bluuebunny/crossref_metadata_2025 huggingface dataset:
Comorbidity of Constrictive Pericarditis and Hemophilia A
Authors: Demiralp Ergun , Ulusoy Rifat Eralp , Kirilmaz Ata , Cebeci Bekir Sitki , Kucukarslan Nezihi , Ozmen Namik , Aparci Mustafa
Published: May 2006

Objective: To report a case of comorbidity of constrictive pericarditis and hemophilia A. Clinical Presentation and Intervention: A 21-year-old male with hemophilia A was referred to our clinic and was examined with the subsequent evaluation of shortness of breath, leg edema and ascites. Clinical and laboratory examinations were performed. The results were consistent with constrictive pericarditis (CP), and the symptoms were completely relieved following institution of medical therapy. Conclusion: Because hemophilia A and pericarditis may be coincidentally present clinical conditions, avoidance of surgical procedures in hemophilic patients is preferable unless the resolution of the symptoms of pericarditis cannot be effected by medical therapy.
Moyamoya Syndrome with Primary Antiphospholipid Syndrome
Authors: Shuja-Ud-Din Mohammed Ali , Ahamed Shefeek Abubacker , Baidas Ghassan , Naeem Mohammad
Published: May 2006

Objectives: To report a rare case of moyamoya syndrome with primary antiphospholipid syndrome (APS). Clinical Presentation and Intervention: A 41-year-old woman was admitted with sudden onset of left-sided hemiparesis. Magnetic resonance imaging and magnetic resonance angiography of the brain showed characteristic features of moyamoya vessels. Laboratory investigations revealed raised levels of anticardiolipin antibody. She made a complete and uneventful recovery with aspirin and intensive physiotherapy over a period of 2 weeks. Conclusion: The association of APS and moyamoya disease may present a dilemma in management. While APS is often considered to be an indication for giving anticoagulation, a trial of antiplatelet agents is preferable to anticoagulation because of the risk of bleeding from the fragile moyamoya vessels.
Unilateral Diaphragm Paralysis Possibly Due to Cervical Spine Involvement in Multiple Myeloma
Authors: Kara Murat , Isik Metin , Ozcakar Levent , Erol Ozlem , Dogan Serkan , Altundag Kadrı , Aksu Salih
Published: May 2006

Objective: To describe a patient with unilateral diaphragmatic paralysis due to multiple myeloma (MM) involving the cervical spine and related structures. Case Presentation and Intervention: A 52-year-old female presented with dyspnea, low back and widespread bone pain. She was diagnosed as having MM with vertebral involvement and unilateral paralysis of the diaphragm. She received two cycles of a chemotherapeutic regimen consisting of vincristine-Adriamycin-dexamethasone. The bisphosphonate zoledronic acid was also initiated at the same time. During follow-up, the back pain disappeared and the complaint of dyspnea decreased, although the paralysis persisted. Conclusion: As part of the differential diagnosis of bone and back pain, we draw attention to MMand the rare complication of diaphragmatic paralysis due to phrenic nerve involvement.
Influence of Different Storage Methods on Laser Fluorescence Values: A Two-Year Study
Authors: Francescut P. , Zimmerli B. , Lussi A.
Published: May 2006

The aim of this study was to assess the influence on the infrared laser fluorescence response of some storage methods commonly used in dental research. Forty extracted permanent teeth, selected from a pool of frozen teeth, were divided into four groups of 10. Three groups were stored at 4°C in 1% chloramine, 10% formalin or 0.02% thymol solution. The fourth group was stored at –20°C (no storage solution added). Fluorescence measurements were performed at 14, 77, 113, 168, 232, 486 and 737 days. After 2 years, significant decreases in fluorescence (p < 0.01) for the samples in formalin (–60%), chloramine (–72%) and thymol (–54%) were observed. The frozen teeth showed a slight but non-significant increase in fluorescence of 5% (p > 0.01). Storing solutions have a significant influence on the fluorescence yield. Samples used for in vitro purposes stored frozen do not significantly change their fluorescence response. Thus, cut-off values obtained under the latter conditions could be extrapolated to the in vivo situation.
Effect of Placing a Clear Sealant on the Validity and Reproducibility of Occlusal Caries Detection by a Laser Fluorescence Device: An in vitro Study
Authors: Deery C. , Iloya J. , Nugent Z.J. , Srinivasan V.
Published: May 2006

The principal aim of this in vitro study was to assess the validity and reproducibility of the detection of occlusal caries using laser fluorescence (LF), prior to and following the placement of a clear fissure sealant. It also aimed to compare the manufacturer’s standard cut-off recommendations with those published for in vitro studies and to compare the validity and reproducibility of LF with clinical visual examination (CVE) for the detection of occlusal caries under sealants. Three clinicians independently examined visually and with LF 37 extracted teeth (25 molars, 12 premolars), with a range of clinical caries from apparently sound to cavitated dentinal caries. Examinations were conducted under dental surgery conditions. Subsequently, the teeth were serially sectioned to provide the validating criterion. Following placement of the sealant, the specificity generally increased but there was an associated loss of sensitivity, at both the D1 (enamel and dentine) and D3 (dentine) diagnostic thresholds. The LF readings were significantly lower after placement of the sealant (p < 0.05). The manufacturer’s recommended cut-offs appear to be the most appropriate to use. The CVE had superior validity and reproducibility when compared to LF. Overall, the placement of a clear sealant does influence the detection of caries by LF but does not prevent the detection of caries by this method.
Accuracy and Consistency of the Visual Diagnosis of Exposed Dentine on Worn Occlusal/Incisal Surfaces
Authors: Ganss C. , Klimek J. , Lussi A.
Published: May 2006

Most indices for the assessment of wear of various aetiologies include the distinction between ‘enamel still present’ and ‘dentine exposed’ for grading. Since the visual diagnosis of exposed dentine has not yet been validated, the present study is a first attempt to investigate its accuracy and consistency. Sixty-one examiners (23 scientists, 18 university dentists and 20 dental students) were asked to diagnose 49 tooth areas with different grades of wear and to decide whether dentine was exposed (positive test) or not (negative test). Afterwards, the teeth were histologically evaluated. In 44 areas, dentine (also in all cases with minor wear) was exposed, and in 5 areas enamel was present. Overall sensitivity was 0.65, specificity 0.88 and the proportion of correct diagnoses was 0.67. The diagnosis ‘dentine is exposed’ was about 5 times as likely and the diagnosis ‘dentine is not exposed’ half as likely to come from an area with exposed dentine than from an enamel-covered area. The closeness of the visual diagnosis to the histological findings was only fair (ĸ = 0.27), no significant impact of professional experience was found. For inter- and intra-examiner agreement, ĸ was 0.28 and 0.55, respectively. It was concluded that the diagnosis of exposed dentine is difficult.
Exposure Time of Enamel and Dentine to Saliva for Protection against Erosion: A Study in vitro
Authors: Wetton S. , Hughes J. , West N. , Addy M.
Published: May 2006

Previous research, mainly on enamel, supports a protective role for salivary pellicle against erosion. Pretreatments have tended to be lengthy (24 h or more) and of questionable relevance to the regular intake of acidic food and drink by many individuals. The aim of this study in vitro was to determine the protective effect of salivary pellicle formed on enamel and dentine over time periods up to 4 h. Flattened, polished human enamel and dentine specimens were pretreated with unstimulated human saliva from a single donor for 2 min, 30 min (enamel only), 1, 2, or 4 h. Controls were exposed to water for the same times. Specimens were then exposed to 0.3% citric acid, pH 3.2 for 10 min with stirring. This cycle was carried out 12 times. Tissue loss was measured by profilometry after 3, 6, 9 and 12 cycles. For enamel, statistically significant protection was found at ≧1 h. For dentine, significant protection was achieved at 2 min. Salivary pellicle offered proportionately greater protection to enamel than dentine. Cautiously extrapolating these in vitro data suggests that pellicle should offer erosion protection to individuals who imbibe acidic drinks at frequencies of 1 h or less.
Brushing Abrasion of Eroded Bovine Enamel Pretreated with Topical Fluorides
Authors: Vieira A. , Lugtenborg M. , Ruben J.L. , Huysmans M.C.D.N.J.M.
Published: May 2006

Topical fluorides have been proposed for the prevention of erosive dental wear. This study evaluated the in vitro effect of a single professional application of 4% titanium tetrafluoride (TiF4), 1% amine fluoride (AmF) and 0.1% difluorosilane varnish (FV) in preventing wear due to combined erosion and brushing abrasion. One hundred and eight bovine enamel samples were used. Control groups were not pretreated with any product (C), pretreated with a fluoride-free varnish (FV-bl) or pretreated with fluoride varnish and subsequently submitted to varnish removal (FV-r). Wear was modeled by submitting the fluoride-treated and control groups to 3 cycles of the following regimens: erosion/remineralization (er/remin), abrasion/remineralization (abr/remin) or erosion/abrasion/remineralization (er/abr/remin). Erosion was simulated by immersion of the samples for 10 min in citric acid 50 mM (pH 3). Abrasion was carried out for 1 min (200 strokes, load 150 g) in a wear device. Remineralization (2 h artificial saliva) took place between the cycles. Two-way ANOVA showed that there was a significant interaction (p ≤ 0.001) between the fluoride treatments and the wear regimens. Under er/remin a significant wear protective effect was found for the FV, FV-r and FV-bl groups. Abr/remin resulted in some enamel loss for the TiF4 and AmF groups, but the amounts lost were not statistically significant (p = 0.185 and p = 1.000, respectively). Under er/abr/remin all products showed a significant protective effect, except for TiF4. It was concluded that FV and AmF protected bovine enamel against erosion followed by brushing abrasion in vitro.
In vitro Evaluation of Acidified Toothpastes with Low Fluoride Content
Authors: Brighenti F.L. , Delbem A.C.B. , Buzalaf M.A.R. , Oliveira F.A.L. , Ribeiro D.B. , Sassaki K.T.
Published: May 2006

Fluoride toothpastes are a risk factor for the development of dental fluorosis. Products with low fluoride content offer a higher security, but their effectiveness must be proven. The aim of this in vitro study was to compare two acidified toothpastes with low fluoride concentration (412 and 550 µg F/g) with neutral toothpastes. Bovine enamel blocks were selected by surface microhardness (SMH) and randomized to twelve groups of 13, according to the fluoride concentration in toothpaste (placebo, 275, 412, 550 or 1,100 µg F/g) and pH (7.0 or 5.5). Two commercially available toothpastes were also studied: a 1,100-µg F/g, pH 7.0 paste (positive control) and a children’s paste (500 µg F/g, pH 7.0). The blocks were subjected to pH cycling for 7 days. The toothpaste treatment was done twice daily. Surface and cross-sectional microhardnesses were assessed to calculate the percentage change of SMH (%SMH) and the mineral loss (ΔZ). The amount of fluoride, calcium and phosphorus in the solutions after the pH cycling was also analyzed. Compared to neutral toothpastes, the acidified toothpastes reduced the %SMH in all F concentrations. Higher F and lower Ca and P concentrations were found in solutions for the acidified toothpastes. Regarding ΔZ, only the positive control, 1,100-µg F/g (acidified and neutral) groups were not statistically different. The acidified toothpastes showed a dose-response relationship with all variables. For the low-fluoride toothpastes evaluated, only the 550-µg F/g acidified paste had the same anticariogenic action as the 1,100-µg F/g neutral paste.
Dentin-Pulp Complex Responses to Carious Lesions
Authors: Lee Y.-L. , Liu J. , Clarkson B.H. , Lin C.-P. , Godovikova V. , Ritchie H.H.
Published: May 2006

To understand the molecular events underlying the dentin-pulp complex responses to carious progression, we systematically analyzed tissue morphology and dentin matrix protein distribution in non-carious teeth and in teeth with enamel and dentin caries. Dentin matrix proteins analyzed included collagen type I, phosphophoryn (PP) and dentin sialoprotein (DSP), all of which play decisive roles in the dentin mineralization process. Human non-carious and carious third molar teeth were freshly collected, demineralized, and processed for hematoxylin and eosin staining. The ABC-peroxidase method was used for immunohistochemical staining of collagen type I, PP and DSP proteins using specific antibodies. In situ hybridization was also performed. In contrast to elongated odontoblasts in non-carious teeth, odontoblasts subjacent to dentin caries were cuboidal and fewer in number. The predentin zone was also dramatically reduced in teeth with dentin caries. The staining intensity for collagen type I, PP and DSP in the dentin-pulp complex increased progressively from non-carious teeth, to teeth with enamel and dentin caries. In situ hybridization studies showed DSP-PP mRNA expression in odontoblasts and dental pulp that was consistent with our immunohistochemical results. These results suggest that carious lesions stimulate the dentin-pulp complex to actively synthesize collagen type I, PP and DSP proteins. This response to carious lesions is likely to provide a basis for reparative and/or reactionary dentin formation.
Inhibition of Acid Production in Dental Plaque Bacteria by Green Tea Catechins
Authors: Hirasawa M. , Takada K. , Otake S.
Published: May 2006

The inhibition of acid production from dental plaque and mutans streptococci by epigallocatechin gallate (EGCg), one of the green tea catechins, was examined. The effect of EGCg solution on dental plaque pH was investigated.Subjects rinsed their mouths with 2 mg/ml EGCg solution and then, after 30-min interval, rinsed their mouths with 10% sucrose. Plaque samples were collected at appropriate times and the pH was measured. The pH values of plaque samples from 15 volunteers were significantly higher after treatment with catechin than after treatment with water. EGCg inhibited pH fall when cariogenic bacteria grown in medium with or without sucrose were incubated with sugar. In medium without sucrose, cultured cells were killed time-dependently by EGCg treatment. However, EGCg did not kill cells cultured in medium containing sucrose. Also, EGCg did not kill oral streptococci adhering to a saliva-coated hydroxyapatite disk. EGCg and epicatechin gallate inhibited lactate dehydrogenase activity much more efficiently than epigallocatechin, epicatechin, catechin or gallocatechin. These results suggest that EGCg is effective in reducing acid production in dental plaque and mutans streptococci.
Evaluation of Microbiological Screening Systems Using Dental Plaque Specimens from Young Children Aged 6–36 Months
Authors: Park J.H. , Tanabe Y. , Tinanoff N. , Turng B.F. , Lilli H. , Minah G.E.
Published: May 2006

Using cotton swab specimens of dental plaque from children aged 6–36 months, four commercial chairside tests for oral bacteria were evaluated by comparison with conventional selective culture: mitis salivarius kanamycin bacitracin agar for mutans streptococci and Rogosa SL agar for lactobacilli. Representative colonies of all isolates were identified by commercial identification kits. According to qualitative evaluations, all chairside tests for mutans streptococci were effective in our population. Those for lactobacilli were not as effective, due mainly to a high recovery of yeast contaminants.
Primary Focal Hyperhidrosis: Disease Characteristics and Functional Impairment
Authors: Hamm Henning , Naumann Markus K. , Kowalski Jonathan W. , Kütt Sandra , Kozma Chris , Teale Chris
Published: May 2006

Background: There are few published data on the clinical characteristics of hyperhidrosis. Objective: To describe the functional impairment caused by primary focal hyperhidrosis. Methods: Patients with hyperhidrosis (n = 345) were enrolled at the Department of Dermatology, University of Würzburg. Controls (n = 154) were a convenience sample of subjects without hyperhidrosis. Hyperhidrosis characteristics, health-related quality of life and functional impairment were assessed. Results: Patients with axillary hyperhidrosis reported a later age at onset and a higher prevalence of a family history of hyperhidrosis than patients with palmar hyperhidrosis. Sixty-three percent of patients reported occupational impairment related to hyperhidrosis. Hyperhidrosis patients reported emotional and physical impairment, with a greater proportion of the axillary group reporting impairment. More than 50% of patients reported moderate to extreme impairment in personal relationships and in social situations. Conclusion: Primary focal hyperhidrosis is a serious medical condition, affecting work productivity, daily activities, emotional well-being and personal relationships.
Dermoscopic Features of Congenital Melanocytic Nevus and Becker Nevus in an Adult Male Population: An Analysis with a 10-Fold Magnification
Authors: Ingordo Vito , Iannazzone Silvia S. , Cusano Francesco , Naldi Luigi
Published: May 2006

Background: Dermoscopic features of congenital melanocytic nevi (CMN) have been mostly assessed by high-resolution videodermoscopy. However, optical dermoscopy with the 10-fold magnification is largely available. In some instances, the differential diagnosis between large CMN and Becker nevus (BN) may be difficult. Objective: The aims of this work were: (1) to assess by dermoscopy with the 10-fold magnification the morphological features which have been previously suggested as useful for the identification of CMN in high-resolution videodermoscopy; (2) to search and point out the dermoscopic features of BN; (3) to explore dermoscopic differences between CMN and BN. Methods: The subjects were observed among about 23,000 consecutive young men assessed at the Draft Council’s Medical Unit of the Italian Navy in Taranto for compulsory recruitment and referred to the Department of Dermatology of the Italian Navy Hospital for dermatological examination. Lesions were examined by the same observer using a dermatoscope with a 10-fold magnification, and both the dermoscopic criteria stated by the international Consensus Net Meeting on Dermoscopy and dermoscopic features previously suggested as useful for the identification of CMN by videodermoscopy were recorded in a predisposed patient’s card. Results: There were 127 male subjects, median age 19 years, with 127 CMN, measuring ≧1.5 to ≤19.9 cm in 78% and ≧20 cm in 22% of cases, and 64 male subjects, median age 19 years, with 64 BN. In the sample of medium-sized and large CMN, dermoscopic features previously identified as characteristic of congenital lesions (i.e. target network, focal thickening of network lines, target globules, skin furrow hypopigmentation, focal hypopigmentation, hair follicles, perifollicular hypopigmentation, vessels and target vessels) were observed in sufficiently high rates. In the BN group, network, focal hypopigmentation, skin furrow hypopigmentation, hair follicles, perifollicular hypopigmentation and vessels were the main dermoscopic features. Focal thickening of network lines, globules, target globules, homogeneous diffuse pigmentation, hyperpigmented areas, blotches and target vessels were more frequently observed in CMN than in BN. Conclusions: (1) The same dermoscopic features observed in small and medium-sized CMN by videodermoscopy with high magnifications are also detectable in medium-sized and large CMN, employing the dermoscopy with the 10-fold magnification. (2) Network, focal, skin furrow and perifollicular hypopigmentation, hair follicles and vessels could be considered as peculiar dermoscopic features of BN. (3) Major differences in the frequency of dermoscopic characteristics were detected between CMN and BN, and dermoscopy seems to provide some diagnostic aid in differentiating CMN from BN in equivocal cases.
A Comparison of the Efficacy, Relapse Rate and Side Effects among Three Modalities of Systemic Corticosteroid Therapy for Alopecia Areata
Authors: Kurosawa Masahiro , Nakagawa Satoshi , Mizuashi Masato , Sasaki Yoshinori , Kawamura Maki , Saito Makiko , Aiba Setsuya
Published: May 2006

Background: Systemic corticosteroids are one of the most commonly used therapeutic modalities for patients with extensive alopecia areata (AA), although they entail several drawbacks. Objective: To determine the best modality for systemic corticosteroid use in terms of their efficacy, relapse rate, and side effects. Methods: Fifty-one patients with single or multiple AA (AA/multiplex) and 38 patients with alopecia totalis or AA universalis (AA totalis/universalis) were enrolled in this open study. They were randomly divided into three groups depending on the time of their initial visit. They were administered (1) oral dexamethasone (Dex) 0.5 mg/day for 6 months (Dex group), (2) intramuscular triamcinolone acetonide (imTA) 40 mg once a month for 6 months followed by 40 mg once every 1.5 months for 1 year (imTA group), and (3) pulse therapy (PT) using oral predonine 80 mg for 3 consecutive days once every 3 months (PT group). After the treatment, each treatment modality was evaluated by the response rate, relapse rate, and side effect profile. Results: The response rate of AA/multiplex was significantly better in the imTA group than in the Dex group. The overall relapse rate and that of AA totalis/universalis were significantly better in the PT group than in the Dex group. Dysmenorrhea was the most common and problematic side effect. Impairment of the adrenocortical reserve was seen in 7% of the PT group and 23% of the imTA group, which was recov ered without any further medical treatment. Conclusion: imTA or pulse therapy is effective for AA and has an acceptable level of side effects. The development of a new strategy to reduce the relapse rate is needed.
Successful Treatment of Nodular Actinic Reticuloid with Tacrolimus Ointment
Authors: Gröne Dirk , Kunz Manfred , Zimmermann Regina , Gross Gerd
Published: May 2006

Actinic reticuloid (AR) is the severest clinical variant of chronic actinic dermatitis (CAD) and describes a persistent photoinduced skin disorder often associated with delayed-type hypersensitivity reactions. Histopathologically, AR resembles pseudolymphoma and may also show features of cutaneous lymphoma. In contrast to other UV-induced skin diseases, AR patients show persistent photosensitivity to UV radiation and visible light parallel to permanent changes of skin texture with infiltrated papules and thickened plaques. Therapeutically, CAD is a problematic condition. Daily application of sun protection has to be combined with local or systemic immunosuppression. However, various therapeutic approaches including systemic corticosteroids and other systemic immunosuppressive agents are limited by severe side effects. Tacrolimus, a Streptomyces-derived immunosuppressive macrolide antibiotic and inhibitor of calcineurin, has been proven successful in vari ous inflammatory skin diseases including atopic eczema, allergic contact dermatitis and photodermatoses without undesired side effects. We present a case of severe recalcitrant and nodular chronic actinic dermatitis responding to topically applied tacrolimus (Protopic®). To avoid further relapses we continued this therapy twice a day over a period of 2 years.
Bothrojaracin, a Bothrops jararaca Snake Venom-Derived (Pro)Thrombin Inhibitor, as an Anti-Thrombotic Molecule
Authors: Zingali Russolina B. , Ferreira Marcos S. , Assafim Mariane , Frattani Flávia S. , Monteiro Robson Q.
Published: May 2006

Bothrojaracin (BJC) is a selective and potent thrombin inhibitor (KD = 0.6 nM) which also binds to prothrombin on proexosite I (KD = 175 nM). Incubation of BJC with human or rat plasma produced a band that co-migrates with purified prothrombin-BJC complex. We further analyzed the in vivo anti-thrombotic effect of BJC on a venous thrombosis model in rats that combines stasis and hypercoagulability. The administration of 1 mg/kg (i.v.) doses of BJC decreased thrombus weight by ∼95%. Evaluation of the in vivo effect of BJC in mice using a pulmonary thromboembolism model induced by thrombin showed that BJC protects 100% of mice from death. Altogether, our data show that BJC is a potent anti-thrombotic agent that could further help the development of new prothrombin-directed drugs.
Contortrostatin, a Snake Venom Disintegrin with Anti-Angiogenic and Anti-Tumor Activity
Authors: Swenson Stephen , Costa Fritz , Ernst William , Fujii Gary , Markland Francis S.
Published: May 2006

Disintegrins are soluble peptides found in snake venom. They bind to Arg-Gly-Asp (RGD)-responsive integrins with high affinity (nM range) and block integrin function. Contortrostatin (CN), the disintegrin from southern copperhead venom, is a homodimer with a molecular weight of 13,500. Each chain contains 65 amino acids with an Arg-Gly-Asp motif. CN has anti-invasive and anti-adhesive activity on tumor cells and endothelial cells in vitro, and binds to integrins αvβ3, αvβ5, and/or α5β1. In vivo studies using the human metastatic breast cancer cell line MDA-MB-435, in an orthotopic xenograft model in nude mice, revealed that CN has potent anti-tumor and anti-angiogenic activity. Recent studies have employed an intravenous liposomal delivery procedure. Liposomal delivery of CN has also been shown to provide effective in vivo anti-tumor and anti-angiogenic activity in a human ovarian cancer animal model.
Development of a Novel Recombinant Disintegrin, Contortrostatin, as an Effective Anti-Tumor and Anti-Angiogenic Agent
Authors: Minea Radu , Swenson Stephen , Costa Fritz , Chen Thomas C. , Markland Francis S.
Published: May 2006

Contortrostatin (CN) (Mr 13,500 Da) is a novel homodimeric disintegrin isolated from the venom of Agkistrodon contortrix contortrix (Southern Copperhead) snake and displays two RGD motifs (one on each chain), which modulate its interaction with integrins on tumor cells and angiogenic vascular endothelial cells. In previous studies, we have shown that native CN administered in a liposomal formulation exhibits potent anti-angiogenic and tumor growth inhibitory activities. Current isolation of the protein from crude venom is difficult and prohibitively expensive for translation into the clinic. In this report, we describe a method amenable to large-scale production of a soluble monomeric form of recombinant CN with biologic activity; the protein is expressed directly in the cytoplasm of an engineered bacterial system with an expression yield of approximately 20 mg/l of culture. We present here the in vitro assays as well as the anti-tumor and anti-angiogenic evaluation of liposomal recombinant CN in an orthotopic, xenograft model of human breast cancer.
C-Terminal Heparin-Binding Peptide of Snake Venom VEGF Specifically Blocks VEGF-Stimulated Endothelial Cell Proliferation
Authors: Yamazaki Yasuo , Tokunaga Yuko , Takani Koji , Morita Takashi
Published: May 2006

Vascular endothelial growth factor-A165 (VEGF-A165) exhibits diverse biological effects through binding to its receptor KDR (VEGFR-2). Heparin-like molecules are known to modulate their interaction. There have been reports that VEGF-A lacking the C-terminal heparin binding region significantly reduced mitogenic activity. Recently, we found novel heparin-binding VEGFs from snake venoms, designated VEGF-Fs, which specifically recognize kinase domain containing receptor (KDR). The C-terminal heparin-binding region is almost completely absent in VEGF-Fs when compared with other heparin-binding VEGFs, despite their heparin-binding potential. In this congress, we report that the C-terminal heparin-binding region of VEGF-F specifically/preferentially interacts with the VEGF-bondable heparin/heparan sulfate, but not with those associated with bFGF or TFPI. We also present the identification of a VEGF receptor-binding protein from the venom of eastern cottonmouth (Agkistrodon piscivorus piscivorus). Sequence analysis revealed the isolated KDR-binding protein (designated KDR-bp) is identical to Lys49PLA2, an inactive PLA2 homologue with strong myoxicity. KDR-bp binds to the extracellular domain of KDR with subnanomolar affinity. The interaction between KDR-bp and KDR was blocked by VEGF-A165, and KDR-bp specifically inhibited VEGF-A165-stimulated endothelial cell proliferation, indicating KDR-bp is an antagonistic ligand for KDR. This is the first observation demonstrating that an exogenous factor antagonizes the VEGF receptor, furthermore, it is the first identification of the target molecule of the myotoxic PLA2 from viper venom.
Serine Proteases Affecting Blood Coagulation and Fibrinolysis from Snake Venoms
Authors: Kini R. Manjunatha
Published: May 2006

Snake venom proteases, in addition to their contribution to the digestion of the prey, affect various physiological functions. They affect platelet aggregation, blood coagulation, fibrinolysis, complement system, blood pressure and nervous system. This review provides a ready reference for serine proteases that interfere in blood coagulation and fibrinolysis. They exhibit their activity by activation of specific zymogens of coagulation factors. These serine proteases serve as tools to study molecular details in the activation of specific factors involved in coagulation and fibrinolytic cascades and are useful in treating various thrombotic and hemostatic conditions.
Gene Structures of Trocarin D and Coagulation Factor X, Two Functionally Diverse Prothrombin Activators from Australian Rough Scaled Snake
Authors: Reza M. Abu , Swarup Sanjay , Kini R. Manjunatha
Published: May 2006

Activation of prothrombin to thrombin is the key reaction in blood coagulation cascade. We have recently shown that Australian rough scaled snake, Tropidechis carinatus, possesses two parallel prothrombin activator systems. Trocarin D, a venom prothrombin activator produced in the venom gland, plays an offensive role as a toxin, whereas factor X is produced in the liver and plays a role in the hemostatic mechanism. These two proteins are structurally similar and have identical domain architecture. Because of the differences in their physiological roles, and tissue-specific expression, we determined the gene structure of these closely related proteins. Both the genes have eight exons similar to all mammalian factor X genes. All the exon-intron boundaries of these two genes are at the same position and the splice junctions are almost identical. Partial sequencing of the introns shows that they share a very high degree of sequence identity indicating that the gene duplication is a recent event. Further studies on the characterization of these two genes particularly the promoter regions are in progress.
Vipera lebetina Venom Contains All Types of Snake Venom Metalloproteases
Authors: Siigur J. , Tõnismägi K. , Trummal K. , Aaspõllu A. , Samel M. , Vija H. , Subbi J. , Kalkkinen N. , Siigur E.
Published: May 2006

Snake venoms contain four classes of metalloproteases that all have a typical zinc-chelating sequence (HEXXHGXXH). N-terminal sequences and internal sequences of different purified metalloproteases were determined using Edman sequencing and LC MS/MS technique. Oligonucleotideswere designed and used as primers for cDNA cloning from Vipera lebetina venom gland cDNA library. We found that isoforms of fibrinolytic enzyme lebetase Le-4 and Le-3 are synthesized in different way: Le-4 is synthesized as P-I type metalloprotease, Le-3 is synthesized with disintegrin-like domain as P-II type protease and processed post-translationally. An endothelial cell apoptosis-inducing heterodimeric glycosylated metalloprotease, V. lebetina apoptosis-inducing protease (VLAIP), belongs to P-III type containing metalloprotease, disintegrin-like and cysteine-rich domains. All these enzymes hydrolyze the Aα-chain and more slowly the Bβ-chain of fibrinogen. Treatment of HUVEC cells with VLAIP induces changes in the attachment of cells to the substrate and causes apoptosis. V. lebetina venom contains also P-IV type-specific coagulant factor X activator (VLFXA) that cleaves the Arg52-Ile53 bond in the heavy chain of human factor X. VLFXA is a glycoprotein composed of a heavy chain and two C-type lectin-like light chains linked by disulfide bonds. The heavy and light chains of VLFXA are synthesized from different genes.
Non-Clinical and Clinical Characterization of a Novel Acting Thrombolytic: Alfimeprase
Authors: Deitcher Steven R. , Toombs Christopher F.
Published: May 2006

Alfimeprase (ALF) is a recombinant, truncated form of fibrolase, a directly fibrinolytic zinc metalloproteinase that was first isolated from the venom of the Southern copperhead snake (Agkistrodon contortrix contortrix). ALF has direct proteolytic activity against the fibrin(ogen) Aα chain. ALF can be covalently bound and neutralized by serum α2-macroglobulin, a prevalent mammalian protease inhibitor. Preclinical pharmacology studies have shown that thrombolysis with ALF is up to 6-times more rapid than with select plasminogen activators. Additional studies suggest that intra-thrombus ALF has the potential to be a fast and effective thrombolytic without generation of a systemic lytic state. Investigations of phases 1 and 2 indicate that ALF is active and generally well tolerated. This paper reviews the biochemical characteristics of ALF and a review of the preliminary clinical experience in subjects with acute peripheral arterial occlusion and in those with central venous access device occlusion.
Exploring New Molecules and Activities from Lonomia obliqua Caterpillars
Authors: Chudzinski-Tavassi Ana Marisa , Alvarez Flores Miryam Paola
Published: May 2006

Skin contact with Lonomia caterpillar bristles causes a consumptive coagulopathy. From a cDNA library we cloned and expressed a prothrombin activator (rLopap) in active form, and from the bristles extract we characterized a FX activator (Losac). Several clones were sequenced and analyzed by expressed sequence tags. A database of about 1,270 sequences was constructed and deposited in NCBI. Both the native protein from the venom (Lopap) and the recombinant form (r-Lopap) promoted prothrombin hydrolysis, generating prethrombin-2, F1.2 and thrombin. Losac is a single-chain (43 kDa) protein that cleaves the FX heavy chain producing FXaα. In HUVECs rLopap and Losac are able to modulate cell survival by preventing apoptosis. rLopap increases NO and PGI2 concentration and Losac induces t-PA expression. Finally, to identify the venom proteins related to human envenomation, a 2D electrophoresis map is being performed as an attempt to find the major toxins recognized by the anti-lonomia venom.
The Potential of Bothrops moojeni Venom in the Field of Hemostasis
Authors: Perchuc Anna Maria , Menin Laure , Stöcklin Reto , Bühler Beatrice , Schöni Reto
Published: May 2006

Early studies in the 1930s on the venom of South American Lancehead snakesofthe Bothrops genuslead to the discovery of compounds active in blood coagulation such as batroxobin and botrocetin. The scope of our investigations is to have a deeper look at the crude venom of B. moojeni using state-of-the-art proteomics methods, as well as newly developed bioassays screening for activities in the different fields of application. The proteomics techniques used up to now have included different chromatography methods, mass spectrometry, and bio-computing. The bioassays are focussed on enzymatic and other activities in the field of hemostasis and fibrinolysis. Besides the known activities several new and interesting ones have been found. They still need to be studied and confirmed in more specific supplementary assays.
Dejerine-Sottas Disease (Progressive Hypertrophic Polyneuropathy)
Authors: Pearce J.M.S.
Published: May 2006

This paper records parts of Dejerine and Sottas’s description of the syndrome that bears their names. It outlines biographical elements of Dejerine’s work. The modern classification and the role of myelin protein mutations are briefly described.
Seasonal Variation in Stroke and Stroke-Associated Mortality in Patients with a Hospital Diagnosis of Nonvalvular Atrial Fibrillation or Flutter
Authors: Frost Lars , Vukelic Andersen Ljubica , Mortensen Leif Spange , Dethlefsen Claus
Published: May 2006

Aim: There are few data on seasonal variation in stroke and seasonal variation in mortality after stroke in patients with atrial fibrillation. We examined the seasonal pattern in stroke occurrence and the effect of the season on mortality after stroke in patients with a history of nonvalvular atrial fibrillation. Methods:We identified all individuals, aged 40–89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980–2002 period and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used periodic regression models to estimate the peak-trough ratio stratified by sex, age and comorbid medical conditions. Seasonal effect on mortality after stroke was analyzed in a Cox proportional hazards model. Results: The relative incidence of stroke estimated as the ratio of the incidence in the month of the peak (January) to the incidence in the month of the trough (July) was 1.11 (95% confidence interval: 1.07–1.15). The relative incidence of stroke was similar for men and women, did not differ by age (stratified by age 75 years) and was essentially similar for comorbid conditions considered. There was no seasonal effect on mortality after stroke. Conclusions: The occurrence of stroke in patients with atrial fibrillation is modestly higher during the winter. Stroke-associated mortality does not vary by season.
Is There Evidence that Geraniol Causes Allergic Contact Dermatitis?
Authors: Hostýnek Jurij J. , Maibach Howard I.
Published: May 2006

The fragrance material geraniol has been cited as a frequent cause of allergic contact dermatitis. A review of the literature shows that when the underlying clinical and experimental data are analyzed, a clear cause-effect relationship has infrequently or rarely been established. On the basis of the generally weak sensitizing potential of this substance coupled with its generally low exposure conditions, the prevalence of clinical cases would not be expected to be particularly high. This is not to say that geraniol is a frequent inducer of type IV allergy in members of the public. It remains to be seen, however, how often such allergy, once established, is responsible for any of the cases of allergic contact dermatitis commonly ascribed in the literature. Indeed, in some cases, patch-test conditions may not be optimal for differentiating between clinically relevant and irrelevant allergy to geraniol. Because of the numerous publications on geraniol-positive patch-test publications, a future effort to ascertain how many of these represent clinical intolerance is indicated. This will also permit determination of the NOEL (no observed effect level) in patch and use testing.
Prediction of Coronary Artery Disease by Transesophageal Echocardiographic Detection of Thoracic Aortic Plaque in Patients with Chronic Kidney Disease
Authors: Leskinen Yrjö , Groundstroem Kaj , Virtanen Vesa , Lehtimäki Terho , Huhtala Heini , Saha Heikki
Published: May 2006

Background/Aims: Our aim was to examine the significance of thoracic aortic plaque detected by transesophageal echocardiography (TEE) in the prediction of coronary artery disease (CAD) in patients with chronic kidney disease (CKD). Methods: We examined 118 patients (mean age 52 ± 12 years) with CKD and followed them for a mean of 3.4 ± 0.8 years. The study group included 52 predialysis patients with moderate to severe CKD (plasma creatinine ≧200 µmol/l), 32 patients on dialysis treatment, and 34 renal transplant recipients. At baseline, TEE was performed to evaluate thoracic aortic atherosclerosis. CAD was defined by a history of a documented myocardial infarction, a coronary angiogram or a post-mortem autopsy finding showing significant occlusive CAD by the end of the follow-up period. Results: CAD was documented in 31 (26%) of the 118 study patients. The presence of thoracic aortic plaque had a sensitivity of 100% and a specificity of 37% for CAD and the positive and negative predictive values were 36 and 100%, respectively. In the subset of 36 patients with morphological findings of coronary arteries by angiogram or autopsy, the presence of large thoracic aortic plaques (≧3 mm in diameter) had a 73% sensitivity and 90% specificity for significant coronary artery stenosis. The positive and negative predictive values were 95 and 56%, respectively. Conclusion: TEE may be used for detecting high-risk patients with CKD; the absence of thoracic aortic plaque predicted the absence of CAD, and the presence of large aortic plaques predicted significant coronary artery stenosis.
Reliability of Magnetic Resonance Imaging for Measuring the Volumetric Indices in Autosomal-Dominant Polycystic Kidney Disease: Correlation with Hypertension and Renal Function
Authors: Lee Young Rae , Lee Kyu-Beck
Published: May 2006

Background: The purpose of this study was to determine if renal volumetric indices can be accurately measured using MRI, and if these volumetric indices are associated with hypertension and renal function in patients with autosomal-dominant polycystic kidney disease (ADPKD). Methods: For testing the accuracy of the MRI-based volume measurements that we proposed for clinical trial, we designed phantoms to simulate cysts within the kidney. Fifty-six patients with ADPKD were included in this study, and their respiratory compensated T2-weighted fast spin-echo images were acquired. The total kidney volume (Vt), cyst volume (Vc), and noncystic parenchymal volume (Vp) were measured and the percent cyst volume (Pc) was calculated. These volumetric indices were compared with the disease progression in the ADPKD patients. Results: The MRI measures of the phantoms were accurate. The Vt, Vc and Pc were significantly greater in the hypertensive group (n = 35) than in the normotensive group (n = 21) (p < 0.01). The Vt, Vc and Pc were significantly greater in the renal failure group (n = 23) than in the normal renal function group (n = 33) (p < 0.01). The Vt, Vc, and Pc were inversely correlated with the creatinine clearance. Conclusion: MRI is a reliable method to measure renal volumetric indices. The MRI-based volume measurements can be employed as useful markers for the progression of disease in ADPKD patients.
Elimination of Piperacillin and Tazobactam by Renal Replacement Therapies with AN69 and Polysulfone Hemofilters: Evaluation of the Sieving Coefficient
Authors: Arzuaga A. , Isla A. , Gascón A.R. , Maynar J. , Corral E. , Pedraz J.L.
Published: May 2006

Background/Aim: Piperacillin-tazobactam is commonly used to treat infections in ICU patients. Controversial data have been published about the sieving/saturation coefficient (Sc/Sa) of piperacillin during continuous renal replacement therapies (CRRT). The objective was to evaluate the Sc/Sa of piperacillin-tazobactam during continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) using AN69 and polysulfone. Methods: Ringer lactate, BSA-containing Ringer lactate and plasma were circulated at 150 ml/min. The ultrafiltrate/dialysis flow was kept at 1,500 ml/min. A bolus was injected and samples were taken. Drugs were measured using HPLC. Sc/Sa was calculated according to standard formula. Results: Free passage of drugs through the membranes was reported with protein free solutions. In the presence of proteins the Sc/Sa lowered and correlated to protein free fraction. Polysulfone had a significantly higher permeability than AN69 during CVVH. Conclusion: Drug binding to albumin contributes to the decrease of the Sc/Sa of piperacillin but it does not completely justify the in vivo value obtained by some authors.
Antiplatelet Cilostazol Is Effective in the Prevention of Pneumonia in Ischemic Stroke Patients in the Chronic Stage
Authors: Shinohara Yukito
Published: May 2006

We have previously reported that the phosphodiesterase inhibitor cilostazol, an antiplatelet agent, is effective and safe for secondary prevention of recurrent cerebral infarction (Cilostazol Stroke Prevention Study; CSPS). We now report the efficacy of this drug in the prevention of pneumonia in the chronic stage of cerebral infarction as a part of our CSPS subgroup analysis. The analysis was conducted in 1,049 subjects; 524 in the cilostazol group and 525 in the placebo group. The incidences of pneumonia during the 3.3-year follow-up were 2.86% (15 in 525 patients) in the placebo group and 0.57% (3 in 524 patients) in the cilostazol group, with a significant reduction in the cilostazol group. The rates of complications and pneumonia risk factors showed no difference between the two groups. We conclude that the administration of cilostazol to patients with cerebral infarction in the chronic stage does not only reduce the recurrence of infarction but also the incidence of pneumonia at least in Japanese patients.
Poststroke Dementia
Authors: Hénon H. , Pasquier F. , Leys D.
Published: May 2006

The association between stroke and dementia is frequent. The prevalence of poststroke dementia (PSD) ranges from 6 to 32%, depending on the population studied, the criteria used for the diagnosis of dementia, and the time interval between the stroke and the neuropsychological assessment. The risk of PSD is high immediately after stroke and remains higher than in controls in stroke patients nondemented 3 months after stroke. Not all cases of PSD are vascular in origin, with about one third of demented patients diagnosed as having Alzheimer’s disease plus stroke. The pathophysiology of PSD is probably multifactorial, with an influence of vascular lesions, associated Alzheimer’s lesions and white matter changes. The risk of dementia is higher in older patients and in patients with preexisting cognitive decline – no dementia, severe stroke, a history of stroke, white matter changes and cerebral atrophy. The influence of stroke location, vascular risk factors and silent infarcts remains to be determined. PSD adversely influences the outcome in stroke patients.