bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimum Rail Height and Design Impact Load for Longitudinal Barriers that Meet Test Level 4 of Manual for Assessing Safety Hardware
Authors: Sheikh Nauman M. , Bligh Roger P. , Holt John M.
Published: January 2013

In 2009, the Manual for Assessing Safety Hardware (MASH) was adopted as an updated replacement of NCHRP Report 350. Under MASH, the impact severity of Test Level 4 (TL-4) (Test 4–12) was increased by 56%. Test vehicle mass was increased from 17,640 to 22,050 lb. Impact speed was increased from 50 to 56 mph. Although this is a significant increase in the amount of lateral energy imparted to the barrier, the 54-kip design impact load currently suggested by the AASHTO load and resistance factor design (LRFD) bridge specifications has not been updated to meet MASH TL-4 requirements. Similarly, the AASHTO LRFD specifications require all TL-4 railings to have a minimum height of 32 in. However, because of the increase in test vehicle mass and impact velocity under MASH, the minimum height for TL-4 railings is expected to be greater than 32 in. This height was verified by a recent unsuccessful MASH Test 4–12 of a New Jersey profile rigid concrete barrier 32 in. tall. The research presented in this paper used finite element analysis and subsequent crash testing to determine the minimum rail height for MASH TL-4 impact conditions. The researchers also determined the appropriate lateral impact design load for use with AASHTO LRFD bridge specifications for the design of TL-4 bridge rails.
Utility Investigation Trends in Texas
Authors: Kraus Edgar , Obeng-Boampong Kwaku , Quiroga Cesar
Published: January 2013

Detection of utility conflicts as early as possible during the project development process can help to substantially improve the timely relocation of utilities and can allow time to develop alternatives to avoid utility relocation. However, collecting accurate information on the location of underground utilities from utility companies can be challenging. This is one reason that subsurface utility engineering (SUE) has become a critical tool in helping to identify and locate utility installations within the right-of-way. Although the benefits of SUE have been well documented, a disconnect between its full potential and its actual use at the Texas Department of Transportation (DOT) was suspected. A survey of staff in diverse organizational units at the Texas DOT was conducted to learn about current utility investigation practices and to gain a better understanding of how the Texas DOT uses SUE. The team found, among other issues, some unfamiliarity with SUE technology and its best uses, a general need for training and education on the use of SUE, and a recent decline in the use of SUE technology that may be linked to frequent uncertainty about the benefits of SUE.
Identification of venous sinus, tumor location, and pial supply during meningioma surgery by transdural indocyanine green videography
Authors: Ueba Tetsuya , Okawa Masakazu , Abe Hiroshi , Nonaka Masani , Iwaasa Mitsutoshi , Higashi Toshio , Inoue Tooru , Takano Koichi
Published: January 2013

Object

Indocyanine green (ICG) videography is commonly used in the neurosurgical field for minimally invasive neurosurgery. The aim of this study was to evaluate a new intraoperative imaging modality by performing transdural ICG videography during surgery for meningiomas.

Methods

Between March 2011 and April 2012, 10 patients with meningiomas received intravenous injection of 12.5 mg ICG just prior to dural opening. The cases comprised 8 convexity meningiomas and 2 foramen magnum meningiomas. Efficacy of the transdural ICG videography was assessed in terms of the tumor volume, the circulation time from the first appearance of the vessel to the appearance of the venous sinus, the tendency to bleed, and the discrimination of the venous sinus.

Results

The mean tumor volume was 71.6 ± 87.9 ml (the mean is expressed ± SD throughout). The cortical arteries, veins, and the venous sinus were identified by the ICG videography transdurally. The projection of the meningiomas was identified by a shadow (which the authors call the eclipse sign). Total eclipse signs were obtained in 8 cases and partial eclipse signs were obtained in 2 cases; tumor volume in the latter was more than 200 ml. In 5 of 10 cases the adjacent venous sinuses were exposed and were successfully visualized by ICG videography in 5.92 ± 1.05 seconds from the first appearance of the vessel. In 5 of 10 cases the total and the partial eclipse signs were diminished in 3.46 ± 1.31 seconds. The diminishment of the total and the partial eclipse sign was earlier than the visualization of the venous sinus (p = 0.011, t-test), revealing bleeding from the tumor that was observed until coagulation of the feeding arteries from the intracranial arteries.

Conclusions

Prior to opening of the dura mater, transdural ICG videography was used successfully to visualize the dural attachment of meningiomas and the venous sinus, resulting in safe and appropriate dural opening. The diminishment of the total and partial eclipse signs may represent significant feeding from the intracranial arteries and a tendency to bleed during resection.
Enhanced antitumor effect of YM872 and AG1296 combination treatment on human glioblastoma xenograft models
Authors: Watanabe Takashi , Ohtani Toshiyuki , Aihara Masanori , Ishiuchi Shogo
Published: January 2013

Object

Blockade of Ca++-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) inhibits the proliferation of human glioblastoma by inhibiting Akt phosphorylation, which is independent of the phosphatidylinositol 3-kinase pathway. Inhibiting platelet-derived growth factor receptor (PDGFR)–mediated phosphorylation causes growth inhibition in glioblastoma cells. The authors of this study investigated the effects of YM872 and AG1296, singly and in combination and targeting different pathways upstream of Akt, on Akt-mediated tumor growth in glioblastoma cells in vivo and in vitro.

Methods

The expression of AMPAR, PDGFR, and c-kit in glioblastoma cells was analyzed via immunofluorescence. Glioblastoma cells, both in culture and in xenografts grown in mice, were treated with YM872 and AG1296, singly or in combination. Inhibition of tumor growth was observed after treatment in the xenograft model. Cell proliferation assays were performed using anti–Ki 67 antibody in vivo and in vitro. The CD34-positive tumor vessel counts within the vascular hot spots of tumor specimens were evaluated. Phosphorylation of Akt was studied using Western blot analysis.

Results

Combined administration of YM872 and AG1296 had a significant enhanced effect on the inhibition of cell proliferation and reduction of tumor vascularity in the xenograft model. These agents singly and in combination demonstrated a significant reduction of Akt phosphorylation at Ser473 and inhibition of tumor proliferation in vitro, although combined administration had no enhanced antitumor effects.

Conclusions

The strongly enhanced antitumor effect of this combination therapy in vivo rather than in vitro may be attributable to disruption of the aberrant vascular niche. This combination therapy might provide substantial benefits to patients with glioblastoma.
Prognosis by tumor location in adults with spinal ependymomas
Authors: Oh Michael C. , Kim Joseph M. , Kaur Gurvinder , Safaee Michael , Sun Matthew Z. , Singh Anahat , Aranda Derick , Molinaro Annette M. , Parsa Andrew T.
Published: January 2013

Object

Ependymomas are primary central nervous system tumors that occur more frequently in the spines of adults than they do there in children. Previous studies consist mainly of retrospective single-institutional experiences or case studies. In this study, a comprehensive literature review was performed on reported cases of spinal ependymoma treated with resection to determine whether tumor location along the spinal axis conveys important prognostic information.

Methods

A PubMed search was performed to identify all papers that included data on patients with spinal ependymoma. Only cases involving adult patients who underwent ependymoma resection with a clearly reported tumor location were included for analysis. Tumor locations were separated into 6 groups: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus + cauda equina. Kaplan-Meier survival and Cox regression analyses were performed to determine the effect of tumor location on progression-free survival (PFS) and overall survival (OS).

Results

A total of 447 patients who underwent resection of spinal ependymomas with clearly indicated location of tumor were identified. The most common locations of spinal ependymomas were the cervical (32.0%) and conus + cauda equina (26.8%) regions. The thoracolumbar and cervicomedullary regions had the fewest tumors (accounting for, respectively, 5.1% and 3.4% of the total number of cases). The conus + cauda equina and thoracolumbar regions had the highest percentage of WHO Grade I tumors, while tumors located above these regions consisted of mostly WHO Grade II tumors. Despite the tendency for benign grades in the lower spinal regions, PFS for patients with spinal ependymomas in the lower 3 regions (thoracic, thoracolumbar, conus + cauda equina) was significantly shorter (p < 0.001) than for those with tumors in the upper regions (cervicomedullary, cervical, cervicothoracic), but the difference in OS did not achieve statistical significance (p = 0.131).

Conclusions

Spinal ependymomas along different regions of spinal axis have different characteristics and clinical behaviors. Tumor grade, extent of resection, and PFS varied by tumor location (upper vs lower spinal regions), while OS did not. Recurrence rates were higher for the lower spinal cord tumors, despite a greater prevalence of lower WHO grade lesions, compared with upper spinal cord tumors, suggesting that tumor location along the spinal axis is an important prognostic factor.
Species-Dependent Functionality of the Human Cytolytic Fusion Proteins Granzyme B-H22(scFv) and H22(scFv)-Angiogenin in Macrophages
Authors: Schiffer Sonja , Hristodorov Dmitrij , Mladenov Radoslav , Aslanian Eric , Huhn Michael , Fischer Rainer , Barth Stefan , Thepen Theo
Published: January 2013

Human cytolytic fusion proteins (hCFPs) are comprised of a specific cell-surface-binding moiety and an effector molecule of human origin. In contrast to common immunotoxins, including bacterial or plant toxins, they are considered not to be immunogenic. Two examples for human pro-apoptotic effector proteins are the serine protease Granzyme B and the RNase Angiogenin. Pre-clinical testing of functionality in in vitro and in vivo studies is essential for therapeutics. Establishing relevant animal models that have predictive value for therapeutic success is a great challenge in biomedical research. In this study, we investigated the species-dependent cytotoxic activity of two hCFPs prior to their application in a murine inflammation model. We found that in vitro and ex vivo either hCFP was able to kill human cells only, leaving murine cells unaffected. In contrast, no species-dependency was found for the bacterial Pseudomonas exotoxin A based immunotoxin H22(scFv)-ETA’. This species-dependent functioning has to be carefully considered when performing pre-clinical studies in animal models.
Exercise Benefits Brain Function: The Monoamine Connection
Authors: Lin Tzu-Wei , Kuo Yu-Min
Published: January 2013

The beneficial effects of exercise on brain function have been demonstrated in animal models and in a growing number of clinical studies on humans. There are multiple mechanisms that account for the brain-enhancing effects of exercise, including neuroinflammation, vascularization, antioxidation, energy adaptation, and regulations on neurotrophic factors and neurotransmitters. Dopamine (DA), noradrenaline (NE), and serotonin (5-HT) are the three major monoamine neurotransmitters that are known to be modulated by exercise. This review focuses on how these three neurotransmitters contribute to exercise affecting brain function and how it can work against neurological disorders.
Compensated Transfer Entropy as a Tool for Reliably Estimating Information Transfer in Physiological Time Series
Authors: Faes Luca , Nollo Giandomenico , Porta Alberto
Published: January 2013

We present a framework for the estimation of transfer entropy (TE) under the conditions typical of physiological system analysis, featuring short multivariate time series and the presence of instantaneous causality (IC). The framework is based on recognizing that TE can be interpreted as the difference between two conditional entropy (CE) terms, and builds on an efficient CE estimator that compensates for the bias occurring for high dimensional conditioning vectors and follows a sequential embedding procedure whereby the conditioning vectors are formed progressively according to a criterion for CE minimization. The issue of IC is faced accounting for zero-lag interactions according to two alternative empirical strategies: if IC is deemed as physiologically meaningful, zero-lag effects are assimilated to lagged effects to make them causally relevant; if not, zero-lag effects are incorporated in both CE terms to obtain a compensation. The resulting compensated TE (cTE) estimator is tested on simulated time series, showing that its utilization improves sensitivity (from 61% to 96%) and specificity (from 5/6 to 0/6 false positives) in the detection of information transfer respectively when instantaneous effect are causally meaningful and non-meaningful. Then, it is evaluated on examples of cardiovascular and neurological time series, supporting the feasibility of the proposed framework for the investigation of physiological mechanisms.
Effects of Convective Heating on Entropy Generation Rate in a Channel with Permeable Walls
Authors: Makinde Oluwole , Eegunjobi Adetayo
Published: January 2013

This study deals with the combined effects of convective heating and suction/injection on the entropy generation rate in a steady flow of an incompressible viscous fluid through a channel with permeable walls. The model equations for momentum and energy balance are solved numerically using shooting quadrature. Both the velocity and temperature profiles are obtained and utilized to compute the entropy generation number. The effects of the key parameters on the fluid velocity, temperature, entropy generation rate and Bejan number are depicted graphically and analyzed in detail.
Biomarkers of Maternal and Fetal Exposure to Organochlorine Pesticides Measured in Pregnant Hispanic Women from Brownsville, Texas
Authors: Sexton Ken , Salinas Jennifer , McDonald Thomas , Gowen Rose , Miller Rebecca , McCormick Joseph , Fisher-Hoch Susan
Published: January 2013

Biomarkers of organochlorine pesticides were measured in both venous and umbilical cord blood from 35 pregnant Hispanic women living in Brownsville, Texas, USA. Gas chromatography with an electron capture detector was used to analyze specimens for 30 individual pesticides or their metabolites. Results indicate that blood concentrations were relatively low for most individual compounds, but that high-end (upper 10th percentile) values for total DDT were comparatively high. Although health effects associated with measured blood concentrations are uncertain, there is concern that fetal exposure to low levels of these OC compounds, either individually or in combination, might contribute to subsequent health problems, including neurodevelopmental effects, cancer, endocrine disruption, obesity and diabetes.
Nature, Nurture and Evolution of Intra-Species Variation in Mosquito Arbovirus Transmission Competence
Authors: Tabachnick Walter
Published: January 2013

Mosquitoes vary in their competence or ability to transmit arthropod-borne viruses (arboviruses). Many arboviruses cause disease in humans and animals. Identifying the environmental and genetic causes of variation in mosquito competence for arboviruses is one of the great challenges in public health. Progress identifying genetic (nature) and environmental (nurture) factors influencing mosquito competence for arboviruses is reviewed. There is great complexity in the various traits that comprise mosquito competence. The complex interactions between environmental and genetic factors controlling these traits and the factors shaping variation in Nature are largely unknown. The norms of reaction of specific genes influencing competence, their distributions in natural populations and the effects of genetic polymorphism on phenotypic variation need to be determined. Mechanisms influencing competence are not likely due to natural selection because of the direct effects of the arbovirus on mosquito fitness. More likely the traits for mosquito competence for arboviruses are the effects of adaptations for other functions of these competence mechanisms. Determining these other functions is essential to understand the evolution and distributions of competence for arboviruses. This information is needed to assess risk from mosquito-borne disease, predict new mosquito-arbovirus systems, and provide novel strategies to mitigate mosquito-borne arbovirus transmission.
Potential Applications of Carbohydrases Immobilization in the Food Industry
Authors: Contesini Fabiano , De Alencar Figueira Joelise , Kawaguti Haroldo , De Barros Fernandes Pedro , De Oliveira Carvalho Patrícia , Da Graça Nascimento Maria , Sato Hélia
Published: January 2013

Carbohydrases find a wide application in industrial processes and products, mainly in the food industry. With these enzymes, it is possible to obtain different types of sugar syrups (viz. glucose, fructose and inverted sugar syrups), prebiotics (viz. galactooligossacharides and fructooligossacharides) and isomaltulose, which is an interesting sweetener substitute for sucrose to improve the sensory properties of juices and wines and to reduce lactose in milk. The most important carbohydrases to accomplish these goals are of microbial origin and include amylases (α-amylases and glucoamylases), invertases, inulinases, galactosidases, glucosidases, fructosyltransferases, pectinases and glucosyltransferases. Yet, for all these processes to be cost-effective for industrial application, a very efficient, simple and cheap immobilization technique is required. Immobilization techniques can involve adsorption, entrapment or covalent bonding of the enzyme into an insoluble support, or carrier-free methods, usually based on the formation of cross-linked enzyme aggregates (CLEAs). They include a broad variety of supports, such as magnetic materials, gums, gels, synthetic polymers and ionic resins. All these techniques present advantages and disadvantages and several parameters must be considered. In this work, the most recent and important studies on the immobilization of carbohydrases with potential application in the food industry are reviewed.
Shear Stress Inhibits Apoptosis of Ischemic Brain Microvascular Endothelial Cells
Authors: Tian Shan , Bai Yulong , Yang Lin , Wang Xinggang , Wu Yi , Jia Jie , Zhu Yulian , Cheng Yong , Zhang Pengyue , Wu Junfa , Wang Nianhong , Xia Guang , Liao Hua , Zhang Yuling , Shen Xiafeng , Yu Huixian , Hu Yongshan
Published: January 2013

As a therapeutic strategy for ischemic stroke, to restore or increase cerebral blood flow (CBF) is the most fundamental option. Laminar shear stress (LS), as an important force generated by CBF, mainly acts on brain microvascular endothelial cells (BMECs). In order to study whether LS was a protective factor in stroke, we investigated LS-intervented ischemic apoptosis of rat BMECs (rBMECs) through PE Annexin V/7-AAD, JC-1 and Hoechst 33258 staining to observe the membranous, mitochondrial and nuclear dysfunction. Real-time PCR and western blot were also used to test the gene and protein expressions of Tie-2, Bcl-2 and Akt, which were respectively related to maintain membranous, mitochondrial and nuclear norm. The results showed that LS could be a helpful stimulus for ischemic rBMECs survival. Simultaneously, membranous, mitochondrial and nuclear regulation played an important role in this process.
Quantitative Structure-Activity Relationships Predicting the Antioxidant Potency of 17β-Estradiol-Related Polycyclic Phenols to Inhibit Lipid Peroxidation
Authors: Prokai Laszlo , Rivera-Portalatin Nilka , Prokai-Tatrai Katalin
Published: January 2013

The antioxidant potency of 17β-estradiol and related polycyclic phenols has been well established. This property is an important component of the complex events by which these types of agents are capable to protect neurons against the detrimental consequences of oxidative stress. In order to relate their molecular structure and properties with their capacity to inhibit lipid peroxidation, a marker of oxidative stress, quantitative structure-activity relationship (QSAR) studies were conducted. The inhibition of Fe3+-induced lipid peroxidation in rat brain homogenate, measured through an assay detecting thiobarbituric acid reactive substances for about seventy compounds were correlated with various molecular descriptors. We found that lipophilicity (modeled by the logarithm of the n-octanol/water partition coefficient, logP) was the property that influenced most profoundly the potency of these compounds to inhibit lipid peroxidation in the biological medium studied. Additionally, the important contribution of the bond dissociation enthalpy of the phenolic O-H group, a shape index, the solvent-accessible surface area and the energy required to remove an electron from the highest occupied molecular orbital were also confirmed. Several QSAR equations were validated as potentially useful exploratory tools for identifying or designing novel phenolic antioxidants incorporating the structural backbone of 17β-estradiol to assist therapy development against oxidative stress-associated neurodegeneration.
2-[(1-Benzamido-2-methoxy-2-oxoethyl)amino]benzoic Acid
Authors: El Houssine Mabrouk , Abdelrhani Elachqar , Abdelilah El , Anouar Alami
Published: January 2013

The carboxylic α,α-diaminoester 2-[(1-benzamido-2-methoxy-2-oxoethyl) amino]benzoic acid is obtained by N-alkylation of methyl α-azido glycinate N-benzoylated with 2-aminobenzoic acid.
Investigation on the Interaction between Cyclophosphamide and Lysozyme in the Presence of Three Different Kind of Cyclodextrins: Determination of the Binding Mechanism by Spectroscopic and Molecular Modeling Techniques
Authors: Mansouri Mahdieh , Pirouzi Malihe , Saberi Mohammad , Ghaderabad Maryam , Chamani Jamshidkhan
Published: January 2013

The interactions between cyclophosphamide (CYC) and lysozyme (LYZ) in the presence of different cyclodextrins (CDs) were investigated by UV absorption, fluorescence spectroscopy, circular dichroism (CD), and molecular modeling techniques under imitated physiological conditions. The UV absorption results showed the formation of complexes between CYC and LYZ in the presence of different CDs. Fluorescence data show that CYC has a stronger quenching effect on LYZ, and the red shifts suggested that the microenvironment of Trp residues was changed and became more hydrophilic. The interaction of CYC with LYZ and quenching properties of the complexes caused strong static fluorescence quenching in binary and ternary systems. The binding affinities as well as the number of binding sites were obtained from interaction between CYC and LYZ in the presence of different CDs as binary and ternary systems by modified Stern-Volmer plots. The Resonance Light Scattering (RLS) technique was utilized to investigate the effect of drug and CDs on conformational changes of LYZ as separate and simultaneous. The results suggested that the enhancement of RLS intensity was attributed to the formation of a complex between drug and protein in absence and presence of CDs. The effect of CYC and cyclodextrins on the conformation of LYZ was analyzed using synchronous fluorescence spectroscopy. Our results revealed that the fluorescence quenching of LYZ originated from the Trp and Tyr residues, and demonstrated conformational changes of LYZ with the addition of CYC and CDs. The molecular distances between the donor (LYZ) and acceptor (CYC and CDs) in binary and ternary systems were estimated according to Forster’s theory and showed static quenching for protein with CYC in the presence of CDs. The CD spectra indicated that the binding of the CYC induced secondary structural changes in LYZ in binary and ternary systems. Molecular modeling suggested the binding sites of CYC in the ternary systems differ from those in the binary systems. estimated the distance between CYC and Trp residues in binary and ternary systems in the presence of CDs and confirmed the experimental results.
Synthesis and Antibacterial Evaluation of Novel Heterocyclic Compounds Containing a Sulfonamido Moiety
Authors: Azab Mohammad , Youssef Mohamed , El-Bordany Eman
Published: January 2013

Aiming for the synthesis of new heterocyclic compounds containing a sulfonamido moiety suitable for use as antibacterial agents, the precursor ethyl {[4-N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenylazo}cyanoacetate was reacted with a variety of active methylene compounds producing pyran, pyridine and pyridazine derivatives. Also, the reactivity of the precursor hydrazone towards hydrazine derivatives to give pyrazole and oxazole derivatives was studied. On the other hand, treatment of the same precursor with urea, thiourea and/or guanidine hydrochloride furnished pyrimidine and thiazine derivatives, respectively. The newly synthesized compounds were tested for antibacterial activity, whereby eight compounds were found to have high activities.
Chamaejasmine Arrests Cell Cycle, Induces Apoptosis and Inhibits Nuclear NF-κB Translocation in the Human Breast Cancer Cell Line MDA-MB-231
Authors: Zhang Tingting , Yu Hongyang , Dong Guanglu , Cai Li , Bai Yuxian
Published: January 2013

In this study, the anticancer activity of chamaejasmine was characterized in the human breast cancer cell line, MDA-MB-231. Cell viability and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Western blotting was performed to determine changes in levels of various proteins. Results showed that treatment with chamaejasmine (4–16 μM) inhibited cell proliferation, which correlated with G2/M phase arrest and apoptosis in MDA-MB-231 cells. Chamaejasmine treatment of MDA-MB-231 cells resulted in induction of WAF1/p21 and KIP1/p27, decrease in cyclins A and cyclins B1. Cyclin-dependent kinase (cdk) 2 and cdc2 was also decreased after chamaejasmine treatment. Moreover, inhibition of nuclear translocation, phosphorylation of NF-κB, activation of IKKα and IKKβ, inhibition of phosphorylation and degradation of IκBα were also detected in this work. Our findings suggested that chamaejasmine could be explored as a preventive and perhaps as a chemotherapeutic agent in the management of breast cancer.
Synthesis of 5α-Androstane-17-spiro-δ-lactones with a 3-Keto, 3-Hydroxy, 3-Spirocarbamate or 3-Spiromorpholinone as Inhibitors of 17β-Hydroxysteroid Dehydrogenases
Authors: Djigoué Guy , Ngatcha Béatrice , Roy Jenny , Poirier Donald
Published: January 2013

We synthesized two series of androstane derivatives as inhibitors of type 3 and type 5 17β-hydroxysteroid dehydrogenases (17β-HSDs). In the first series, four monospiro derivatives at position C17 were prepared from androsterone (ADT) or epi-ADT. After the protection of the alcohol at C3, the C17-ketone was alkylated with the lithium acetylide of tetrahydro-2-(but-3-ynyl)-2-H-pyran, the triple bond was hydrogenated, the protecting groups hydrolysed and the alcohols oxidized to give the corresponding 3-keto-17-spiro-lactone derivative. The other three compounds were generated from this keto-lactone by reducing the ketone at C3, or by introducing one or two methyl groups. In the second series, two dispiro derivatives at C3 and C17 were prepared from epi-ADT. After introducing a spiro-δ-lactone at C17 and an oxirane at C3, an aminolysis of the oxirane with L-isoleucine methyl ester provided an amino alcohol, which was treated with triphosgene or sodium methylate to afford a carbamate- or a morpholinone-androstane derivative, respectively. These steroid derivatives inhibited 17β-HSD3 (14–88% at 1 μM; 46–94% at 10 μM) and 17β-HSD5 (54–73% at 0.3 μM; 91–92% at 3 μM). They did not produce any androgenic activity and did not bind steroid (androgen, estrogen, glucocorticoid and progestin) receptors, suggesting a good profile for prostate cancer therapy.
Total Flavonoids of Scutellaria barbata Inhibit Invasion of Hepatocarcinoma via MMP/TIMP in Vitro
Authors: Dai Zhi-Jun , Wang Bao-Feng , Lu Wang-Feng , Wang Zhi-Dong , Ma Xiao-Bin , Min Wei-Li , Kang Hua-Feng , Wang Xi-Jing , Wu Wen-Ying
Published: January 2013

Metastasis is the major cause of cancer-related deaths. Targeting the process of metastasis has been proposed as a strategy to fight cancer. Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is used for treatment of many diseases, including cancer. This study aimed to determine the anti-metastatic effect of total flavonoids of S. barbata (TF-SB) using the human hepatocarcinoma MHCC97H cell line with high metastatic potential. Our results show that TF-SB could significantly inhibit the proliferation and invasion of MHCC97H cells in a dose-dependent manner. MMP-2 and MMP-9 expression were obviously decreased after TF-SB treatment at both the mRNA and protein level. TIMP-1 and TIMP-2 expression were simultaneously increased. The present study indicates that TF-SB could reduce the metastatic capability of MHCC97H cell, probably through decrease of the MMP expression, and simultaneous increase of the TIMP expression.
Evaluation of Antioxidant Potential of “Maltese Mushroom” (Cynomorium coccineum) by Means of Multiple Chemical and Biological Assays
Authors: Zucca Paolo , Rosa Antonella , Tuberoso Carlo , Piras Alessandra , Rinaldi Andrea , Sanjust Enrico , Dessì Maria , Rescigno Antonio
Published: January 2013

Cynomorium coccineum is an edible, non-photosynthetic plant widespread along the coasts of the Mediterranean Sea. The medicinal properties of Maltese mushroom — one of the oldest vernacular names used to identify this species — have been kept in high regard since ancient times to the present day. We evaluated the antioxidant potential of fresh specimens of C. coccineum picked in Sardinia, Italy. Both aqueous and methanolic extracts were tested by using multiple assay systems (DPPH, FRAP, TEAC, ORAC-PYR). Total phenolics and flavonoids were also determined. Gallic acid and cyanidin 3-O-glucoside were identified as the main constituents and measured. Both extracts showed antioxidant capacities; ORAC-PYR assay gave the highest antioxidant value in both cases. The methanolic extract was further investigated with in vitro biological models of lipid oxidation; it showed a significant activity in preventing cholesterol degradation and exerted protection against Cu2+-mediated degradation of the liposomal unsaturated fatty acids. Results of the present study demonstrate that the extracts of C. coccineum show a significant total antioxidant power and also exert an in vitro protective effect in different bio-assays of oxidative stress. Therefore, Maltese mushroom can be considered a valuable source of antioxidants and phytochemicals useful in the preparation of nutraceuticals and functional foods.
Advanced Land Observing Satellite Phased Array Type L-Band SAR (ALOS PALSAR) to Inform the Conservation of Mangroves: Sundarbans as a Case Study
Authors: Cornforth William , Fatoyinbo Temilola , Freemantle Terri , Pettorelli Nathalie
Published: January 2013

Mangroves are an important bulkhead against climate change: they afford protection for coastal areas from tidal waves and cyclones, and are among the most carbon-rich forests in the tropics. As such, protection of mangroves is an urgent priority. This work provides some new information on patterns of degradation in the Sundarbans, the largest contiguous mangrove forest in the world, which are home to more than 35 reptile species, 120 commercial fish species, 300 bird species and 32 mammal species. Using radar imagery, we contrast and quantify the recent impacts of cyclone Sidr and anthropogenic degradation on this ecosystem. Our results, inferred from changes in radar backscatter, confirm already reported trends in coastline retreat for this region, with areas losing as much as 200 m of coast per year. They also suggest rapid changes in mangrove dynamics for Bangladesh and India, highlighting an overall decrease in mangrove health in the east side of the Sundarbans, and an overall increase in this parameter for the west side of the Sundarbans. As global environmental change takes its toll in this part of the world, more detailed, regular information on mangroves’ distribution and health is required: our study illustrates how different threats experienced by mangroves can be detected and mapped using radar-based information, to guide management action.
First Evidence of Placental Transfer of Ochratoxin A in Horses
Authors: Minervini Fiorenza , Giannoccaro Alessandra , Nicassio Michele , Panzarini Giuseppe , Lacalandra Giovanni
Published: January 2013

Ochratoxin A (OTA) is a renal mycotoxin and transplacental genotoxic carcinogen. The aim of this study was to evaluate the natural occurrence of OTA in equine blood samples and its placental transfer. For the assessment of OTA levels, serum samples were collected from 12 stallions, 7 cycling mares and 17 pregnant mares. OTA was found in 83% of serum samples (median value = 121.4 pg/mL). For the assessment of placental transfer, serum samples were collected from the 17 mares after delivery and from the umbilical cords of their foals, after foaling. Fourteen serum samples from pregnant mares contained OTA (median value = 106.5 pg/mL), but only 50% of their foals were exposed (median values = 96.6 pg/mL). HPLC analysis carried out on four serum samples (collected from two mares and their respective foals) supported the ELISA results on OTA placental transfer. This is the first report on the natural occurrence of OTA in horse serum samples and placental transfer in horses.
Influence of Botulinum Toxin Therapy on Postural Control and Lower Limb Intersegmental Coordination in Children with Spastic Cerebral Palsy
Authors: Degelaen Marc , De Borre Ludo , Kerckhofs Eric , De Meirleir Linda , Buyl Ronald , Cheron Guy , Dan Bernard
Published: January 2013

Botulinum toxin injections may significantly improve lower limb kinematics in gait of children with spastic forms of cerebral palsy. Here we aimed to analyze the effect of lower limb botulinum toxin injections on trunk postural control and lower limb intralimb (intersegmental) coordination in children with spastic diplegia or spastic hemiplegia (GMFCS I or II). We recorded tridimensional trunk kinematics and thigh, shank and foot elevation angles in fourteen 3–12 year-old children with spastic diplegia and 14 with spastic hemiplegia while walking either barefoot or with ankle-foot orthoses (AFO) before and after botulinum toxin infiltration according to a management protocol. We found significantly greater trunk excursions in the transverse plane (barefoot condition) and in the frontal plane (AFO condition). Intralimb coordination showed significant differences only in the barefoot condition, suggesting that reducing the degrees of freedom may limit the emergence of selective coordination. Minimal relative phase analysis showed differences between the groups (diplegia and hemiplegia) but there were no significant alterations unless the children wore AFO. We conclude that botulinum toxin injection in lower limb spastic muscles leads to changes in motor planning, including through interference with trunk stability, but a combination of therapies (orthoses and physical therapy) is needed in order to learn new motor strategies.
Difference in F-Actin Depolymerization Induced by Toxin B from the Clostridium difficile Strain VPI 10463 and Toxin B from the Variant Clostridium difficile Serotype F Strain 1470
Authors: May Martin , Wang Tianbang , Müller Micro , Genth Harald
Published: January 2013

Clostridium difficile toxin A (TcdA) and toxin B (TcdB) are the causative agent of the C. difficile-associated diarrhea (CDAD) and its severe form, the pseudomembranous colitis (PMC). TcdB from the C. difficile strain VPI10463 mono-glucosylates (thereby inactivates) the small GTPases Rho, Rac, and Cdc42, while Toxin B from the variant C. difficile strain serotype F 1470 (TcdBF) specifically mono-glucosylates Rac but not Rho(A/B/C). TcdBF is related to lethal toxin from C. sordellii (TcsL) that glucosylates Rac1 but not Rho(A/B/C). In this study, the effects of Rho-inactivating toxins on the concentrations of cellular F-actin were investigated using the rhodamine-phalloidin-based F-actin ELISA. TcdB induces F-actin depolymerization comparable to the RhoA-inactivating exoenzyme C3 from C. limosum (C3-lim). In contrast, the Rac-glucosylating toxins TcdBF and TcsL did not cause F-actin depolymerization. These observations led to the conclusion that F-actin depolymerization depends on the toxin’s capability of glucosylating RhoA. Furthermore, the integrity of focal adhesions (FAs) was analyzed using paxillin and p21-activated kinase (PAK) as FA marker proteins. Paxillin dephosphorylation was observed upon treatment of cells with TcdB, TcdBF, or C3-lim. In conclusion, the Rho-inactivating toxins induce loss of cell shape by either F-actin depolymerization (upon RhoA inactivation) or the disassembly of FAs (upon Rac1 inactivation).
Approaches for Identification of HIV-1 Entry Inhibitors Targeting gp41 Pocket
Authors: Yu Fei , Lu Lu , Du Lanying , Zhu Xiaojie , Debnath Asim , Jiang Shibo
Published: January 2013

The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR) domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon), was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD), it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs.
A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence
Authors: Shoen Carolyn , DeStefano Michelle , Hager Cynthia , Tham Kyi-Toe , Braunstein Miriam , Allen Alexandria , Gates Hiriam , Cynamon Michael , Kernodle Douglas
Published: January 2013

Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.
Visual Outcomes and Safety of a Refractive Corneal Inlay for Presbyopia Using Femtosecond Laser
Authors: Limnopoulou Aliki N. , Bouzoukis Dimitrios I. , Kymionis George D. , Panagopoulou Sophia I. , Plainis Sotiris , Pallikaris Aristophanes I. , Feingold Vladimir , Pallikaris Ioannis G.
Published: January 2013

PURPOSE:

To evaluate the outcomes and safety of a refractive inlay (Flexivue Micro-Lens, Presbia Coöperatief U.A.) for the corneal compensation of presbyopia.

METHODS:

This prospective, interventional clinical study comprised 47 emmetropic presbyopes with a mean age of 52±4 years (range: 45 to 60 years). The inlay was inserted, centered on the line of sight, inside a corneal pocket created in the patient’s nondominant eye, using a femtosecond laser. Follow-up was 12 months. Visual acuity, corneal topography, wavefront aberrometry, contrast sensitivity, structural corneal alterations, and questionnaires were evaluated.

RESULTS:

Twelve months after surgery, uncorrected near visual acuity was 20/32 or better in 75% of operated eyes, whereas mean uncorrected distance visual acuity (UDVA) of operated eyes was statistically significantly decreased from 0.06±0.09 logMAR (20/20) (range: −0.08 to 0.26) preoperatively to 0.38±0.15 logMAR (20/50) (range: 0.12 to 0.8) (
P
<.001), and mean binocular UDVA was not significantly altered (
P
=.516). Seventeen patients lost one line of corrected distance visual acuity in the operated eye. No patient lost 2 lines in CDVA in the operated eye. Overall, higher order aberrations increased and contrast sensitivity decreased in the operated eye. No tissue alterations were found using corneal confocal microscopy. No intra- or postoperative complications occurred.

CONCLUSIONS:

Twelve months after implantation, the Flexivue Micro-Lens intracorneal refractive inlay seems to be an effective method for the corneal compensation of presbyopia in emmetropic presbyopes aged between 45 and 60 years old.
Topography-guided Transepithelial PRK After Intracorneal Ring Segments Implantation and Corneal Collagen CXL in a Three-Step Procedure for Keratoconus
Authors: Coskunseven Efekan , Jankov Mirko R. , Grentzelos Michael A. , Plaka Argyro D. , Limnopoulou Aliki N. , Kymionis George D
Published: January 2013

PURPOSE:

To present the results of topography-guided transepithelial photorefractive keratectomy (PRK) after intracorneal ring segments implantation followed by corneal collagen cross-linking (CXL) for keratoconus.

METHODS:

In this prospective case series, 10 patients (16 eyes) with progressive keratoconus were included. All patients underwent topography-guided transepithelial PRK after Keraring intracorneal ring segments (Mediphacos Ltda) implantation, followed by CXL treatment. The follow-up period was 6 months after the last procedure for all patients. Time interval between both intracorneal ring segments implantation and CXL and between CXL and topography-guided transepithelial PRK was 6 months.

RESULTS:

LogMAR mean uncorrected distance visual acuity and mean corrected distance visual acuity were significantly improved (
P
<.05) from 1.14±0.36 and 0.75±0.24 preoperatively to 0.25±0.13 and 0.13±0.06 after the completion of the three-step procedure, respectively. Mean spherical equivalent refraction was significantly reduced (
P
<.05) from −5.66±5.63 diopters (D) preoperatively to −0.98±2.21 D after the three-step procedure. Mean steep and flat keratometry values were significantly reduced (
P
<.05) from 54.65±5.80 D and 47.80±3.97 D preoperatively to 45.99±3.12 D and 44.69±3.19 D after the three-step procedure, respectively.

CONCLUSIONS:

Combined topography-guided transepithelial PRK with intracorneal ring segments implantation and CXL in a three-step procedure seems to be an effective, promising treatment sequence offering patients a functional visual acuity and ceasing progression of the ectatic disorder. A longer follow-up and larger case series are necessary to thoroughly evaluate safety, stability, and efficacy of this innovative procedure.
Reduced Cross-linking Demarcation Line Depth at the Peripheral Cornea After Corneal Collagen Cross-linking
Authors: Yam Jason C. S. , Cheng Arthur C. K.
Published: January 2013

PURPOSE:

To compare the corneal collagen cross-linking (CXL) demarcation line depth between the central and peripheral cornea after cross-linking using anterior segment optical coherence tomography.

METHODS:

Retrospective interventional case series of 38 eyes with keratoconus or postoperative LASIK ectasia treated with riboflavin ultraviolet A CXL (UV-X, IROC). CXL demarcation line depth, corneal thickness, and the ratio of the CXL demarcation line depth to the corneal thickness were measured using anterior segment optical coherence tomography at the central cornea and at 2 and 4 mm from the corneal center in four regions: temporal, nasal, superior, and inferior. The CXL demarcation line depths at the center and periphery were compared using the Friedman test.

RESULTS:

The CXL demarcation line was deepest in the central cornea (302 μm; range: 180 to 397 μm) and was reduced progressively toward the peripheral cornea, at nasal 2 mm (289.5 μm; range: 125 to 370 μm), at nasal 4 mm (206.5 μm; range: 100 to 307 μm), at temporal 2 mm (278.5 μm; range: 128 to 375 μm), and at temporal 4 mm (194 μm; range: 80 to 325 μm) (
P
<.001). The penetration proportion was greatest at the central cornea (64.8%; range: 44% to 80%) and was decreased toward the periphery, at nasal 2 mm (53.8%; range: 30% to 74%), at nasal 4 mm (33.8%; range: 19% to 53%), at temporal 2 mm (54.1%; range: 29% to 77%), and at temporal 4 mm (34.1%; range: 15% to 54%) (
P
⩽.001).

CONCLUSIONS:

Both the CXL demarcation line depth and its proportion over the corneal thickness were greater at the central cornea than the peripheral cornea.