bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum, cheek cell and breast milk fatty acid compositions in infants with atopic and non‐atopic eczema
Authors: Laitinen K. , Sallinen J. , Linderborg K. , Isolauri E.
Published: January 2006

Background
The major theory implicating diet with allergic diseases is associated with altered food consumption and subsequent changes in fatty acid composition.

Objective
To investigate fatty acid compositions among infants with atopic and non‐atopic eczema and healthy infants and to evaluate the expediency of non‐invasive cheek cell phospholipid fatty acid composition as a marker in patients with eczema.

Methods
Diagnosis of eczema in infants was confirmed clinically and by positive (atopic eczema, n=6) or negative (non‐atopic eczema, n=6) skin prick testing in comparison with controls (n=19). The fatty acid compositions of infant cheek cell and serum phospholipids and breast milk total lipids were analysed by gas chromatography.

Results
The distinction between atopic and non‐atopic eczema was manifested in cheek cell phospholipids as linoleic acid (14.69 (13.67–15.53)% of total fatty acids; the median (interquartile range)), the sum of n‐6 fatty acids (19.94 (19.06–20.53)%) and the sum of polyunsaturated fatty acids (22.70 (21.31–23.28)%) were higher in infants with atopic eczema compared with non‐atopic eczema (12.69 (10.87–13.93); 17.72 (15.63–18.91) and 19.90 (17.64–21.06), respectively; P<0.05) and controls (12.50 (12.16–13.42); 18.19 (17.43–18.70) and 20.32 (19.32–21.03), respectively; P<0.05). Serum phospholipid γ‐linolenic acid was lower in both atopic and non‐atopic eczema compared with controls (P<0.05) and additionally eicosapentaenoic acid was higher in atopic eczema compared with controls (P<0.05).

Conclusion
These preliminary results suggest differences in fatty acid compositions between the two types of eczema, calling for further evaluation in a larger setting. The two types of eczema may be regulated by different immunological processes, and fatty acids may have a more profound role in the atopic type.
Handle with care: targeting neutrophils in chronic obstructive pulmonary disease and severe asthma?
Authors: Beeh K. M. , Beier J.
Published: January 2006

Neutrophils play an important role in the pathogenesis of airway inflammation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Currently available drugs have only limited effects on neutrophilic airway inflammation, particularily in COPD. Therefore, great efforts are undertaken to address neutrophilic inflammation in chronic respiratory disorders, in particular COPD. This review summarizes the rationale for anti‐neutrophilic treatment in COPD and asthma and gives a critical overview of current developments in drug therapy. Moreover, unanswered questions and limitations of clinical trial design and choice of outcome parameters for proof‐of‐concept studies with novel anti‐neutrophilic drugs are discussed as well as potential safety issues.
Respiratory symptoms, bronchial hyper‐responsiveness, and eosinophilic airway inflammation in patients with moderate‐to‐severe atopic dermatitis
Authors: Kyllönen H. , Malmberg P. , Remitz A. , Rytilä P. , Metso T. , Helenius I. , Haahtela T. , Reitamo S.
Published: January 2006

BackgroundPatients with atopic dermatitis (AD) often have symptoms suggestive of asthma or rhinitis. The prevalence and signs of respiratory disease in AD patients have been studied to a limited extent.

ObjectivesTo assess the prevalence and clustering of respiratory symptoms, bronchial hyper‐responsiveness (BHR), and eosinophilic airway inflammation in patients with moderate‐to‐severe AD.

MethodsEighty‐six consecutive patients with moderate‐to‐severe AD and 49 randomly selected control subjects without AD were studied by questionnaire, flow volume spirometry, histamine challenge to detect BHR, induced sputum test to detect eosinophilic airway inflammation, and skin prick tests (SPTs) and total serum immunoglobulin (Ig)E measurements to detect atopy.

ResultsThe patients with AD showed increased risk of physician‐diagnosed asthma (36% vs. 2%, odds ratio (OR) 10.1, confidence interval (CI) 1.3–79.7,P=0.03), physician‐diagnosed allergic rhinitis (AR) (45% vs. 6%, OR 4.5, CI 1.2–16.7,P=0.02), BHR (51% vs. 10%, OR 5.5, CI 1.5–20.1,P=0.01), and sputum eosinophilia (81% vs. 11%, OR 76.1, CI 9.3‐623.5,P<0.0001) compared with the control subjects. In AD patients, elevated s‐IgE and positive SPTs were associated with the occurrence of physician‐diagnosed asthma and AR, BHR, and the presence of sputum eosinophilia.

ConclusionsBHR and eosinophilic airway inflammation are more common in patients with AD than in control subjects. The highest prevalences were seen in patients with AD who were SPT positive and had high IgE levels. Longitudinal studies are needed to assess the outcome of patients with signs of airway disease, in order to identify those who need early initiation of asthma treatment.
Recurrent childhood upper respiratory tract infections do not reduce the risk of adult atopic disease
Authors: Balemans W. A. F. , Rovers M. M. , Schilder A. G. M. , Sanders E. A. M. , Kimpen J. L. L. , Zielhuis G. A. , van der Ent C. K.
Published: January 2006

Background
Children of large families and those attending day care are at increased risk of respiratory tract infections, which in turn may protect against the development of allergic disease. Longitudinal studies investigating these associations beyond childhood are, however, scarce.

Objective
To investigate the association between childhood recurrent upper respiratory tract infections (URTI) and asthma, allergic rhinitis (AR) and eczema in adulthood.

Methods
A birth cohort of 1055 members followed prospectively from the ages of 2 to 21 years. Detailed information on URTI between the ages of 2 and 4 years was collected at 3 monthly intervals in a standardized interview. At the age of 8 years, a parental questionnaire regarding URTI between the ages of 4 and 8 years was used. The incidence of asthma and atopic disease at the age of 21 years was determined using a standardized questionnaire.

Results
Of the original cohort, 693 (66%) members completed the questionnaire. Children who experienced recurrent URTI before the age of 2 years, between the ages of 2–4 years and between ages of 4 and 8 years were not less likely to have asthma at 21 years of age than children who did not experience recurrent URTI, relative risk (RR) 0.97 (95% confidence interval (CI) 0.65–1.46), RR 1.45 (CI 0.95–2.21) and RR 1.51 (CI 0.97–2.36), respectively. Neither were recurrent URTI associated with a decreased risk of AR, nor eczema at the age of 21 years.

Conclusions
Recurrent URTI in childhood did not reduce the risk of atopic disease in young adulthood.
The common G‐allele of interleukin‐18 single‐nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study
Authors: Imboden M. , Nicod L. , Nieters A. , Glaus E. , Matyas G. , Bircher A. J. , Ackermann‐Liebrich U. , Berger W. , Probst‐Hensch N. M. ,   SAPALDIA Team
Published: January 2006

Background
IL‐18 is a pleiotrophic cytokine involved in both, T‐helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL‐18 gene have been associated with increased risk of atopy and asthma.

Objective
To examine the relationship of a genetic, haplotype‐tagging promotor variant −137G/C in the IL‐18 gene with atopic asthma in a large, well‐characterized and population‐based study of adults.

Methods
Prospective cohort study design was used to collect interview and biological measurement data at two examination time‐points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy.

Results
The G‐allele of the IL‐18 promotor variant (−137G/C) was associated with a markedly increased risk for the prevalence of physician‐diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL‐18 −137 G‐allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64–8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66–1.94). The interaction between IL‐18 −137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype.

Conclusion
Our results strongly suggest that this variant of the IL‐18 gene is an important genetic determinant involved in the development of atopic asthma.
Indomethacin disrupts the protective effect of phosphatidylcholine against bile salt‐induced ileal mucosa injury
Authors: Venneman N. G. , Petruzzelli M. , van Dijk J. E. , Verheem A. , Akkermans L. M. A. , Kroese A. B. A. , van Erpecum K. J.
Published: January 2006

Background  Indomethacin (Indo) exerts local toxic effects on small intestinal mucosa, possibly in association with hydrophobic bile salts. We investigated the potential toxic effects of Indo on ileal mucosa and the role of phosphatidylcholine (PC).

Materials and methods  Transmucosal resistance and Na‐fluorescein permeability of ileal mucosa segments from female Wistar rats were determined in Ussing chambers during a 30‐min incubation with model systems containing: control‐buffer, taurodeoxycholate (TDC), Indo, TDC‐Indo, TDC‐PC, or TDC‐PC‐Indo. Decrease of resistance and increase of permeability were considered as parameters for mucosal injury. After incubation in Ussing chambers, the histopathology was examined to quantify the extent of mucosal injury. Also, in CaCo‐2 cells, LDH‐release was determined as a measure of cytotoxicity, after incubation with various model systems.

Results  Decrease of resistance and increase of permeability were highest in systems containing TDC‐Indo (P < 0·01). Phosphatidylcholine protected against the cytotoxic effects of TDC in absence of Indo only. Extent of mucosal injury by histological examination was also highest in systems containing TDC‐Indo (P = 0·006). Again, PC exhibited protective effects in absence of Indo only. The LDH‐release by CaCo2‐cells was strongest in TDC‐Indo systems (P < 0·001).

Conclusions  Indomethacin disrupts protective effects of PC against bile salt‐induced ileal mucosa injury. This finding is relevant for small intestinal injury induced by non‐steroidal anti‐inflammatory drugs.
Effects of simvastatin withdrawal on serum matrix metalloproteinases in hypercholesterolaemic patients
Authors: Huang C. Y. , Wu T. C. , Lin W. T. , Leu H. B. , Lin C. P. , Lin S. J. , Chen J. W.
Published: January 2006

Background  Serum matrix metalloproteinase (MMP) levels have been related to clinical outcomes in patients with coronary artery disease. Though statin treatment might reduce serum MMPs the change of levels after statin withdrawal remains obscure.

Materials and method  Sixty‐one consecutive hypercholesterolaemic patients whose lipid profiles had been well controlled by regular simvastatin (20 mg day−1) treatment for more than 6 months were enrolled. Statin was discontinued after their lipid profiles reached the treatment goal of the ATP‐III guideline. The lipid profiles, serum MMP‐2, MMP‐3 and MMP‐9, tissue inhibitor of MMP and highly sensitive C‐reactive protein (hsCRP) levels were measured on the day of simvastatin withdrawal and 120 days later. A further 50 hyperlipidaemia patients who had never received statin treatment (positive control group) and 28 healthy patients with normal lipid profiles (negative control group) were also studied as control groups.

Results  While the lipid profiles had been normalized, the levels of serum inflammatory markers were still higher in hypercholesterolaemic patients than in the healthy subjects. Up to 120 days after statin withdrawal there was no coronary event, but the lipid profiles and serum hsCRP levels had significantly rebounded in study patients. However, serum MMP‐2 and MMP‐9 levels remained unchanged and the MMP‐3 level was even further reduced after statin withdrawal (115·04 ± 84·54 vs. 92·71 ± 66·71 ng mL−1, P = 0·022). Moreover, the amplitudes of variation (%) of each parameter including MMPs, TIMP, hsCRP and lipid profiles after statin withdrawal were inversely correlated to their respective baseline levels before withdrawal (r = −0·702 to −0·284; P < 0·005).

Conclusions  The effects of short‐term discontinuation of statin were different on serum hsCRP and MMPs levels in hypercholesterolaemic patients. While lipid profiles and serum hsCRP level had rebounded the serum MMPs levels were still unchanged, or even reduced, suggesting the prolonged effect of statin treatment, especially on serum MMP‐3 level up to 120 days after simvastatin withdrawal. Further work is required to clarify the situation both in terms of these serum markers and clinical effects.
Is carbon within the global terrestrial biosphere becoming more oxidized? Implications for trends in atmospheric O2
Authors: RANDERSON J. T. , MASIELLO C. A. , STILL C. J. , RAHN T. , POORTER H. , FIELD C. B.
Published: January 2006

Measurements of atmospheric O2 and CO2 concentrations serve as a widely used means to partition global land and ocean carbon sinks. Interpretation of these measurements has assumed that the terrestrial biosphere contributes to changing O2 levels by either expanding or contracting in size, and thus serving as either a carbon sink or source (and conversely as either an oxygen source or sink). Here, we show how changes in atmospheric O2 can also occur if carbon within the terrestrial biosphere becomes more reduced or more oxidized, even with a constant carbon pool. At a global scale, we hypothesize that increasing levels of disturbance within many biomes has favored plant functional types with lower oxidative ratios and that this has caused carbon within the terrestrial biosphere to become increasingly more oxidized over a period of decades. Accounting for this mechanism in the global atmospheric O2 budget may require a small increase in the size of the land carbon sink. In a scenario based on the Carnegie–Ames–Stanford Approach model, a cumulative decrease in the oxidative ratio of net primary production (NPP) (moles of O2 produced per mole of CO2 fixed in NPP) by 0.01 over a period of 100 years would create an O2 disequilibrium of 0.0017 and require an increased land carbon sink of 0.1 Pg C yr−1 to balance global atmospheric O2 and CO2 budgets. At present, however, it is challenging to directly measure the oxidative ratio of terrestrial ecosystem exchange and even more difficult to detect a disequilibrium caused by a changing oxidative ratio of NPP. Information on plant and soil chemical composition complement gas exchange approaches for measuring the oxidative ratio, particularly for understanding how this quantity may respond to various global change processes over annual to decadal timescales.
Comparative dynamics of avian communities across edges and interiors of North American ecoregions
Authors: Karanth Krithi K. , Nichols James D. , Sauer John R. , Hines James E.
Published: January 2006

Aim Based ona priorihypotheses, we developed predictions about how avian communities might differ at the edges vs. interiors of ecoregions. Specifically, we predicted lower species richness and greater local turnover and extinction probabilities for regional edges. We tested these predictions using North American Breeding Bird Survey (BBS) data across nine ecoregions over a 20‐year time period.

Location Data from 2238 BBS routes within nine ecoregions of the United States were used.

Methods The estimation methods used accounted for species detection probabilities < 1. Parameter estimates for species richness, local turnover and extinction probabilities were obtained using the program COMDYN. We examined the difference in community‐level parameters estimated from within exterior edges (the habitat interface between ecoregions), interior edges (the habitat interface between two bird conservation regions within the same ecoregion) and interior (habitat excluding interfaces). General linear models were constructed to examine sources of variation in community parameters for five ecoregions (containing all three habitat types) and all nine ecoregions (containing two habitat types).

Results Analyses provided evidence that interior habitats and interior edges had on average higher bird species richness than exterior edges, providing some evidence of reduced species richness near habitat edges. Lower average extinction probabilities and turnover rates in interior habitats (five‐region analysis) provided some support for our predictions about these quantities. However, analyses directed at all three response variables, i.e. species richness, local turnover, and local extinction probability, provided evidence of an interaction between habitat and region, indicating that the relationships did not hold in all regions.

Main conclusions The overall predictions of lower species richness, higher local turnover and extinction probabilities in regional edge habitats, as opposed to interior habitats, were generally supported. However, these predicted tendencies did not hold in all regions.
Pathology of Edwardsiella tarda infection in turbot, Scophthalmus maximus (L.)
Authors: Padrós F , Zarza C , Dopazo L , Cuadrado M , Crespo S
Published: January 2006

Macroscopic and histopathological changes in cultured turbot, Scophthalmus maximus (L.), in Spain caused by infection with Edwardsiella tarda are described. Eye tumefaction, inflammation, haemorrhages, ascites and the presence of a purulent fluid were the main macroscopic lesions observed. Histopathological lesions were found in the kidney, spleen and liver. In the kidney and spleen these were characterized by a severe apostematous inflammatory reaction, with a large number of abscesses. The liver was affected to a lesser degree and only some phagocytes loaded with bacteria were observed. Ultrastructural observations indicated that macrophages were the main cell type implicated in the inflammatory response. Most of the bacteria observed within the phagocyte cytoplasm showed no degenerative changes and some were dividing. Degenerative changes observed in macrophages indicate their failure in preventing the infection.
Dietary β‐1,3 glucan potentiates innate immunity and disease resistance of Asian catfish, Clarias batrachus (L.)
Authors: Kumari J , Sahoo P K
Published: January 2006

This study investigated the effects of short and prolonged administration of a yeast β‐glucan on non‐specific immune parameters, growth rate and the disease resistance of Asian catfish, Clarias batrachus. Fish fed with a basal diet (control) and test diet (basal diet supplemented with 0.1% glucan) for 1, 2 and 3 weeks were assayed for superoxide production, serum myeloperoxidase (MPO) content, natural haemagglutinin level, complement and lysozyme activities. Fish were weighed at weekly intervals and specific growth rate (SGR, % increase in body weight per day) was determined. After each week, fish were challenged with Aeromonas hydrophila to measure the level of protection. Results showed that glucan administration at 0.1% in feed, significantly (P < 0.05) enhanced MPO and lysozyme levels, superoxide production, haemagglutination titre and level of protection against A. hydrophila challenge, irrespective of length of exposure. The alternative complement activity and SGR were not affected by the dietary supplementation of yeast glucan. As glucan feeding at 0.1% for 1 week is able to enhance the non‐specific immunity and disease resistance of catfish efficiently, short‐term feeding might be used in farmed catfish diets to enhance disease resistance.
Structure of the Mycobacterium tuberculosis proteasome and mechanism of inhibition by a peptidyl boronate
Authors: Hu Guiqing , Lin Gang , Wang Ming , Dick Lawrence , Xu Rui‐Ming , Nathan Carl , Li Huilin
Published: January 2006

Mycobacterium tuberculosis (Mtb) has the remarkable ability to resist killing by human macrophages. The 750 kDa proteasome, not available in most eubacteria except Actinomycetes, appears to contribute to Mtb's resistance. The crystal structure of the Mtb proteasome at 3.0 Å resolution reveals a substrate‐binding pocket with composite features of the distinct β1, β2 and β5 substrate binding sites of eukaryotic proteasomes, accounting for the broad specificity of the Mtb proteasome towards oligopeptides described in the companion article [Lin et al. (2006), Mol Microbiol doi:10.1111/j.1365‐2958.2005.05035.x]. The substrate entrance at the end of the cylindrical proteasome appears open in the crystal structure due to partial disorder of the α‐subunit N‐terminal residues. However, cryo‐electron microscopy of the core particle reveals a closed end, compatible with the density observed in negative‐staining electron microscopy that depended on the presence of the N‐terminal octapetides of the α‐subunits in the companion article, suggesting that the Mtb proteasome has a gated structure. We determine for the first time the proteasomal inhibition mechanism of the dipeptidyl boronate N‐(4‐morpholine)carbonyl‐β‐(1‐naphthyl)‐l‐alanine‐l‐leucine boronic acid (MLN‐273), an analogue of the antimyeloma drug bortezomib. The structure improves prospects for designing Mtb‐specific proteasomal inhibitors as a novel approach to chemotherapy of tuberculosis.
Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two disease entities in the same patient. Case report and review of the literature
Authors: Chong Wei‐Sheng , Thomas Anjula , Goh Chee‐Leok
Published: January 2006

Background  Much controversy has existed with regard to the relationship between Kimura's disease and angiolymphoid hyperplasia with eosinophilia. They were initially thought to represent the same disease spectrum, but it has now been widely accepted that they are two separate disease entities. To our knowledge, there have been no reports to date describing a case of both Kimura's disease and angiolymphoid hyperplasia with eosinophilia coexisting in the same patient.

Methods  We describe a patient presenting initially with a right postauricular subcutaneous swelling and subsequently developing multiple erythematous facial papules and nodules. The medical literature is reviewed.

Results  Clinical features of the right postauricular subcutaneous swelling and multiple erythematous facial papules/nodules suggest Kimura's disease in the former and angiolymphoid hyperplasia with eosinophilia in the latter. Histopathological examinations of these lesions helped to confirm the diagnosis of Kimura's disease and angiolymphoid hyperplasia with eosinophilia, respectively.

Conclusions  Kimura's disease and angiolymphoid hyperplasia with eosinophilia can coexist in the same patient. Coexistence of the two types of lesions in one patient may also be considered evidence that Kimura's disease and angiolymphoid hyperplasia with eosinophilia form a spectrum in one disease.
Clinico‐epidemiological features of primary hereditary ichthyoses in the Eastern province of Saudi Arabia
Authors: Al‐Zayir Ahmad A. , Al‐Amro Al‐Alakloby Omar M.
Published: January 2006

Background  A total of 10 455 new dermatology patients were seen in the dermatology clinics of King Fahad Hospital of the University (KFHU), Al‐Khobar, Saudi Arabia, between January 1990 and December 1995. We identified 71 patients with a histopathologically confirmed diagnosis of specific forms of primary hereditary ichthyoses (PHI). We have reviewed the epidemiological and clinical features of these patients.

Objective  To document the epidemiological and clinical features of patients with PHI in the Eastern Province of Saudi Arabia.

Methods  We used the dermatology out‐patient department (OPD) logbooks to identify cases of PHI from new patients presenting with different dermatological problems over a 6‐year period. We used specifically designed protocol forms to extract epidemiological and clinical data from the study patients’ medical records. These were entered into a computer database and analyzed using standard statistical software.

Results  A total of 71 patients, 44 males and 27 females (male : female sex ratio of 1.63 : 1), were identified from a total of 10 455 new patients seen in our dermatology clinics between January 1990 and December 1995. The occurrence rate of PHI, in our clinics, was 0.67% or 7 per 1000 new dermatology cases. The clinical pattern of PHI showed that Icthyosis Vulgaris was the most common form seen, followed by Nonbullous Ichthyosiform Erythroderma. Thirty‐one patients (44.7%) with Ichthyosis Vulgaris (IV) were seen: 12 patients (16.9%) with X‐linked Recessive Ichthyosis (XLRI), four patients (5.6%) with Lamellar Ichthyosis (LI), three patients (4.2%) with Bullous Ichthyosiform Erythroderma (BIE) and 21 patients (29.6%) with Nonbullous Ichthyosiform Erythroderma (NBIE). There was a significantly high consanguinity rate in our patients (85%), and the family history was positive in 53 cases out of the 71 (75%).

Conclusions  This preliminary study is the first report of its kind from Saudi Arabia and documents the clinico‐epidemiological features of PHI patients in the Eastern Province. The high rate of parental consanguinity among our Saudi patients may account for the high proportion of patients with a positive family history. Consanguinity also probably explains why the most severe forms of PHI were seen in a significant number of new patients’ siblings. These severe forms of PHI (Nonbullous Ichthyosiform Erythroderma, Bullous Ichthyosiform Erythroderma and Lamellar Ichthyosis) together constituted nearly 40% of all cases.
A case of hydroxyurea‐induced transverse melanonychia
Authors: Teo Rachael Yu Lin , Tan Eileen
Published: January 2006

A 33‐year‐old Malay female presented to our clinic for the evaluation of nail pigmentation. She had been diagnosed with essential thrombocytosis 2 years previously, but had failed to return for follow‐up. She presented again to the hematology department with symptoms of giddiness, blurring of vision, and left‐sided weakness and was started on hydroxyurea 3 g/day.

Hydroxyurea was stopped after 1 month of administration because of pancytopenia. Concurrent medications taken included anagrelide, buscopan, allopurinol, omeprazole, and sangobion. None of these medications are known to cause nail pigmentation.

She first presented to our department when she noticed nail pigmentation 7 weeks after starting hydroxyurea, but was otherwise well. There were no other cutaneous features of hyperpigmentation. Clinical examination revealed transverse bands which were seen on all 20 nails. These involved the proximal half of the fingernails and the proximal third of the toenails and were colored brown (seeFig. 1).

Transverse bands on all 10 fingernails 9 weeks after the commencement of hydroxyurea therapy

image
Compound heterozygosity in sibling patients with recessive dystrophic epidermolysis bullosa associated with a mild phenotype
Authors: Shibusawa Y. , Negishi I. , Ishikawa O.
Published: January 2006

We describe two cases of a 3‐year‐old Japanese boy and his 1‐year‐old sister presenting recessive dystrophic epidermolysis bullosa; a relatively mild phenotype. Blistering and scarring were limited to the acral region, and some fingernails and toenails were lost. PCR‐RFLP and DNA sequencing analyses revealed compound heterozygotes for a splice‐site mutation (6573 +1GtoC) and a nonsense mutation (E2857X) in the type VII collagen gene (COL7A1). Both mutations caused a premature termination codon (PTC). The mutation E2857X was located behind the candidate cleavage site within the NC‐2 domain required for the assembly of anchoring fibrils. This PTC position may explain their mild phenotype.
Beneficial effect of laserpitin, a coumarin compound from Angelica keiskei, on lipid metabolism in stroke‐prone spontaneously hypertensive rats
Authors: Ogawa Hiroshi , Nakamura Rei , Baba Kimiye
Published: January 2006

1. Recently, we found that 4‐hydroxyderricin, one of the major chalcones in Angelica keiskei extract (an ethyl acetate extract from the yellow liquid of stems), suppressed increases in systolic blood pressure and reduced both serum very low‐density lipoprotein levels and liver triglyceride content in stroke‐prone spontaneously hypertensive rats (SHRSP). In the present study, we have isolated laserpitin, a characteristic coumarin, from the A. keiskei extract and examined the effect of dietary laserpitin on blood pressure and lipid metabolism in SHRSP.

2. Six‐week‐old male SHRSP were fed diets containing 0.1% laserpitin for 7 weeks with free access to the diet and water. Bodyweight gain was reduced by dietary laserpitin after 4 weeks through to 7 weeks without any significant change in daily food intake. Serum total cholesterol, phospholipid and apolipoprotein (apo) E levels were significantly increased, which was due to significant increases in cholesterol, phospholipid and apoE contents in the low‐ and high‐density lipoprotein (LDL and HDL, respectively) fractions. These results suggest that dietary laserpitin increases serum apoE‐HDL levels.

3. In the liver, significant decreases in relative liver weight and triglyceride content were found after treatment with laserpitin for 7 weeks.

4. An investigation of hepatic mRNA expression of proteins involved in lipid metabolism indicated that a significant decrease in hepatic triglyceride lipase may be responsible for the increase in serum HDL levels and also indicated that a marked decrease in adipocyte determination and differentiation factor 1 may be responsible, at least in part, for the decrease in hepatic triglyceride content.

5. In conclusion, dietary laserpitin produces increases in serum HDL levels, especially apoE‐HDL, and decreases in the hepatic triglyceride content in SHRSP.
Bradykinin B2 receptor antagonism attenuates inflammation, mast cell infiltration and fibrosis in remote myocardium after infarction in rats
Authors: Koike Marcia Kiyomi , De Carvalho Frimm Clovis , De Lourdes Higuchi Maria
Published: January 2006

1. Bradykinin may interfere with myocardial remodelling by promoting inflammation and mast cell activation or, alternatively, by counteracting angiotensin II‐dependent collagen accumulation. The aim of the present study was to investigate the role of bradykinin B2 receptor antagonism in inflammatory and mast cell infiltration, fibroplasia and fibrosis accumulation following myocardial infarction (MI).

2. Myocardial infarction was produced by the ligature of the left coronary artery in male Wistar rats that were 10 weeks of age. Immediately after MI, rats received the B2 receptor antagonist Hoe140 (0.5 µg/kg per min, s.c.) or saline over a period of 3 days, 1 week or 4 weeks, constituting three separate groups and their respective controls.

3. Coronal myocardial tissue sections underwent haematoxylin and eosin, Giemsa and picrosirius red staining, as well as immunohistochemistry for α‐smooth muscle actin (SMA). Morphometric studies were undertaken in three different myocardial regions: MI, remote non‐infarcted subendocardium (non‐MI SE) and remote non‐infarcted interventricular septum (non‐MI IVS).

4. The MI size was comparable between Hoe140‐treated groups and their respective controls (day 3: 42 ± 4%, n = 8, vs 43 ± 3%, n = 6; week 1: 37 ± 5%, n = 5, vs 39 ± 2%, n = 5; week 4: 35 ± 3%, n = 9, vs 36 ± 3%, n = 7). At day 3, Hoe140 treatment reduced inflammatory cell reaction within the MI (585 ± 59 vs 995 ± 170 cells/mm2; P = 0.02), non‐MI SE (77 ± 12 vs 214 ± 57 cells/mm2; P = 0.02) and non‐MI IVS (93 ± 16 vs 135 ± 14 cells/mm2; P = 0.03) regions. Mast cells were reduced within the non‐MI IVS region (0.8 ± 0.1 vs 2.5 ± 0.4 cells/mm2; P = 0.006), but not within the MI region. In non‐MI SE, mast cells were rarely found. At week 1, Hoe140 treatment reduced α‐SMA‐positive myofibroblast infiltration within the MI (2535 ± 383 vs 5636 ± 968 cells/mm2; P = 0.01) and non‐MI SE (222 ± 33 vs 597 ± 162 cells/mm2; P = 0.03) regions. In the non‐MI IVS region, α‐SMA‐positive myofibroblasts were rarely found. At week 4, Hoe140 treatment reduced collagen volume fraction within the MI (37 ± 4 vs 53 ± 4%; P = 0.03), non‐MI SE (1.3 ± 0.2 vs 2.6 ± 0.3%; P = 0.001) and non‐MI IVS (1.1 ± 0.2 vs 1.8 ± 0.2%; P = 0.01) regions.

5. Bradykinin promotes inflammation, fibroplasia and fibrosis after MI. Mast cells may have a role in fibrosis deposition through a bradykinin‐related mechanism.
Vasodilator actions of the endothelium‐derived relaxing factorl‐S‐nitrosocysteine in anaesthetized rats are markedly diminished by peroxynitrite
Authors: Graves Jonathan E , Bates James N , Kooy Neil W , Lewis Stephen J
Published: January 2006

1. The aim of the present study was to assess the effects of the potent oxidant and nitrating agent peroxynitrite on the haemodynamic actions of the endothelium‐derivedS‐nitrosothioll‐S‐nitrosocysteine.

2. The haemodynamic actions ofl‐S‐nitrosocysteine (12.5–100 nmol/kg, i.v.) were determined in pentobarbital‐anaesthetized rats before and after the induction of tachyphylaxis to peroxynitrite achieved by giving 10 intravenous injections of a 10 µmol/kg dose.

3. l‐S‐Nitrosocysteine elicited dose‐dependent reductions in mean arterial blood pressure and in hindquarter and mesenteric vascular resistance.

4. Thel‐S‐nitrosocysteine‐induced responses were substantially attenuated after administration of peroxynitrite.

5. We have reported previously that nitric oxide‐mediated vasodilation is not diminished after the induction of tachyphylaxis to peroxynitrite. Taken together, these findings support the concept that peroxynitrite reduces the vasodilator actions ofl‐S‐nitrosocysteine via oxidation and/or nitration of putative membrane‐boundS‐nitrosothiol recognition sites.
GENE–ENVIRONMENT INTERACTIONS, NEURONAL DYSFUNCTION AND PATHOLOGICAL PLASTICITY IN HUNTINGTON'S DISEASE
Authors: Van Dellen Anton , Grote Helen E , Hannan Anthony J
Published: January 2006

1. Huntington's disease (HD) is a fatal autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. The dynamic mutation that causes the disease is common to numerous other brain disorders, which may share similar pathogenic mechanisms.

2. Much progress has been made in the past decade in understanding how a trinucleotide (CAG) repeat expansion, encoding an expanded polyglutamine tract in the huntingtin protein, induces dysfunction at molecular and cellular levels. The present review integrates various lines of experimental evidence in an attempt to move towards a unifying mechanistic framework, which may explain the pathogenesis of HD, from molecular through to neuronal network and behavioural levels.

3. Recent evidence, using transgenic mouse models, also suggests that environmental factors can modify the onset and progression of HD. The effects of specific environmental manipulations are discussed in the context of gene–environment interactions and experience‐dependent plasticity in the healthy and diseased brain, particularly the cerebral cortex.
Somerset's family interventions in psychosis service: an update
Authors: Burbach Frank , Stanbridge Roger
Published: January 2006

This paper describes a project in which family interventions in psychosis services were successfully established in a routine clinical setting. This has involved the development of a whole‐team training approach, an accredited one‐year training course, and a clinical approach which integrates the systemic and cognitive‐behavioural psychoeducational approaches. Since the original description of this project (Burbach and Stanbridge, 1998) the training course and service have been evaluated and the clinical approach has been further developed. These developments, particularly the ‘cognitive interactional’ approach and collaborative therapeutic stance, are detailed. The paper explores the factors which have contributed to the successful establishment and maintenance of the service, and describes more recent initiatives to bring about more family/carer‐friendly mental health services.
Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update
Authors: Haaz S. , Fontaine K. R. , Cutter G. , Limdi N. , Perumean‐Chaney S. , Allison D. B.
Published: January 2006

Obesity is a major health problem facing the developed and developing world. Efforts by individuals, health professionals, educators, and policy makers to combat the escalating trend of growing obesity prevalence have been multifaceted and mixed in outcome. Various dietary supplements have been marketed to reduce obesity. These products have been suggested to accomplish this by decreasing energy intake and energy absorption, and/or increasing metabolic rate. Ephedra, one such supplement, was banned from sale in the US market because of concerns about adverse events. Another substance, Citrus aurantium, which contains several compounds including synephrine alkaloids, has been suggested as a safe alternative. This review examines the evidence for safety and efficacy of C. aurantium and synephrine alkaloids as examined in animal studies, clinical weight loss trials, acute physiologic studies and case reports. Although at least three reviews of C. aurantium have been published, our review expands upon these by: (i) distinguishing and evaluating the efficacy of C. aurantium and related compounds; (ii) including results from previously unreviewed research; (iii) incorporating recent case reports that serve to highlight, in an anecdotal way, potential adverse events related to the use of C. aurantium and related compounds; and (iv) offering recommendations to guide the design of future trials to evaluate the safety and efficacy of C. aurantium. While some evidence is promising, we conclude that larger and more rigorous clinical trials are necessary to draw adequate conclusions regarding the safety and efficacy of C. aurantium and synephrine alkaloids for promoting weight loss.
Metabolically active functional food ingredients for weight control
Authors: Kovacs E. M. R. , Mela D. J.
Published: January 2006

The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post‐absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium‐chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control.
Energy balance adiposity and breast cancer – energy restriction strategies for breast cancer prevention
Authors: Harvie M. , Howell A.
Published: January 2006

Excess adiposity over the pre‐ and postmenopausal years is linked to risk of postmenopausal breast cancer. Weight loss could potentially reduce risk amongst those with excess weight via beneficial effects on the hormonal (decreased circulating levels of oestradiol, testosterone, insulin) and secretory profiles of adipocytes (decreased production of leptin, tumour necrosis factor‐α, interleukin 6 and increased production of adiponectin). Only modest reductions in adipose tissue are achieved and sustained with current weight loss programmes, which makes strategies to mitigate the adverse metabolic effect of adiposity a priority for cancer prevention. The adverse hormonal and secretory effects of adipose tissue are influenced substantially by acute changes in energy balance prior to changes in adiposity. Human and animal studies have shown dietary energy restriction to bring about favourable changes in circulating levels of insulin, leptin, sex hormone binding globulin, insulin‐like growth factor‐1, oestradiol, testosterone, reactive oxygen species, and the production and secretion of locally acting adipokines and inflammatory cytokines, that is, increased adiponectin and decreased interleukin‐6. Achieving and sustaining energy restriction remains a difficult challenge. Intermittent energy restriction is a potential strategy for promoting periods of energy restriction on a long‐term basis. Animal and human data suggest that intermittent energy restriction may have cancer preventative effects beyond that of chronic energy restriction and weight loss. Intermittent energy restriction may be a potential strategy for the primary prevention of breast cancer.
Obesity drugs and their targets: correlation of mouse knockout phenotypes with drug effects in vivo
Authors: Powell D. R.
Published: January 2006

Sequencing of the human genome has yielded thousands of potential drug targets. The difficulty now is in determining which targets have real therapeutic value and should be the focus of a drug discovery effort. The available evidence suggests that knockout technology can be used prospectively to identify targets that are amenable to drug development for the treatment of a variety of diseases. This review compares the knockout phenotypes of 21 potential obesity targets with the effects of therapeutics designed for those targets on rodents and, when data were available, on humans. The phenotypes of obesity target knockouts model the effects seen when therapeutics designed for those obesity targets are delivered to rodents; of the 21 obesity targets reviewed, 16 showed a correspondence between knockout phenotype and drug effect in mice and/or rats. This suggests that, at least in terms of evaluating obesity targets, it is rare for compensatory developmental changes caused by the gene knockout to prevent detection of the relevant phenotype. In the majority of cases, the knockout phenotypes also modelled the effects seen when the relevant therapeutics were delivered to humans. Thus, it seems rational to use mouse knockout technology prospectively to identify genes that regulate body fat in vivo, and then to develop anti‐obesity therapeutics by targeting the human protein products of these genes. Ultimately, the value of using this approach to identify novel targets for human anti‐obesity therapies will be judged by future studies examining the anti‐obesity effect, in humans, of the therapeutics that result from this approach.
Asynchronous access to conventional course delivery: a pilot project
Authors: Simpson Natalie
Published: January 2006

This study describes a technological pilot project providing 160 graduate students with asynchronous access to the ongoing proceedings of a lecture‐based course. Exactly half of the students spoke the language of instruction, English, as a second language (ESL). While the asynchronous video‐on‐demand service proved popular overall, ESL students were markedly heavier users of the system and reported most enthusiastically on its benefits. Asynchronous access was valued as much for empowering the learner with control of the lecture as it was for the issue of convenience. Furthermore, the medium of video capture was found to create an impression of intimacy simultaneously cleansed of environmental distractions, an experience not necessarily consistent with live attendance. These findings became the foundation of a course distribution system now providing lectures to over 1,500 undergraduates each semester, yet many of the observed benefits remain to be confirmed by future research.
Do Divorcing Couples Become Happier by Breaking up?
Authors: Gardner Jonathan , Oswald Andrew J.
Published: January 2006

Divorce is a leap in the dark. The paper investigates whether people who split up actually become happier. Using the British Household Panel Survey, we can observe an individual's level of psychological well-being in the years before and after divorce. Our results show that divorcing couples reap psychological gains from the dissolution of their marriages. Men and women benefit equally. The paper also studies the effects of bereavement, of having dependant children and of remarriage. We measure well-being by using general health questionnaire and life satisfaction scores.
Public Debt, the Unit Root Hypothesis and Structural Breaks: A Multi‐Country Analysis
Authors: UCTUM MERIH , THURSTON THOM , UCTUM REMZI
Published: January 2006

We assess fiscal performances in G7 and selected Latin American and Asian countries. We consider two questions: (i) Have public finances been sustainable? (ii) Do countries follow more restrictive fiscal policies when debt starts to rise? We find that: (i) the traditional unit root tests often overlook the corrective actions taken by many governments; controlling for structural breaks changes the non‐stationarity results dramatically among the three groups; (ii) estimation of a reaction function for governments, expanded by incorporating structural breaks, provides further evidence for significant active anti‐debt policies among G7 countries, and to a lesser extent in the other regions.
Multiple cutaneous osteomas of the face associated with chronic inflammatory acne
Authors: Thielen AM , Stucki L , Braun RP , Masouyé I , Germanier L , Harms M , Salomon D , Borradori L
Published: January 2006

Multiple miliary osteoma cutis of the face represents a rare and frequently unrecognized complication of chronic inflammatory acne. Their differentiation from microcomedones and macrocomedones may be challenging. The case of a 46‐year‐old Asian woman who suffered from chronic inflammatory acne is described. She had multiple papular lesions of the cheeks that did not respond to various topical and systemic therapies including oral isotretinoin. Light microscopy studies as well as ultrasound and computed tomography (CT) scan investigations demonstrated the presence of multiple osteoma cutis. Needle microincisions followed by mechanical extirpation of the bony formation resulted in a considerable cosmetic improvement of her skin disease. Knowledge of this rare complication of acne is mandatory, as its treatment is different from that of retentional and inflammatory acne and frequently relies on surgical modalities. Our novel technique consisting of needle microincisions with curettage of the lesions is simple and safe, leading to good cosmetic results.
Widespread skin necrosis associated with unfractionated heparin therapy in a patient under chronic coumarin anticoagulation
Authors: Sanchez‐Politta S , Angelillo‐Scherrer A , Masouyé I , Borradori L
Published: January 2006

Coumarins and heparins are commonly used for temporary or long‐term anticoagulation. These molecules have potentially devastating side‐effects, including widespread skin necrosis. We report the case of an elderly patient under oral anticoagulation with coumarins, who developed widespread necrotic cutaneous lesions upon introduction of intravenous and subcutaneous unfractionated heparin administration for a surgical procedure. Laboratory investigations revealed the presence of circulating antibodies directed against heparin‐platelet factor 4. The lesions slowly resolved after withdrawal of heparin, whereas oral coumarin was re‐introduced without complications. This case illustrates the rare occurrence of skin necrosis as a result of unfractionated heparin in a patient under chronic coumarin medication. Recognition of this rare complication and appropriate laboratory testing is mandatory for prompt institution of alternative anticoagulant therapies.