bluuebunny/crossref_metadata_2025 huggingface dataset:
Papulonodular Mucinosis Associated with Subacute Cutaneous Lupus erythematosus
Authors: Sonntag Monika , Lehmann Percy , Megahed Mosaad , Ruzicka Thomas , Kuhn Annegret
Published: May 2003

Mucin deposition is a common histopathologic finding in lupus erythematosus (LE) but is rarely present in sufficient quantity to produce clinically apparent skin lesions. Until now, fewer than 40 cases of papulonodular mucinosis associated with LE have been reported in the literature, and it was associated with either systemic LE or discoid LE. For the first time, to our knowledge, we describe 2 patients with subacute cutaneous LE who presented with papulonodular mucinosis as a major clinical manifestation of their disease.
Management of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome): An Update
Authors: Tas S. , Simonart T.
Published: May 2003

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rather distinct severe adverse drug reaction characterised by skin rash, fever, lymph node enlargement and internal organ involvement. Our aim was to review the available data regarding the management of this probably underrecognised subset of drug reaction. So far, the only undisputed way to treat severe hypersensitivity reactions is prompt withdrawal of the offending drug. The use of systemic corticosteroids remains controversial. The benefit of therapies aimed at accelerating the elimination of the causative drug deserves further studies. In the absence of a well-established therapy, primary and secondary prevention have a key role in the management of DRESS syndrome.
Prolonged Imiquimod Treatment and Graft-versus-Host Reaction: Histological Mimicry in the Skin Infiltration Pattern of the Monocyte-Macrophage-Dendrocyte Lineage
Authors: Hermanns-Lê Trinh , Paquet Philippe , Nikkels Arjen F. , Piérard-Franchimont Claudine , Piérard Gérald E.
Published: May 2003

Factor-XIIIa-positive dendrocytes belong to the monocyte-macrophage-dendrocyte (MMD) lineage which is considered to play a pivotal role in the skin response to the immune response modifier imiquimod. The same cells are also boosted in low-grade graft-versus-host reaction (GVHR) with skin manifestations. Both conditions are characterized by specific epidermal damage. The aim of the present study was to compare them using immunohistochemistry to identify MMD subsets and other inflammatory cells in the dermis. We compared 3 cases of long-term (4, 9 and 11 months) imiquimod topical applications on normal skin, 25 low-grade GVHR controlled by immunosuppressive therapy and 25 control cases with normal skin. Compared to the normal dermis, cells of the MMD lineage were considerably boosted in the dermis of GVHR and at the imiquimod-treated sites. By contrast, only minimal accumulations of lymphocytes and Langerhans cells were disclosed in the dermis. The pattern of dermal infiltration by MMD cells was similar in GVHR and after imiquimod treatment. However, intraindividual differences in densities were obvious irrespective of the skin condition. In conclusion, there is great mimicry in the MMD involvement in the dermis during low-grade GVHR and after chronic applications of imiquimod.
Early Treatment of Hemangiomas with Lasers
Authors: Al Buainian H. , Verhaeghe E. , Dierckxsens L. , Naeyaert J.M.
Published: May 2003

Hemangiomas can present a difficult problem in management. Much controversy exists over whether it is better to watch and wait for natural involution or to be more aggressive and attempt to prevent some of the potential negative sequelae. Different modalities have been employed in the treatment of hemangiomas, including systemic therapy – antiangiogenic drugs, i.e. systemic corticosteroids and α-interferon – and local therapy – surgical procedures, arterial embolization and cryotherapy. Overall, a very conservative approach to therapy has been recommended because of treatment risks, treatment inadequacy and lack of evidence showing superiority over natural involution. Recently laser treatment has been used in the therapeutic approach of hemangiomas. This review discusses the pros and contras of early laser treatment of hemangiomas. For superficial hemangiomas, the flashlamp pumped pulsed dye laser in particular has proven itself in numerous studies. In the treatment of hemangiomas with subcutaneous components, the Nd:YAG laser is the treatment of choice.
Tinea capitis in Brussels: Epidemiology and New Management Strategy
Authors: Kolivras Athanassios , Lateur Nadine , De Maubeuge Josiane , Scheers Christelle , Wiame Lucy , Song Micheline
Published: May 2003

Background: We found pre-established directives inadequate to cope with the current increase in anthropophilic tinea capitis in Brussels. Objectives: To study new epidemiological profiles and to define new strategies for management and prevention. Patients and Methods: A total of 122 children affected by tinea capitis were followed in our department from October 1, 2001, until September 30, 2002. The results were assessed retrospectively. Results: Anthropophilic tinea capitis represented 89.34% of the cases. The implicated anthropophilic dermatophytes were by decreasing frequency: Microsporum langeronii (39.34%), Trichophyton soudanense (28.69%), Trichophyton violaceum (18.03%) and Trichophyton tonsurans (3.28%). Conclusion: The responsible pathogens reflect immigration flows originating mostly from Black and North Africa. Precise recommendations for each visit are detailed.
Framing the Future of Antifungals in Atopic Dermatitis
Authors: Nikkels Arjen F. , Piérard Gérald E.
Published: May 2003

Atopic dermatitis (AD) is a frequent chronic inflammatory skin disease. Some fungal colonization or infection of the skin may exacerbate AD severity, particularly the so-called head and neck variant. In addition, excessive intestinal colonization by Candida albicans may represent an additional triggering factor. Hence, there is a rationale to use antifungals in selected AD patients. Early trials with topical ketoconazole in head and neck AD showed a decrease in Malassezia colonization, but no significant improvement was observed in the clinical severity. In contrast, clinical improvement and decreased serum IgE were obtained in patients with positive Malassezia radioallergosorbent tests (RASTs) who were treated by oral ketoconazole. Some preliminary data suggested that oral itraconazole treatment in AD patients reduced the need for topical corticosteroids, provided clinical improvement particularly in head and neck AD, reduced the cutaneous and intestinal fungal colonization that may trigger AD, reduced the percentage of positive Malassezia cultures and demonstrated a decrease in C. albicans and Malassezia RAST values. Furthermore, beside its antifungal action, itraconazole in part relieves pruritus and inflammation. In conclusion, oral itraconazole treatment can alleviate AD severity in selected patients. Fluconazole is also effective. Further research is warranted to identify whether the load in skin surface fungal agents, the fungal RAST values and specific prick testing should be assessed in order to optimize the antifungal management in AD patients.
Mycobacterial Glycolipid Cord Factor Trehalose 6,6’-Dimycolate Causes a Decrease in Serum Cortisol during the Granulomatous Response
Authors: Actor Jeffrey K. , Indrigo Jessica , Beachdel Christopher M. , Olsen Margaret , Wells Alice , Hunter Jr. Robert L. , Dasgupta Amitava
Published: May 2003

Serum cortisol levels were evaluated in mice following intravenous administration of purified mycobacterial glycolipid trehalose 6,6′-dimycolate (TDM). C57BL/6 mice develop lung granulomas in response to TDM, while A/J mice are deficient in this process. Administration of TDM to C57BL/6 mice led to a rapid reduction in serum cortisol, concurrent with initiation of the granulomatous response and cytokine and chemokine mRNA induction. Cortisol levels were lowest on day 5 after TDM administration, but there was significant production of IL-6, TNF-α and IL-1β messages. Granuloma formation and full immune responsiveness to TDM were only apparent upon a sufficient decrease in levels of systemic cortisol. Treatment of the C57BL/6 mice with hydrocortisone abolished inflammatory responses. Histologically nonresponding A/J mice exhibited higher constitutive serum cortisol and demonstrated different kinetics of cortisol reduction upon administration of TDM. A/J mice demonstrated hyperplastic morphology in the suprarenal gland with a high degree of vacuolization in the medullary region and activation of cells in the zona fasciculata and zona reticularis. The A/J mice were dysregulated with respect to cytokine responses thought to be necessary during granuloma formation. The high constitutive serum cortisol in the A/J mice may therefore contribute to pulmonary immunoresponsiveness and the establishment of an environment counterproductive to the initiation of granulomatous responses. The identification of a mycobacterial glycolipid able to influence serum cortisol levels is unique and is discussed in relation to immunopathology during tuberculosis disease.
Modulation of Interleukin-1 Receptors Followed by Endotoxin Lipopolysaccharide Treatment in the Mouse AtT-20 Pituitary Tumor Cell Line
Authors: Kumagai Chizuru , Takao Toshihiro , Matsumoto Reiko , Asaba Koichi , Hashimoto Kozo
Published: May 2003

Objective: We have previously reported the characterization and regulation of interleukin-1 (IL-1) receptors utilizing [125I]IL-1 binding assay in male C57BL/6 mice and the mouse AtT-20 pituitary tumor cells. In the present study, we examine IL-1 receptors using an immunoblotting method to further characterize the mechanisms regulating the interactions of IL-1 receptors with endotoxin, lipopolysaccharide (LPS). Methods: We established Western blotting for IL-1 receptors using AtT-20 mouse pituitary tumor cells. Results: Several bands were seen; however, only the 105-kD band was neutralized with a 5-fold excess of IL-1 receptor- blocking peptides, suggesting that this band is specific for IL-1 receptors. Next, we investigated the effect of LPS and IL-1β on IL-1 receptors. Treatment of AtT-20 cells with 0.01 µg/ml of LPS did not affect IL-1 receptors. In contrast, 1 µg/ml of LPS significantly increased IL-1 receptors in AtT-20 cells compared with the control group. In addition, [125I]IL-1β binding was markedly increased followed by 1 µg/ml of LPS. In contrast, 1 nM recombinant human IL-1β significantly decreased IL-1 receptors in AtT-20 cells compared with the control group although treatment of AtT-20 cells with 0.01 nM IL-1β did not affect IL-1 receptors. LPS (0.1 and 1 µg/ml) did not affect IL-1β concentrations in the medium of AtT-20 cell culture. IL-1β concentrations in the homogenates from AtT-20 cells were significantly decreased after 1 µg/ml of LPS treatment but not after 0.01 µg/ml LPS. Conclusions: These data demonstrate that LPS and IL-1β differentially modulate IL-1 receptors in AtT-20 cells and LPS-induced modulation of IL-1 receptors may provide a novel mechanism for the actions of LPS to alter pituitary function during endotoxemia. Additional in vivo studies are necessary to determine the physiological relevance of this in vitro phenomenon.
RFLP Analysis of mtDNA from Six Platyrrhine Genera: Phylogenetic Inferences
Authors: Ruiz-García M. , Alvarez D.
Published: May 2003

This study investigates the phylogenetic relationships of 10 species of platyrrhine primates using RFLP analysis of mtDNA. Three restriction enzymes were used to determine the restriction site haplotypes for a total of 276 individuals. Phylogenetic analysis using maximum parsimony was employed to construct phylogenetic trees. We found close phylogenetic relationships between Alouatta, Lagothrix and Ateles. We also found a close relationship between Cebus and Aotus, with Saimiri clustering with the atelines. Haplotype diversity was found in four of the species studied, in Cebus albifrons, Saimiri sciureus, Lagothrix lagotricha and Ateles fusciceps. These data provide additional information concerning the phylogenetic relationships between these platyrrhine genera and species.
Transcranial Color Duplex Sonography in Cerebrovascular Disease: A Systematic Review
Authors: Baumgartner Ralf W.
Published: May 2003

Transcranial color-coded duplex sonography (TCCS) enables the reliable assessment of intracranial stenoses (sensitivity 94–100%, specificity 99–100%), occlusions (middle cerebral artery: sensitivity 93–100%, specificity 98–100%) and cross-flow through the anterior (sensitivity 98%, specificity 100%) and posterior (sensitivity 84%, specificity 94%) communicating arteries without using potentially dangerous compression tests, as well as the midline shift in hemispheric infarcts. Ultrasound contrast agents (UCAs) increase the number of conclusive TCCS studies and allow the definite evaluation of intracranial arteries in most patients. TCCS is also useful for diagnosis and monitoring of vasospasm and detection of supratentorial hematomas (sensitivity 94%, specificity 95%) and aneurysms (sensitivity per patient 40–78%, specificity 90–91%), and may identify arteriovenous malformations. New developments are (1) UCAs that may increase the number of conclusive TCCS studies, (2) cerebral perfusion assessment, (3) measurement of arteriovenous cerebral transit time, which might enable the detection of small-vessel disease, and (4) site-targeted UCAs that may improve diagnosis and local drug delivery.
Public Perception of Stroke in Spain
Authors: Segura Tomás , Vega Gema , López Salvador , Rubio Francisco , Castillo José
Published: May 2003

Background and Purpose: Stroke is one of the leading causes of death and disability in western countries. Improving attention to stroke demands better public information about the illness. The aim of the present study was to determine the current knowledge of stroke among the Spanish population. Methods: We conducted a population-based telephone interview in Spain. A total of 3,000 respondents were selected at random following a systematic procedure aimed at filling the sex/age community quotas. Results: A total of 16,016 telephone calls were made. Three thousand respondents were eligible and 2,884 completed the telephone interview. Only 4.5% of respondents knew the term stroke, 1,719 (59.6%) participants were able to mention at least one stroke risk factor, and only 940 (32.6%) could mention at least one stroke sign without prompting. Most respondents considered stroke to be a severe and dangerous illness that can be treated, but less than half of the respondents went immediately to a hospital when faced with a stroke event. Suitable stroke knowledge was only achieved by 302 (10.5%) respondents. Those who had home-based occupations and no previous stroke experience were less likely to have suitable stroke knowledge. Conclusions: This study confirms that our community is still unfamiliar with stroke. Wide population-based educational programs are needed to increase public knowledge of stroke. Our results indicate that people with home-based occupations should be the main target of our education campaigns.
An East-West Approach to the Management of Central Post-Stroke Pain
Authors: Yen Hwee Ling , Chan William
Published: May 2003

The development of neuropathic pain following stroke is not uncommon. The consequences include significant disabilities and depression. Treatment can often be difficult and responses unsatisfactory. We report a patient with severe central post-stroke pain (CPSP) of the right leg benefiting from a combination of Western multidisciplinary therapies and acupuncture. A literature search has revealed that relatively few studies have been done on the management of CPSP, compared with other types of neuropathic pain. Amitriptyline and carbamazepine were found to produce positive effects on post-stroke pain in one small study; lamotrigine and gabapentin are two newer drugs which appear promising. To the best of our knowledge, the use of acupuncture for the treatment of CPSP has not been previously reported.
The Antiplatelet Aggregation Effects of Aspirin Suppositories
Authors: Nakayasu Hiroyuki , Maeda Masanobu , Soda Takao , Iijima Kenji , Ishimoto Manabu , Ieiri Ichiro , Tabuchi Fumie , Otsubo Kenji , Nakashima Kenji
Published: May 2003

To confirm that aspirin suppositories are an effective treatment for acute ischemic stroke, we examined the suppressive effects of 200-mg aspirin suppositories on platelet aggregation. Aspirin suppositories suppressed platelet aggregation induced by ADP or collagen, and the suppression continued for 24 h. There was no significant difference in suppression of platelet aggregation between aspirin administered by suppository and orally given aspirin. These results suggest that aspirin suppositories are a useful treatment for acute ischemic stroke.
Contrast Media Effect on Cerebral Blood Flow Regulation after Performance of Cerebral or Coronary Angiography
Authors: Rosengarten B. , Steen-Müller M.K. , Müller A. , Traupe H. , Voss R.K. , Kaps M.
Published: May 2003

Objective: The immediate hemodynamic effects of contrast agents are well documented. Less is known about their longer-lasting effects. We investigated the later effect of iopromide on the neurovascular coupling mechanism after the performance of cerebral or coronary angiography. Neurovascular coupling is a fine-tuned and reliable mechanism adapting cerebral blood flow to cortical activity. When performing a visual stimulation and measuring the resultant flow velocity change in the posterior cerebral artery transcranial Doppler has been used to determine vascular integrity. Methods: The visually evoked blood flow velocity response in the posterior cerebral artery was measured with transcranial Doppler before, 1–2 h after and the day after angiography. The overshoot of the flow velocity response and the stable flow velocity level at the end of the stimulation phase were used to compare the different conditions. Results: A significantly diminished overshoot was found 1–2 h after angiography only in patients undergoing cerebral angiography. The stable blood flow velocity levels at the end of the stimulation phase remained unchanged in all cases. Conclusions: Our finding demonstrates effects of contrast media on dynamic blood flow regulation of the cerebral vasculature 1–2 h after application of direct contrast agent suggesting a possible concentration effect of the contrast agent. However, since the relative blood flow velocity increase under stable blood flow conditions remained constant, this dynamic alteration does not cause a reduction in cerebral blood flow.
Effect of Heart Rate on Regulative Features of the Cortical Activity-Flow Coupling
Authors: Rosengarten B. , Budden C. , Osthaus S. , Kaps M.
Published: May 2003

Objective: Heart rate plays an important role in compensatory conditions of arterial pressure changes. Very little information, however, exists on its role in the dynamic adjustment of stimulated organ perfusion. We studied the influence of heart rate on the activity-flow coupling mechanism which adapts local cerebral blood flow in accordance with cortical activity. Since it does not affect heart rate or arterial blood pressure by itself, the commonly observed heart rate variability in test conditions was used to compare the flow response between different heart rate groups. For evaluation under stable heart rate conditions we performed a short test paradigm with a transcranial Doppler technique with the necessary high time resolution. Methods: 168 healthy young volunteers (24 ± 3 years of age) were grouped according to their heart rate in decade steps from 60 to 100 beats/min (mean: 82 ± 9 beats/min). The visually evoked flow velocity responses in the posterior cerebral artery were evaluated according to a control system approach. Peak systolic and end diastolic data were evaluated separately. Results: A correlation analysis between heart rate and baseline flow velocity as well as each of the control system parameters, i.e. gain, attenuation, rate time and natural frequency, revealed no significance. The flow responses did not differ among the heart rate groups as concluded from an ANOVA test. Discussion: The increase in heart rate and the possible stress factors responsible for this seem to be of no relevance in regulative features of the activity-flow coupling. The almost identical time course of flow velocity responses among the groups showing a heart rate difference of up to 50% indicates an integrative principle in flow regulation supporting simplified concepts of flow adaptation.
Doppler Investigation of Within-Session Reproducibility in a Visual Stimulation Task to Assess the Volunteer-Dependent Variation
Authors: Rosengarten B. , Osthaus S. , Kaps M.
Published: May 2003

Objective: In functional magnetic resonance imaging (MRI) studies in humans the tightness of activity-flow coupling was questioned due to a notable within-session variability of the signals obtained. To differentiate between moments of volunteer-dependent or technique-inherent variation in hemodynamic MRI measurements a method with a low technique-inherent variation is needed. Therefore, and because temporal features might also be of some relevance, we used the transcranial Doppler method. Methods: In 22 healthy volunteers the flow-velocity response to a visual stimulation task was evaluated. Conditions of 20 s of eye closure were altered with 40 s of silent reading, repeated 10 times. Averaged individual flow-velocity responses were evaluated from conditions of 40 s of stimulation and a 5-second time interval prior to the beginning of stimulation. The averaged data were subtracted from each single recording to calculate the mean squared differences (MSD). Statistical evaluation was performed according to a two-way ANOVA for repeated measures. To obtain additional qualitative data of the flow response, the individual flow curves were evaluated according to a control system approach specifying a second-order linear model. Results: The coefficient of variation (COV) of the within-session MSD was 7% for the stimulation phase and 2.9% for the resting phase, whereas the respective COVs were 15 and 8.1% for the interindividual MSDs. The interindividual COVs of control system parameters ranged from 3.6 to 7.6%. The ANOVA resulted in a significant (p < 0.003) difference for the MSD values between stimulation conditions, whereas the test repetition (p = 0.55) and the test for an interaction of repetition and stimulation condition (p = 0.54) revealed no significance. Discussion: Confirming the notion of a tight coupling between cortical activity and cerebral blood flow and being indicative of a low technique-inherent variation, we found a high within-session reproducibility in a functional Doppler test.
Cervical and Intracranial Atherosclerosis and Silent Brain Infarction in Japanese Patients with Coronary Artery Disease
Authors: Uekita Kazumi , Hasebe Naoyuki , Funayama Naoki , Aoyama Hidefumi , Kuroda Kenji , Aizawa Hitoshi , Kataoka Ryo , Kikuchi Kenjiro
Published: May 2003

Purpose: To investigate the prevalence of cervical and intracranial atherosclerosis and silent brain infarction in patients with coronary artery disease (CAD). Methods: Cervical and intracranial atherosclerotic lesions on magnetic resonance angiography (MRA) and silent brain infarctions on magnetic resonance imaging (MRI) were investigated in comparison with the findings of coronary angiography in 133 consecutive patients with CAD. Results: The mean severity scores of cervical and intracranial MRA lesions were significantly higher in the three-vessel CAD (0.40 and 0.53, respectively) than in the zero-vessel CAD group (0.04 and 0.11). The mean scores of the maximal size and multiplicity of MRI lesion were also significantly greater in the two-vessel (1.00 and 1.44) and three-vessel CAD (0.94 and 1.26) than in the zero-vessel CAD group (0.27 and 0.50). The incidence of MRA lesion was markedly higher in patients with brain MRI lesion than in those without (51.1 vs. 6.5%). Conclusions: Serious coronary artery lesions were commonly accompanied by latent atherosclerotic lesions in the cervical and intracranial arteries besides silent brain infarction in patients with CAD.
Serial Changes in Static and Dynamic Cerebral Autoregulation after Acute Ischaemic Stroke
Authors: Dawson Suzanne L. , Panerai Ronney B. , Potter John F.
Published: May 2003

Background: The longitudinal changes in static and dynamic cerebral autoregulation (CA) following acute ischaemic stroke are unknown and were assessed in this study. Methods: Fifty-four ischaemic stroke patients were studied within 96 h of ischaemic stroke and again 7–14 days later, using transcranial Doppler techniques to measure CA. Results were compared to an age-, sex- and blood pressure (BP)-matched control group. Static BP pressor stimulus was produced by thigh cuff inflation and dynamic stimulus by rapid thigh cuff release. Results: Dynamic, but not static, CA was globally impaired at initial (mean dynamic CA index 3.9 ± 3.1 vs. 6.2 ± 2.3, p < 0.005) and follow-up studies (dynamic CA 3.9 ± 2.8 vs. 6.2 ± 2.3, p < 0.01) in stroke patients compared to controls. Static CA was similar in stroke patients and controls and was unchanged during follow-up. Conclusions: Dynamic, but not static, CA is impaired after acute ischaemic stroke and remains abnormal for at least 1–2 weeks post ictus. These changes are present in both the affected and non-affected hemispheres and are unrelated to previous antihypertensive treatment, baseline BP levels or BP changes after stroke, age or stroke type.
Low Triglyceride, Not Low Cholesterol Concentration, Independently Predicts Poor Outcome following Acute Stroke
Authors: Weir Christopher J. , Sattar Naveed , Walters Matthew R. , Lees Kennedy R.
Published: May 2003

Background: Recent data have shown an unexpected association between poor outcome after acute stroke and lower serum cholesterol. Triglyceride concentration has been linked to coronary heart disease and stroke; however, there are currently no data on the relationship between triglyceride and stroke outcome. Such information may yield further mechanistic information on the relationship between lipids and stroke outcome. Methods: We studied 1,310 nondiabetic patients presenting to our acute stroke unit with computed tomography-confirmed acute stroke. Fasting blood samples were drawn within 24 h of admission for glucose, lipids and a standard battery of biochemistry and hematological tests. Information on age, stroke type, admission blood pressure, smoking status, presence of atrial fibrillation, resolution time of symptoms and Oxfordshire Community Stroke Project clinical classification was collated. Stepwise proportional hazards regression was used to estimate the effect of the above variables on survival following stroke. Results: Increased age (p < 0.0001), presence of atrial fibrillation (p = 0.009), hyperglycemia (p = 0.0005) and lower triglyceride level (p < 0.0001) independently predicted higher mortality; early resolution of symptoms (p = 0.005) independently predicted lower mortality. Although serum cholesterol level predicted outcome after adjusting for other prognostic factors, it did not remain significant when triglyceride level was entered into the model. The relative hazard per additional quartile of triglyceride was 0.84 (95% confidence interval 0.77–0.91). Conclusions: Low triglyceride concentration strongly predicts higher mortality following stroke, whereas serum cholesterol level is not an independent predictor. Outcome following stroke is thus related more strongly to triglyceride-rich than to cholesterol-rich lipoprotein concentrations. The mechanisms explaining this require further investigation.
Preservation of Endothelial Function by the HMG-CoA Reductase Inhibitor Fluvastatin through Its Lipid-Lowering Independent Antioxidant Properties in Atherosclerotic Rabbits
Authors: Mitani Hironobu , Egashira Kensuke , Ohashi Noriko , Yoshikawa Masayoshi , Niwa Satoru , Nonomura Kazuhiko , Nakashima Akinori , Kimura Masaaki
Published: May 2003

Recent evidence suggests that the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on entothelial function and cardiovascular ischemic events may be attributed not only to their lipid-lowering effects but also to cholesterol-lowering independent (direct) effects on the atherosclerotic vessel wall. This study was designed to test the hypothesis that fluvastatin (Flu) preserves the endothelial function by its cholesterol-lowering independent actions. Rabbits were fed a 0.5% high-cholesterol (HC) diet for 12 weeks (progression phase) and then fed the HC diet either containing or not containing Flu 2 mg/kg/day for an additional 8 weeks (treatment phase). Rabbits fed a normal diet were used as controls. Plasma total and low-density lipoprotein cholesterol concentrations did not differ during the treatment phase: Endothelium-dependent/NO-mediated relaxation (acetylcholine and A23187) was impaired in the HC diet group, whereas it was preserved in the HC plus Flu treatment group. The endothelium-independent relaxation (sodium nitroprusside) was similar between the three groups. Interestingly, aortic oxidative stress (lipid peroxides and isoprostane F2α-III contents) and NADPH oxidase component (p22phox and gp91phox) mRNA expression were increased in the HC group but not in the HC plus Flu group. The A23187-induced nitric oxide production from the aorta was increased in both HC and HC plus Flu groups. There was no significant difference in tissue endothelial-type nitric oxide synthase mRNA expression. Plaque area and intimal thickening of the aorta were significantly lowered in the HC plus Flu group. Flu treatment preserved the endothelial function associated with the decrease in markers of oxidative stress in this experiment. These beneficial endothelial effects of Flu are likely to occur independently of plasma lipid concentrations and to be mediated by its antioxidant action.
Comparison between CL-316243- and CGP-12177A-Induced Relaxations in Isolated Canine Ureter
Authors: Tomiyama Yoshitaka , Murakami Makoto , Yamazaki Yoshinobu , Kojima Masami , Akahane Masuo
Published: May 2003

We compared the effects of CL-316243, a selective β3-adrenoceptor agonist, and CGP-12177A, a nonconventional partial β-adrenoceptor agonist, on the KCl-induced contraction in the isolated canine ureter. CL-316243 concentration dependently relaxed the ureteral contraction, the pD2 value being 7.75 ± 0.11. This relaxation was competitively antagonized by the selective β3-adrenoceptor antagonist SR58894A and by the nonselective β-adrenoceptor antagonist bupranolol, their pA2 values being 7.08 ± 0.08 and 6.43 ± 0.09, respectively. CGP-12177A concentration dependently reduced the KCl-induced contraction, the pD2 value being 6.30 ± 0.25. Even at 1 × 10–5 mol/l, CGP-20712A (a selective β1- adrenoceptor antagonist) did not shift the concentration-response curves for CL-316243 or CGP-12177A. SR58894A did not induce a parallel rightward shift in the concentration-response curve for CGP-12177A, but bupranolol did produce such a shift, pA2 and slope values in the Schild plot being 7.15 ± 0.77 and 0.60 ± 0.15, respectively. Hence, the competition characteristics for SR58894A and bupranolol differed between the CL- 316243-induced and CGP-12177A-induced relaxations. Our results suggest that CGP-12177A produces ureteral relaxation in the dog via an atypical β-adrenoceptor (possibly, an atypical site/state of the β3-adrenoceptor) as well as via the typical β3-adrenoceptor.
Effects of Nonsteroidal Anti-Inflammatory Drugs on Prostacyclin and Thromboxane in the Kidney
Authors: Lomnicka Magdalena , Karouni Katayoun , Sue Michele , Wessel Lauren A. , Bing Richard J.
Published: May 2003

Dose-response curves were obtained relating the effects of increasing amounts of aspirin, a nonselective cyclooxygenase (COX) inhibitor, and celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on the concentrations of prostacyclin and thromboxane in renal cortex and medulla of rabbits. The concentrations of the two agonists (aspirin and celecoxib) which elicit a half-maximal response on the prostanoid concentration (EC50) were compared. Additionally, controls for prostacyclin and thromboxane were related to values for the experimental groups. The EC50 values for celecoxib were considerably lower than those for aspirin, indicating that celecoxib was more effective in suppressing prostanoid production. There were also significant differences between the majority of experimental groups and their respective controls, further evidence for the greater inhibitory activity of celecoxib on prostacyclin. Celecoxib lowered the ratio prostacyclin/thromboxane in the renal medulla; mercuric chloride further diminished the concentration of prostacyclin in the renal medulla. The results confirm that in the normal rabbit kidney, both nonselective and specific COX inhibitors interfere with renal prostanoid synthesis, but that a selective COX-2 inhibitor is more effective.
‘In vitro’ Cytokine Secretion by Peripheral Blood and Decidual Lymphocytes during the Third Trimester of Normal Pregnancy
Authors: Wilczynski J.R. , Tchórzewski H. , Głowacka E. , Banasik M. , Szpakowski M. , Wieczorek A. , Wilczynski J.R.
Published: May 2003

If the ‘Th2 phenomenon’ is dependent on trophoblastic antigens and cytokines, the profile of cytokines secreted by decidual lymphocytes (DL) should indicate stronger Th2 shift than that of peripheral blood lymphocytes (PBL). We studied spontaneous and mitogen-stimulated ‘in vitro’ cytokine secretion of cultured lymphocytes isolated from peripheral blood (n = 21) and decidua (n = 11) of third trimester healthy pregnant women not being in labor. The ELISA method was used for estimation of IL-2, IL-4, IL-6, IL-10, IL-12, IFN-γ and TGF-β. The results (given in pg/ml) were found to be statistically significant in the Mann-Whitney U-test (p < 0.05). Compared to PBL, DL produced spontaneously decreased concentrations of IL-12, IL-6, IFN-γ and TGF-β and upon mitogen stimulation increased quantities of IL-2, IL-4 and IL-10. It demonstrates that DL play an active role in local Th2-like immunoregulation and that their cytokine secretion pattern estimated in ‘in vitro’ conditions is biased towards Th2 activity more than that of PBL.
Two Episodes of Hemoperitoneum from Luteal Cysts Rupture in a Patient with Congenital Factor X Deficiency
Authors: Dafopoulos Konstantinos , Galazios Georgios , Georgadakis Georgios , Boulbou Maria , Koutsoyiannis Dimitrios , Plakopoulos Apostolos , Anastasiadis Panagiotis
Published: May 2003

The clinical manifestation of two episodes of hemoperitoneum from ruptured corpus luteum cysts, during the luteal phase of the cycle in a young patient with the rare congenital factor X deficiency, is reported for the first time in literature. The correct diagnosis of the underlying disorder, the gynecological management and the regular follow-up can minimize the risks of this potentially life-threatening hematological disorder.
Cyclophosphamide Pulse Therapy in Advanced Progressive IgA Nephropathy
Authors: Rasche Franz Maximilian , Klotz Christoph Hubert , Czock David , Karges Wolfram , Muche Rainer , Jehle Peter Michael , Mertz Andreas , Keller Frieder
Published: May 2003

For advanced progressive primary IgA nephropathy (IgAN) no established therapy exists. We conducted a prospective, uncontrolled trial to evaluate the effect of intravenous cyclophosphamide pulse (CyP) therapy on the course of advanced progressive IgAN. Twenty-one patients (mean age 52 ± 10 years; male/female 20/1) with biopsy-proven IgAN without crescentic extracapillary proliferation and a serum creatinine of more than 2.0 mg/dl and/or an increase more than 25% in the previous 3 months were included. Patients were treated with CyP (750 mg/m2 body surface area) every 4 weeks for 6 months and low dose oral prednisolone. The loss of renal function per year was significantly reduced from 16% before therapy to 4% after therapy (p < 0.001). A further increase >25% of serum creatinine after therapy was observed in 8 patients after 0.7 years (range 0.3–3.0 years), and 3 of these patients developed end-stage renal disease. Proteinuria decreased significantly during CyP therapy. A low nadir of white blood cell and platelet count was associated with a better renal outcome (p = 0.025). In conclusion, CyP therapy and low dose oral prednisolone is effective in preserving renal function in a subgroup of patients with advanced progressive IgAN.
What Are Renal Defensins Defending?
Authors: Donovan Kieron L. , Topley Nicholas
Published: May 2003

Defense against the susceptibility and damaging effects of urinary tract infection is complex and vital, as injury can lead to progressive renal injury and chronic renal failure. Recently the defensins, a family of small cationic antimicrobial peptides found in neutrophils and renal epithelial cells, have been shown to have a number of key biological properties that equip them to undertake a pivotal role in combating infection. We describe the capability of these ubiquitous and abundant peptides in the process of innate immunity, and more recently discovered roles in the adaptive immune response to infection. Furthermore, we also discuss their potential to influence other key components of the inflammatory response to infection. Despite the current state of knowledge, we are only just beginning to understand the significance of defensins as pivotal peptides in host defence and their possibilities as therapeutic targets of the future.
Growth Hormone Increases Low-Density Lipoprotein Receptor and HMG-CoA Reductase mRNA Expression in Mesangial Cells
Authors: Machado Marcos O. , Hirata Rosario D.C. , Hirata Mario H. , Hirszel Przemyslaw , Sellitti Donald F. , Doi Sonia Q.
Published: May 2003

A dysregulation of the negative feedback mechanism of the low-density lipoprotein receptor (LDL-r) induced by hormones and cytokines may contribute to the development of glomerular injury and specifically could underlie growth hormone (GH)-induced glomerulosclerosis. The present study investigates the role of GH in the regulation of LDL-r and HMG-CoA reductase mRNA expression in mesangial cells. Mouse mesangial cells were equilibrated in a medium containing 5% lipoprotein-deprived serum (LPDS) for 48 h, prior to addition of GH (0.25 µM). Transcript levels of LDL-r, HMG-CoA reductase and GH-receptor (GH-r) were measured at days 2 and 4 and intracellular lipid content was evaluated by oil red-O staining. The addition of GH significantly increased both the LDL-r and HMG-CoA reductase transcript levels at day 2 compared to control. Oil red-O positive staining increased following the initial period of 48 h lipoprotein deprivation, but addition of GH in a subsequent 48-hour period did not alter lipid content to a measurable degree compared with control. The present study demonstrates that GH significantly increased HMG-CoA reductase and LDL-r transcript levels in mesangial cells deprived of lipoproteins suggesting that abnormal levels of GH may play a role in glomerular lipid accumulation.
Mechanisms of Down-Regulation of the Renal Parathyroid Hormone Receptor in Rats with Chronic Renal Failure
Authors: Josifovska Tatjana , Nonoguchi Hiroshi , Machida Kenji , Tomita Kimio
Published: May 2003

Hypocalcemia, hyperphosphatemia and resistance to the action of parathyroid hormone (PTH) are well-characterized features in advanced chronic renal failure (CRF). Their pathogenesis has been attributed to both PTH receptor (PTH-R) down-regulation and postreceptor abnormalities. In this study, we examined the renal expression of the PTH-R mRNA in CRF (5/6 nephrectomy) rats. Experiments were also performed to determine whether an acidic condition and PTH itself influence PTH-R mRNA expression. RT-competitive PCR was used to examine mRNA expression, and polyclonal antibody against PTH-R was used for Western blot. PTH-R mRNA expression was abundant in glomeruli, proximal convoluted and straight tubules (PCT, PST), small in medullary and cortical thick ascending limbs, and cortical collecting ducts and not detectable in outer and inner medullary collecting ducts. The expression was significantly decreased in PCT and PST in CRF rats. Decrease in PTH-R mRNA expression was observed 1 week after the induction of CRF. PTH-R protein was decreased at 2 (–23%) and 4 (–45%) weeks in renal cortex, but not in medulla in CRF rats. PTH-R mRNA expression in PST was decreased by low pH (7.1 or 6.7) incubation compared with that at pH 7.4. PTH(1–34) (10–9 M) increased PTH-R mRNA expression in PST from control rats by 250%. The stimulatory effect of PTH on PTH-R mRNA expression was decreased by the incubation at low pH medium. In summary, renal PTH-R is down-regulated in CRF rats. The decrease in mRNA expression in PCT and PST causes the decrease in PTH-R protein. Metabolic acidosis may participate in the down-regulation of PTH-R in early stage of CRF. This abnormality could be important in the pathogenesis of secondary hyperparathyroidism of CRF.
Vitamin D Receptor Binding to DNA Is Altered without the Change in Its Expression in Human Renal Clear Cell Cancer
Authors: Madej Agnieszka , Puzianowska-Kuznicka Monika , Tanski Zbigniew , Nauman Janusz , Nauman Alicja
Published: May 2003

Vitamin D co-regulates cell proliferation, differentiation and apoptosis, the processes that are disturbed in cancer tissues. It acts through the vitamin D nuclear receptor (VDR) that binds to DNA in the regulatory sequences of the target genes. As the kidney is one of the key organs for vitamin D metabolism and action, we analyzed VDR expression and its DNA binding activity in human renal clear cell cancer. 24 tumors, 24 controls that were excised from the opposite pole of the same kidney and 7 controls originating from kidneys without cancer were examined. Independently of tumor grading neither Northern blots nor immunoblotting demonstrated statistically significant differences of the mean VDR mRNA and protein amounts, respectively, in the cancer as compared to both control types. In contrast, the amount of VDR-DNA complexes was lower in 52.2% of the tumors in comparison to their corresponding controls. After normalization against VDR receptor protein amount in 34.8% of the tumors VDR-DNA binding was at least 3–4 times weaker than in the controls. However, the expression of vitamin D-dependent P21 gene on the mRNA level was not decreased in these cancers. It remains to be elucidated if altered VDR function due to its impaired binding to DNA contributes to the process of tumorigenesis, and what potential vitamin D-dependent mechanisms are involved in this process.
Extracellular Actin Impairs Glomerular Capillary Repair in Experimental Mesangioproliferative Glomerulonephritis
Authors: Janssen Ulf , Eitner Frank , Kunter Uta , Ostendorf Tammo , Wolf Gunter , Chaponnier Christine , Gabbiani Giulio , Kerjaschki Dontscho , Floege Jürgen
Published: May 2003

Exogenous administration of actin prevents tumour growth in mice by specifically antagonizing angiogenin, a potent inducer of neovascularization. To investigate whether the angiogenin/actin system is also of importance in renal disease, we examined the effect of actin during glomerular capillary repair in anti-Thy-1.1 mesangioproliferative glomerulonephritis. Male Wistar rats were injected intravenously with actin, a control protein, i.e. albumin, or vehicle alone at 8, 16, 24, 32, 40 and 48 h after disease induction. On day 8, actin-treated rats showed significantly more microaneurysms and persistent mesangiolysis as compared to both control groups. This was associated with increased proteinuria in actin-treated rats. Moreover, actin-treated rats showed increased counts of glomerular macrophages (+40%) and polymorphonuclear leukocytes (+100%) on day 3 as well as a decrease in glomerular endothelial area on days 3 and 8. However, no difference in early glomerular endothelial as well as non-endothelial cell proliferation was noted in actin-treated rats as compared to controls. Actin treatment had no apparent influence on mesangial cell activation (i.e. de novo expression of α-smooth muscle actin) or glomerular accumulation of fibronectin or type IV collagen. Additional in vitro studies demonstrated that extracellular actin inhibits the angiogenin but not VEGF165-induced proliferation of (glomerular) endothelial cells. Moreover, actin inhibited other, yet unidentified, serum-derived angiogenic factors. In conclusion, exogenous actin impairs glomerular capillary repair in experimental mesangioproliferative glomerulonephritis possibly due to interference with angiogenic factors such as angiogenin. Our combined in vivo and in vitro observations suggest that the release of intracellular actin during mesangiolysis is an endogenous pathway by which glomerular capillary damage is augmented.
Volume Control, Blood Pressure and Cardiovascular Function
Authors: Charra Bernard , Chazot Charles
Published: May 2003

The balance of sodium, through its dietary intake and renal excretion, determines extracellular fluid volume (ECV). Chronic renal failure and dialysis patients present with a positive sodium balance and increased ECV. The consequences are systemic hypertension and vascular and cardiac remodelling, especially left ventricular hypertrophy (LVH). High blood pressure (BP) and LVH increase the mortality risk of dialysis patients. Correction of ECV overload with ultrafiltration has led to the dry weight concept, which is the postdialysis body weight that allows BP to remain normal until the next dialysis session, without the need for antihypertensive medication and despite interdialytic weight gain. Blood pressure is the key indicator of ECV and is used to set the body weight target at each dialysis session. Normalization of BP indicates normalization of ECV, usually with a lag-time. Shortening dialysis time, which increases intradialytic morbidity, compromises the achievement of dry weight and normalization of ECV. Such intradialytic events may also lead to an increase in dialysate sodium concentration, which causes thirst, and greater interdialytic weight gain, positive sodium balance and worsening BP. These complications have led to the development of other tools for ECV assessment, such as inferior vena cava diameter, bioimpedance, and blood volume monitoring; their usefulness is discussed.
Maize Activator Transposase Expressed in Saccharomyces cerevisiae from a Genomic Clone: Detection via Elisa, and Proposed Use in Complementation Studies
Authors: MacRae Amy F.
Published: May 2003

The maize Activator (Ac) transposase (TPase) was expressed as a histidine (His)-tagged protein in Saccharomyces cerevisiae from a full-length genomic clone. Expression was demonstrated via the highly specific nickel-coated Elisa plate method, using an anti-His antibody and 2 separate anti-Ac TPase antibodies, to Ac residues 103–465 and 189–807. Ac TPase expression in S. cerevisiae is important for two reasons: (a) because the expression from a genomic clone herein permits the future study of RNA splicing mechanisms in common between maize and yeast systems, and (b) because a yeast system can easily be used for demonstrating complementation of function. Thus, such transformed yeast systems could be used in future to experimentally test whether Ac TPase could complement various yeast mutations. Specifically, Ac TPase may be able to complement (i.e., provide the same function) to yeast transcription factor mutants, or, to genes mutated in other essential yeast functions. If confirmed, this would lend support to Barbara McClintock’s hypothesis that transposable elements can serve as ‘controlling elements’ within the genome, by their ability to supplement other essential genes’ functions, as needed. Work herein is contrasted with existing studies on Ac in yeast.