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Many Diseases (many + disease)
Selected AbstractsMouse models for genetic dissection of polygenic gastrointestinal diseasesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2003S. Hillebrandt Abstract Many diseases with a major public health impact are the result of complex interactions between environmental factors and multiple genes. In the past decade, methods for genome analysis, in particular quantitative trait locus (QTL) analysis in animal models, were developed to identify and localize the genes responsible for multifactorial (polygenic) diseases; QTL analysis is based on experimental crosses between inbred strains with high and low genetic susceptibility. Recently the genes underlying several QTLs could be cloned successfully. Here we describe the impact of these genomic approaches in mice on our understanding of the multifactorial genetics of three gastrointestinal diseases related to metabolism (cholesterol cholelithiasis), development (gastroschisis), and colorectal cancer. The examples demonstrate how mouse models continue to be an invaluable tool in unravelling complex pathomechanisms and unlocking our understanding of human diseases. [source] Genetic association tests with age at onsetGENETIC EPIDEMIOLOGY, Issue 2 2003L. Hsu Abstract Many diseases or traits exhibit a varying age at onset. Recent data examples of prostate cancer and childhood diabetes show that compared to simply treating the disease outcome as affected vs. unaffected, incorporation of age-at-onset information into the transmission/disequilibrium type of test (TDT) does not appear to change the results much. In this paper, we evaluate the power of TDT as a function of age at onset, and show that age-at-onset information is most useful when the disease is common, or the relative risk associated with the high-risk genotype varies with age. Moreover, an extremely old unaffected subject can contribute substantially to the power of the TDT, sometimes as much as old-onset subjects. We propose a modified test statistic for testing no association between the marker at the candidate locus and age at onset. The simulation study was conducted to evaluate the finite sample properties of proposed and the TDT test statistics under various sampling schemes for trios of parents and offspring, as well as for sibling clusters where unaffected siblings were used as controls. Genet Epidemiol 24:118,127, 2003. © 2003 Wiley-Liss, Inc. [source] Cutaneous sterile granulomas/pyogranulomas, leishmaniasis and mycobacterial infectionsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 11 2008D. Santoro Cutaneous "sterile" granulomas represent a group of uncommon skin disorders of unknown aetiopathogenesis. Many diseases are included in this group (for example, sterile granuloma/pyogranuloma syndrome and reactive histiocytosis). The definition of sterile is based on the exclusion of other possible aetiological agents (for example, microorganisms or foreign body). Many techniques are used to rule out a microbial aetiology including cytology, histology, immunohistochemistry and culture. However, some organisms are "fastidious" and difficult to culture or to identify with routine methods, and molecular studies are necessary. This is particularly true for mycobacteria (for example, canine leproid granuloma syndrome) and Leishmania. Recently, studies in human and veterinary medicine have proved the presence of microorganisms (mycobacteria and Leishmania) using a polymerase chain reaction technique in specimens previously diagnosed as sterile. Therefore, it is very important, with the development of new technologies, to use a multidisciplinary diagnostic approach to definitively rule out any microorganism before declaring a disease sterile. [source] Body fluid proteomics: Prospects for biomarker discoveryPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2007Sung-Min Ahn Abstract Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e., the tissue interstitial fluid, TIF). A major challenge of clinical chemistry is to quantitatively map these perturbed protein profiles , the so-called "signatures of disease" , using modern proteomic technologies. This information can be utilized to design protein biomarkers for the early detection of disease, monitoring disease progression and efficacy of drug action. Here, we discuss the use of body fluids in the context of prospective biomarker discovery, and the marked 1000,1500-fold dilution of body fluid proteins, during their passage from TIF to the circulatory system. Further, we discuss proteomics strategies aimed at depleting major serum proteins, especially albumin, in order to focus on low-abundance protein/peptides in plasma. A major limitation of depletion strategies is the removal of low-molecular weight protein/peptides which specifically bind major plasma proteins. We present a prototype model, using albumin, for understanding the multifaceted nature of biomarker research, highlighting the involvement of albumin in Alzheimer's disease. This model underscores the need for a system-level understanding for biomarker research and personalized medicine. [source] A Censored Quantile Regression Analysis of Vegetable Demand: The Effects of Changes in Prices and Total ExpenditureCANADIAN JOURNAL OF AGRICULTURAL ECONOMICS, Issue 4 2006Geir Wæhler Gustavsen Many diseases are linked to dietary behavior. One major diet-related risk factor is a low consumption of vegetables. The consumption may be increased through public policies. The effects on vegetable purchases of either removing the value added tax on vegetables or a general income support are investigated. Adverse health effects are most serious in households consuming low quantities of vegetables. Therefore, the effects on high- and low-consuming households are estimated by using quantile regressions (QRs). Since many households did not purchase any vegetable during each survey period, censored as well as ordinary QRs are used. Our results suggest that the effects of the policy variables differ in different parts of the conditional distribution of vegetable purchases. None of the proposed policy options is likely to substantially increase vegetable purchases among low-consuming households. Bon nombre de maladies découlent des habitudes alimentaires. La faible consommation de légumes constitue un important facteur de risque liéà l'alimentation. Cette consommation pourrait être accrue par l'instauration de politiques gouvernementales. Nous avons examiné les effets de l'abolition de la taxe sur la valeur ajoutée ou d'un soutien du revenu sur les achats de légumes. Les effets néfastes sur la santé sont plus graves chez les ménages qui consomment de faibles quantités de légumes. Nous avons donc estimé les effets chez les ménages à forte et à faible consommation de légumes à l'aide de régressions par quantile. Comme de nombreux ménages n'ont pas acheté de légumes au cours des périodes sondées, nous avons utilisé des régressions par quantile censurées et des régressions par quantile ordinaires. Nos résultats ont indiqué que les effets des variables concernant les politiques diffèrent dans différentes parties de la distribution conditionnelle des achats de légumes. Aucune des options politiques proposées ne semble susceptible d'accroître substantiellement les achats de légumes chez les ménages qui en consomment peu. [source] Gene therapy and enhancement for diabetes (and other diseases): the multiplicity of considerationsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2010Marta Bertolaso Abstract Gene therapy has reached the forefront of studies and research over the last 30 years because of its potential for curing, treating, and preventing diseases associated with DNA mutations. Type 1 and type 2 diabetes are two examples of very common polygenic and multifactorial diseases. The huge amount of scientific literature on this topic reflects a growing general interest in the possibilities of altering our genetic heritage and thus controlling the onset of diseases associated with mutations and relative risk factors. We have focussed on the new treatment opportunities and possibility of enhancing an individual's health, physical well-being, and even an individual's behaviour through technologies specially designed for therapeutic purposes, which have been presented in literature. This historical perspective shows how this type of research, however, was immediately subjected to an ethical evaluation, especially regarding the decoding of the human genome and the questions raised by the alteration of our genetic heritage through new biotechnologies. Moreover, understanding the limitations of gene therapy protocol experiments and the multifactorial nature of many diseases, which have a genetic base, also contributes to these considerations. Copyright © 2010 John Wiley & Sons, Ltd. [source] Hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid that selectively induce apoptosis in leukemia cells but not in fibroblasts,,DRUG DEVELOPMENT RESEARCH, Issue 4 2008Anna Galkin Abstract New apoptosis modulating agents are widely sought, because failure in regulation of apoptosis is associated with many diseases. In this study, we have evaluated apoptosis inducing the potential of ten new hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid. Cancerous leukemia cells (HL-60) and non-malignant fibroblasts (Swiss 3T3) were incubated with test compounds for 24,h and morphologically evaluated. The changes in mitochondrial membrane potential (,,m) and caspase-3 activity were used to confirm the results and to study early induction of apoptosis. Cytotoxicity was determined using the lactate dehydrogenase (LDH) assay and mutagenicity with miniaturized Ames-test. The most potent selective apoptosis inducers were compounds 1c and 1,h having IC50 values of 41 and 23,µM, respectively, in leukemia cells (HL-60) while effects in fibroblasts (Swiss 3T3) were insignificant. Reduction of ,,m and increase in caspase-3 activity were observed already during the first 2,hr in the HL-60 cells treated with compounds 1,c and 1,h. Neither of the compounds was cytotoxic or mutagenic. The results indicate that compounds 1,c and 1,h are selective apoptosis inducers and should be studied further for possible use in cancer therapy. Drug Dev. Res. 69: 185,195, 2008. © 2008 Wiley-Liss, Inc. [source] Determinants of urinary 8-hydroxy-2,-deoxyguanosine in Chinese children with acute leukemiaENVIRONMENTAL TOXICOLOGY, Issue 5 2009You Yang Abstract The 8-hydroxy-2,-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage, but might also be a risk factor for many diseases including cancer. Elevated level of urinary 8-OHdG has been detected in patients with various malignancies. In the present study, the level of urinary 8-OHdG was examined in 116 Chinese children with acute leukemia (94 acute lymphoid leukemia, ALL, 22 acute myeloid leukemia, AML), and its correlation with urinary metal elements was investigated. Our result showed that the level of urinary 8-OHdG in children with acute leukemia before treatment was significantly elevated compared with that in normal controls (11.92 ± 15.42 vs. 4.03 ± 4.70 ng/mg creatinine, P < 0.05). In particular, urinary 8-OHdG was higher in children with acute leukemia aged under 3 years (20.86 ± 21.75 ng/mg creatinine) than in those aged 3,15 years (8.09 ± 9.65 ng/mg creatinine), whereas no differences were shown in terms of gender, parental smoking and education, household income, place of residence, and use of paracetamol. In addition, urinary 8-OHdG levels were similar among different subtypes of acute lymphoid leukemia (ALL) patients. Furthermore, linear regression analysis revealed a significant correlation between urinary 8-OHdG and urinary Cr, but not Fe or As, in group aged <3 years compared with group aged 3,15 years (P = 0.041), indicating that the metal elements may be involved in increasing urinary 8-OHdG level in younger children with acute leukemia. Our results suggest that children with acute leukemia undergo an increased risk of oxidative DNA damage, which may be correlated with high level of Cr exposure in Chinese children with acute leukemia. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source] Chronic neuropathic pain: mechanisms, drug targets and measurementFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Nanna B. Finnerup Abstract Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems. Preclinical research provides several promising targets for treatment such as sodium and calcium channels, glutamate receptors, monoamines and neurotrophic factors; however, treatment is often insufficient. A mechanism-based treatment approach is suggested to improve treatment. Valid and reliable tools to assess various symptoms and signs in neuropathic pain and knowledge of drug mechanisms are prerequisites for pursuing this approach. The present review summarizes mechanisms of neuropathic pain, targets of currently used drugs, and measures used in neuropathic pain trials. [source] Migration of naive, effector and memory T cells: implications for the regulation of immune responsesIMMUNOLOGICAL REVIEWS, Issue 1 2001Jürgen Westermann Summary: T cells play an important role in protective immune responses and in the pathogenesis of many diseases. Understanding the mechanisms regulating their distribution in vivo may therefore be of therapeutic value. Reviewing studies that have followed the migration of labelled naive, effector and memory T cells in healthy animals reveals that all T-cell subsets enter all organs investigated. Within the tissue, two principally different migration patterns can be identified. First, naive and memory T cells accumulate in lymphoid organs for about 48 h after injection, as the time needed for migration through lymphoid organs is longer than through non-lymphoid organs. During this time, surface molecule expression is temporarily modified. These changes are reversed before leaving the lymphoid organs and entering the blood to start a new cycle of migration. Second, effector T cells are evenly distributed throughout the body, and most die in the tissues within 24 h. However, depending on the presence of cytokines, some are able to survive and to proliferate, and thereby accumulate in defined microenvironments of the body. Analysing the principles regulating T-cell migration and survival within the tissue may lead to the development of new options for the treatment of disease. [source] Secretion of interferon-, by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18IMMUNOLOGY, Issue 3 2009Laila Darwich Summary The interferon (IFN)-, component of the immune response plays an essential role in combating infectious and non-infectious diseases. Induction of IFN-, secretion by human T and natural killer (NK) cells through synergistic costimulation with interleukin (IL)-12 and IL-18 in the adaptive immune responses against pathogens is well established, but induction of similar activity in macrophages is still controversial, with doubts largely focusing on contamination of macrophages with NK or T cells in the relevant experiments. The possible contribution of macrophages to the IFN response is, however, an important factor relevant to the pathogenesis of many diseases. To resolve this issue, we analysed the production of IFN-, at the single-cell level by immunohistochemistry and by enzyme-linked immunosorbent spot (ELISPOT) analysis and unequivocally demonstrated that human macrophages derived from monocytes in vitro through stimulation with a combination of IL-12 and IL-18 or with macrophage colony-stimulating factor (M-CSF) were able to produce IFN-, when further stimulated with a combination of IL-12 and IL-18. In addition, naturally activated alveolar macrophages immediately secreted IFN-, upon treatment with IL-12 and IL-18. Therefore, human macrophages in addition to lymphoid cells contribute to the IFN-, response, providing another link between the innate and acquired immune responses. [source] Progress towards achieving new vaccine and vaccination goalsINTERNAL MEDICINE JOURNAL, Issue 7 2003G. Ada Abstract Viral and bacterial vaccines, especially for childhood use, are one of the most successful public health measures of the last two centuries and have a good safety record. However, there are still many diseases that are caused by infectious agents for which vaccines are not available. Our increasing ability to manipulate the immune system offers hope that, in the future, at least some of these infections may be prevented by vaccination. A surprising recent development is the use of vaccine technology to test whether a range of other generally non-communicable diseases can be prevented (or at least controlled) in this way. Investigation of these diseases is still mainly at the experimental level, however the list includes different types of cancers, allergies, drug addiction and neurodegenerative diseases. (Intern Med J 2003; 33: 297,304) [source] Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseasesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2007Ala'eddin Jebreel Summary Angiogenesis is critical for the growth and metastatic spread of tumours. Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many diseases. The purpose of this study was to evaluate the relation between VEGF, its receptors (VEGFR-1 and VEGFR-2) and microvessel density (MVD) in thyroid diseases. Immunostaining for VEGF and VEGF receptors was performed in 66 specimens of thyroid tissue, comprising 17 multinodular goitre (MNG), 14 Graves' disease, 10 follicular adenoma, 8 Hashimoto's thyroiditis, 7 papillary carcinoma and 10 normal thyroid specimens. Thyrocyte positivity for VEGF and VEGF receptors was scored 0,3. Immunohistochemistry for CD31, and CD34 on the same sections was performed to evaluate MVD. Immunohistochemical staining of VEGF in thyrocytes was positive in 92% of all the thyroid tissues studied. Using an immunostaining intensity cut off of 2, increased thyrocyte staining was seen in follicular adenoma specimens, MNG and normal thyroids compared with Hashimoto's thyroiditis and Graves' disease (P < 0.05). Similarly, VEGF thyrocyte expression in Graves' disease was less than other pathologies (P < 0.05). VEGFR-1 expression and the average MVD score did not differ between the different thyroid pathologies. VEGF expression was lower in autoimmune pathologies compared to autonomous growth processes. Conversely, both VEGFR-1 and VEGFR-2 were widely expressed in benign and neoplastic thyroid disease, suggesting that the up-regulation of VEGF and not its receptors occurs as tissue becomes autonomous. There was no clear relationship between MVD measurement and thyroid pathology. [source] HLA allele and haplotype frequencies in the Albanian population and their relationship with the other European populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2009G. Sulcebe Summary Human leucocyte antigen (HLA) alleles are very interesting markers in identifying population relationships. Moreover, their frequency distribution data are important in the implementation of donor,recipient registry programs for transplantation purposes and also in determining the genetic predisposition for many diseases. For these reasons, we studied the HLA class I and II allele and haplotype frequencies in 160 healthy, unrelated Albanian individuals originating from all regions of the country. The HLA genotyping was performed through a 2-digit resolution SSOP method. The data were analysed with Arlequin and Phylip programs. No deviation was found from the Hardy,Weinberg equilibrium. A total of 17 A*, 30 B*, 12 Cw*, 13 DRB1* and 5 DQB1* alleles were identified. The six most frequent HLA-A-B-DRB1 haplotypes were A*02,B*18,DRB1*11 (5.60%), A*02,B*51,DRB1*16 (4.74%), A*01,B*08,DRB1*03 (3.48%), A*24,B*35,DRB1*11 (2.77%), A*02,B*51,DRB1*13 (2.21%), A*24,B*35,DRB1*14 (1.89%). Interestingly, 12 HLA-A-B-Cw-DRB1-DQB1 haplotypes occurred at a frequency >1%. When compared with the other populations, a close relationship was found with North Greek, Bulgarian, Macedonian, Romanian, Turkish, Cretan, Serbian, Croatian and Italian populations. A higher differentiation in allele frequency level was found with Western Europe populations. These data are the first report of HLA allele and haplotype distribution in an Albanian population inside this country. When compared with other populations, their distribution frequencies show close similarities with neighbouring populations of the entire Balkan area. [source] C3 and C4 hypocomplementemia and associated diseases in ArabiansINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2005Emad A. KOSHAK Abstract Background:, Hypocomplementemia, which is a state of decrease in the complement (C) proteins in the serum, is frequently encountered in a wide range of diseases. Objective:, To explore the diversity of C3 and C4 hypocomplementemia and associated diseases in patients seen at King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia. Methods:, Serum samples send to the clinical immunology laboratory with requests for the measurements of C3 and C4 tests by nephelometry were studied. Files of patients with C3 and/or C4 hypocomplementemia were reviewed for demographic and diagnostic data. Results:, Out of 270 complement tests, C3 and/or C4 hypocomplementemia was found in 196 different tests (72.6%), and only 175 tests were studied. Their ages ranged between 1 week and 81 years (mean 26 ± 17 SD), and female sex was predominant in 143 tests (81.3%). Hypocomplementemia was detected as follows: C3 in 64 tests (23.7%) with sole C3 in 3 tests only (1.5%); C4 in 193 samples (71.5%) with sole C4 in 132 tests (67.3%); and combined C3 with C4 hypocomplementemia in 61 tests (22.6%). Cross-tabulation revealed that 95% of C3 hypocomplementemia were significantly associated with C4 hypocomplementemia (P < 0.001). Conversely, only 31% of C4 hypocomplementemia were significantly associated with C3 hypocomplementemia (P < 0.001). SLE was the predominant disease associated with hypocomplementemia in 104 tests (53.1%), followed by kidney diseases in 20 tests (10.2%) and chronic liver disease in eight tests (4.1%). Conclusion:, C4 hypocomplementemia was a common laboratory verdict in patients at KAUH. Of interest, most of C3 hypocomplementemia tests were associated with C4 hypocomplementemia and lone C3 hypocomplementemia is rare. The diagnosis of systemic lupus erythematosus was the predominant disease associated with hypocomplementemia. Supplementary awareness of immunopathological mechanisms leading to involvement of complement proteins in many diseases is essential to enhance its clinical utility. [source] Genetic Approaches to the Study of AgingJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9s 2005Richard A. Miller MD Can mouse genetics teach us enough about the biology of aging to guide the search for anti-aging medicines that can delay late-life illness? Recent progress gives reason for optimism, with new data showing that changes in single genes can extend average and maximal life span by 40%. Mice with these genetic variants remain healthy, active, and cognitively intact at average ages that correspond to 110,120 years of human life span. Multiple lines of evidence now point to a hormone, IGF-I, as a key influence on life span, with low IGF-I levels associated with extended longevity in multiple model systems. The goal of this research is not gene therapy,we have no idea of what genes to change, how to change them, or what harm such changes might do,but instead to use insights from the cell biology and endocrinology of genetically long-lived mice and other species to help develop drugs that manipulate aging and thus postpone the many diseases and disabilities that are typically troublesome in old age. The complete conquest of cancer or heart disease would each lead to an increase of a mere,3% in mean life span in humans, i.e. about a tenth of what can be accomplished, today, in laboratory animals of delayed aging. In this context the paltry commitment to research in biological gerontology (six cents per $100 of NIH funding, for example) seems worth reconsideration. [source] A biodegradable copolymer for the slow release of growth hormone expedites scarring in diabetic ratsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2007Francisco García-Esteo Abstract In many diseases wound healing is impaired. This study was designed to establish whether the healing process in diabetes could be improved using a site-specific polymer delivery system containing hGH. The system was first optimized in in vitro experiments performed on cultured fibroblasts taken from healthy and diabetic rats and then tested in an incisional wound model created in the diabetic Wistar rat. In the in vitro experiments using cultured fibroblasts, cell viability, growth, and proliferation were determined, along with polymer degradation, hormone release rates and the expression of TGF,1 in the culture medium. For the in vivo experiments, polymer discs with/without GH were inserted through 3 cm incisions made on the backs of the animals. Wound specimens were obtained 7 and 30 days after surgery to evaluate inflammatory/apoptotic cells, metalloprotease expression and neoangiogenesis using microscopy and immunohistochemical techniques. The local administration of GH using a polymer delivery system did not affect the normal wound healing process. Conversely, when used in diabetic animals, epidermal and dermal repair was expedited. Our findings indicate that GH induces cell proliferation, enhances CD4+ infiltration; increases extracellular matrix protein deposition; stimulates angiogenesis; and diminishes apoptosis at the diabetic wound site. These effects give rise to a comparable wound healing process to that observed in healthy animals. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] Cellular response to oxidative stress: Signaling for suicide and survival,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2002Jennifer L. Martindale Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley-Liss, Inc. [source] HELICOBACTER INFECTION IN CHILDREN WITH APPENDICITIS AND LACTOSE INTOLERANCEJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2000Eva J. Soelaeman Helicobacter pylori eradication has been debated. Most investigators do not recommended treating the infection except in severe case. We report a unique case: H. pylori infection with appendicitis and lactose intolerance. Case report: A 6 year old girl was brought to children and maternity Hospital Harapan Kita due to abdominal pain and vomiting. She had 6- month history of epigastric pain. In the past 2 days, she suffered from abdominal pain arround Mc. Burney area. On physical examination, she was in pain. Her weight was 19 Kg. Vital signs were normal. Findings in heart, lung and extremities were also normal. Abdomen: severe pain in the epigastric and Mc. burney area.Laboratory investigations showed hemoglobin 12 g/dl, leukocyte 12800/ul. Platelets 289000/ul. Bleeding and clotting time were normal. Abdominal ultrasonography revealed inflammation of appendix with 9-mm diameter. Stool examination was normal.Appendectomy was done at the same time with esofagogastroduodenoscopy (EGD). On EGD, we found moderete anthral gastritis. On histopathological examination, we found H. pylori at antral of the stomach. Breath hydrogen test was positive. After H. pylori eradication and milk avoidance, abdominal pain has never occurred. Conclusion: Abdominal: pain is not specific for H. pylori infection. The pain caused by many diseases including H. pylori infection. In our case, we can control abdominal pain by H. pylori eradication. [source] Tau oligomers and aggregation in Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Marco A. Meraz-Ríos J. Neurochem. (2010) 112, 1353,1367. Abstract We are analyzing the physiological function of Tau protein and its abnormal pathological behavior when this protein is self-assemble into pathological filaments. These aggregates of Tau protein are the main components in many diseases such as Alzheimer's disease (AD). Recent studies suggest that Tau acquires complex oligomeric conformations which may be toxic. In this review, we emphasized the possible phenomena implicated in the formation of these oligomers. Studies with chemical inductors indicates that the microtubule-binding domain is the most important region involved in Tau aggregation and showed the requirement of a pre-arrange Tau in abnormal conformation to promote self-assembly. Transgenic animal models and AD neuropathology studies showed that post-translational modifications are also implicated in Tau aggregation and neural cell death during AD development. Therefore, we analyzed some events that could be present during Tau aggregation. Finally, we included a brief discussion of the possible relation between glucose metabolism dysfunction in AD, and data of Tau aggregation by using aggregation inhibitors. In conclusion, the process Tau aggregation deserves further investigations to design possible therapeutic targets to inhibit the toxicity of these aggregates and it is possible that could be extended to other diseases with similar etiology. [source] The effect of a promoter polymorphism on the transcription of nitric oxide synthase 1 and its relevance to Parkinson's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2009Terrie Rife Abstract Transcriptional changes of the enzyme nitric oxide synthase I (NOS1) are believed to play a role in the development of many diseases. The gene for NOS1 has 12 alternative first exons (1A,1L). The 1F exon is one of the most highly utilized first exons in the brain and has a polymorphism ((TG)mTA(TG)n) located in its promoter region. The polymorphism's length has been suggested to affect NOS1 transcription and play a role in Parkinson's disease (PD); however, the actual influence of the polymorphism on NOS1 transcription has not been studied. To better characterize the links of the polymorphism with PD, a genotyping study was done comparing polymorphism length among 170 PD patients and 150 age-matched controls. The pattern of changes between the two group's allele frequencies shows statistical significance (P = 0.0359). The smallest polymorphism sizes are more predominant among PD patients than controls. To study the effects of this polymorphism on NOS1 gene transcription, reporter gene constructs were made by cloning the NOS1 1F promoter with polymorphism lengths of either 42, 54, or 62 bp in front of the luciferase gene and transfecting them into HeLa or Sk-N-MC cells. NOS1-directed reporter gene constructs with the 62-bp polymorphism increased transcription of luciferase 2.2-fold in HeLa and 1.8-fold in Sk-N-MC cells compared with reporter gene constructs with the 42-bp polymorphism. These data suggest that if smaller polymorphism size contributes to the higher NOS1 levels in PD patients, an as yet unknown transcriptional mechanism is required. © 2009 Wiley-Liss, Inc. [source] Cell death regulation in oral squamous cell carcinoma: methodological considerations and clinical significanceJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2003L. L. Loro Abstract In the last three decades, more work has been done on apoptosis and its role in the pathogenesis of many diseases including cancer. In almost all instances of cancer, dysregulation of cell death (apoptosis) and cell proliferation have been found to play a major role in tumourigenesis. A lot of progress has been made on understanding the molecular basis of apoptosis and its regulatory mechanisms. This review focuses on current knowledge on the regulation of apoptosis in oral squamous cell carcinoma, current methodologies and methodological consideration in estimation of cell death in tissue sections and the clinical significance of apoptosis related molecules in progression of oral squamous cell carcinoma. [source] Glycoengineering: The effect of glycosylation on the properties of therapeutic proteinsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2005Angus M. Sinclair Abstract Therapeutic proteins have revolutionized the treatment of many diseases but low activity or rapid clearance limits their utility. New approaches have been taken to design drugs with enhanced in vivo activity and half-life to reduce injection frequency, increase convenience, and improve patient compliance. One recently used approach is glycoengineering, changing protein-associated carbohydrate to alter pharmacokinetic properties of proteins. This technology has been applied to erythropoietin and resulted in the discovery of darbepoetin alfa (DA), a hyperglycosylated analogue of erythropoietin that contains two additional N-linked carbohydrates, a threefold increase in serum half-life and increased in vivo activity compared to recombinant human erythropoietin (rHuEPO). The increased serum half-life allows for less frequent dosing to maintain target hemoglobin levels in anemic patients. Carbohydrates on DA and other molecules can also increase molecular stability, solubility, increase in vivo biological activity, and reduce immunogenicity. These properties are discussed. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1626,1635, 2005 [source] Antibacterial, antiviral, antiproliferative and apoptosis-inducing properties of Brackenridgea zanguebarica (Ochnaceae)JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2006Maren Möller Brackenridgea zanguebarica is a small tree that is used in traditional African medicine as a type of cure-all for many diseases, including the treatment of wounds. The yellow bark of B. zanguebarica was used for the preparation of an ethanolic extract, which was tested in various concentrations against eleven bacteria, Herpes simplex virus type 1 (HSV-1) and different human tumour cell lines. The extract that contains different polyphenolic substances like calodenin B. Cell growth inhibition, assessed via MTT-assay, was found in all tested human cell lines with IC50 values (concentration of extract that reduced cell viability by 50%) between 33 ,g dry extract/mL for HL-60 human myeloid leukaemia cells and 93 ,g dry extract/mL for HaCaT human keratinocytes. Staining with Annexin-V-FLUOS and JC-1 followed by subsequent analysis via flow cytometry revealed significant apoptosis-inducing properties. Analysis of caspase activity using a fluorogenic caspase-3 substrate showed a significant caspase activity in Jurkat T-cells after incubation with the extract. The bark extract had a pronounced activity against free HSV-1 and a strong antibacterial activity against Gram-positive strains (MICs: 6,24 ,g dry extract/mL), which are often involved in skin infections. Additionally, no irritating properties of the extract could be observed in hen-egg test chorioallantoic membrane (HET-CAM) assay. These findings give a rationale for the traditional use of B. zanguebarica and are a basis for further analysis of the plant's components, their biological activity, and its use in modern phytotherapy. [source] Prediction of Volatile Components Retention Time in Blackstrap Molasses by Least-Squares Support Vector MachineMOLECULAR INFORMATICS, Issue 5 2008Yongna Yuan Abstract House flies are pestiferous insects that have the potential to spread many diseases to humans and livestock, so it is very significant for us to manage house fly populations. Many commercial types of bait are available to attract house flies, but most are designed for outdoor or limited indoor use, due to their malodorous components. This study sought to identify compounds present in blackstrap molasses that might be attractive to house flies. An effective Quantitative Structure-Property Relationship (QSPR) model between the Retention Time (RT) and five molecular descriptors of the volatile compounds in blackstrap molasses, was built using a modified algorithm of Least-Squares Support Vector Machine (LS-SVM). Descriptors calculated from the molecular structures alone were used to represent the characteristics of compounds. The five molecular descriptors selected by the Heuristic Method (HM) in CODESSA were used as inputs for LS-SVM. The results obtained by LS-SVM were compared with those obtained by the HM. The LS-SVM model gives better results with the predicted correlation coefficient () 0.919 and Root Mean-Square Errors (RMSE) 2.193 for the test set, as well as that 0.824 and 2.728 in the MLR model. The prediction results of log RT are in very good agreement with the experimental values. This paper provided a new and effective method for predicting the chromatography retention index. [source] Promoting screening and early detection of cancer in menNURSING & HEALTH SCIENCES, Issue 4 2001John M. Lantz RN Abstract Gender is a factor in the risk assessment for many diseases. It may also impact on the way in which men assess their personal health or illness status and take action to prevent illness or promote well-being. This paper is focused on three objectives: (i) to foster an understanding of gender differences in health promoting behaviors; (ii) to review three health issues affecting males for which dissemination of health education, increased personal awareness and early detection may be beneficial in the reduction of morbidity and mortality; and (iii) to offer suggestions for nurses and other health care professionals to promote positive patient,provider interactions within a health-care framework for action. [source] Agreement between GPRD smoking data: a survey of general practitioners and a population-based survey,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2004James D. Lewis MD, MSCE Abstract Background Cigarette smoking is a common habit that is associated with many diseases. Smoking is often an important confounding variable in pharmacoepidemiological studies. The General Practice Research Database (GPRD) is widely used in pharmacoepidemiological research. In this study, we compare data recorded in the GPRD with the smoking history obtained from direct query of general practitioners (GPs) and from a population-based survey. Methods We completed a mailed survey of GPs caring for a random sample of 150 patients with inflammatory bowel disease. The survey asked the GP to categorize the patients smoking status on a specified date. These results were then compared to the data recorded in the GPRD. Smoking status of 225,308 randomly selected GPRD patients without inflammatory bowel disease was compared to the results of a population-based household survey. Results Completed surveys with usable data were received from GPs on 136 of the 150 patients (91%). The sensitivity and positive predictive value of the database for current smoking were 78% (95%,CI: 52,94) and 70% (95%,CI: 46,88) respectively. The sensitivity and positive predictive value of former smoking were 53% (95%,CI: 28,77) and 60% (95%,CI: 32,84) respectively. Current and former smoking rates in the GPRD were 79% and 29% respectively of expected rates according to the population-based survey . Conclusions Current smoking is more completely recorded in the GPRD than former smoking. These data need to be considered when planning GPRD studies where smoking is an important exposure variable. Copyright © 2003 John Wiley & Sons, Ltd. [source] Radix Astragali extract promotes angiogenesis involving vascular endothelial growth factor receptor-related phosphatidylinositol 3-kinase/Akt-dependent pathway in human endothelial cellsPHYTOTHERAPY RESEARCH, Issue 9 2009Yi Zhang Abstract Angiogenesis plays an important role in a wide range of physiological processes and many diseases are associated with dysregulation of angiogenesis. Radix Astragali, commonly used in traditional Chinese medicine, is a potential candidate for treating such diseases. However, the biological effects of Radix Astragali on angiogenesis and its underlying mechanisms are yet to be elucidated fully. This study describes the angiogenic effects of Radix Astragali extract (RAE) on human umbilical vein endothelial cells (HUVEC) in vitro. It was shown that RAE treatment stimulated HUVEC to proliferate. A significant increase in migration was observed in RAE-treated HUVEC using the wound healing migration assay. In addition, a significant increase in the number of branching points was observed during endothelial cell capillary formation after RAE treatment. It was shown that RAE enhances vascular endothelial growth factor (VEGF) mRNA expression, and that a specific blocker of VEGF receptor 2 (KDR/Flk) inhibited the RAE-induced HUVEC proliferation. In addition, a decrease in the RAE-induced HUVEC proliferation was observed after treatment with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt and endothelial nitric oxide synthase (eNOS). Taken together, these data suggest that RAE is a potent stimulator of angiogenesis and that its pro-angiogenic effects involve the VEGF-KDR/Flk and PI3K-Akt-eNOS pathways. Copyright © 2009 John Wiley & Sons, Ltd. [source] Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro and zebrafish in vivoPHYTOTHERAPY RESEARCH, Issue 5 2009Si-Jia Hong Abstract Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. In fact, many diseases are associated with imbalance in the regulation of angiogenesis in which there is either excessive or insufficient blood vessel formation. Panax notoginseng, a blood circulation invigorating herb, is commonly used in traditional Chinese medicine to treat circulation-related diseases. However, the biological effects of saponin extract from Panax notoginseng (PNS) on angiogenesis and the underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of PNS on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish in vivo. The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)5[(phenylamino)carbonyl]2H-tetrazolium hydroxide (XTT) assay and microscopic cell counting demonstrated that the extract was able to stimulate the proliferation of HUVECs. Meanwhile, the numbers of invaded cells and tube branches were significantly increased in PNS treatment groups. PNS was also shown to promote changes in the subintestinal vessels, a feature of angiogenesis, in zebrafish. In addition, by using real-time polymerase chain reaction (PCR), PNS was found to enhance vascular endothelial growth factor (VEGF) and kinase-domain region/fetal liver kinase-1 in mice (KDR/Flk-1) mRNA expression, and the PNS-induced HUVECs proliferation could be abolished by a KDR/Flk-1 inhibitor. Furthermore, the proliferation of HUVECs induced by PNS was significantly attenuated by inhibitors of PI3K-Akt-eNOS. All the results suggest that PNS can promote angiogenesis, and that the proangiogenic effects involve the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effect of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) hull extracts on testosterone release from rat Leydig cellsPHYTOTHERAPY RESEARCH, Issue 5 2009Shih-Min Hsia Abstract Adlay has been used as a traditional Chinese medicine for the treatment of many diseases. However, few studies have reported the effects of adlay seeds on the endocrine system. In the present study, the effects of methanol extracts of adlay hull (AHM) on testosterone synthesis were studied. Rat Leydig cells were incubated with different reagents including human chorionic gonadotropin, 8-bromo-adenosine-3,,5,-cyclic monophosphate, forskolin, A23187, progesterone and androstenedione in the presence or absence of AHM. The rat anterior pituitary (AP) gland was treated with gonadotropin-releasing hormone (GnRH) in vitro in the presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in the media were measured. AHM decreased testosterone release via the inhibition of (1) the PKA and PKC signal transduction pathways, (2) 17, -HSD enzyme activity in rat Leydig cells, and (3) in vitro GnRH-induced LH secretion. Copyright © 2008 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||||||||