bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation of Left Brain-Damaged Ischemic Stroke Patients: The Role of Comprehension Language Deficits
Authors: Paolucci Stefano , Matano Alessandro , Bragoni Maura , Coiro Paola , De Angelis Domenico , Fusco Francesca Romana , Morelli Daniela , Pratesi Luca , Venturiero Vincenzo , Bureca Ivana
Published: October 2005

Background: Aphasia is considered a risk factor for disability after stroke. The aim of this study was to assess the specific influence of aphasia on rehabilitation results. Method: A case-control study in consecutive left brain-damaged stroke inpatients, enrolled in three homogeneous subgroups [nonaphasic (NA) patients, aphasic with comprehension deficit (CD), and without comprehension deficit (NCD)] matched for age and onset-admission interval. Rehabilitation results (gain, efficiency, effectiveness of treatment, percentage and odds ratio of dropouts and of each degree of therapeutic response, assessed by Barthel Index and Rivermead Mobility Index) were compared among the subgroups. Results: Two hundred and forty patients with sequelae of a first stroke were enrolled. CD patients, as compared with NCD and NA ones, had a significantly more severe basal neurological and functional status at admission, minor effectiveness on ADL and mobility, a higher percentage of low responders on ADL and urinary incontinence at discharge, and a risk of low therapeutic response on ADL nearly 4 times higher than the other patients (OR = 4.22, 95% CI = 1.90–9.38). The rehabilitative behavior between NCD and NA was similar. However, all subgroups (NA, CD and NCD) showed a significant improvement (p < 0.001) between their basal and discharge score, both on BI and RMI. Conclusions: Comprehension language deficit was confirmed to be a strong negative rehabilitation prognostic factor despite the speech therapy done by all CD patients.
Epidemiological Study of Muscular Disorders in Assiut, Egypt
Authors: El-Tallawy Hamdy N. , Khedr Eman M. , Qayed Mohammad H. , Helliwell Timothy R. , Kamel Nageh F.
Published: October 2005

Few comprehensive epidemiological studies of the prevalence of muscle diseases have been undertaken, and none has been carried out in our locality. The present cross-sectional study was conducted in Assiut Governorate (Upper Egypt) to estimate the prevalence of different types of primary muscular disorder in 1997. The study involved 52,203 subjects, 15,617 (30%) from the rural community and 36,586 (70%) from the urban community. Patients were identified from a door-to-door survey, and all were subjected to a full clinical examination, with confirmation of the diagnosis through electrophysiological, and biochemical investigations. Histopathological studies were performed for the classification of muscular dystrophies. Forty patients with muscular disorders were identified, with a point prevalence of 76.6 per 100,000 in the total community with no significant differences between the rural and urban communities. The creatine kinase level was abnormally high (>225 IU/l) in 80% of the cases, increased in all patients with muscular dystrophy or myositis, in 88.8% of patients with systemic myopathy and 66.6% of patients with myotonia. None of the cases of myasthenia showed an increase in the creatine kinase level. The lifetime prevalence per 100,000 was 26.8 for muscular dystrophy, 11.49 for myotonia, 11.49 for myositis, 17.24 for systemic myopathy and 9.57 for myasthenia.
The Effectiveness of Oral Tin Mesoporphyrin Prophylaxis in Reducing Bilirubin Production after an Oral Heme Load in a Transgenic Mouse Model
Authors: DeSandre Glenn H. , Wong Ronald J. , Morioka Ichiro , Contag Christopher H. , Stevenson David K.
Published: October 2005

Background: Neonatal jaundice is commonly encountered and rarely associated with morbidity and mortality. Nonetheless, infants with glucose-6-phosphate dehydrogenase deficiency often have hemolysis (a heme load) caused by an environmental oxidant trigger, thus increasing their risk for serious morbidity. The use of tin mesoporphyrin (SnMP) has been proposed for interdicting the development of severe hyperbilirubinemia in a variety of conditions. Objectives: We studied the in vivo effects of prophylactic oral SnMP on heme oxygenase (HO) activity and bilirubin production, as indexed by the excretion rate of carbon monoxide (VeCO), following a subsequent oral heme load. Methods: Adult mice were exposed serially to heme and assessed for in vivo bilirubin production rates, HO-1 transcription and protein, and HO activity. The effect of prophylaxis with a single oral dose of SnMP prior to an oral heme load was assessed by measuring VeCOand tissue HO activities. Results: After serial heme exposures, VeCO, HO-1 transcription and protein, and liver and spleen HO activities increased incrementally. After pretreatment with oral SnMP, bilirubin production decreased in response to an oral heme load. Also, heme-mediated increases in liver, spleen, and intestine HO activities were significantly dampened. Conclusions: A single oral dose of SnMP results in durable inhibition of bilirubin production and HO activity for at least 24 h in a mouse model of oral heme loading. Further studies are needed to fully elucidate the duration of this protection against hyperbilirubinemia due to a delayed heme load and any long-term consequences of prophylaxis with SnMP on HO-1 transcription and HO-1 protein.
IgE Binding to Pepsin-Digested Food Extracts
Authors: Akkerdaas Jaap H. , Wensing Marjolein , Asero Riccardo , Rivas Montserrat Fernandez , Knulst André C. , Bolhaar Suzanne , Hefle Susan L. , Aalberse Rob C. , van Ree Ronald
Published: October 2005

Background: Pepsin resistance of allergens like lipid transfer protein and 2S albumin has been suggested as explanation for the severity of symptoms often induced by these allergens. Component-resolved diagnosis with purified labile and stable allergens has therefore been proposed to better characterize the risk involved in a positive in vitroIgE test. However, for many foods, purified allergens are not (yet) available. Objective: It was the aim of this study to evaluate the potential of pepsin-digested whole-food extracts to distinguish between IgE responses to stable (potentially severe) and labile (mild) allergens. Methods: Sera (n = 143) from Italian, Spanish and Dutch patients with hazelnut and/or apple ingestion-related symptoms were analyzed for residual IgE binding to pepsin-resistant hazelnut and/or apple allergens. Control and pepsin-digested hazelnut and apple extracts were used for radioallergosorbent test analysis and immunoblot analysis. Results: Pepsin digestion of food extracts, like from hazelnut and apple used for in vitro diagnostic tests, provides a way to distinguish sensitization to pepsin-resistant allergens from that to pepsin-susceptible allergens. In this selected group of patients, IgE reactivity to pepsin-digested extracts correlated with sensitization to the stable allergen lipid transfer protein. The analysis further revealed that the use of soluble pepsin can result in false-positive in vitro tests (2/143). Conclusion: Pepsin-digested food extracts are a convenient tool to identify patients with IgE antibodies against potentially dangerous stable allergens, in particular for those foods where the relevant stable allergens have not yet been identified. This can increase the clinical prognostic value of food allergy serology.
The Effect of Desloratadine on Eosinophil/Basophil Progenitors and Other Inflammatory Markers in Seasonal Allergic Rhinitis: A Placebo-Controlled Randomized Study
Authors: Cyr Michael M. , Hayes Lisa M. , Crawford Lynn , Baatjes Adrian J. , Keith Paul K. , Denburg Judah A.
Published: October 2005

Background: Eosinophil/basophil (Eo/B) progenitors fluctuate in the peripheral circulation during seasonal allergen exposure in atopic subjects. Several drugs have been shown to modulate Eo/B progenitor levels in the peripheral blood but, to date, the possible effect of antihistamines on Eo/B progenitors has not been explored. Our objective was to evaluate whether the antihistamine desloratadine (DL) can modulate peripheral blood Eo/B progenitors or other markers of allergic inflammation. Methods: We performed a randomized double-blind placebo-controlled study on the effects of DL on peripheral blood Eo/B progenitors in subjects with symptomatic, seasonal allergic rhinitis during a ragweed pollen season. Forty-five subjects were randomized to treatment for 4 weeks with DL 20 mg daily or placebo. Results: The expected fall in the number of Eo/B progenitors from baseline to 2 weeks of treatment was seen in the placebo group [median drop of 1.0 colony-forming unit (CFU)/106 cells], and was greater than in the DL group (median drop of 0.0 CFU/106 cells) (p = 0.013). The change in histamine concentration per colony from baseline to 2 weeks of treatment was lower in the DL group (median decrease of 6.1 pg/colony) compared to placebo (median increase of 1.8 pg/colony) (p = 0.01). An increase in the nasal lavage eotaxin concentration from baseline to 4 weeks of treatment was statistically significant in the placebo group but not in the DL group. Eo/B CFU were not affected by varyingin vitro concentrations of DL. Conclusion: These results suggest that DL can modulate aspects of allergic inflammation in vivo through mechanisms other than simple blockade of H1 histamine receptors.
Allergic Sensitisation in Tuberculosis and Leprosy Patients
Authors: Ellertsen L.K. , Wiker H.G. , Egeberg N.T. , Hetland G.
Published: October 2005

Background: A negative association has been observed between infections and allergy in several studies. The aim of the present study was to examine whether tuberculosis and leprosy patients have more or fewer allergies than healthy individuals. Method:Sera from tuberculosis patients, leprosy patients and healthy controls were analysed by ELISA and Pharmacia Unicap® for serological markers for allergy and mycobacterial infection. The serological markers for allergy were total IgE, specific IgE using Phadiatop and specific IgE to the dust mite allergen Dermatophagoides pteronyssinus 1 (Der p 1). Serological markers for mycobacterial infections included specific IgG to a mixture of bacille Calmette-Guérin culture filtrate antigens, to purified mannose-capped lipoarabinomannan (manLAM) and to purified secreted antigen 85B. Results:Both tuberculosis and leprosy patients had significantly higher levels of total IgE than controls. Furthermore, a significantly higher level of specific IgE (Phadiatop) was also found in the tuberculosis patients compared with controls. A similar result, but not statistically significant, was observed for the leprosy group. Specific IgG to antigen 85B and to manLAM was found to be significantly higher in both tuberculosis and leprosy patients compared with controls. In addition, leprosy patients had significantly more IgG to the BCG culture filtrate antigen than controls. Conclusions:The results indicate that patients with mycobacterial infections have allergic sensitisation more frequently compared with healthy controls. This is seemingly in contrast with the notion that there is a negative association between allergy and infection (‘hygiene hypothesis’). However, since only one in ten of those infected with Mycobacterium tuberculosis will develop the disease, patients with active mycobacterial disease represent a selected group. A similar relationship applies for leprosy. It is conceivable that those predisposed to allergy are less resistant to mycobacterial infections.
Are the Asthma Guideline Goals Achieved in Daily Practice? A Population-Based Study on Treatment Adequacy and the Control of Asthma
Authors: de Marco Roberto , Cazzoletti Lucia , Cerveri Isa , Corsico Angelo , Bugiani Massimiliano , Accordini Simone , Carrozzi Laura , Dallari Rossano , De Togni Aldo , Marinoni Alessandra , Pirina Pietro , Janson Christer
Published: October 2005

Background: The guidelines for asthma recommend that the use of anti-inflammatory therapy should be adapted to the severity of the disease. However, few data are available to assess the adequacy of the use of drugs and its influence on the control of asthma in ‘real life’. Methods: The adequacy of the current use of anti-asthmatic medication according to the Global Initiative for Asthma (GINA) guidelines was assessed in a random sample of 400 asthmatics identified in the frame of the Italian Study on Asthma in Young Adults. Asthma severity was assessed using the GINA criteria; accordingly, a patient was classified as receiving inadequate treatment if his/her current use of drugs was lower than that suggested by the guidelines for the corresponding severity level. The absence of asthma attacks in the last 3 months was used as an indicator of the disease control. Results: Fifty-five percent of the patients had persistent asthma. Overall, 48% (95% CI 41.2–54.8) of persistent asthmatics were receiving inadequate treatment, and 66% (95% CI 59.5–72.4) had not used their medication daily over the past 3 months. Persistent asthmatics who were inadequately treated had a significantly greater frequency of asthma attacks (geometric mean ratio 3.7; 95% CI 2.1–6.6) than those using an adequate dose of medication. Mild and moderate persistent asthmatics using an adequate medication regimen reported a low number of asthma attacks (median 0). At the multivariate analysis, a good control of the disease was positively associated with an adequate dose of anti-inflammatory medication (OR = 2.2; 95% CI 1.1–4.5) and was negatively associated with a later onset of asthma (OR = 0.96; 95% CI 0.93–0.99) and severe asthma (OR = 0.37; 95% CI 0.17–0.81). Conclusions: Despite the increase in the use of inhaled corticosteroids, half of the persistent asthmatics from the general population are using a medication regimen below their severity level. When the use of drugs follows the GINA guideline recommendations, a good control of asthma is also achievable in the daily management of the disease, particularly in the case of mild and moderate asthmatics.
Occupational Asthma to Carmine in a Butcher
Authors: Ferrer Ðngel , Marco Francisco M. , Andreu Carmen , Sempere José M.
Published: October 2005

Hypersensitivity to carmine (E120) has been identified as a cause of food intolerance and occupational asthma. We present a case of occupational asthma following exposure to carmine in a manufacturer of sausages and review the literature. Case Report: A 42-year-old non-atopic male presented with a 5-year history of rhinoconjunctivitis and asthma on occupational exposure to food additive dusts. Symptoms increased after work. The patient had been exposed for more than 20 years. Methods: Skin prick tests were performed with a battery of common inhalant allergens and spices. Cochineal, carmine lake and additive mixes used by the patient were extracted and subsequently used for skin prick test, bronchial provocation and in vitro measurements (specific IgE, Western blot and chromatographic fractionation). Results: Prick tests were positive to carmine and carmine-containing additives; carmine-specific IgE and bronchial challenge tests were also positive (PC20 = 0.0004 mg/ml and 1.6 kU/l). Western blot showed IgE binding to bands of about 30 kDa on cochineal extract and a diffuse pattern at 40–97 kDa on carmine. This result was confirmed by gel filtration chromatography and dot blot. Carmine completely inhibited IgE binding to cochineal extract. Discussion: Carmine is a potential sensitizer in an occupational setting: 18 cases of occupational asthma have been described to date. Carmine allergens are poorly defined; in general, proteins from cochineal not removed by the extraction process are considered as the main allergens in carmine. Our results are consistent with this, but show that these proteins may be subject to chemical modification.
Epistatic Effect of TLR4 and IL4 Genes on the Risk of Asthma in Females
Authors: Ådjers Kati , Karjalainen Jussi , Pessi Tanja , Eklund Carita , Hurme Mikko
Published: October 2005

Background: Many studies have demonstrated a connection between asthma and T-cell cytokine genes, such as genes coding for interleukin-4 (IL4) and IL-13, which are involved in the regulation of the TH1/TH2 balance. The toll-like receptor 4 (TLR4), the principal receptor for bacterial endotoxin, has attracted attention as a potential risk factor for asthma. We examined whether the polymorphisms of the TLR4 (A/G at +896) and IL4 (C/T at –590) showed an epistatic effect on the risk of asthma or atopy. Methods: Gene polymorphism analyses and skin prick tests were performed on asthmatic and nonasthmatic adult subjects of a Finnish population-based case-control study. The phenotype studied was persistent asthma. Results: The results showed that genotypes of neither the TLR4 SNP at +896 nor IL4 SNP at –590 were separately found to be associated with asthma. However, the female carriers of allele G (i.e. genotype AG or GG) of TLR4 and allele T (genotype CT or TT) of IL4 had a significantly increased risk for asthma. No association of these genes and atopy was found. Conclusions: Our results indicate that in females the TLR4 and IL4 genes show an epistatic effect on the risk of asthma. The low LPS-responsive allele G of TLR4 and high IgE production allele T of IL4 were found to be the predisposing combination. However, there was no epistatic effect on the risk of atopy.
Different Profiles of Wheat Antigens Are Recognised by Patients Suffering from Coeliac Disease and IgE-Mediated Food Allergy
Authors: Constantin Claudia , Huber Wolf Dietrich , Granditsch Gerhard , Weghofer Margit , Valenta Rudolf
Published: October 2005

Background: Dietary intake of wheat can cause two distinct immunologically mediated diseases with severe gastrointestinal manifestations, coeliac disease (CD) and IgE-mediated food allergy. The pathomechanisms underlying these diseases are different, but the profile of the target antigens in wheat has not been compared for the two diseases. Methods: We compared IgA- and IgE-reactive antigens in wheat using sera from patients with coeliac disease (n = 35) and food allergy to wheat (n = 16) by one- and two-dimensional immunoblotting. Furthermore, the IgG subclass (IgG1–IgG4) reactivity to wheat antigens was studied by enzyme-linked immunosorbent assay. Results: IgA antibodies from CD patients and IgE antibodies from allergic patients recognised distinct profiles of wheat antigens. Furthermore, the IgG subclass responses to wheat antigens were different in CD and wheat-allergic patients. Conclusion: This study thus demonstrates that wheat contains antigens/epitopes which are preferentially recognised by CD patients, whereas others elicit IgE-mediated food allergy. This finding suggests that the nature of a food antigen may influence the quality of the pathological immune response in the gut and has implications for the diagnosis and therapy of hypersensitivity to wheat.
Naturally Occurring Parainfluenza Virus 3 Infection in Adults Induces Mild Exacerbation of Asthma Associated with Increased Sputum Concentrations of Cysteinyl Leukotrienes
Authors: Matsuse Hiroto , Kondo Yuki , Saeki Sachiko , Nakata Hiroko , Fukushima Chizu , Mizuta Yohei , Kohno Shigeru
Published: October 2005

Background:Viral respiratory tract infections represent the most frequent cause of asthma exacerbation in both children and adults, but the precise mechanism of such exacerbation remains unknown. Objectives: To determine the critical mediator of naturally occurring parainfluenza virus (PIV) 3-induced mild asthma exacerbations in adults. Methods: The study subjects were 19 adult asthmatics with mild asthma exacerbation (peak expiratory flow = 60–80% of predicted before bronchodilator use and >80% of predicted after initial bronchodilator treatment). Differential cell counts and concentrations of inflammatory markers including eosinophil cationic protein (ECP), cysteinyl leukotrienes (cysLTs), interleukin (IL)-5, IL-10 and IL-12 were measured in the induced sputum obtained from adults with PIV3- (n = 9) and non-cold-induced (n = 10) exacerbation of asthma during both acute and convalescent phases. Results: PIV3 infection was confirmed by the presence of viral RNA in nasopharyngeal aspirates. Mild exacerbation of asthma was not associated with significant changes in sputum differential cell counts. Concentrations of sputum ECP and cytokines were comparable between PIV3 and non-cold-induced patients. In contrast, PIV3 infection was associated with a significant increase in sputum cysLTs during the acute phase of mild asthma exacerbation. Conclusions: Our results identified cysLTs as a critical mediator of PIV3-induced acute asthma exacerbation.
Influence of Epithelium and Isoprenaline Incubation on Responsiveness of Guinea-Pig Trachea to Methacholine
Authors: Boskabady M.H. , Aslani M.R. , Tabatabaei A.
Published: October 2005

There are reports regarding harmful effect of long-term use of β2-agonist drugs on asthma severity and airway responsiveness. In the present study, the responses of guinea pig trachea with intact and denuded epithelium (groups 1 and 2, n = 10) to methacholine as EC50 were measured in tissues nonincubated or incubated with 10 µmol/l isoprenaline during the resting period. The same protocol was performed in groups 3 and 4 (n = 5 for each group) with an additional 30 min rest time after isoprenaline incubation. The response of trachea with denuded epithelium (groups 2 and 4) to methacholine was significantly higher than that with intact epithelium both in incubated and nonincubated conditions (groups 1 and 3, p < 0.05 to p < 0.001). Incubation with isoprenaline caused a significant reduction in the tracheal response to methacholine in both the denuded groups (p < 0.005 and p < 0.001) and intact epithelium groups (p < 0.005 for both cases). The reduction in tracheal responsiveness to methacholine due to incubation in epithelium denuded trachea (groups 2 and 4) was nonsignificantly greater than that of intact epithelium tissues. There was no difference between groups 3 and 4 with those of groups 1 and 2 in both incubated and non incubated conditions. The maximum contractility response to methacholine was not different between tracheal chains with denuded and intact epithelium and did not change due to incubation with isoprenaline. The results of this study indicate reduction of tracheal response to methacholine due to incubation of tissues with isoprenaline, which was relatively more pronounced in epithelium denuded trachea.
The Impact of Age and Intrauterine Contraception on the Clinical Course of Pelvic Inflammatory Disease
Authors: Viberga I. , Odlind V. , Berglund L.
Published: October 2005

Background: The aim of the study was to investigate the clinical course of pelvic inflammatory disease (PID) and factors that could predict failed conservative treatment of PID. Additionally, the study aimed to examine the role of age and intrauterine device (IUD) use on the severity of PID. Method: Fifty-one women admitted to hospital with the diagnosis of acute PID were recruited. Of those, 17 patients were subsequently operated because of failed conservative treatment. All women underwent careful examination and completed a questionnaire at admission. Their clinical course was followed and the clinician responsible for the patient completed forms at admission and at discharge. Two groups were established retrospectively, those who were treated conservatively and those who underwent surgery. The outcome results were analyzed with regard to IUD use, duration of IUD use (≧5 or <5 years), and with regard to age below or above 35 years. All data were analyzed using the statistical package SAS. A p value <0.05 was considered significant. Results: Women who subsequently underwent surgical treatment were significantly older and significantly more frequently, current IUD users. There was no significant difference with regard to other socio-demographic characteristics. Women who subsequently underwent surgery had significantly more frequent complaints of severe abdominal pain, elevated body temperature, symptoms of peritoneal irritation, and appearance of adnexal mass. No differences were found between groups with regard to anaerobic microbiological findings, nor with regard to the finding of Actinomyces. IUD use and age ≧35 were found to be highly significant risk factors for surgery in patients with PID. Conclusion: Age over 35 years and IUD use, independently of each other, were factors strongly associated with an increased risk of surgery for PID as a result of failed conservative treatment.
Dietary Echinacea purpurea during Murine Pregnancy: Effect on Maternal Hemopoiesis and Fetal Growth
Authors: Chow G. , Johns T. , Miller S.C.
Published: October 2005

Background: The medicinal benefits of Echinacea sp. plants in several disease conditions, including insect bites, respiratory ailments, and even cancer and AIDS, have been touted for decades. Echinacea sp.-based phytoceuticals are among the top selling herbals in the Western marketplace today. However, evidence is very scant concerning the effects of using Echinacea species herbals during pregnancy. While available data indicates that fetal malformations do not occur during pregnancy in humans consuming this herb, there are no formal studies aimed at assessing the possibility that consuming Echinacea herbals may promote spontaneous abortions, thereby reducing the number of live births upon which to assess the presence or absence of malformations. Objectives: We undertook a study in which pregnant mice were fed daily Echinacea purpurea from pregnancy onset until gestational days 10, 11, 12, 13, and 14. Methods: Maternal spleen and bone marrow were taken for enumeration of cells in each of five separate hemopoietic lineages/organ, and fetal status was recorded. Results: The data indicate that the significant, pregnancy-induced elevation in splenic lymphocytes and nucleated erythroid cells was all but eliminated in those females which consumed E. purpurea daily throughout their pregnancy. Moreover, consuming E. purpurea during pregnancy reduced the number of viable fetuses. Conclusions: The data may be extrapolated to suggest that in humans, abstention from consuming Echinacea products during the early/mid stages of pregnancy, may be prudent.
A Novel Growth Hormone Secretagogue-1a Receptor Antagonist That Blocks Ghrelin-Induced Growth Hormone Secretion but Induces Increased Body Weight Gain
Authors: Halem Heather A. , Taylor John E. , Dong Jesse Z. , Shen Yeelana , Datta Rakesh , Abizaid Alfonso , Diano Sabrina , Horvath Tamas L. , Culler Michael D.
Published: October 2005

Ghrelin, the natural ligand for the growth hormone secretagogue-1a (GHS-1a) receptor, has received a great deal of attention due to its ability to stimulate weight gain and the hope that an antagonist of the GHS-1a receptor could be a treatment for obesity. We have discovered an analog of full-length human ghrelin, BIM-28163, which fully antagonizes GHS-1a by binding to but not activating the receptor. We further demonstrate that BIM-28163 blocks ghrelin activation of the GHS-1a receptor, and inhibits ghrelin-induced GH secretion in vivo. Unexpectedly, however, BIM-28163 acts as an agonist with regard to stimulating weight gain. These results may suggest the presence of an unknown ghrelin receptor that modulates ghrelin actions on weight gain. In keeping with our results on growth hormone (GH) secretion, BIM-28163 acts as an antagonist of ghrelin-induced Fos protein immunoreactivity (Fos-IR) in the medial arcuate nucleus, an area involved in the ghrelin modulation of GH secretion. However, in the dorsal medial hypothalamus (DMH), a region associated with regulation of food intake, both ghrelin and BIM-28163 act as agonists to upregulate Fos-IR. The observation that ghrelin and BIM-28163 have different efficacies in inducing Fos-IR in the DMH, and that concomitant administration of ghrelin and an excess of BIM-28163 results in the same level of Fos-IR as BIM-28163 administered alone may demonstrate that in the DMH both ghrelin and BIM-28163 act via the same receptor. If so, it is unlikely that this receptor is GHS-1a. Collectively, our findings suggest that the action of ghrelin to stimulate increased weight gain may be mediated by a novel receptor other than GHS-1a, and further imply that GHS-1a may not be the appropriate target for anti-obesity strategies.
Matrix GLA Protein Gene Polymorphisms: Clinical Correlates and Cardiovascular Mortality in Chronic Kidney Disease Patients
Authors: Brancaccio Diego , Biondi Maria Luisa , Gallieni Maurizio , Turri Olivia , Galassi Andrea , Cecchini Federica , Russo Domenico , Andreucci Vittorio , Cozzolino Mario
Published: October 2005

Background: Increased vascular calcification plays an important role in the pathogenesis of cardiovascular events in chronic kidney disease (CKD) patients. It is the result of an active ossification process counteracted by ‘protective’ proteins, such as matrix GLA protein (MGP). Polymorphisms of MGP have been identified. Methods: The aim of this study was to define the distribution of two MGP polymorphisms (–7, –138) in 99 hemodialysis (HD) patients, in 26 patients with CKD stage 3 and in 135 age- and sex-matched healthy controls. Patients were followed up for 12 months to record any cardiovascular deaths. The cause of death was determined by medical doctors, considering the medical history of each patient. The primers were designed with Primer Express software. Results: MGP –138TT homozygotes were more frequent in the HD group versus controls (p = 0.0004). Additionally, the frequency of the T allele was significantly higher in the HD group (p = 0.0006). The frequency of the A allele of MGP-7 was significantly higher both in the HD group (p = 0.033) and in the CKD group (p = 0.0017) versus controls. MGP-7 GG homozygotes were significantly less common in the CKD group than in controls (p = 0.037). Combination –138TT –7AA was significantly more frequent in both CKD patients (p = 0.001) and in HD patients (p = 0.029) than in controls. Seventeen out of 99 HD patients experienced fatal cardiovascular events. Sixteen (94.1%) were –138TT homozygotes and either –7AA homozygotes or –7GA heterozygotes. Conclusion: This study suggests that CKD and HD patients have a different distribution of MGP gene polymorphism as compared with the normal population. Altered MGP gene polymorphism may be a negative prognostic factor for the progression to end-stage renal disease and for cardiovascular events in CKD patients.
Catastrophe Theory Model for Decelerations of Fetal Heart Rate
Authors: Kikuchi Akihiko , Unno Nobuya , Horikoshi Tsuguhiro , Kozuma Shiro , Taketani Yuji
Published: October 2005

Background: Decelerations of fetal heart rate (FHR) are the results of many pathophysiological factors that modulate the intrinsic rate of the heart. FHR change is a complex phenomenon and can be viewed as a type of nonlinear dynamic system. This paper presents a qualitative model of FHR decelerations based on catastrophe theory, especially to account for abrupt heart rate changes seen in variable decelerations. Methods: One of the elementary catastrophes, the cusp catastrophe, was used to model FHR changes seen in variable, late, and early decelerations. Results: Catastrophe theory describes typical variable decelerations as an abrupt response to a slowly changing force of attack (uterine contraction) and physiological defense. Because of its three-dimensionality and topological features, the cusp catastrophe model provides a qualitatively satisfying description of FHR decelerations. Conclusion: The organized complexity of living systems offers the best hope for the application of catastrophe theory. The nature of the elementary catastrophes will be essential knowledge in the mathematical analysis of biology.
Clinical and Subclinical ACTH-Independent Macronodular Adrenal Hyperplasia and Aberrant Hormone Receptors
Authors: Christopoulos Stavroula , Bourdeau Isabelle , Lacroix André
Published: October 2005

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a very rare cause of endogenous Cushing’s syndrome (CS). In this review, the clinical characteristics, the pathophysiology, and the management of AIMAH are described. AIMAH typically presents with overt CS, but subclinical oversecretion of cortisol has been increasingly described. The diagnosis is suspected by adrenal nodular enlargement on conventional imaging following the demonstration of ACTH-independent hypercortisolism. Final diagnosis is established by histological examination of the adrenal tissue. Bilateral adrenalectomy is the treatment of choice but unilateral adrenalectomy has been proposed in selected cases. In patients with subclinical CS, the decision to treat should be individualized. The pathophysiology of this condition has begun to be elucidated in recent years. Diverse aberrant membrane-bound receptors expressed in a non-mutated form in the adrenal gland have been found to be implicated in the regulation of steroidogenesis in AIMAH. When systematically screened, most patients with AIMAH and CS or subclinical CS exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. A protocol designed to screen patients for the presence of these aberrant receptors should be undertaken in all patients with AIMAH. The identification of these receptors provides the potential for novel pharmacological therapies by suppressing the endogenous ligands or blocking the receptor with specific antagonists.
β1-Adrenergic Receptors Maintain Fetal Heart Rate and Survival
Authors: Chandra Rashmi , Portbury Andrea L. , Ray Alisa , Ream Margie , Groelle Marybeth , Chikaraishi Dona M.
Published: October 2005

β-Adrenergic receptor (βAR) activation has been shown to maintain heart rate during hypoxia and to rescue the fetus from the fetal lethality that occurs in the absence of norepinephrine. This study examines whether the same subtype of βAR is responsible for survival and heart rate regulation. It also investigates which βARs are located on the early fetal heart and whether they can be directly activated during hypoxia. Cultured E12.5 mouse fetuses were treated with subtype-specific βAR antagonists to pharmacologically block βARs during a hypoxic insult. Hypoxia alone reduced heart rate by 35–40% compared to prehypoxic levels. During hypoxia, heart rate was further reduced by 31% in the presence of a β1AR antagonist, CGP20712A, at 100 nM, but not with a β2 (ICI118551)- or a β3 (SR59230A)-specific antagonist at 100 nM. Survival in utero was also mediated by β1ARs. A β1 partial agonist, xamoterol, rescued 74% of catecholamine-deficient (tyrosine-hydroxylase-null) pups to birth, a survival rate equivalent to that with a nonspecific βAR agonist, isoproterenol (87%). Receptor autoradiography showed that β1ARs were only found on the mouse heart at E12.5, while β2ARs were localized to the liver and vasculature. To determine if the response to hypoxia was intrinsic to the heart, isolated fetal hearts were incubated under hypoxic conditions in the presence of a βAR agonist. Heart rate was reduced to 25–30% by hypoxia alone, but was restored to 63% of prehypoxic levels with 100 nM isoproterenol. Restoration was completely prevented if β1ARs were blocked with CGP20712A at 300 nM, a concentration that blocks β1ARs, but not β2- or β3ARs. Our results demonstrate that β1ARs are located on the heart of early fetal mice and that β1AR stimulation maintains fetal heart rate during hypoxia and mediates survival in vivo.
Effects of an Intratracheally Delivered Anti-Inflammatory Protein (rhCC10) on Physiological and Lung Structural Indices in a Juvenile Model of Acute Lung Injury
Authors: Miller Thomas L. , Shashikant Beth N. , Pilon Aprile L. , Pierce Richard A. , Shaffer Thomas H. , Wolfson Marla R.
Published: October 2005

Background: Mechanical ventilation results in acute lung trauma that can stimulate processes that alter lung development. Activation of matrix metalloproteinases (MMPs) and their tissue-produced inhibitors (TIMPs) is initiated by the inflammatory response to mechanical ventilation and are involved in breakdown of the basement membrane and parenchymal modeling. Objectives: The aim of this study was to test the hypothesis that rhCC10, a lung anti-inflammatory mediator, would foster improved lung function, structural preservation, and a reduction in net MMP activity in a juvenile model of acute lung injury. Methods: Twenty-four juvenile rabbits were saline-lavage-injured and treated with 100 or 25 mg/kg surfactant (Survanta®, Ross Labs) with or without rhCC10 (Claragen, Inc.; n = 6 per group). Animals were ventilated for 4 h, then euthanized for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, MMP-7, and MMP-9 and TIMPs 1 and 2 in the lung. Results: Apical lung expansion, reduced with the lower dose of surfactant, was partially restored with the addition of rhCC10. Alveolar septal wall thickness was reduced (p < 0.05) with low-dose surfactant plus rhCC10 compared to high-dose surfactant alone. Increased within-group variance in MMP-2 and MMP-9 proteolytic activity was found with the low-dose surfactant and was abolished with rhCC10. MMP-7 was reduced (p < 0.05) with rhCC10 administration, independent of surfactant dose. Conclusions: Intratracheal administration of the anti-inflammatory rhCC10 resulted in preserved lung structure and MMP/TIMP profile after 4 h of mechanical ventilation, in a surfactant dose-dependent manner.
Finding Associations in Dense Genetic Maps: A Genetic Algorithm Approach
Authors: Clark Taane G. , De Iorio Maria , Griffiths Robert C. , Farrall Martin
Published: October 2005

Large-scale association studies hold promise for discovering the genetic basis of common human disease. These studies will consist of a large number of individuals, as well as large number of genetic markers, such as single nucleotide polymorphisms (SNPs). The potential size of the data and the resulting model space require the development of efficient methodology to unravel associations between phenotypes and SNPs in dense genetic maps. Our approach uses a genetic algorithm (GA) to construct logic trees consisting of Boolean expressions involving strings or blocks of SNPs. These blocks or nodes of the logic trees consist of SNPs in high linkage disequilibrium (LD), that is, SNPs that are highly correlated with each other due to evolutionary processes. At each generation of our GA, a population of logic tree models is modified using selection, cross-over and mutation moves. Logic trees are selected for the next generation using a fitness function based on the marginal likelihood in a Bayesian regression frame-work. Mutation and cross-over moves use LD measures to pro pose changes to the trees, and facilitate the movement through the model space. We demonstrate our method and the flexibility of logic tree structure with variable nodal lengths on simulated data from a coalescent model, as well as data from a candidate gene study of quantitative genetic variation.
Antioxidant and Nitric Oxide-Sparing Actions of Dihydropyridines and ACE Inhibitors Differ in Human Endothelial Cells
Authors: Lob Heinrich , Rosenkranz Anke Claudia , Breitenbach Thomas , Berkels Reinhard , Drummond Grant , Roesen Renate
Published: October 2005

The effects of dihydropyridine Ca2+ channel blockers (DHP) and ACE inhibitors on superoxide formation and nitric oxide (NO) bioavailability were compared in human EA.Hy926 endothelial cells (EC). EC were stimulated 4 h with angiotensin II (Ang II, 10 nM) ± study drugs. Specific superoxide formation was measured by lucigenin-enhanced chemiluminescence, reduction of cytochrome c and rhodamine-123 fluorescence. Free NO release was determined with an amperometric NO sensor. NADPH oxidase subunits expression was examined with Western Blot. In untreated EC the intracellular superoxide is –64.3 ± 6.0% decreased compared to Ang II stimulated EC. Elevated extracellular superoxide formation was on a –43.0 ± 1.7% lower level in untreated EC. The DHP Ca2+-channel agonist BayK8644 and ACE inhibitors captopril and ramiprilat led extracellular superoxide concentration to control level. Enalaprilat blocked extracellular superoxide, the DHP amlodipine and nisoldipine prevented intracellular increases only (n = 8–9, p < 0.05). Icatibant (HOE 140), a kinin-B2 receptor antagonist, attenuated antioxidant actions of all tested agents except of nisoldipine. Ang II-induced superoxide was elevated by the phorbolester PMA and blocked by the protein kinase C (PKC) inhibitor chelerythrine. Suppression of substance P-evoked NO release by Ang II (>70%, n = 6) was reversed by the PKC inhibitor chelerythrine, the DHP amlodipine and nisoldipine and the ACE inhibitor ramiprilat. Further, Ang II reduces Nox-4 expression by 34.5 ± 4.9. Nox-2 expression was not regulated. DHP and ACE inhibitors exert different antioxidant effects in human EC stimulated with Ang II, but both improve NO bioavailability via bradykinin and modulation of redox-regulating enzymes.
Effects of Tobacco Smoking on the Kinetics of the Pupillary Light Reflex: A Comparison between Smokers and Non-Smokers
Authors: Morte A. , Benito L. , Grasa E. , Clos S. , Riba J. , Barbanoj M.J.
Published: October 2005

Background: The time course of the pupillary light reflex (PLR) is determined by the successive activation of parasympathetic and sympathetic innervations of the iris, latency and amplitude reflecting parasympathetic activity and recovery time showing mainly sympathetic activity. Objective: To determine the effects of tobacco cigarette smoking on the PLR in smokers after an abstinence period of at least 12 h. Methods: Ten smokers (mean 15.7 cigarettes/day) and 10 non-smokers participated in a randomised, non-intervention controlled, cross-over study that included a parallel control group. Smokers underwent two sessions with a time interval between 3 and 8 days; two recordings were taken at each session, separated by 20 min: session 1, without smoking, and session 2, smoking 3 cigarettes within a 30-min period. Non-smokers underwent one session; two recordings were taken separated by 20 min. At each recording, in both groups, PLR was elicited with four light flashes of increasing luminance. Results: The relationship between PLR parameters and light intensity was linear in each subject. The slope of the regression line for relative amplitude increase versus intensity was significantly flatter in abstinent smokers than in non-smokers (p = 0.033); the slope returned significantly after smoking (p = 0.043). No other significant effects were obtained. Conclusions: Kinetic parameters of PLR provide a sensitive pharmacological test to detect cholinergic neurotransmission manipulation effects, as they seem to detect changes in moderate smokers after 12 h of abstinence, and their reversal on return to smoking. These results suggest an enhancement in the suppression of the parasympathetic oculomotor reflex arc rather than a facilitation of the sympathetic drive to the iris.
Obsessive-Compulsive Disorder, Factor-Analyzed Symptom Dimensions and Serotonin Transporter Polymorphism
Authors: Kim Se Joo , Lee Hong Shick , Kim Chan-Hyung
Published: October 2005

Recently, on the basis of the effects of serotonin (5-HT) reuptake inhibitors in obsessive-compulsive disorder (OCD) treatment, several candidate genes related to 5-HT regulation have been hypothesized to play an important role in the development of OCD. One of them is 5-HT transporter gene. Therefore, the aims of this study were to investigate the associations between 5-HT transporter polymorphism and OCD. One hundred and twenty-four OCD patients and 171 normal controls participated in this study. Genomic DNA was extracted from their blood. Comparison of the genotypes and allele frequencies of the SERTPR polymorphism between the OCD group and the control group was made. Using principal component analysis, we derived four factors from thirteen main contents of the Y-BOCS checklist and investigated the association between these four factors and the SERTPR polymorphism. In this case-control study, we could not find any associations between the SERTPR polymorphism and the development of OCD. In the OCD group, patients with the L genotype had higher scores for the religious/somatic factor than with the S genotype. In conclusion, the SERTPR polymorphism does not affect the development of OCD. But SERTPR polymorphisms affect certain factors of OC symptoms. Moreover, the factor analytic approach used in the present study has identified meaningful symptom dimensions to help guide future research.
Interictal Slow-Wave Focus in Left Medial Temporal Lobe during Bilateral Electroconvulsive Therapy
Authors: Neuhaus Andres H. , Gallinat Juergen , Bajbouj Malek , Reischies Friedel M.
Published: October 2005

The interictal state between two electroconvulsive therapy (ECT) sessions is clinically characterised by possible cognitive adverse effects like mild amnestic syndrome. ECT-induced mnestic deficits can persist for several weeks after ECT. Electrophysiologically, slowing of brain electrical activity in the interictal state has often been reported. Especially, for bilateral ECT a correlation between enhanced left frontotemporal theta activity and retrograde amnesia has been demonstrated. This study focuses on the topographic distribution of cortical slow-wave oscillations during the interictal state of a bilateral ECT cycle. Twelve patients with major depression have been investigated with 32-channel resting EEG 24 h after the 6th ECT session. As controls, 8 major depressive patients were investigated prior to antidepressive treatment. The generating sources of slow-wave activity are estimated within the theta frequency band with low-resolution brain electromagnetic tomography. Source analysis revealed a distinct pattern of theta activity in the depth of the left temporal lobe (fusiform and parahippocampal gyri, Brodmann areas 37 and 36, respectively; p< 0.05) during the interictal state. This finding suggests a dysfunction of the left medial temporal lobe memory system during the interictal state of a bilateral ECT cycle. It will further be discussed whether it is possible to obtain information about activity of deep brain structures like the hippocampal formation from scalp-recorded signals.
Identification of Potentially Cross-Reactive Peanut-Lupine Proteins by Computer-Assisted Search for Amino Acid Sequence Homology
Authors: Guarneri Fabrizio , Guarneri Claudio , Benvenga Salvatore
Published: October 2005

Background: Allergic cross-reactions are an issue of major concern because of implications for public health. The molecular basis of cross-allergy is the similarity of epitopes belonging to proteins of different organisms. Lupine is an emerging cause of food allergy, which has become a ‘hot topic’ because of recent large-scale introduction into processed foods and frequent cross-reactions with other members of the legume family. However, no lupine allergen has been characterized thus far. Prompted by a recently reported case of peanut-lupine cross-allergy, we wished to identify the possible cross-reactive allergen(s) between the two vegetal species. Methods: We used computer-aided amino acid sequence comparison, a well-established technique for the study of protein homology, and followed the FAO/WHO guidelines for the identification of potential allergens. We also performed a three-dimensional modeling of the suspected cross-reactive proteins to compare their molecular surfaces. Results: We found a highly significant sequence homology and molecular similarity between allergen Ara h 8 of peanut and pathogenesis-related protein PR-10 of white lupine. Another protein of lupine, the β-conglutin precursor, was found to be significantly homologous to the Ara h 1 allergen of peanut. The molecular surfaces of Ara h 8 and PR-10 were remarkably similar. Conclusions: Our in silico data allow to predict the allergenicity of PR-10 and β-conglutin precursor of white lupine according to FAO/WHO guidelines. Amino acid sequence homology also suggests that these proteins could be responsible, at least in part, for some of the allergic cross-reactions between peanut and lupine reported in the literature.