bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Fetal Vasculature and Severe Protein C Deficiency
Authors: Douglas A.G.L. , Rafferty H. , Hodgkins P. , Nagra A. , Foulds N.C. , Morgan M. , Temple I.K.
Published: August 2010

Persistent fetal vasculature (PFV) is most often a condition of unknown cause. It represents persisting elements of fetal ocular vessels including the hyaloid arterial network. Protein C is a vitamin K-dependent serine protease, which regulates coagulation. Deficiency of protein C leads to a prothrombotic state. We report the case of a male infant born at 34 weeks gestation to non-consanguineous parents. Ophthalmic examination found bilateral PFV, microphthalmia and vitreoretinal dysplasia. He also suffered bilateral renal vein thrombosis and purpura fulminans and was diagnosed with severe protein C deficiency. Genetic analysis of the PROC gene revealed two separate pathogenic mutations, confirming compound heterozygote status. Both parents were found to be heterozygous. While ocular manifestations (commonly haemorrhages) are often seen in protein C-deficient patients, a search of the literature reveals very few recorded cases of PFV in severe protein C deficiency. We hypothesise that protein C deficiency was the cause of PFV in this patient. Intraocular thrombotic events in utero could affect the normal development of ocular vessels and lead to persistent elements of fetal vasculature in the eye. Consideration should be given to the possibility of protein C deficiency in patients presenting with PFV, particularly if bilateral.
Diagnosis of Macular Edema
Authors: Cunha-Vaz José , Coscas Gabriel
Published: August 2010

Macular edema may be intracellular or extracellular. Intracellular accumulation of fluid (cytotoxic edema) is an alteration of the cellular ionic distribution. Extracellular accumulation of fluid is more frequent and clinically more relevant, and is directly associated with an alteration of the blood-retinal barrier. Fluorescein angiography has been critical for detecting macular edema and currently remains the ‘gold standard’ for its diagnosis by identifying the characteristic stellar pattern of cystoid macular edema, also providing a qualitative assessment of vascular leakage essential for identifying treatable lesions. The clinical diagnosis of macular edema, recognition of its main etiologies and its treatment have greatly improved due to multiple and remarkable advances in modern imaging technologies. By correlating results from fluorescein angiography and optical coherence tomography (OCT), fluid accumulation within and under the sensory retina can be confirmed and located. We are now able to measure changes in retinal thickness and use noninvasive instrumentation in a clinical setting to identify macular edema. Moreover, spectral-domain OCT can characterize the presence and integrity of the external limiting membrane and the photoreceptor inner and outer segments, which is useful information for prognosis as well as a guide for treatment. The diagnosis of macular edema and its clinical forms is now based primarily on the correlation of these imaging techniques.
Water Immersion-Induced Skin Wrinkling Is Related to Heart Rate Variability
Authors: Win Sithu , Salciccioli Louis , Kamran Haroon , Baweja Paramdeep , Stewart Mark , Lazar Jason M.
Published: August 2010

Water immersion-induced skin wrinkling (WISW) is dependent on intact peripheral sympathetic function. WISW was hypothesized to reflect autonomic function in subjects without peripheral neuropathy. We prospectively studied 70 healthy subjects (aged 31 ± 8 years, 63% females) without cardiovascular risk factors or neurological disease. All subjects underwent short-term heart rate variability (HRV) studies. Time and frequency domain variables were derived including the HRV index. WISW was graded using a previously validated scale of 1–4 of which 18.6% of subjects exhibited grade 1 (minimal) WISW and 35.7% had grade 2 WISW. On multivariate analysis using the HRV index, WISW was independently related to height and the HRV index. We conclude that WISW is related to central autonomic function.
Association of the Preoperative Photoreceptor Layer Defect as Assessed by Optical Coherence Tomography with the Functional Outcome after Macular Hole Closure: A Long Follow-Up Study
Authors: Grigoropoulos Vlassis G. , Theodossiadis George P. , Theodossiadis Panagiotis G.
Published: August 2010

Background: To evaluate the correlation between the extent of the inner/outer segment (IS/OS) defect preoperatively and improvement in postoperative best-corrected visual acuity (BCVA) associated with IS/OS line restoration. Methods: Forty-six eyes (46 patients) with successfully operated idiopathic full-thickness macular holes were studied using Stratus OCT3 with a mean follow-up of 34.7 months (range 24–60 months). The preoperative extent of the IS/OS junction defect, macular hole base diameter (MHBD) and BCVA were studied before surgery. The degree of IS/OS line restoration, macular thickness and BCVA were measured after treatment. Results: The mean preoperative MHBD and IS/OS defect size were 783 and 1,973 µm, respectively. Postoperative continuity of the IS/OS junction was observed in 11 of 46 cases 12 months after treatment. In the remaining 35 patients, the IS/OS line was interrupted at 12 months of follow-up. The size of the preoperative IS/OS defect line was negatively correlated with the size of the postoperative IS/OS line and BCVA at 6 months and 12 months only (p < 0.0001). In all 46 eyes, the mean BCVA before and 12 months after treatment was 10 and 36.7 letters, respectively. BCVA remained almost unchanged after the first postoperative year of observation. Conclusions: The degree of reorganization of the photoreceptor layer after successful macular hole closure varies and is mostly related to the preoperative extent of the IS/OS defect line and the MHBD. A small-sized IS/OS preoperative defect favors improvement and restoration of the IS/OS line after treatment. The IS/OS junction line and BCVA are mostly restored during the first 12 months after treatment.
Heavy-Chain Complementarity-Determining Regions Determine Conformation Selectivity of Anti-Aβ Antibodies
Authors: Sehlin Dag , Hedlund Marie , Lord Anna , Englund Hillevi , Gellerfors Pär , Paulie Staffan , Lannfelt Lars , Pettersson Frida Ekholm
Published: August 2010

Background/Aims: Amyloid-β (Aβ) protofibrils are neurotoxic soluble intermediates in the Aβ aggregation process eventually forming senile plaques in Alzheimer’s disease. This Aβ species is a potential biomarker for Alzheimer’s disease and also a promising target for immunotherapy. In this study, we investigated the characteristics of conformation-dependent Aβ antibodies specific for Aβ protofibrils. Methods: Mice were immunized with Aβ protofibrils to generate hybridomas producing Aβ-specific monoclonal antibodies. Binding of antibodies to different Aβ conformations was investigated with inhibition ELISA. The antibodies’ complementarity-determining region (CDR) sequences were determined and compared. Results: A majority of the antibodies were of the IgM class, all selectively binding to aggregated Aβ. Two IgG antibodies were generated: one with selective affinity for Aβ protofibrils and the other bound Aβ in all conformations. A high degree of similarity between the heavy-chain CDRs of the conformation-dependent antibodies was found, and all high-affinity Aβ antibodies displayed a high degree of sequence similarity in the light-chain CDRs. Conclusion: Sequence similarity in the heavy-chain CDRs is associated with conformation selectivity of the antibodies, while sequence similarity in the light-chain CDRs correlates with the affinity for Aβ.
Feeding Ecology, Food Availability and Ranging Patterns of Wild Hamadryas Baboons at Filoha
Authors: Schreier Amy L.
Published: August 2010

Most hamadryas baboons rely on Acacia species for subsistence in their semidesert habitats. Unlike other hamadryas sites, palm forests at Filoha in Awash National Park, Ethiopia, provide the baboons with a preferred food resource close to a commonly used sleeping site. The baboons are expected to feed on doum palm trees when fruit is available, and this resource use should play a role in ranging patterns. This paper describes the feeding ecology, food availability and ranging patterns of a band of wild hamadryas baboons at Filoha from March 2005 to February 2006. Data on feeding and ranging behavior derive from band scans during all-day follows of baboons, and data on food availability derive from monthly phenological monitoring of frequently consumed food species. The baboons fed predominantly on palms when fruit was available, and preferred the flowers of Acacia senegal to its leaves. There was no relationship between daily path length and the proportion of palm fruit in the baboons’ diet, but changes in the availability of fruit across the Filoha region appear to mirror the baboons’ shifting use of its home range. The large band sizes at Filoha may obscure the effects doum palm fruit might have on ranging patterns.
Detection of Paroxysmal Atrial Fibrillation in Acute Stroke Patients
Authors: Rizos T. , Rasch C. , Jenetzky E. , Hametner C. , Kathoefer S. , Reinhardt R. , Hepp T. , Hacke W. , Veltkamp R.
Published: August 2010

Background: Atrial fibrillation (AF) is a frequent cause of stroke, but detecting paroxysmal AF (pAF) poses a challenge. We investigated whether continuous bedside ECG monitoring in a stroke unit detects pAF more sensitively than 24-hour Holter ECG, and tested whether examining RR interval dynamics on short-term ECG recordings using an automated screening algorithm (ASA) for pAF detection is a useful tool to predict the risk of pAF outside periods of manifest AF. Methods: Patients >60 years with acute ischemic stroke or transient ischemic attacks (TIA) were prospectively enrolled unless initial ECG revealed AF or they had a history of paroxysmal or persistent AF. ASA was performed on 1- to 2-hour ECG recordings in the emergency room and patients were classified into 5 risk categories for pAF. All patients underwent continuous bedside ECG monitoring for >48 h. Additionally, 24-hour Holter ECG was performed. Results: 136 patients were enrolled (median age: 72 years, male: 58.8%). In 29 (21.3%), pAF was newly diagnosed by continuous bedside ECG monitoring. pAF increased with age (p = 0.031). Median time to first pAF detection on continuous bedside ECG monitoring was 36 h. In 16 patients, pAF was detected by continuous bedside ECG monitoring prior to the performance of 24-hour Holter ECG. Thirteen of the remaining patients were pAF positive on continuous bedside ECG monitoring, but 24-hour Holter detected only 3 patients. Accordingly, the sensitivity of 24-hour Holter was 0.23. Sensitivity of higher-risk categories of ASA compared to continuous bedside ECG monitoring was 0.72, and specificity 0.63. Conclusion: Continuous bedside ECG monitoring is more sensitive than 24-hour Holter ECG for pAF detection in acute stroke/TIA patients. Screening patients for pAF outside AF episodes using ASA requires further development.
Nicotinic Ligands Modulate Ethanol-Induced Dopamine Function in Mice
Authors: Sajja Ravi K. , Dwivedi Chandradhar , Rahman Shafiqur
Published: August 2010

The aim of the present study was to examine the effects of two neuronal nicotinic acetylcholine receptor ligands on acute ethanol-induced dopamine (DA) function in the C57BL/6J mouse ventral striatumusing an ex vivo assay and high-performance liquid chromatography coupled with electrochemicaldetection. Acute systemic injection of ethanol (2.5 g/kg) significantly increased the DA and dihydroxyphenylacetic acid (DOPAC) content in the ventral striatum. Pretreatment with lobeline (1 or 10 mg/kg) inhibited the ethanol-induced increase in the tissue DA and DOPAC content in the ventral striatum. Similarly, pretreatment with cytisine (0.5 or 3 mg/kg) also reduced the ethanol-induced increase in the tissue DA and DOPAC content in the ventral striatum. However, when given alone lobeline or cytisine did not produce significant effect on the DA or DOPAC content in the ventral striatum compared with controls. These findings provide evidence that lobeline and cytisine modulate ethanol-induced DA function by targeting nicotinic acetylcholine receptors in the ventral striatum, a reward-relevant brain region implicated in ethanol dependence.
An Alternative Approach to Determine Oral Bioavailability of Drugs That Follow Michaelis-Menten Elimination: A Case Study with Vorizonazole
Authors: Araujo Bibiana Verlindo de , Farias da Silva Cristófer , Dalla Costa Teresa
Published: August 2010

Background/Aims: The determination of oral bioavailability of drugs which follow nonlinear pharmacokinetics is difficult and few methods are available. In this work, an alternative approach to determine oral bioavailability of voriconazole (VRC), used as a model drug, is presented. Methods: VRC pharmacokinetics was investigated in Wistar rats after p.o. (40 mg/kg) and i.v. administration (2.5, 5 and 10 mg/kg). VRC elimination showed saturation in all doses investigated, except the lower i.v. dose in which case a 3-compartment model with linear elimination adequately fitted the data. Data for the 2 higher i.v. doses were best described by a 3-compartment model with Michaelis-Menten elimination. A 1-compartment disposition with a saturable metabolic elimination model described the oral profile. VRC absolute oral bioavailability was determined by simultaneous fitting of the i.v. and oral profiles. Results: The Michaelis constant and the maximum velocity estimated after 5 and 10 mg/kg i.v. dosing were 0.54 ± 0.25 µg/ml and 2.53 ± 0.54 µg/h, and 0.62 ± 0.12 µg/ml and 2.74 ± 0.84 µg/h, respectively. VRC oral bioavailability was determined to be 82.8%. Conclusion: The approach presented is an alternative for determining the bioavailability of drugs with similar nonlinear behavior.
Does Basal Cell Carcinoma Belong to the Spectrum of Sorafenib-Induced Epithelial Skin Cancers?
Authors: Degen A. , Satzger I. , Voelker B. , Kapp A. , Hauschild A. , Gutzmer R.
Published: August 2010

The multikinase inhibitor sorafenib is therapeutically used in various malignancies. Multiple cutaneous side effects are well described but recent reports indicated a possible association of epithelial skin cancer growth during sorafenib therapy. To our knowledge, few cases of actinic keratoses and variants of squamous cell carcinomas associated with sorafenib have been published. We report 2 patients who developed a basal cell carcinoma (BCC) while treated with sorafenib. Interestingly BCC is a tumor which has not been described yet in association with sorafenib therapy. The tumors were excised completely. After termination of sorafenib treatment, no new BCCs or other epithelial skin cancers occurred. There is accumulating evidence in the literature that sorafenib and possibly other targeted agents are associated with an increased occurrence of epithelial skin cancers. These observations are summarized here and complemented by the new observation that al- so BCCs might be associated with sorafenib therapy. The pathogenetic mechanisms are unclear so far but induction of the mitogen-activated protein kinase pathway in wild-type RAF cells by RAF inhibitors might play a role. Patients should be informed of this possible side effect and undergo regular dermatological controls before and during sorafenib therapy.
Multiple Symmetric Lipomatosis: Substantial Subcutaneous Adipose Tissue Accumulation Did Not Induce Glucose and Lipid Metabolism Dysfunction
Authors: Chen Ke , Xie Yanhong , Hu Pinan , Zhao Shaoli , Mo Zhaohui
Published: August 2010

Objective: To study whether substantial subcutaneous adipose tissue (SCAT) can induce glucose and lipid metabolism dysfunction and possible underlying mechanisms. Methods: We report a male patient with multiple symmetrical lipomatosis (MSL) suffering from increased adipose tissue accumulation in abdomen and back for 7 years, accompanied by the gradual expansion of excess adipose tissue to the nuchal region, upper thorax, upper arms and shoulders. Four obese male adults of similar age and body mass index were chosen as controls (only 4 subjects consented to blood and tissue sampling).Blood samples were collected before anesthesia in the early morning after overnight fasting, and tissue samples from all subjects and the patient were obtained under general anesthesia. Glucose tolerance, insulin resistance in the oral glucose tolerance test and insulin-releasing test were studied. A pathologic examination was made and expression of SCAT-related genes was determined. Results: Although adipose tissue mainly accumulated in SCAT, the patient had no impaired glucose tolerance, insulin resistance and dyslipidemia. Importantly, the circulating adiponectin concentration was higher than in the control group (50.3 ± 3.2 vs. 28.4 ± 2.2 µg/ml, p < 0.05). Accordingly, adiponectin and leptin mRNA expression in SCAT was higher than in the control group (1.83 and 3.75 times, p < 0.05) but TNF-α and IL-6 mRNA levels were lower (decreased by 79 and 45%, p < 0.05). Furthermore, pathologically, adipocyte size in the patient’s SCAT was smaller than in the control group (66.2 ± 6.1 vs. 78.9 ± 6.6 and 98.6 ± 12.8 µm in SCAT and omentum adipose tissue, respectively, p < 0.05). Conclusion: In spite of the patient’s SCAT accumulation, glucose and lipid metabolism dysfunction was absent. The mechanism may involve the interaction of different factors, including the subcutaneous formation of small adipocytes, the secretion of protective adipokines such as adiponectin and anti-inflammatory effects of SCAT.
Peripheral B Cells May Serve as a Reservoir for Persistent Hepatitis C Virus Infection
Authors: Ito Masahiko , Masumi Atsuko , Mochida Keiko , Kukihara Hiroshi , Moriishi Kohji , Matsuura Yoshiharu , Yamaguchi Kazunari , Mizuochi Toshiaki
Published: August 2010

A recent study by our group indicated that peripheral B cells in chronic hepatitis C (CHC) patients are infected with hepatitis C virus (HCV). This raised the logical question of how HCV circumvents the antiviral immune responses of B cells. Because type I interferon (IFN) plays a critical role in the innate antiviral immune response, IFNβ expression levels in peripheral B cells from CHC patients were analyzed, and these levels were found to be comparable to those in normal B cells, which suggested that HCV infection failed to trigger antiviral immune responses in B cells. Sensing mechanisms for invading viruses in host immune cells involve Toll-like receptor-mediated and retinoic acid-inducible gene-I (RIG-I)-mediated pathways. Both pathways culminate in IFN regulatory factor-3 (IRF-3) translocation into the nucleus for IFNβ gene transcription. Although the expression levels of RIG-I and its adaptor molecule, IFN promoter-stimulator-1, were substantially enhanced in CHC B cells, dimerization and subsequent nuclear translocation of IRF-3 were not detectable. TANK-binding kinase-1 (TBK1) and IĸB kinase Ε (IKKΕ) are essential for IRF-3 phosphorylation. Constitutive expression of both kinases was markedly enhanced in CHC B cells. However, reduced expression of heat shock protein of 90 kDa, a TBK1 stabilizer, and enhanced expression of SIKE, an IKKΕ suppressor, were observed in CHC B cells, which might suppress the kinase activity of TBK1/IKKΕ for IRF-3 phosphorylation. In addition, the expression of vesicle-associated membrane protein-associated protein-C, a putative inhibitor of HCV replication, was negligible in B cells. These results strongly suggest that HCV utilizes B cells as a reservoir for persistent infection.
Liver Transplantation in Swine without Venovenous Bypass
Authors: Heuer M. , Reinhardt R. , Kneiseler G. , Würzinger P. , Zou X. , Hua F. , Jian F. , Paul A. , Kaiser G.M.
Published: August 2010

Introduction: A model of orthotopic liver transplantation in swine was developed to investigate an advanced reperfusion approach. Thereby, we consciously disclaim otherwise commonly practiced venovenous bypass during the recipient operation. Material and Methods: Ten liver transplantations were performed according to the described technique without using venovenous bypass. In each swine the observation period was 48 h. Results: All transplantations were carried out after a median cold ischemic time of 307.5 min (295–340); the median warm ischemic time in these cases was 25 min (20–32). Eight of 10 swine survived 48 h after the operation. Conclusion: Orthotopic liver transplantations in the recipient swine are feasible even without using venovenous bypass.
New Developments in Corticosteroid Therapy for Uveitis
Authors: Taylor Simon R.J. , Isa Hazlita , Joshi Lavnish , Lightman Sue
Published: August 2010

Corticosteroids remain the mainstay of the management of patients with uveitis. Topical corticosteroids are effective in the control of anterior uveitis, but vary in strength, ocular penetration and side effect profile. Systemic corticosteroids are widely used for the management of posterior segment inflammation which requires treatment, particularly when it is associated with systemic disease or when bilateral ocular disease is present. However, when ocular inflammation is unilateral, or is active in one eye only, local therapy has considerable advantages, and periocular injections of corticosteroid are a useful alternative to systemic medication and are very effective in controlling mild or moderate intraocular inflammation. More recently, the injection of intraocular corticosteroids such as triamcinolone have been found to be effective in reducing macular oedema and improving vision in uveitic eyes which have proved refractory to systemic or periocular corticosteroids. The effect is usually transient, lasting around 3 months, but can be repeated although the side effects of cataract and raised intraocular pressure are increased in frequency with intraocular versus periocular corticosteroid injections. This has led to the development of new intraocular corticosteroid devices which are designed to deliver sustained-release drugs and obviate the need for systemic immunosuppressive treatment. The first such implant was Retisert, which is surgically implanted (in the operating theatre) and is designed to release fluocinolone over a period of about 30 months. More recently, Ozurdex, a ‘bioerodible’ dexamethasone implant which can be inserted in an office setting, has completed phase III clinical trials in patients with intermediate and posterior uveitis. This implant lasts approximately 6 months, and has been found to be effective with a much better side effect profile than Retisert or intravitreal triamcinolone injection, at least for one injection.
Effect of Intravenous Morphine Comedication on Bile Duct Visualization, Diameter and Volume Applying Intravenous CT Cholangiography in a Porcine Liver Model
Authors: Sommer C.M. , Schwarzwaelder C.B. , Bellemann N. , Stampfl U. , Stiller W. , Schindera S.T. , Omri W. , Nickel F. , Gehrig T. , Kenngott H.G. , Richter G.M. , Meinzer H.P. , Kauczor H.U. , Radeleff B.A.
Published: August 2010

Background/Aims: To determine whether intravenous morphine comedication improves bile duct visualization, diameter and/or volume applying intravenous CT cholangiography in a porcine liver model. Methods: 12 Landrace pigs underwent intravenous CT cholangiography. Eight minutes after initiation of the contrast material infusion, either morphine sulfate (n = 6 animals) or normal saline (n = 6 animals) was administered. Eighteen consecutive CT scans of the liver were acquired with 2-min intervals starting with initiation of the contrast material infusion. Maximum bile duct visualization scores, diameters and volumes and time to maximum bile duct visualization scores, diameters and volumes were determined. Results: Maximum bile duct visualization scores, diameters and volumes and time to maximum bile duct visualization scores, diameters and volumes were not significantly different when the morphine group was compared to the normal saline group. Maximum bile duct visualization scores ranged between 4.00 ± 0.00 and 2.83 ± 1.47. Maximum bile duct diameters ranged between 6.77 ± 0.40 and 2.10 ± 1.35 mm. Maximum bile duct volume was 16.41 ± 7.33 ml in the morphine group and 16.79 ± 5.65 ml in the normal saline group. Conclusion: Intravenous morphine comedication failed to improve bile duct visualization and to increase bile duct diameter and volume applying CT cholangiography.
Infiltration of Natural Caries Lesions with Experimental Resins Differing in Penetration Coefficients and Ethanol Addition
Authors: Meyer-Lueckel H. , Paris S.
Published: August 2010

Resin infiltration of enamel caries lesions requires materials optimized for penetration into the capillary structures of the lesion body. With increasing penetration coefficients (PC) improved penetration and caries-inhibiting properties of low-viscosity resins (infiltrants) could be observed in artificial caries lesions. The aim of the present in vitro study was to compare the penetrativity of experimental resins varying in PC and ethanol addition into natural caries lesions using this technique. Extracted human molars and premolars showing proximal white spot lesions (International Caries Detection and Assessment System: code 2) were etched for 2 min using 15% hydrochloric acid gel. After drying, the lesions were stained with tetramethylrhodamine isothiocyanate and 1 of 4 experimental resins (PC63; PC185; PC204; PC391) was applied for 5 min. The materials consisted of bisphenol-A-glycidyl-methacrylate (B), tri-ethylene-glycol-dimethacrylate (T) and ethanol (E) in ratios (B:T:E) of PC63: 25:75:0; PC185: 20:60:20; PC204: 0:100:0; PC391: 0:80:20. Excess material was removed before light curing. The teeth were sectioned perpendicularly to the lesion surfaces and unbound dye was bleached by immersion in hydrogen peroxide. The remaining lesion pores were stained with fluorescein solution. Lesion and penetration depths were analyzed using confocal microscopy (n = 60). At deep lesion sites the percentage penetration of PC204 was significantly higher compared to PC63 and PC391 (p < 0.05; Mann-Whitney test) but only slightly higher than PC185 (p > 0.05). It can be concluded that materials with high PC (infiltrants) are capable of penetrating almost completely into enamel parts of natural caries lesions in vitro. A solvent-free resin mainly consisting of triethylene glycol dimethacrylate seems to be preferable.
Resistance of Liposomal Sunscreen Formulations against Plain Water as well as Salt Water Exposure and Perspiration
Authors: Korting H.C. , Schöllmann C.
Published: August 2010

The present in vivo investigation using a total of 30 healthy adult volunteers with Fitzpatrick skin type II examines the persistent efficacy of sunscreens using liposomal suspensions as the vehicle. Based on the COLIPA guidelines, the protective effect of a single application of 4 different liposomal sunscreen formulations (sun protection factors, SPFs: 50+, 30, 25 and 15) against sunburn at the recommended amount of 2 mg/cm2 was determined after exposure of the skin to plain water and salt water and after profuse perspiration. Under the influence of plain water, salt water and sweating, the SPF values of sunscreen 1 (labeled SPF of 50+) were reduced only marginally to 97, 96 and 99%, respectively, those of sunscreen 2 (labeled SPF of 30) to 97, 96 and 99%, respectively, those of sunscreen 3 (labeled SPF of 25) to 90, 83 and 91%, respectively, and those of sunscreen 4 (labeled SPF of 15) to 96, 96 and 95%, respectively. This set of data shows that despite plain water and salt water immersion or profuse sweating, the liposomal sunscreen formulation may deliver a long-lasting protective effect in everyday situations encountered by outdoor workers or during leisure activities.
Tau-Proteins as Gender-Specific State Markers in Amnestic Mild Cognitive Impairment
Authors: Riepe Matthias W. , Karl Johann , Tumani Hayrettin , von Arnim Christine A.F.
Published: August 2010

Background/Aims: Our purpose was to assess whether cerebrospinal fluid (CSF) markers of Alzheimer’s disease (AD) reflect trait or state of disease in patients with AD and amnestic mild cognitive impairment (aMCI). Methods: Analysis of CSF levels of A-β-(1, 42), total tau and phospho-tau-181 (t-tau and p-tau-181), cognitive scaling with the cognitive part of the Alzheimer’s Disease Assessment Scale and detailed neuropsychological testing including the California Verbal Learning Test (CVLT) and the Visual Reproduction Test from the Wechsler Memory Scale (WMS). Results: We assessed healthy elderly controls, patients with aMCI (Petersen criteria; n = 62; age 67.9 ± 7.6 years; MMSE score = 28.0 ± 1.6; mean ± standard deviation) and patients with AD (DSM-IV and NINCDS-ADRDA criteria; n = 106; age = 71.8 ± 7.5 years; MMSE score ≧20, 23.7 ± 2.4) from an outpatient memory clinic. In the aMCI subjects, but not in the controls or patients with AD, the CVLT and the WMS scores correlated with the levels of t-tau and p-tau-181. More specifically, the CSF levels of p-tau-181 and t-tau correlated with the CVLT score in females and WMS score in males. Conclusions: Neurochemical markers of AD are gender-specific state markers in aMCI. This forms the basis for future preventive studies aiming at delaying manifest AD.
Association of Four Genetic Loci with Uric Acid Levels and Reduced Renal Function: The J-SHIPP Suita Study
Authors: Tabara Yasuharu , Kohara Katsuhiko , Kawamoto Ryuichi , Hiura Yumiko , Nishimura Kunihiro , Morisaki Takayuki , Kokubo Yoshihiro , Okamura Tomonori , Tomoike Hitonobu , Iwai Naoharu , Miki Tetsuro
Published: August 2010

Background: Recent genome-wide association studies have identified several genetic variants as susceptibility loci for serum uric acid (UA) levels. We also identified a common nonsense mutation, W258X, responsible for renal hypouricemia. Here, we investigated clinical implications of these genetic variants by cross-sectional and longitudinal genetic epidemiological analysis. Methods: The study enrolled 5,165 Japanese subjects aged 64 ± 12 years from the general population. Clinical parameters were obtained from the personal health records, evaluated at medical checkups. Results: Serum UA levels were significantly different between the SLC22A12 rs11231825 (CC/CT/TT: 4.5 ± 1.6, 5.0 ± 1.4, 5.3 ± 1.4 mg/dl; p = 7.6 × 10–20), SLC2A9 rs1014290 (TT/TG/GG: 4.9 ± 1.4, 5.1 ± 1.4, 5.3 ± 1.4 mg/dl; p = 3.1 × 10–11) and ABCG2 rs2231142 (TT/TG/GG: 5.3 ± 1.5, 5.2 ± 1.4, 5.1 ± 1.4 mg/dl; p = 2.0 × 10–5) genotypes. During 9.4 years of follow-up, 87 new cases of hyperuricemia were diagnosed. Multiple logistic regression analysis identified the accumulation of risk alleles as a significant determinant of future development of hyperuricemia (OR = 7.94; 95% CI: 1.97–53.6). In contrast, subjects with nonsense mutation predominantly showed lower UA levels (XX/XW/WW: 1.3 ± 1.7, 3.6 ± 1.0, 5.2 ± 1.4 mg/dl; p = 9.3 × 10–82). However, these subjects showed significantly reduced renal function (β = –0.111; p < 0.001) independently of possible covariates. Conclusion: Accumulation of risk genotypes was an independent risk factor for future development of hyperuricemia. Genetically developed hypouricemia was an independent risk factor for decreased renal function.
Increased Low-Density Lipoprotein S-Homocysteinylation in Chronic Kidney Disease
Authors: Zinellu Angelo , Loriga Giacomina , Scanu Bastianina , Pisanu Elisabetta , Sanna Manuela , Deiana Luca , Satta Andrea Ercole , Carru Ciriaco
Published: August 2010

Background: Since low-density lipoprotein (LDL) S-homocysteinylation has been recently reported to enhance atherogenicity of lipoprotein, we have investigated the levels of homocysteine (Hcy) linked to LDL in chronic proteinuric patients in which lipid abnormalities highly contribute to the excess of morbidity and mortality. Methods: We used capillary electrophoresis to measure LDL-bound thiol Hcy, cysteine (Cys), cysteinylglycine (Cys-Gly), glutathione (GSH), and glutamylcysteine (Glu-Cys) in 30 chronic kidney disease (CKD) individuals and 60 healthy volunteers. Results: We found more elevated levels of total plasma Hcy, Cys, GSH and Glu-Cys in patients than in controls and also found that Hcy and Cys bound to LDL were significantly increased in nephropathic subjects. By multiple linear regression, we found that in healthy people, total Hcy was the most important determinant of LDL-bound Hcy and Cys-Gly was negatively associated with apoB-Hcy concentrations. In CKD the most important determinant of homocysteinylation was creatinine while total plasma Hcy is weakly associated with apoB-Hcy. Conclusions: The increased levels in Hcy-LDL observed in CKD patients might account, at least in part, for the excess of cardiovascular risk; thus LDL S-homocysteinylation can be considered a key marker of risk for cardiovascular disease in these individuals.
Late Sequelae of Whiplash Injury with Dissection of Cervical Arteries
Authors: Hauser Vital , Zangger Peter , Winter Yaroslav , Oertel Wolfgang , Kesselring Jürg
Published: August 2010

Background/Aims: The objective of our study was to estimate the incidence of posttraumatic dissections of cervical arteries in patients with whiplash injury acquired in a car accident. Methods and Patients: We performed a retrospective analysis of medical records of 500 patients with whiplash injury acquired in car accidents between 1996 and 2005 and searched for dissections of cervical arteries occurring within 12 months after injury. Results: Eight cases of cervical arterial dissection occurred within 12 months following whiplash injury. In 7 cases (87.5%), the dissection was complicated by brain infarction. The incidence of posttraumatic dissections after whiplash injuries was much higher than the overall incidence of cervical arterial dissections in the general population (1.6 vs. 0.0041%). The risk of cerebrovascular events was still increased 4–12 months after whiplash injury (0.6 vs. 0.003075% in the general population). Conclusions: There is an increased risk of posttraumatic dissection and cerebrovascular events within 12 months after whiplash injury. Car accident is an important risk factor for arterial dissections. The victims of car accidents should be screened for arterial dissections. The results of this study should be more thoroughly investigated in a prospective trial of car accident victims as a risk factor for arterial dissections.
Effects of Paricalcitol and Enalapril on Atherosclerotic Injury in Mouse Aortas
Authors: Husain Kazim , Suarez Edu , Isidro Angel , Ferder Leon
Published: August 2010

Aims: This study investigated the protective effect of vitamin D analog paricalcitol combined with angiotensin-converting enzyme inhibitor (enalapril) on aortic oxidative injury in atherosclerotic mice. Methods: Female mice were treated for 16 weeks as follows: (1) ApoE deficient + vehicle, (2) ApoE deficient + paricalcitol (200 ng 3 times a week), (3) ApoE deficient + enalapril (30 mg/l in drinking water), (4) ApoE deficient + paricalcitol + enalapril, and (5) wild-type controls. Results: ApoE-deficient mice developed hypertension which was prevented by enalapril or enalapril + paricalcitol treatment but not by paricalcitol treatment. Histology showed atherosclerotic plaque in the aorta of ApoE-deficient mice which was prevented by paricalcitol, enalapril, and paricalcitol + enalapril treatments. Aortic malondialdehyde levels, NADPH oxidase subunit p22phox, manganese-superoxide dismutase (Mn-SOD), inducible nitric oxide synthase, monocyte chemoattaractant protein-1, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 protein expressions increased, whereas glutathione levels, CuZn-SOD, and endothelial protein expressions decreased in ApoE-deficient mice compared to controls. Treatment with paricalcitol and enalapril alone or in combination protected the inflammatory and oxidative endothelial injury of the aorta in atherosclerotic mice. Conclusion: Combination therapy affords greater protection against aortic inflammatory and oxidative injury in atherosclerosis than monotherapy.
Implantable Defibrillators Improve Survival in End-Stage Renal Disease: Results from a Multi-Center Registry
Authors: Hiremath Swapnil , Punnam Sujeeth R. , Brar Somjot S. , Goyal Sandeep K. , Gardiner Joseph C. , Shah Ashok J. , Thakur Ranjan K.
Published: August 2010

Background: Small retrospective analyses suggest that end-stage renal disease (ESRD) patients do not obtain as much of a survival benefit from an implantable cardioverter-defibrillator (ICD) as non-ESRD patients do. We aimed to assess the survival effect of an ICD in ESRD patients with left ventricular dysfunction. Methods: Data from two registries identified ESRD patients with an ICD and ESRD patients with left ventricular dysfunction (defined as ejection fraction <0.35). Cox proportional hazards regression was performed, including certain predefined covariates to assess the effect of an ICD on survival. Results: Overall survival in the full cohort was a median of 4.7 years with 20 deaths in the ICD group and 29 deaths in the no-ICD group. The median survival in the ICD group was 8.0 years and 3.1 years in the no-ICD group. Crude analysis showed a better survival in the ICD group as compared to the no-ICD group (p = 0.016). The multivariable analysis confirmed that the ICD group had significantly less all-cause mortality compared to the no-ICD group (HR: 0.40; 95% CI: 0.19, 0.82; p = 0.013). Conclusion: An ICD is associated with a higher survival in ESRD patients with left ventricular dysfunction. This result merits further study in a larger cohort of patients.
Electropharmacograms of Rasagiline, Its Metabolite Aminoindan and Selegiline in the Freely Moving Rat
Authors: Dimpfel Wilfried , Hoffmann Josef A.
Published: August 2010

Background: Rasagiline and selegiline are classified as monoamine oxidase B (MAO-B) inhibitors. The present investigation deals with time-dependent electrical frequency changes (electropharmacograms) induced by these, as well as by aminoindan, the major metabolite of rasagiline. Method: Adult rats (day-night converted, >5 months old) were fitted with 4 bipolar concentric steel electrodes connected to a small base plate, which was positioned stereotactically for insertion of the electrodes into the frontal cortex, hippocampus, striatum and reticular formation. The plate carried a small plug to receive a telemetric device during the experimental session. Changes in field potentials were recorded during a pre-drug reference period of 45 min, followed by intraperitoneal administration and 5 h of recording thereafter. Data were transmitted wirelessly for frequency analysis. Data from 10 animals treated within a crossover design were averaged. Results: A dose of 0.25 mg/kg i.p. rasagiline produced statistically significant decreases in spectral alpha2 and beta1 power. Higher dosages showed a linear enhancement of this effect. A similar pattern was obtained after administration of aminoindan (2–10 mg/kg), but of shorter duration. Selegiline produced a similar pattern only for the first 1–2 h. After this, statistically significant increases in delta and theta power were observed. Conclusion: Despite the feature of MAO-B inhibition in both drugs and its reflection in the initial changes of the frequency pattern during the first hour, the pharmacological action of selegiline during the following hours differs profoundly from that of rasagiline, presumably due to the toxicity of its major metabolites methamphetamine and amphetamine.
When Faces Signal Danger: Event-Related Potentials to Emotional Facial Expressions in Animal Phobics
Authors: Sarlo Michela , Munafò Marianna
Published: August 2010

Attentional bias research indicates that specific phobics prioritize the processing of disorder-relevant stimuli, although the time course of attentional allocation to the phobic threat remains unclear. The present study employed event-related potentials (ERPs) to investigate whether a processing bias also exists towards specific facial expressions that are able to signal potential phobic cues in the environment. Fifteen women with snake phobia and 15 healthy controls performed an attention-shifting task in which angry, fearful, disgusted and neutral faces were presented as emotional cues. ERP to facial expressions and reaction times to target stimuli were collected during the task. The P200 amplitude was significantly lower in phobics than in controls, specifically in response to facial expressions of fear and disgust. Such reduction in cortical activity may reflect reduced processing associated with rapid cognitive avoidance. Such an avoidance response would not be determined by the threat value of the face stimuli per se, but rather by the ability of fearful and disgusted faces to avert attention by signaling a possible phobic threat in the surrounding area. In addition, phobics showed relatively greater positivity to negative than neutral facial expressions in the later processing stages, indicating a general hypervigilant processing mode.
Stereotactic Radiosurgery for Spine Tumors: Review of Current Literature
Authors: Hsu Wesley , Nguyen Trang , Kleinberg Lawrence , Ford Eric C. , Rigamonti Daniele , Gokaslan Ziya L. , Lim Michael
Published: August 2010

Stereotactic radiosurgery (SR) is increasingly utilized for the treatment of intracranial and extracranial pathology. It is considered an important adjuvant to surgery, chemotherapy or fractionated radiotherapy, and the role of SR as a primary treatment modality continues to be explored. Although SR for spinal lesions is in its infancy, there is a growing body of literature supporting its efficacy. The purpose of this review is to summarize the pertinent literature regarding the use of SR for lesions of the spine and spinal cord. Particular emphasis will be placed on large clinical series of both primary and secondary spine tumors.
Differential Response of Dystonia and Parkinsonism following Globus Pallidus Internus Deep Brain Stimulation in X-Linked Dystonia-Parkinsonism (Lubag)
Authors: Oyama Genko , Fernandez Hubert H. , Foote Kelly D. , Zeilman Pam , Hwynn Nelson , Jacobson, IV Charles E. , Malaty Irene A. , Rodriguez Ramon L. , Okun Michael S.
Published: August 2010

Background: X-linked dystonia-parkinsonism (XDP; DYT3; Lubag) is an adult-onset hereditary progressive dystonia/parkinsonism which is typically minimally responsive to pharmacological treatment. Case Report: We report a 63- year-old man with a diagnosis of XDP who underwent bilateral globus pallidus internus deep brain stimulator (GPi-DBS) placement. His course initially began with right hand tremor and dystonia at age 57 and progressed to also include bradykinesia and rigidity. The patient tolerated the procedure without significant complications. GPi-DBS improved his right hand dystonia, but did not significantly improve his parkinsonism. Conclusion: DBS may be a therapeutic option for select cases of XDP, but its specificindications must be carefully discussed, as the available cases have had mixed responses. Whether other targets may be more effective is not known.
Acute Kidney Injury in a Chinese Hospitalized Population
Authors: Fang Yi , Ding Xiaoqiang , Zhong Yihong , Zou Jianzhou , Teng Jie , Tang Ying , Lin Jing , Lin Pan
Published: August 2010

Objectives: This study’s objective was to determine the incidence and mortality rate of acute kidney injury (AKI) among hospitalized adult patients in a tertiary metropolitan hospital of China, and to evaluate the impact of AKI on in-hospital mortality, cost and length of stay (LOS). Methods: Patients who were admitted to Zhongshan Hospital, Fudan University, Shanghai, China between September 1st, 2004 and June 30th, 2008 were involved. The presence and severity of AKI were assessed using absolute and relative increases from baseline to peak serum creatinine concentration during hospitalization. AKI was defined as a relative 50% increase or an absolute increment of 0.3 mg/dl (26.5 µmol/l) in serum creatinine within 48 h. After screening the computer-based data on kidney function, patients with AKI were identified and further history reviews were performed to obtain information regarding patients’ demography, prognosis, severity of kidney injury and causes of AKI. Results: There were 176,155 admissions during the study period and 5,619 met the diagnostic criteria of AKI. The overall incidence rate of AKI was 3.19%. Cardiovascular diseases followed by urogenital diseases and malignancy were the most common admission diagnoses. In-hospital mortality rate was 2.84% in all discharges and 19.68% in patients with AKI. Of AKI patients, old age, intensive care unit admission, Acute Kidney Injury Network score, need for renal replacement therapy and organ system failure number were independent predictors of hospital mortality according to forward conditional logistic regression. Conclusions: AKI is prevalent in the Chinese hospitalized patients. Slight elevations of serum creatinine are associated with significantly increased mortality, LOS and hospital cost. Moreover, outcomes are related directly to the severity of AKI characterized by percent changes in serum creatinine.
Synergistic Cytotoxicity and Molecular Interaction on Drug Targets of Sorafenib and Gemcitabine in Human Pancreas Cancer Cells
Authors: Ricciardi Simona , Mey Valentina , Nannizzi Sara , Pasqualetti Giuseppe , Crea Francesco , Del Tacca Mario , Danesi Romano
Published: August 2010

Background: Current treatments have a modest impact on survival of pancreatic cancer patients and this study investigates the interaction between sorafenib and gemcitabine and the molecular pharmacodynamics of this combination. Methods: The pancreatic cancer cells were treated with sorafenib and gemcitabine, alone or in combination. The effects of treatments were evaluated on cell proliferation, cell cycle, apoptosis, phosphorylation of Akt, c-Kit, ERK and VEGFR2, and expression of genes related to drug activity. Results: Gemcitabine and sorafenib synergistically interacted on the inhibition of cell proliferation, and assessment of apoptosis demonstrated that drug associations increased the apoptotic index. Sorafenib reduced c-Kit, ERK and VEGFR2 activation and on the other hand, gemcitabine inhibited Akt phosphorylation. Moreover, quantitative PCR showed that sorafenib modulated the expression of genes related to gemcitabine activity, while gemcitabine induced the expression of RKIP. Conclusion: These data demonstrate that gemcitabine and sorafenib combination displays a synergistic effect in pancreatic cancer cells.
Dimers of Nostocarboline with Potent Antibacterial Activity
Authors: Locher Hans H. , Ritz Daniel , Pfaff Philippe , Gaertner Mika , Knezevic Andreja , Sabato Daniela , Schroeder Susanne , Barbaras Damien , Gademann Karl
Published: August 2010

Objectives: In this study, the in vitro antimicrobial activity and spectrum of new dimeric compounds derived from the cyanobacterial alkaloid nostocarboline were investigated. The mechanism of action and selectivity to bacteria were studied and compared to the cationic antiseptic chlorhexidine. Methods:Minimal inhibitory concentrations were determined against clinical isolates and against a panel of microbial reference strains using the CLSI microdilution method. Bacterial membrane damage was addressed by measuring ATP leakage and the mode of action was investigated in Escherichia coli reporter strains. Selectivity was tested by a cytotoxicity assay using MTS. Results: The antimicrobial potency of dimers varied with length of the hydrophobic linker. The most potent compounds, NCD9 and NCD10, had a C10 and C12 linker, respectively, and showed strong activity against Gram-positive bacteria, notably methicillin-resistant Staphylococcus aureus strains. Similar to chlorhexidine, these compounds showed a rapid concentration-dependent bactericidal effect, which correlated with membrane damage as indicated by ATP leakage. NCD9, in contrast to NCD10 and chlorhexidine, lacked activity against yeast strains and showed low cytotoxicity in CHO cells indicating a high degree of selectivity. In E. coli reporter strains, NCD9 induced the DegP response pathway as well as the SOS response, suggesting interaction with both the cell envelope and DNA metabolism. Conclusions: The results presented in this report indicate the potential of this new class of cationic antimicrobial compounds for the design of potent and selective antibacterials with low cytotoxicity.