can alter the GAG content. Cryopreservation of the aortic valve in an open leaflet position can preserve the matrix more efficiently and might prolong the durability of the aortic allograft.
Regional Differences in Vein Wall Dynamics Under Arterial Hemodynamic Conditions: Comparison With Arteries
Authors: Zócalo Yanina , Pessana Franco , Santana Daniel Bia , Armentano Ricardo L.
Published: April 2006

Abstract:  Factors that explain the different results among veins, and causes of the superior performance of vein grafts for small arterial reconstructions, remain unclear. The aim was to compare the biomechanical behavior of veins and arteries from different regions and sizes under arterial conditions. In vitro pressure and diameter were measured in four different veins and three different ovine arteries. A diameter–pressure transfer function was designed, and compliance, viscous, and inertial indexes, and viscous energy and buffering function were calculated. Regional differences in vein mechanical behavior and energy dissipation were found. Veins and arteries vary in mechanical properties and buffering, but the differences were lesser when considering the smallest artery. The differences among veins’ viscosity, compliance, and energy dissipation, but not in the buffering capability, could be related to different performances of veins when used as arterial grafts. The major biomechanical matching could contribute to explain veins with better results in small arteries reconstruction.
Prometheus Versus Molecular Adsorbents Recirculating System: Comparison of Efficiency in Two Different Liver Detoxification Devices
Authors: Evenepoel Pieter , Laleman Wim , Wilmer Alexander , Claes Kathleen , Kuypers Dirk , Bammens Bert , Nevens Frederik , Vanrenterghem Yves
Published: April 2006

Abstract:  Albumin dialysis by the molecular adsorbents recirculating system (MARS) and by fractionated plasma separation, adsorption, and dialysis (Prometheus[PROM]) represent novel nonbiological liver support systems specifically designed to remove albumin‐bound substances. Preliminary evidence suggests a favorable impact of MARS on the course and outcome of liver failure. This study aimed at comparing the detoxification capacity of both devices. For this purpose, we performed a retrospective analysis on data prospectively collected in patients with acute‐on‐chronic liver failure treated with either the MARS (n = 9) or the PROM (n = 9) device on 2–5 consecutive days. Each treatment was performed for at least 5 h at identical blood and dialysate flows. Blood clearances were calculated during the first treatment session for urea nitrogen, creatinine, total bilirubin, and bile acids from paired arterial and venous line samples after 1, 4, and 6 h of treatment. Reduction ratios for all single‐treatment sessions, and the overall treatment phase, were calculated from pretreatment and post‐treatment values. For all markers but bile acids, the single‐treatment as well as the overall treatment phase reduction ratios obtained with PROM were significantly higher compared with those obtained with MARS. PROM led at all time points to higher clearances for all evaluated solutes. Blood clearances of protein‐bound substances declined over time with MARS, but not with PROM. In conclusion, a significant decline in the serum level of water‐soluble and protein‐bound toxins was achieved with both devices. PROM produces higher blood clearances for most toxins, which results in higher delivered treatment doses compared with a matching treatment with MARS.
A Modeling Study of Bilirubin Kinetics During Molecular Adsorbent Recirculating System Sessions
Authors: Magosso Elisa , Ursino Mauro , Colì Luigi , Baraldi Olga , Bolondi Luigi , Stefoni Sergio
Published: April 2006

Abstract:  This work presents a quantitative description, by means of a mathematical model, of bilirubin removal during Molecular Adsorbent Recirculating System sessions. The model includes four compartments: two for the patient, and two for the albumin circuit. Equations in each compartment express mass preservation, mass exchange between compartments, and bilirubin–albumin binding kinetics. Model development and validation are based on in vivo data of bilirubin concentration acquired in eight sessions at different times during the session. The accuracy of the model in reproducing real data is high (error in blood = −0.3 ± 0.93 mg/dL), if three parameters, representing the depurative efficacy of the system (the dialysance of the blood filter and the initial and final clearance of the depurative elements in the albumin circuit), are estimated on each single session. However, model accuracy is only slightly deteriorated (error in blood = −0.4 ± 0.99 mg/dL) if a single set of parameters (fixing the three parameters at their mean values) is adopted. These results suggest that the model may be used a priori (i.e., using a single set of parameters) to achieve a satisfactory prediction of the overall bilirubin removal, as well as a posteriori for the estimation of device parameters. The latter use may allow the investigation of the dependence of these parameters on the operative and clinical conditions, in the effort to arrive at a rationalization and optimization of the treat‐ment.
Physiological Control of Blood Pumps Using Intrinsic Pump Parameters: A Computer Simulation Study
Authors: Giridharan Guruprasad A. , Skliar Mikhail
Published: April 2006

Abstract:  Implantable flow and pressure sensors, used to control rotary blood pumps, are unreliable in the long term. It is, therefore, desirable to develop a physiological control system that depends only on readily available measurements of the intrinsic pump parameters, such as measurements of the pump current, voltage, and speed (in revolutions per minute). A previously proposed ΔP control method of ventricular assist devices (VADs) requires the implantation of two pressure sensors to measure the pressure difference between the left ventricle and aorta. In this article, we propose a model‐based method for estimating ΔP, which eliminates the need for implantable pressure sensors. The developed estimator consists of the extended Kalman filter in conjunction with the Golay–Savitzky filter. The performance of the combined estimator–VAD controller system was evaluated in computer simulations for a broad range of physical activities and varying cardiac conditions. The results show that there was no appreciable performance degradation of the estimator–controller system compared to the case when ΔP is measured directly. The proposed approach effectively utilizes a VAD as both a pump and a differential pressure sensor, thus eliminating the need for dedicated implantable pressure and flow sensors. The simulation results show that different pump designs may not be equally effective at playing a dual role of a flow actuator and ΔP sensor.
Reliability, Validity, and Clinical Utility of the Migraine‐ACT Questionnaire
Authors: Kilminster Shaun G. , Dowson Andrew J. , Tepper Stewart J. , Baos Vicente , Baudet Francis , D'Amico Domenico
Published: April 2006

Background.—The 4‐item Migraine‐ACT questionnaire is an assessment tool for use by primary care physicians to identify patients who require a change in their current acute migraine treatment. It has been shown to be easy to use, and to be reliable and accurate in its assessments.

Objectives.—To further analyze the Migraine‐ACT study database, providing additional information on the reliability, validity, and potential clinical utility of the questionnaire.

Methods.—Reliability was assessed by recording the distribution of Migraine‐ACT scores recorded at baseline and 1 week later (test–retest reliability). Analyses of consistency of Migraine‐ACT scores were conducted on the total sample of patients and for the separate centers, using Pearson and Spearman correlations. Validity was assessed by comparing the t‐discrimination values for clinically relevant questions within domains of the original 27‐item questionnaire. Reliability and validity were also assessed by constructing an “alternative” (Form B) Migraine‐ACT questionnaire, derived from an analysis of the second‐best items in each domain in the original study data. Clinical utility was assessed using Pearson pairwise correlations to compare Migraine‐ACT scores with clinically defined criteria as analyzed by the SF‐36 Quality of Life questionnaire, the Migraine Disability Assessment (MIDAS) questionnaire, and the Migraine Therapy Assessment (MTAQ) questionnaire.

Results.—The distribution of Migraine‐ACT scores between the 2 completions of the questionnaire was consistent for the total sample (test–retest reliability, r= .81) and between the individual countries (r= .61 to .92). In this study, the validity (assessed as t‐discrimination) of the Migraine‐ACT “impact” and “global assessment of relief” questions were markedly higher than those of other endpoints used in migraine clinical studies. The Form B Migraine‐ACT questionnaire was almost as reliable and accurate as the original Form A questionnaire. The distribution of Migraine‐ACT scores was: 0 = 12.6%, 1 = 13.7%, 2 = 14.7%, 3 = 20.5%, and 4 = 38.4%. The change in Migraine‐ACT score correlated with, and had a linear relationship with changes in SF‐36, MIDAS, and MTAQ scores, and indicated that a Migraine‐ACT score of ≤2 corresponded with a need to consider changing the patient's acute medication. About 40% of the migraine patients in the study scored ≤2 and may have had significant unmet treatment needs.

Conclusions.—These data confirm the excellent reliability and validity of the Migraine‐ACT questionnaire and provide further evidence for its utility in clinical practice.
Subcutaneous Sumatriptan for Refractory Trigeminal Neuralgia
Authors: Kanai Akifumi , Saito Miwako , Hoka Sumio
Published: April 2006

Background.—Mechanical compression of the trigeminal root by an artery is thought to cause trigeminal neuralgia. The 5‐HT1B/1D receptor agonist may inhibit neurogenic inflammation and vasodilation near the irritated trigeminal root.

Objective.—To examine the effectiveness of a 5‐HT1B/1D receptor agonist, sumatriptan, on a paroxysmal pain in trigeminal neuralgia.

Methods.—Twenty‐four patients with trigeminal neuralgia refractory to previous treatment were randomized to receive subcutaneously either 3 mg (1 mL) of sumatriptan or 1 mL of saline placebo. Following a 7‐day period, patients crossed over to receive the alternative treatment. Paroxysmal pain triggered by touching or moving the face was assessed with VAS before and 15 minutes after the treatment. Patients used a descriptive scale to pain‐grade outcome, and asked to note whether the pain returned and how long after therapy it recurred.

Results.—Subcutaneous sumatriptan, but not placebo, significantly decreased VAS from 8.3 ± 2.1 to 2.4 ± 3.0 cm (mean ± SD). The number of patients who described their pain as moderately or slightly better was 20 in the sumatriptan group and 1 in the placebo group. The effect of subcutaneous sumatriptan persisted for a median period of 7.9 hours (range: 1–20 hours).

Conclusions.—Subcutaneous sumatriptan produced prompt analgesia without serious adverse reactions in patients with trigeminal neuralgia refractory to previous treatment.
Platelet Levels of Dopamine Are Increased in Migraine and Cluster Headache
Authors: D'Andrea Giovanni , Granella Franco , Perini Francesco , Farruggio Angelo , Leone Massimo , Bussone Gennaro
Published: April 2006

Objective.—To measure plasma and platelet levels of dopamine in patients with migraine with aura, migraine without aura, and cluster headache.

Background.—Clinical, genetic, and pharmacological evidences suggest that an abnormality of dopaminergic system plays a role in migraine pathogenesis. Direct evidence of an abnormal metabolism of dopamine in migraine, however, is lacking.

Methods.—Plasma and platelet levels of dopamine were measured in patients with migraine with aura or migraine without aura during headache‐free periods and in patients with cluster headache during the remission and active periods, as compared with healthy control subjects, using a multichannel electrochemical high‐performance liquid chromatography system.

Results.—Plasma levels of dopamine were not detectable with our methodology. Platelet levels of dopamine were higher in both types of migraine (migraine without aura = .20 ± .17 ng/108 platelets; migraine with aura = .16 ± .19 ng/108 platelets) than in control subjects (.10 ± .11 ng/108 platelets), although in migraine with aura patients the difference was not significant. Patients with cluster headache showed the highest levels of platelet dopamine (.34 ± .36 ng/108 platelets).

Conclusions.—Our results support the hypothesis that the dopaminergic system is impaired in migraine and cluster headache and suggest that high platelet levels of dopamine may represent an abnormal biochemical phenotypic trait of these primary headaches.
Color Vision but not Visual Attention Is Altered in Migraine
Authors: Shepherd Alex J.
Published: April 2006

Objective.—To examine visual search performance in migraine and headache‐free control groups and to determine whether reports of selective color vision deficits in migraine occur preattentively.

Background.—Visual search is a classic technique to measure certain components of visual attention. The technique can be manipulated to measure both preattentive (automatic) and attentive processes. Here, visual search for colored targets was employed to extend earlier reports that the detection or discrimination of colors selective for the short‐wavelength sensitive cone photoreceptors in the retina (S or “blue” cones) is impaired in migraine.

Method.—Visual search performance for small and large color differences was measured in 34 migraine and 34 control participants. Small and large color differences were included to assess attentive and preattentive processing, respectively. In separate conditions, colored stimuli were chosen that would be detected selectively by either the S‐, or by the long‐ (L or “red”) and middle (M or “green”)‐wavelength sensitive cone photoreceptors.

Results.—The results showed no preattentive differences between the migraine and control groups. For active, or attentive, search, differences between the migraine and control groups occurred for colors detected by the S‐cones only, there were no differences for colors detected by the L‐ and M‐cones. The migraine group responded significantly more slowly than the control group for the S‐cone colors.

Conclusions.—The pattern of results indicates that there are no overall differences in search performance between migraine and control groups. The differences found for the S‐cone colors are attributed to impaired discrimination of these colors in migraine and not to differences in attention.
OPTIMIZATION OF IRON‐DEPENDENT CYANOBACTERIAL (SYNECHOCOCCUS, CYANOPHYCEAE) BIOREPORTERS TO MEASURE IRON BIOAVAILABILITY1
Authors: Hassler Christel S. , Twiss Michael R. , McKay R. Michael L. , Bullerjahn George S.
Published: April 2006

Complex chemistry and biological uptake pathways render iron bioavailability particularly difficult to assess in natural waters. Bioreporters are genetically modified organisms that are useful tools to directly sense the bioavailable fractions of solutes. In this study, three cyanobacterial bioreporters derived from Synechococcus PCC 7942 were examined for the purpose of optimizing the response to bioavailable Fe. Each bioreporter uses a Fe‐regulated promoter (isiAB, irpA and mapA), modulated by distinct mechanisms under Fe deficiency, fused to a bacterial luciferase (luxAB). In order to provide a better understanding of the way natural conditions may affect the ability of the bioreporter to sense iron bioavailability, the effect of relevant environmental parameters on the response to iron was assessed. Optimal conditions (and limits of applicability) for the use of these bioreporters on the field were determined to be: a 12 h (12–24 h) exposure time, temperature of 15°C (15°C–22°C), photon flux density of 100 μmol photons·m−2·s−1 (37–200 lmol photons·m−2·s−1), initial biomass of 0.6–0.8 lg chlorophyll a (chl a)·L−1 (0.3–1.5 lg chl a·L−1) or approximately 105 bioreporter cells·mL−1, high phosphate (10 lM), and low micronutrients (absent). The measured luminescence was optimal with an exogenous addition of 60 lM aqueous decanal substrate allowing a 5 min reaction time in the dark before analysis. This study provides important considerations relating to the optimization in the use of bioreporters under field conditions that can be used for method development of other algal and cyanobacterial bioreporters in aquatic systems.
A MULTI‐GENE MOLECULAR INVESTIGATION OF THE KELP (LAMINARIALES, PHAEOPHYCEAE) SUPPORTS SUBSTANTIAL TAXONOMIC RE‐ORGANIZATION1
Authors: Lane Christopher E. , Mayes Charlene , Druehl Louis D. , Saunders Gary W.
Published: April 2006

Every year numerous ecological, biochemical, and physiological studies are performed using members of the order Laminariales. Despite the fact that kelp are some of the most intensely studied macroalgae in the world, there is significant debate over the classification within and among the three “derived” families, the Alariaceae, Laminariaceae, and Lessoniaceae (ALL). Molecular phylogenies published for the ALL families have generated hypotheses strongly at odds with the current morphological taxonomy; however, conflicting phylogenetic hypotheses and consistently low levels of support realized in all of these studies have resulted in conservative approaches to taxonomic revisions. In order to resolve relationships within this group we have sequenced over 6000 bp from regions in the nuclear, chloroplast, and mitochondrial genomes and included 42 taxa in Bayesian, neighbor‐joining, and parsimony analyses. The result is the first comprehensive and well‐supported molecular phylogeny for the ALL complex of the Laminariales. We maintain the three recognized families (Alariaceae, Laminariaceae, and Lessoniaceae), but with vastly different compositions, as well as propose the Costariaceae fam. nov. for Agarum, Costaria, Dictyoneurum, and Thalassiophyllum, the only genera in the Laminariales with flattened, occasionally terete, stipes and either a perforate or reticulate blade. In addition, our data strongly support a split of the genus Laminaria. We resurrect the genus Saccharina Stackhouse for the Laminaria clade that does not contain L. digitata (Hudson) J.V. Lamouroux, the type of the genus.