bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocannabinoids Regulate the Migration of Subventricular Zone-Derived Neuroblasts in the Postnatal Brain
Authors: Oudin Madeleine J. , Gajendra Sangeetha , Williams Gareth , Hobbs Carl , Lalli Giovanna , Doherty Patrick
Published: March 2011

In the adult brain, neural stem cells proliferate within the subventricular zone before differentiating into migratory neuroblasts that travel along the rostral migratory stream (RMS) to populate the olfactory bulb with new neurons. Because neuroblasts have been shown to migrate to areas of brain injury, understanding the cues regulating this migration could be important for brain repair. Recent studies have highlighted an important role for endocannabinoid (eCB) signaling in the proliferation of the stem cell population, but it remained to be determined whether this pathway also played a role in cell migration. We now show that mouse migratory neuroblasts express cannabinoid receptors, diacylglycerol lipase α (DAGLα), the enzyme that synthesizes the endocannabinoid 2-arachidonoylglycerol (2-AG), and monoacylglycerol lipase, the enzyme responsible for its degradation. Using a scratch wound assay for a neural stem cell line and RMS explant cultures, we show that inhibition of DAGL activity or CB1/CB2receptors substantially decreases migration. In contrast, direct activation of cannabinoid receptors or preventing the breakdown of 2-AG increases migration. Detailed analysis of primary neuroblast migration by time-lapse imaging reveals that nucleokinesis, as well as the length and branching of the migratory processes are under dynamic control of the eCB system. Finally, similar effects are observedin vivoby analyzing the morphology of green fluorescent protein-labeled neuroblasts in brain slices from mice treated with CB1or CB2antagonists. These results describe a novel role for the endocannabinoid system in neuroblast migrationin vivo, highlighting its importance in regulating an additional essential step in adult neurogenesis.
Regulation of the PMP22 Gene through an Intronic Enhancer
Authors: Jones Erin A. , Lopez-Anido Camila , Srinivasan Rajini , Krueger Courtney , Chang Li-Wei , Nagarajan Rakesh , Svaren John
Published: March 2011

Successful myelination of the peripheral nervous system depends upon induction of major protein components of myelin, such as peripheral myelin protein 22 (PMP22). Myelin stability is also sensitive to levels of PMP22, as a 1.4 Mb duplication on human chromosome 17, resulting in three copies ofPMP22, is the most common cause of the peripheral neuropathy Charcot-Marie-Tooth disease. The transcription factor Egr2/Krox20 is required for induction of high level expression of Pmp22 in Schwann cells but its activation elements have not yet been determined. Using chromatin immunoprecipitation analysis of the ratPmp22locus, we found a major peak of Egr2 binding within the large intron of thePmp22gene. Analysis of a 250 bp region within the largest intron showed that it is strongly activated by Egr2 expression in reporter assays. Moreover, this region contains conserved binding sites not only for Egr2 but also for Sox10, which is also required for Schwann cell development. Our analysis shows that Sox10 is required for optimal activity of the intronic site as well asPMP22expression. Finally, mouse transgenic analysis revealed tissue-specific expression of this intronic sequence in peripheral nerve. Overall, these data show that Egr2 and Sox10 activity are directly involved in mediating the developmental induction ofPmp22expression.
Autoantibodies in Melanoma-Associated Retinopathy Target TRPM1 Cation Channels of Retinal ON Bipolar Cells
Authors: Dhingra Anuradha , Fina Marie E. , Neinstein Adam , Ramsey David J. , Xu Ying , Fishman Gerald A. , Alexander Kenneth R. , Qian Haohua , Peachey Neal S. , Gregg Ronald G. , Vardi Noga
Published: March 2011

Melanoma-associated retinopathy (MAR) is characterized by night blindness, photopsias, and a selective reduction of the electroretinogram b-wave. In certain cases, the serum contains autoantibodies that react with ON bipolar cells, but the target of these autoantibodies has not been identified. Here we show that the primary target of autoantibodies produced in MAR patients with reduced b-wave is the TRPM1 cation channel, the newly identified transduction channel in ON bipolar cells. Sera from two well characterized MAR patients, but not from a control subject, stained human embryonic kidney cells transfected with theTRPM1gene, and Western blots probed with these MAR sera showed the expected band size (∼180 kDa). Staining of mouse and primate retina with MAR sera revealed immunoreactivity in all types of ON bipolar cells. Similar to staining for TRPM1, staining with the MAR sera was strong in dendritic tips and somas and was weak or absent in axon terminals. This staining colocalized with GFP in Grm6-GFP transgenic mice, where GFP is expressed in all and only ON bipolar cells, and also colocalized with Gαo, a marker for all types of ON bipolar cells. The staining in ON bipolar cells was confirmed to be specific to TRPM1 because MAR serum did not stain these cells in aTrpm1−/−mouse. Evidence suggests that the recognized epitope is likely intracellular, and the sera can be internalized by retinal cells. We conclude that the vision of at least some patients with MAR is compromised due to autoantibody-mediated inactivation of the TRPM1 channel.
Brain Infiltration of Leukocytes Contributes to the Pathophysiology of Temporal Lobe Epilepsy
Authors: Zattoni Michela , Mura Maria Luisa , Deprez Francine , Schwendener Reto A. , Engelhardt Britta , Frei Karl , Fritschy Jean-Marc
Published: March 2011

Clinical and experimental evidence indicates that inflammatory processes contribute to the pathophysiology of epilepsy, but underlying mechanisms remain mostly unknown. Using immunohistochemistry for CD45 (common leukocyte antigen) and CD3 (T-lymphocytes), we show here microglial activation and infiltration of leukocytes in sclerotic tissue from patients with mesial temporal lobe epilepsy (TLE), as well as in a model of TLE (intrahippocampal kainic acid injection), characterized by spontaneous, nonconvulsive focal seizures. Using specific markers of lymphocytes, microglia, macrophages, and neutrophils in kainate-treated mice, we investigated with pharmacological and genetic approaches the contribution of innate and adaptive immunity to kainate-induced inflammation and neurodegeneration. Furthermore, we used EEG analysis in mutant mice lacking specific subsets of lymphocytes to explore the significance of inflammatory processes for epileptogenesis. Blood–brain barrier disruption and neurodegeneration in the kainate-lesioned hippocampus were accompanied by sustained ICAM-1 upregulation, microglial cell activation, and infiltration of CD3+T-cells. Moreover, macrophage infiltration was observed, selectively in the dentate gyrus where prominent granule cell dispersion was evident. Unexpectedly, depletion of peripheral macrophages by systemic clodronate liposome administration affected granule cell survival. Neurodegeneration was aggravated in kainate-lesioned mice lacking T- and B-cells (RAG1-knock-out), because of delayed invasion by Gr-1+neutrophils. Most strikingly, these mutant mice exhibited early onset of spontaneous recurrent seizures, suggesting a strong impact of immune-mediated responses on network excitability. Together, the concerted action of adaptive and innate immunity triggered locally by intrahippocampal kainate injection contributes seizure-suppressant and neuroprotective effects, shedding new light on neuroimmune interactions in temporal lobe epilepsy.
Recoil and conversion electron considerations of the 166Dy/166Ho in vivo generator
Authors: Zeevaart J. R. , Szücs Z. , Takács S. , Jarvis N. V. , Jansen D.
Published: March 2011

The use of radionuclides as potential therapeutic radiopharmaceuticals is increasingly investigated. An important aspect is the delivery of the radionuclide to the target, i.e. the radionuclide is not lost from the chelating agent. For in vivo generators, it is not only the log K of complexation between the metal ion and the chelator that is important, but also whether the daughter radionuclide stays inside the chelator after decay of the parent radionuclide. In our previous work, we showed that the classical recoil effect is only applicable for decays with a Q value higher than 0.6 MeV (in the atomic mass range around 100). However, Zhernosekov et al. [1] published a result for140Nd/140Pr (Q = 0.222 MeV) which indicated that >95% of the daughter (140Pr) was lost by a DOTA chelator upon decay of140Nd. The authors ascribed this to the & ldquo;post-effect”. Their experiment was repeated with the166Dy/166Ho generator to ascertain whether our calculations were correct. It was found that 72% of the daughter (166Ho) was liberated from the DOTA chelator, indicating that the “post effect” does exist in contrast to our recoil calculations. Upon further investigation, we determined that one should not only consider recoil energy levels but also the mode of decay which was able to explain the partial recoil found for166Dy/166Ho. It is concluded for the166Dy/166Ho system that the low recoil energy of the daughter nucleus166Ho is not a sufficient reason to rule out release of the nuclide from chelators. On the other hand, we found that the ratio of the166Ho that gets released corresponds to the ratio of relaxation of Ho atoms via the Auger process.
Threshold Photoelectron Spectrum of Isolated NTCDA
Authors: Fischer Kathrin H. , Fischer Ingo , Bodi Andras
Published: March 2011

The threshold photoelectron spectrum of NTCDA (1,4,5,8-naphthalene-tetracarboxylic dianhydride) has been recorded using synchrotron radiation. An ionization energy of 9.66 eV was observed. The experiments are supported by DFT computations that yield a value of 9.51 eV, in good agreement with the measured value. Several bands corresponding to excited electronic states of the cation are also visible and can be assigned with the aid of computations.
Highly Ordered 3D-Macroporous Poly(Para-Phenylene) Films Made by Electropolymerization of Benzene in an Ionic Liquid
Authors: Al Zoubi Mohammad , Al-Salman Rihab , Li Yao , Endres Frank
Published: March 2011

A simple and efficient method for the preparation of highly ordered 3-dimensional macroporous polyparaphenylene (3DOM-PPP) conducting polymer films is reported for the first time. The method involves the simple electropolymerization of benzene inside a polystyrene opal template at mild reaction conditions. The ionic liquid 1-hexyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate ([HMIm]FAP) containing benzene as a precursor is used as the electrolyte. Polystyrene colloidal crystals with average sphere-diameters of 240, 370 and 600 nm on ITO-glass substrates were used as templates. The obtained PPP inverse opal structures showed strong blue, green, yellow and red colors due to light diffraction caused by the 3-D highly ordered macroporous structure. A complete filling of the PS template with PPP can be easily achieved at room temperature. The electrochemical process was investigated by cyclic voltammetry and the deposits were characterized by SEM and IR analysis.
Vitamin E ameliorates iodine-induced cytotoxicity in thyroid
Authors: Yu Jiashu , Shan Zhongyan , Chong Wei , Mao Jinyuan , Geng Yuxiu , Zhang Caixia , Xing Qian , Wang Weiwei , Li Ningna , Fan Chenling , Wang Hong , Zhang Hongmei , Teng Weiping
Published: March 2011

Acute and excessive iodine supplementation leads to iodine-induced thyroid cytotoxicity. Excessive oxidative stress has been suggested to be one of the underlying mechanisms in the development of thyroid cytotoxicity. The aim of this study was to investigate whether vitamin E (VE), an important antioxidant, could ameliorate iodine-induced thyroid cytotoxicity. A goiter was induced in rats by feeding a low-iodine (LI) diet for 12 weeks. Involution of hyperplasia was obtained by administering a twofold physiological dose of iodine in feeding water with/without the supplementation of 25-, 50-, or 100-fold physiological dose of VE in the LI diet for 4 weeks. In iodine-supplemented rats, thyroid epithelial cell ultrastructure injuries remained and were more severe. Relative weights of iodine-induced involuting glands were significantly reduced compared with the goiter, but still higher than control. Immunohistochemistry indicated that the expression of 4-hydroxynonenal, 8-hydroxyguanine, peroxiredoxin 5, and CD68 in thyroid increased (P<0.01), whereas thioredoxin reductase 1 decreased (P<0.01). VE supplementation attenuated thyroid cytotoxicity induced by iodine. A 50-fold VE dose was optimal in attenuating twofold iodine-induced thyroid cytotoxicity. However, VE supplementation did not reduce the weight or relative weight of the iodine-induced involuting gland. These results show that excess iodine leads to thyroid damage and VE supplementation can partly ameliorate iodine-induced thyroid cytotoxicity.
A Single, Recent Origin of the Accessory B Chromosome of the Grasshopper Eyprepocnemis plorans
Authors: Muñoz-Pajares A Jesús , Martínez-Rodríguez Laura , Teruel María , Cabrero Josefa , Camacho Juan Pedro M , Perfectti Francisco
Published: March 2011

B chromosomes are dispensable chromosomes found in >2000 eukaryotic species, usually behaving as genomic parasites. Most B chromosomes seem to be made up of the same kind of DNA sequences present in the A chromosomes. This sequence similarity makes it difficult to obtain specific molecular probes that may permit B-presence diagnosis without cytogenetic analysis. We have developed a sequence-characterized amplified region (SCAR) marker for B chromosomes in the grasshopper Eyprepocnemis plorans, which specifically amplifies a 1510-bp DNA fragment exclusively in B-carrying individuals. Fluorescent in situ hybridization and fiber FISH analyses showed that this marker is a tandemly repeated DNA sequence closely intermingled with 45S rDNA. PCR reactions showed the presence of SCAR-like sequences in the A chromosomes, but in two separate fragments, supporting the intraspecific origin of B chromosomes in this species. SCAR marker DNA sequence showed to be identical in B chromosome variants from several localities from Spain and Morocco, and it was very similar to those found in B chromosome variants from Greece and Armenia. This strongly suggests that this sequence was already present in the ancestral B chromosome of this species. In addition, the scarce sequence variation observed among several B variants from very distant populations suggests either a functional constraint or, more likely, a recent and unique origin for B chromosomes in this species.
A Map-Based Cloning Strategy Employing a Residual Heterozygous Line Reveals that the GIGANTEA Gene Is Involved in Soybean Maturity and Flowering
Authors: Watanabe Satoshi , Xia Zhengjun , Hideshima Rumiko , Tsubokura Yasutaka , Sato Shusei , Yamanaka Naoki , Takahashi Ryoji , Anai Toyoaki , Tabata Satoshi , Kitamura Keisuke , Harada Kyuya
Published: March 2011

Flowering is indicative of the transition from vegetative to reproductive phase, a critical event in the life cycle of plants. In soybean (Glycine max), a flowering quantitative trait locus, FT2, corresponding to the maturity locus E2, was detected in recombinant inbred lines (RILs) derived from the varieties “Misuzudaizu” (ft2/ft2; JP28856) and “Moshidou Gong 503” (FT2/FT2; JP27603). A map-based cloning strategy using the progeny of a residual heterozygous line (RHL) from the RIL was employed to isolate the gene responsible for this quantitative trait locus. A GIGANTEA ortholog, GmGIa (Glyma10g36600), was identified as a candidate gene. A common premature stop codon at the 10th exon was present in the Misuzudaizu allele and in other near isogenic lines (NILs) originating from Harosoy (e2/e2; PI548573). Furthermore, a mutant line harboring another premature stop codon showed an earlier flowering phenotype than the original variety, Bay (E2/E2; PI553043). The e2/e2 genotype exhibited elevated expression of GmFT2a, one of the florigen genes that leads to early flowering. The effects of the E2 allele on flowering time were similar among NILs and constant under high (43°N) and middle (36°N) latitudinal regions in Japan. These results indicate that GmGIa is the gene responsible for the E2 locus and that a null mutation in GmGIa may contribute to the geographic adaptation of soybean.
Genetic Architecture of Flowering-Time Variation in Arabidopsis thaliana
Authors: Salomé Patrice A , Bomblies Kirsten , Laitinen Roosa A E , Yant Levi , Mott Richard , Weigel Detlef
Published: March 2011

The onset of flowering is an important adaptive trait in plants. The small ephemeral species Arabidopsis thaliana grows under a wide range of temperature and day-length conditions across much of the Northern hemisphere, and a number of flowering-time loci that vary between different accessions have been identified before. However, only few studies have addressed the species-wide genetic architecture of flowering-time control. We have taken advantage of a set of 18 distinct accessions that present much of the common genetic diversity of A. thaliana and mapped quantitative trait loci (QTL) for flowering time in 17 F2 populations derived from these parents. We found that the majority of flowering-time QTL cluster in as few as five genomic regions, which include the locations of the entire FLC/MAF clade of transcription factor genes. By comparing effects across shared parents, we conclude that in several cases there might be an allelic series caused by rare alleles. While this finding parallels results obtained for maize, in contrast to maize much of the variation in flowering time in A. thaliana appears to be due to large-effect alleles.
Entrepreneurs' Self‐reported Health, Social Life, and Strategies for Maintaining Good Health
Authors: Gunnarsson Kristina , Josephson Malin
Published: March 2011

Entrepreneurs' Self‐reported Health, Social Life, and Strategies for Maintaining Good Health: Kristina Gunnarsson, et al. Department of Occupational and Environmental Medicine, Uppsala University Hospital, Sweden—

Objectives

This study investigated the association between self‐reported good health and self‐valued good social life. An additional aim was to examine entrepreneur's strategies for maintaining good health.

Methods

The study design included a two‐wave questionnaire, with ive years between the surveys (2001 and 2006), and qualitative interviews. The study group consisted of 246 entrepreneurs from the central region of Sweden and represented ten different trades. Entrepreneurs reporting good health in both 2001 and 2006 were compared with entrepreneurs reporting poor health on both occasions or with inconsistent answers. Six of the entrepreneurs were strategically chosen for the interview study.

Results

Consistent good health was reported by 56% of the entrepreneurs. Good social life in 2001 was associated with an increased odds ratio (OR) for consistent good health when the analyses were adjusted for physical work conditions and job satisfaction (OR 2.12, 95% CI 1.07–4.17). Findings for good leisure time, weekly moderate physical exercise, and a rating of work being less or equally important as other life areas, were similar but not statistically significant when job satisfaction was considered in the analyses. Strategies for maintaining good health included good planning and control over work, lexibility at work, good social contact with family, friends and other entrepreneurs, and regular physical exercise.

Conclusion

This study demonstrated an association between self‐reported good health and good social life for entrepreneurs in small‐scale enterprises. In addition, the entrepreneurs emphasised strategies such as planning and control over work and physical exercise are important for maintaining good health.
Recovery of Chronic Noise Exposure Induced Spatial Learning and Memory Deficits in Young Male Sprague‐Dawley Rats
Authors: Chengzhi Chen , Yan Tang , Xuejun Jiang , Xiang Li , Youbin Qi , Baijie Tu
Published: March 2011

Recovery of Chronic Noise Exposure Induced Spatial Learning and Memory Deficits in Young Male Sprague‐Dawley Rats: Chen Chengzhi, et al. Department of Occupational and Environmental Medicine, School of Public Health, Chongqing Medical University, China—

Objective

Noise has always been an important environmental public health issuefor mankind. Although reports exist on hippocampal dependent spatial learning and memory (LM) impairment due to noise, there are only a few studies that have examined the effects of recovery from noise stress on LM impairments. Therefore, the present study investigated the effects of recovery from chronic noise exposure on LM Deficits.

Materials and Methods

In this study, the detrimental effects of noise stress on young male rats in the Morris water maze (MWM) were investigated at 1, 10, 20, 30, and 40 days after the discontinuation of chronic noise exposure of 80 dB or 100 dB for 4 h per day, for 30 days. The levels of monoamine neurotransmitters in the hippocampus were also evaluated by HPLC‐EC at the end of each behavioral test.

Results

Statistical analysis revealed that rats in the noise‐treated groups failed to reach the same level of performance as the controls in the MWM. Further, the levels of dopamine (DA), norepinephrine (NE) and 5‐hydroxytryptamine (5‐HT) were significantly decreased in the hippocampus after noise exposure. However, the reduction in monoamine levels and impaired water maze performance recovered over time, so that by 30th day after cessation of noise exposure the 80 dB group showed no performance difference from the controls, and by 40th day, the 100 dB group also showed no performance difference from the control.

Conclusion

Our indings suggest that noise impaired LM in young male rats and reduced monoamine neurotransmitters in the hippocampus. However, the noise‐induced water maze Deficits recovered over time, and the concurrent restoration of hippocampal monoamine neurotransmitter levels suggest that they are involved in LM impairments.
Targeting the Phosphatidylinositol 3-Kinase Signaling Pathway in Breast Cancer
Authors: Hernandez-Aya Leonel F. , Gonzalez-Angulo Ana M.
Published: March 2011

Learning Objectives

After completing this course, the reader will be able to: Describe how PTEN loss, PIK3CA mutations, and AKT dysregulation affect the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling network in human breast cancer.Review the current state of AKT and mTOR inhibitor development, and describe its potential for clinical applications.

This article is available for continuing medical education credit at CME.TheOncologist.com

The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) network plays a key regulatory function in cell survival, proliferation, migration, metabolism, angiogenesis, and apoptosis. Genetic aberrations found at different levels, either with activation of oncogenes or inactivation of tumor suppressors, make this pathway one of the most commonly disrupted in human breast cancer. The PI3K-dependent phosphorylation and activation of the serine/threonine kinase AKT is a key activator of cell survival mechanisms. The activation of the oncogene PIK3CA and the loss of regulators of AKT including the tumor suppressor gene PTEN are mutations commonly found in breast tumors. AKT relieves the negative regulation of mTOR to activate protein synthesis and cell proliferation through S6K and 4EBP1. The common activation of the PI3K pathway in breast cancer has led to the development of compounds targeting the effector mechanisms of the pathway including selective and pan-PI3K/pan-AKT inhibitors, rapamycin analogs for mTOR inhibition, and TOR-catalytic subunit inhibitors. The influences of other oncogenic pathways such as Ras-Raf-Mek on the PI3K pathway and the known feedback mechanisms of activation have prompted the use of compounds with broader effect at multiple levels and rational combination strategies to obtain a more potent antitumor activity and possibly a meaningful clinical effect. Here, we review the biology of the network, its role in the development and progression of breast cancer, and the evaluation of targeted therapies in clinical trials.
Internal Fixation of Type-C Distal Femoral Fractures in Osteoporotic Bone
Authors: Mückley Thomas , Wähnert Dirk , Hoffmeier Konrad L. , von Oldenburg Geert , Fröber Rosemarie , Hofmann Gunther O.
Published: March 2011

BACKGROUND:

Fixation of distal femoral fractures remains a challenge, especially in osteoporotic bone. This study was performed to investigate the biomechanical stability of four different fixation devices for the treatment of comminuted distal femoral fractures in osteoporotic bone.

METHODS:

Four fixation devices were investigated biomechanically under torsional and axial loading. Three intramedullary nails, differing in the mechanism of distal locking (with two lateral-to-medial screws in one construct, one screw and one spiral blade in another construct, and four screws [two oblique and two lateral-to-medial with medial nuts] in the third), and one angular stable plate were used. All constructs were tested in an osteoporotic synthetic bone model of an AO/ASIF type 33-C2 fracture. Two nail constructs (the one-screw and spiral blade construct and the four-screw construct) were also compared under axial loading in eight pairs of fresh-frozen human cadaveric femora.

RESULTS:

The angular stable plate constructs had significantly higher torsional stiffness than the other constructs; the intramedullary nail with four-screw distal locking achieved nearly comparable results. Furthermore, the four-screw distal locking construct had the greatest torsional strength. Axial stiffness was also the highest for the four-screw distal locking device; the lowest values were achieved with the angular stable plate. The ranking of the constructs for axial cycles to failure was the four-screw locking construct, with the highest number of cycles, followed by the angular stable plate, the spiral blade construct, and two-screw fixation. The findings in the human cadaveric bone were comparable with those in the synthetic bone model. Failure modes under cyclic axial load were comparable for the synthetic and human bone models.

CONCLUSIONS:

The findings of this study support the concept that, for intramedullary nails, the kind of distal interlocking pattern affects the stabilization of distal femoral fractures. Four-screw distal locking provides the highest axial stability and nearly comparable torsional stability to that of the angular stable plate; the four-screw distal interlocking construct was found to have the best combined (torsional and axial) biomechanical stability.

CLINICAL RELEVANCE:

The enhanced distal interlocking stability of the four-screw distal locking construct may be beneficial to the stabilization of complex distal femoral fractures, especially in osteoporotic bone.

ORIGINAL ABSTRACT CITATION:

“Internal Fixation of Type-C Distal Femoral Fractures in Osteoporotic Bone” (2010;92:1442-52).
Diabetes, Gestational Diabetes and the Risk of Cancer in Women: Epidemiologic Evidence and Possible Biologic Mechanisms
Authors: Chodick Gabriel , Zucker Inbar
Published: March 2011

At present, more than 10% of adult American women are diagnosed with diabetes mellitus (DM). As the prevalence of the disease increases, there is greater interest in the relationship between DM and other major health issues, such as cancer – one of the leading causes of death in the western world. This paper reviews the literature on the relationship between Type 2 DM and different types of cancer among women. We discuss the possible biological mechanisms that may link diabetes and cancer, important confounders, shared risk factors and a short review of the epidemiologic literature on the association between Type 2 DM and cancer of specific organs (pancreas, liver, colorectal, bladder, endometrial, non-Hodgkin's lymphoma and breast). We also examine the association between gestational diabetes, a closely related risk factor for DM in women, and subsequent risk of cancer. Cancer survival of diabetic women is also briefly discussed. The paper concludes with an agenda for future research targeting the relationship between diabetes and cancer.
Basal Phenotype Breast Cancer: Implications for Treatment and Prognosis
Authors: Pazaiti Anastasia , Fentiman Ian S
Published: March 2011

Breast cancer is the most common malignancy in females. The origins and biology of breast carcinomas remain unclear. Cellular and molecular heterogeneity results in different distinct groups of tumors with different clinical behavior and prognosis. Gene expression profiling has delineated five molecular subtypes based on similarities in gene expression: luminal A, luminal B, HER2 overexpressing, normal-like and basal-like. Basal-like breast cancer (BLBC) lacks estrogen receptor, progesterone receptor and HER2 expression, and comprises myoepithelial cells. Specific features include high proliferative rate, rapid growth, early recurrence and decreased overall survival. BLBC is associated with ductal carcinoma in situ, BRCA1 mutation, brain and lung metastasis, and negative axillary lymph nodes. Currently, chemotherapy is the only therapeutic choice, but demonstrates poor outcomes. There is an overlap in definition between triple-negative breast cancer and BLBC due to the triple-negative profile of BLBC. Despite the molecular and clinical similarities, the two subtypes respond differently to neoadjuvant therapy. Although particular morphologic, genetic and clinical features of BLBC have been identified, a variety of definitions among studies accounts for the contradictory results reported. In this article the molecular morphological and histopathological profile, the clinical behavior and the therapeutic options of BLBC are presented, with emphasis on the discordant findings among studies.
Tranexamic Acid: A Novel Oral Formulation for the Treatment of Heavy Menstrual Bleeding
Authors: Lukes Andrea S , Kouides Peter A , Moore Keith A
Published: March 2011

Tranexamic acid, a synthetic lysine derivative, is an antifibrinolytic drug that prevents the breakdown of fibrin by competitively blocking binding sites of plasminogen. Tranexamic acid is often considered a first-line treatment for the management of heavy menstrual bleeding (HMB). A new oral formulation of tranexamic acid provides a nonhormonal HMB therapy that is safe, effective and well tolerated; is administered only during menstruation; addresses the excessive fibrinolysis implicated in many cases of HMB; and improves women's health-related quality of life by reducing limitations on physical, social and leisure activities. This article provides a summary of the clinical development, therapeutic efficacy and tolerability profile of this novel formulation of tranexamic acid for the treatment of HMB.
Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities
Authors: Mohareb Rafat , Moustafa Hosam
Published: March 2011

Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities

The aim of the work was to synthesize heterocyclic compounds from 2-aminoprop-1-ene-1,1,3-tricarbonitrile and to study their antitumor activities. The title reagent reacted with cyclohexanone to give the ethylidene derivative 2. The reactivity of the latter product towards different chemical reagents was studied to give tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives. The newly synthesized products were screened as antitumor agents on the in vitro growth of three human tumor cell lines representing different tumor types, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268). It was found that some of these compounds showed inhibitory effects on the three cell lines, indicating their potential use in the development of oncology products.
Development of hydroxyapatite-ciprofloxacin bone-implants using »Quality by design«
Authors: Nayak Amit , Laha Bibek , Sen Kalyan
Published: March 2011

Development of hydroxyapatite-ciprofloxacin bone-implants using »Quality by design«

The present study deals with the development of hydroxyapatite (HAp)-ciprofloxacin bone-implants using the »Quality by design« approach. The effect of various synthesis parameters like drug amount added in the process, stirring speed and addition rate of orthophosphoric acid in the synthesis on drug concentration in the HAp-ciprofloxacin system synthesized by the precipitation technique using 23factorial design was analyzed. Optimization methodology utillizing the first-order polynomial equation was used to search for optimal drug concentration in the HAp-ciprofloxacin implant system. The observed responses coincided well with the predicted values from the optimization technique. New implants were manufactured using various HAp-ciprofloxacin composites and 1.5 % (m/V) guar gum as a binder. Characterization of the delivery system was done by XRPD, FTIR spectroscopy and SEM. Even at highest drug concentration (76.6 ± 0.5 %,m/m), ciprofloxacin was present in noncrystalline state. Thein vitrociprofloxacin release from various bone-implants was sustained for several weeks and the drug release pattern correlated well with the Korsmeyer- Peppas model.
Simultaneous spectrophotometric determination of valsartan and hydrochlorothiazide by H-point standard addition method and partial least squares regression
Authors: Lakshmi Karunanidhi , Lakshmi Sivasubramanian
Published: March 2011

Simultaneous spectrophotometric determination of valsartan and hydrochlorothiazide by H-point standard addition method and partial least squares regression

Simultaneous determination of valsartan and hydrochlorothiazide by the H-point standard additions method (HPSAM) and partial least squares (PLS) calibration is described. Absorbances at a pair of wavelengths, 216 and 228 nm, were monitored with the addition of standard solutions of valsartan. Results of applying HPSAM showed that valsartan and hydrochlorothiazide can be determined simultaneously at concentration ratios varying from 20:1 to 1:15 in a mixed sample. The proposed PLS method does not require chemical separation and spectral graphical procedures for quantitative resolution of mixtures containing the titled compounds. The calibration model was based on absorption spectra in the 200-350 nm range for 25 different mixtures of valsartan and hydrochlorothiazide. Calibration matrices contained 0.5-3 μg mL-1 of both valsartan and hydrochlorothiazide. The standard error of prediction (SEP) for valsartan and hydrochlorothiazide was 0.020 and 0.038 μg mL-1, respectively. Both proposed methods were successfully applied to the determination of valsartan and hydrochlorothiazide in several synthetic and real matrix samples.
Simultaneous determination of iron and copper in children's sera by FAAS
Authors: Luterotti Svjetlana , Kordić Tončica , Dodig Slavica
Published: March 2011

Simultaneous determination of iron and copper in children's sera by FAAS

A new and simple flame atomic-absorption spectrometric (FAAS) method is proposed for simultaneous determination of iron and copper in children's sera. It is based on single-step sample pretreatment (deproteinization with 3 mol L-1HCl, ratio 1:1) and single-step calibration using 1.5 mol L-1HCl standard. During method's optimization a short multifactorial design experiment was used. The proposed method assures accuracy, sensitivity and precision comparable to that of the reference methods. The new approach is simple and time-, labour- and serum-saving, the latter being especially important in pediatric diagnostics.
Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects
Authors: Florea Ana-Maria , Büsselberg Dietrich
Published: March 2011

Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects.
The Potential Use of N-Myristoyltransferase as a Biomarker in the Early Diagnosis of Colon Cancer
Authors: Kumar Sujeet , Dimmock Jonathan R , Sharma Rajendra K
Published: March 2011

Colon cancer is one of the most common malignant diseases and a major cause of mortality in the Western world. Metastasis to lymph nodes and other gastrointestinal organs, especially to the liver and lungs, is most common and occurs in up to 25% of cancer patients when initially diagnosed. The majority of colon cancers develop from noncancerous adenomatous polyps on the lining of the colon which grow over the years to become cancerous. If detected early, the surgical resections of the growth, often in combination with chemotherapy, significantly increases life expectancy. We have shown that the enzyme N-myristoyltransferase (NMT) which carries out lipid modification of several proteins (including many of those involved in oncogenesis) is expressed at higher levels in cancerous tissues from the colon. We have also shown that in peripheral blood mononuclear cells (PBMC) and bone marrow (BM) cells collected from colon cancer patients and from azoxymethane-induced rats the expression and localization of NMT is altered. We have observed strong positivity for NMT in immunohistochemical analysis for PBMC from colon cancer patients as compared to control groups. Furthermore, in the bone marrow (BM) mononuclear cells, NMT was found to be confined to the nuclei whereas in control groups it was observed to be located in the cytoplasm. In conclusion, this strikingly differential localization offers the basis of a potential investigational tool for screening or diagnosis of individuals at risk for or suspected of having colon cancer.
Epigenetic Regulation by Lysine Demethylase 5 (KDM5) Enzymes in Cancer
Authors: Blair Lauren P. , Cao Jian , Zou Mike Ran , Sayegh Joyce , Yan Qin
Published: March 2011

Similar to genetic alterations, epigenetic aberrations contribute significantly to tumor initiation and progression. In many cases, these changes are caused by activation or inactivation of the regulators that maintain epigenetic states. Here we review our current knowledge on the KDM5/JARID1 family of histone demethylases. This family of enzymes contains a JmjC domain and is capable of removing tri- and di- methyl marks from lysine 4 on histone H3. Among these proteins, RBP2 mediates drug resistance while JARID1B is required for melanoma maintenance. Preclinical studies suggest inhibition of these enzymes can suppress tumorigenesis and provide strong rationale for development of their inhibitors for use in cancer therapy.
Socioeconomic Differences in Exposure to Tobacco Smoke Pollution (TSP) in Bangladeshi Households with Children: Findings from the International Tobacco Control (ITC) Bangladesh Survey
Authors: Abdullah Abu S. , Hitchman Sara C. , Driezen Pete , Nargis Nigar , Quah Anne C.K. , Fong Geoffrey T.
Published: March 2011

This study assessed the pattern of exposure to tobacco smoke pollution (TSP; also known as, secondhand smoke) in Bangladeshi households with children and examined the variations in household smoking restrictions and perception of risk for children’s exposure to TSP by socioeconomic status. We interviewed 1,947 respondents from Bangladeshi households with children from the first wave (2009) of the International Tobacco Control (ITC) Bangladesh Survey. 43.5% of the respondents had complete smoking restrictions at home and 39.7% were very or extremely concerned about TSP risk to children’s health. Participants with lower level of education were significantly less likely to be concerned about the risk of TSP exposure to children’s health and less likely to adopt complete smoking restrictions at home. Logistic regression revealed that the predictors of concern for TSP exposure risk were educational attainment of 1 to 8 years (OR = 1.94) or 9 years or more (OR = 4.07) and being a smoker (OR = 0.24). The predictors of having complete household smoking restrictions were: urban residence (OR = 1.64), attaining education of 9 years or more (OR = 1.94), being a smoker (OR = 0.40) and being concerned about TSP exposure risk to children (OR = 3.25). The findings show that a high proportion of adults with children at home smoke tobacco at home and their perceptions of risk about TSP exposure to children’s health were low. These behaviours were more prevalent among rural smokers who were illiterate. There is a need for targeted intervention, customized for low educated public, on TSP risk to children’s health and tobacco control policy with specific focus on smoke-free home.
Long-Term Low-Level Arsenic Exposure Is Associated with Poorer Neuropsychological Functioning: A Project FRONTIER Study
Authors: O’Bryant Sid E. , Edwards Melissa , Menon Chloe V. , Gong Gordon , Barber Robert
Published: March 2011

Exposure to elements in groundwater (toxic or beneficial) is commonplace yet, outside of lead and mercury, little research has examined the impact of many commonly occurring environmental exposures on mental abilities during the aging process. Inorganic arsenic is a known neurotoxin that has both neurodevelopmental and neurocognitive consequences. The aim of this study was to examine the potential association between current and long-term arsenic exposure and detailed neuropsychological functioning in a sample of rural-dwelling adults and elders. Data were analyzed from 434 participants (133 men and 301 women) of Project FRONTIER, a community-based participatory research study of the epidemiology of health issues of rural-dwelling adults and elders. The results of the study showed that GIS-based groundwater arsenic exposure (current and long-term) was significantly related to poorer scores in language, visuospatial skills, and executive functioning. Additionally, long-term low-level exposure to arsenic was significantly correlated to poorer scores in global cognition, processing speed and immediate memory. The finding of a correlation between arsenic and the domains of executive functioning and memory is of critical importance as these are cognitive domains that reflect the earliest manifestations of Alzheimer’s disease. Additional work is warranted given the population health implications associated with long-term low-level arsenic exposure.
Chitin Scaffolds in Tissue Engineering
Authors: Jayakumar Rangasamy , Chennazhi Krishna Prasad , Srinivasan Sowmya , Nair Shantikumar V. , Furuike Tetsuya , Tamura Hiroshi
Published: March 2011

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.
Natural-Synthetic Hybrid Polymers Developed via Electrospinning: The Effect of PET in Chitosan/Starch System
Authors: Espíndola-González Adolfo , Martínez-Hernández Ana Laura , Fernández-Escobar Francisco , Castaño Victor Manuel , Brostow Witold , Datashvili Tea , Velasco-Santos Carlos
Published: March 2011

Chitosan is an amino polysaccharide found in nature, which is biodegradable, nontoxic and biocompatible. It has versatile features and can be used in a variety of applications including films, packaging, and also in medical surgery. Recently a possibility to diversify chitosan properties has emerged by combining it with synthetic materials to produce novel natural-synthetic hybrid polymers. We have studied structural and thermophysical properties of chitosan + starch + poly(ethylene terephthalate) (Ch + S + PET) fibers developed via electrospinning. Properties of these hybrids polymers are compared with extant chitosan containing hybrids synthesized by electrospinning. Molecular interactions and orientation in the fibers are analyzed by infrared and Raman spectroscopies respectively, morphology by scanning electron microscopy and thermophysical properties by thermogravimetric analysis and differential scanning calorimetry. Addition of PET to Ch + S systems results in improved thermal stability at elevated temperatures.