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Related Diseases (relate + disease)
Selected AbstractsComments on ,Significance of developmental expression of amphioxus Branchiostoma belcheri and zebrafish Danio rerio Hsd17b10 in biological and medical research'JOURNAL OF FISH BIOLOGY, Issue 8 2009X. He The reported data on the developmental expression of Hsd17b10 gene in Danio rerio is crucial to the utilization of the D. rerio embryo as an animal model for human developmental disorders caused either by mutations on HSD17B10 (formerly HADH2) or by defective expression of the gene. Related diseases were summarized, and it was noticed that hyperinsulinaemic hypoglycaemia is not linked to HSD17B10. This inherited disease is actually caused by a deletion in the HADH gene on chromosome 4. Moreover, it was found by a revision of the reported phylogenetic tree that hydroxyacyl-CoA dehydrogenase II or rather hydroxysteroid (17beta) dehydrogenase 10 (HSD10) of amphioxus Branchiostoma belcheri,occupies a transition position from HSD10 orthologs of invertebrates to those of vertebrates. [source] MYH9 related disease: four novel mutations of the tail domain of myosin-9 correlating with a mild clinical phenotypeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2010Alessandro Pecci Abstract MYH9 -related disease (MYH9 -RD) is a rare autosomal dominant disorder caused by mutations in MYH9, the gene encoding the heavy chain of non-muscle myosin IIA. All patients present congenital macrothrombocytopenia and inclusion bodies in neutrophils. Some of them can also develop sensorineural deafness, presenile cataract, and/or progressive nephropathy leading to end-stage renal failure. We report four families, each with a novel mutation: two missense mutations, in exons 31 and 32, and two out of frame deletions in exon 40. They were associated with no bleeding diathesis, normal, or only slightly reduced platelet count and no extra-hematological manifestations, confirming that alterations of the tail domain cause a mild form of MYH9 -RD with no clinically relevant defects. [source] Helicobacter pylori Stimulates a Mixed Adaptive Immune Response with a Strong T-Regulatory Component in Human Gastric MucosaHELICOBACTER, Issue 3 2007Rasmus Goll Abstract Background:, Host factors play an important role in the pathophysiology of Helicobacter pylori infection and development of gastritis and related disease. The established opinion is that the T-cell-mediated immune response to H. pylori infection is of Th1 type. Our earlier immune cell phenotype studies indicate a mixed Th1,Th2 profile of the effector cells. Therefore, an extensive adaptive and regulatory cytokine gene expression profile was conducted by quantitative real-time polymerase chain reaction (qPCR). Materials and Methods:, Biopsies from gastric mucosa of 91 patients diagnosed as H. pylori negative, H. pylori positive with gastritis, or H. pylori positive with peptic ulcer were obtained by endoscopy. Gene expressions of nine cytokines and CagA status were measured by qPCR. Results:, All cytokine genes showed higher expression levels in the presence of H. pylori when compared to H. pylori- negative samples (fold increase: IL8: × 11.2; IL12A: × 2.4; TNF-,: × 5.2; IFN-,: × 4.3; IL4: × 3.6; IL6: × 14.7; and IL10: × 6.7). Patients infected with CagA-positive strains had higher expression of IL1-, and IL18 compared to patients infected with CagA-negative strains (× 1.6 for IL1-, and × 2.0 for IL18). Patients with duodenal ulcer had a lower antral Th1/Th2 ratio than other H. pylori -positive patients. Conclusions:, The cytokine profile of H. pylori -infected gastric mucosa shows a mixed Th1,Th2 profile. Furthermore, a high IL10 expression may indicate that also regulatory T cells play a role in the chronic phase of H. pylori infection. [source] Disease-specific Helicobacter pylori Virulence Factors: The Unfulfilled PromiseHELICOBACTER, Issue S1 2000David Y. Graham A number of putative virulence factors for Helicobacter pylori have been identified including cagA, vacA and iceA. The criteria for a true virulence factor includes meeting the tests of biologically plausibility with the associations being both experimentally and epidemiologically consistent. Although disease-specific associations have been hypothesized/claimed, there are now sufficient data to conclusively state that none of these putative virulence factors have disease specificity. CagA has been claimed to be associated with increased mucosal IL-8 and inflammation, increased density of H. pylori in the antrum, duodenal ulcer (DU), gastric cancer, and protection against Barrett's cancer. Only the increase in IL-8/inflammation is direct and substantiated. Different H. pylori strains with functional cag pathogenicity islands do not vary in virulance as it has been shown that mucosal IL-8 levels are proportional to the number of cagA +H. pylori independent of the disease from which the H. pylori were obtained. It is now known that the density of either cagA + and cagA,H. pylori in the antrum of patients with H. pylori gastritis is the same. In contrast, the mean density of H. pylori in the antrum in DU is greater than in the antrum of patients with H. pylori gastritis. Of interest, the density of H. pylori is higher in the corpus of patients with H. pylori gastritis than those with DU, suggesting that acid secretion plays a critical role in these phenomena. The presence of a functional cag pathogenicity island increases inflammation and it is likely that any factor that results in an increase in inflammation also increases the risk of a symptomatic outcome. Nevertheless, the presence of a functional cag pathogenicity island has no predictive value for the presence, or the future development of a clinically significant outcome. The hypothesis that iceA has disease specificity has not been confirmed and there is currently no known biological or epidemiological evidence for a role for iceA as a virulence factor in H. pylori -related disease. The claim that vacA genotyping might prove clinically useful, e.g. to predict presentation such as duodenal ulcer, has been proven wrong. Analysis of the worldwide data show that vacA genotype s1 is actually a surrogate for the cag pathogenicity island. There is now evidence to suggest that virulence is a host-dependent factor. The pattern of gastritis has withstood the test of time for its relation to different H. pylori -related diseases (e.g. antral predominant gastritis with duodenal ulcer disease). The primary factors responsible for the different patterns of gastritis in response to an H. pylori infection are environmental (e.g. diet), with the H. pylori strain playing a lesser role. Future studies should work to eliminate potential bias before claiming disease associations. Controls must exclude regional or geographic associations related to the common strain circulation and not to the outcome. The authors must also control for both the presence of the factor and for the disease association. The study should be sufficiently large and employ different diseases and ethnic groups for the results to be robust. The findings in the initial sample (data derived hypothesis) should be tested in a new group (hypothesis testing), preferably from another area, before making claims. Finally, it is important to ask whether the results are actually a surrogate for another marker (e.g. vacA s1 for cagA) masquerading for a new finding. Only the cag pathogenicity island has passed the tests of biological plausibility (increased inflammation) and experimental and epidemiological consistency. [source] A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post,liver transplantation hepatitis B prophylaxis,HEPATOLOGY, Issue 5 2008Peter W. Angus Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen,positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 ,mol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was $8,290 versus $13,718 IM HBIG/lamivudine. Conclusion: Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost. (HEPATOLOGY 2008.) [source] Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9 -related disease,HUMAN MUTATION, Issue 3 2008Alessandro Pecci Abstract MYH9 -related disease (MYH9 -RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease. We have evaluated 108 consecutive MYH9 -RD patients belonging to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis. We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9 -RD cases). We concluded that mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. These findings are relevant not only to patients' clinical management but also to the elucidation of the pathogenesis of the disease. Hum Mutat 29(3), 409,417, 2008. © 2007 Wiley-Liss, Inc. [source] The pathology of ageing: concepts and mechanisms,THE JOURNAL OF PATHOLOGY, Issue 2 2007JE Martin Abstract The rising numbers and proportion of aged individuals in the population is a global demographic trend. The diseases associated with ageing are becoming more prevalent, and the associated healthcare costs are having a significant economic impact in all countries. With these changes have come great advances in our understanding of the mechanisms of ageing. The mechanisms of cellular ageing at a genetic, protein and organelle level are becoming clearer, as are some of the more complex associations between environment and ageing. System ageing is also becoming better understood, and the potential biological advantages of ageing are being explored. Many of the advances in these fields are opening up the prospect of targeted therapeutic intervention for ageing and age related disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] FOOD INSECURITY IN BUHAYA: THE CYCLE OF WOMEN'S MARGINALIZATION AND THE SPREAD OF POVERTY, HUNGER, AND DISEASEANNALS OF ANTHROPOLOGICAL PRACTICE, Issue 1 2009Valerie Githinji This chapter focuses on how the marginalization of Bahaya women increases poverty, thus exacerbating issues of hunger and related disease in a region characterized by a history of environmental degradation, agricultural change and decline, rural poverty and disease. In the past several decades, diminishing sizes of banana farms, an overall decline in cattle, decreasing soil fertility, and an increase in food crop pathogens have posed challenges to achieving adequate agricultural yields in Buhaya of northwestern Tanzania. This situation has resulted in an increase in poverty, food insecurity, nutrition insecurity, and related disease. Culturally, women are the primary agriculturalists and producers and providers of food in Buhaya. However, Bahaya cultural practices hinder women from achieving equal representation in society, thus blocking their access to self advancement and resources such as money, land, education, and agricultural inputs. These constraints marginalize and hinder women from fulfilling their social role as primary farmers and provisioners of food, nutrition, and care. As patriarchal practices and ecological challenges work to constrain women's roles, poverty, food scarcity, and disease increase, affecting and weakening the foundation of Bahaya society and culture. [source] Incidence of dental trauma associated with facial trauma in Brazil: a 1-year evaluationDENTAL TRAUMATOLOGY, Issue 1 2004Alessandro Costa Da Silva Abstract,,, Dental trauma occurs frequently in young people, and mostly occurs in conjunction with facial trauma. In the literature, there are still few reports relating dental trauma, facial trauma, and soft-tissue injuries. This research aimed to evaluate: (i) the overall incidence of dental trauma in 340 patients who presented with facial trauma over a 1-year-period, (ii) the epidemiology of these related diseases, and (iii) the most common dental trauma when a facial trauma was present. Of all facial trauma, 15.29% presented dental trauma, of which luxations and avulsions were the most frequent injuries (40.30% each), occurring mainly on weekends (38.46%) and in October (15.38%), followed by March and June (13.46% each). The sex ratio presented the proportion of 3.3:1 (M:F). Trauma occurred mainly in the second decade (44.23%). These results highlight the high incidence of dental and facial trauma, and suggest the importance of the adoption of appropriate prevention protocols and effective therapeutic methods. [source] Enhanced Activation of Cyclooxygenase-2 Downregulates Th1 Signaling Pathway in Helicobacter pylori -infected Human Gastric MucosaHELICOBACTER, Issue 3 2007Antonia Pellicanò Abstract Background:, Evidence suggests that an impaired T-cell response against Helicobacter pylori plays a role in the pathogenesis of H. pylori -related diseases. Cyclooxygenase (COX) 2 has been shown to inhibit the production of T-helper (Th) 1 cytokines. This study aimed to ascertain whether COX-2 downregulates Th1 signaling pathway in human gastric mucosa colonized by H. pylori. Methods:, COX-2 expression and prostaglandin E2 (PGE2) production were determined in total proteins extracted from freshly obtained gastric biopsies of H. pylori -infected and uninfected patients by Western blotting and enzyme-linked immunosorbent assay (ELISA). Phosphorylated (p)STAT4, pSTAT1, T-bet, and pSTAT6 expression and interleukin (IL)-12, interferon (IFN)-,, and IL-4 production were also determined by Western blotting and ELISA, respectively, in total protein extracts from gastric biopsy cultures of H. pylori -infected patients treated without and with COX-2 inhibitor NS-398. Results:, Enhanced expression of COX-2 and production of PGE2 was found in H. pylori -infected compared to uninfected patients. COX-2 inhibition significantly increased expression of Th1 transcription factors along with production of IL-12 and IFN-,. By contrast, no changes in the expression of STAT6 and production of IL-4 were found. Conclusion:, This study provides a mechanism by which H. pylori may actually interfere with normal T-cell activation in human gastric mucosa, possibly enhancing its pathogenicity. The use of COX-2 selective inhibitors as immunomodulators in the course of H. pylori infection deserves investigations. [source] Disease-specific Helicobacter pylori Virulence Factors: The Unfulfilled PromiseHELICOBACTER, Issue S1 2000David Y. Graham A number of putative virulence factors for Helicobacter pylori have been identified including cagA, vacA and iceA. The criteria for a true virulence factor includes meeting the tests of biologically plausibility with the associations being both experimentally and epidemiologically consistent. Although disease-specific associations have been hypothesized/claimed, there are now sufficient data to conclusively state that none of these putative virulence factors have disease specificity. CagA has been claimed to be associated with increased mucosal IL-8 and inflammation, increased density of H. pylori in the antrum, duodenal ulcer (DU), gastric cancer, and protection against Barrett's cancer. Only the increase in IL-8/inflammation is direct and substantiated. Different H. pylori strains with functional cag pathogenicity islands do not vary in virulance as it has been shown that mucosal IL-8 levels are proportional to the number of cagA +H. pylori independent of the disease from which the H. pylori were obtained. It is now known that the density of either cagA + and cagA,H. pylori in the antrum of patients with H. pylori gastritis is the same. In contrast, the mean density of H. pylori in the antrum in DU is greater than in the antrum of patients with H. pylori gastritis. Of interest, the density of H. pylori is higher in the corpus of patients with H. pylori gastritis than those with DU, suggesting that acid secretion plays a critical role in these phenomena. The presence of a functional cag pathogenicity island increases inflammation and it is likely that any factor that results in an increase in inflammation also increases the risk of a symptomatic outcome. Nevertheless, the presence of a functional cag pathogenicity island has no predictive value for the presence, or the future development of a clinically significant outcome. The hypothesis that iceA has disease specificity has not been confirmed and there is currently no known biological or epidemiological evidence for a role for iceA as a virulence factor in H. pylori -related disease. The claim that vacA genotyping might prove clinically useful, e.g. to predict presentation such as duodenal ulcer, has been proven wrong. Analysis of the worldwide data show that vacA genotype s1 is actually a surrogate for the cag pathogenicity island. There is now evidence to suggest that virulence is a host-dependent factor. The pattern of gastritis has withstood the test of time for its relation to different H. pylori -related diseases (e.g. antral predominant gastritis with duodenal ulcer disease). The primary factors responsible for the different patterns of gastritis in response to an H. pylori infection are environmental (e.g. diet), with the H. pylori strain playing a lesser role. Future studies should work to eliminate potential bias before claiming disease associations. Controls must exclude regional or geographic associations related to the common strain circulation and not to the outcome. The authors must also control for both the presence of the factor and for the disease association. The study should be sufficiently large and employ different diseases and ethnic groups for the results to be robust. The findings in the initial sample (data derived hypothesis) should be tested in a new group (hypothesis testing), preferably from another area, before making claims. Finally, it is important to ask whether the results are actually a surrogate for another marker (e.g. vacA s1 for cagA) masquerading for a new finding. Only the cag pathogenicity island has passed the tests of biological plausibility (increased inflammation) and experimental and epidemiological consistency. [source] Immunization with an adjuvant hepatitis B vaccine after liver transplantation for hepatitis B-related diseaseHEPATOLOGY, Issue 4 2003Ulrich Bienzle M.D. Patients who undergo transplantation for hepatitis B virus (HBV)-related diseases are treated indefinitely with hepatitis B hyperimmunoglobulin (HBIG) to prevent endogenous HBV reinfection of the graft. Active immunization with standard hepatitis B vaccines in these patients has recently been reported with conflicting results. Two groups of 10 liver transplant recipients on continuous HBIG substitution who were hepatitis B surface antigen (HBsAg) positive and HBV DNA negative before transplantation were immunized in a phase I study with different concentrations of hepatitis B s antigen formulated with the new adjuvants 3-deacylated monophosphoryl lipid A (MPL) and Quillaja saponaria (QS21) (group I/vaccine A: 20 ,g HBsAg, 50 ,g MPL, 50 ,g QS21; group II/vaccine B: 100 ,g HBsAg, 100 ,g MPL, 100 ,g QS21). Participants remained on HBIG prophylaxis and were vaccinated at weeks 0, 2, 4, 16, and 18. They received 3 additional doses of vaccine B at bimonthly intervals if they did not reach an antibody titer against hepatitis B surface antigen (anti-HBs) greater than 500 IU/L. Sixteen (8 in each group) of 20 patients (80%) responded (group I: median, 7,293 IU/L; range, 721,45,811 IU/L anti-HBs; group II: median, 44,549 IU/L; range, 900,83, 121 IU/L anti-HBs) and discontinued HBIG. They were followed up for a median of 13.5 months (range, 6,22 months). The vaccine was well tolerated. In conclusion, most patients immunized with the new vaccine can stop HBIG immunoprophylaxis for a substantial, yet to be determined period of time. (Hepatology 2003;38:811,819). [source] Pathological development of the gastric mucosa in Helicobacter pylori -related diseasesJOURNAL OF DIGESTIVE DISEASES, Issue 4 2001Tianshu Liu OBJECTIVE: To study the relationship between Helicobacter pylori eradication and the pathological development of the gastric mucosa in H. pylori -related diseases. METHODS: One hundred and ninety-one H. pylori -infected patients were randomly given anti- H. pylori or non-anti- H. pylori medications. Endoscopic examination was carried out 1 year after treatment. Pathological classifications followed the Sydney System. RESULTS: Of the 191 patients, those with chronic inflammation of the gastric mucosa improved (P < 0.05), as did those with atrophy and intestinal metaplasia (P < 0.05). Helicobacter pylori was eradicated in 107 patients, but not in 84 patients. Compared with those patients in whom H. pylori was not eradicated, those with H. pylori eradicated had ameliorated chronic inflammation of the gastric mucosa (P < 0.05) and active inflammation reduced in some cases (P < 0.05). Notwithstanding a stratification of different gastric diseases and different treatments, patients with H. pylori eradicated showed a more marked improvement in mucosal chronic inflammation than did patients in whom H. pylori was not eradicated (P < 0.05). CONCLUSIONS: These results suggest that H. pylori infection is closely related to active inflammation of the gastric mucosa. Helicobacter pylori eradication is beneficial in improving chronic inflammation of the gastric mucosa. [source] Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2007Mitsushige Sugimoto Abstract Background and Aim:, In Western countries, polymorphism of pro-inflammatory cytokine genes is associated with the development of gastric cancer and duodenal ulcer. The aim of this study was to clarify the association of polymorphisms of interleukin (IL) -1, and tumor necrosis factor (TNF) -, with susceptibility to peptic ulcer diseases and gastric cancer in Japan. Methods:, The IL-1, -511/-31 and TNF-, -308/-857/-863/-1031 genotypes were determined in Helicobacter pylori -positive patients with gastritis only (n = 164), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and in H. pylori -negative controls (n = 172). Results:, Carriage of the alleles TNF-,- 857 T (odd ratio [OR], 1.826; 95% confidence interval [CI], 1.097,3.039), TNF-,- 863 A (OR, 1.788; 95% CI, 1.079,2.905) and TNF-, -1031 C (OR, 1.912; 95% CI, 1.152,3.171) was associated with increased risk for gastric ulcer development. Carriage of the alleles TNF-,- 857 T (OR, 1.686; 95% CI, 1.003,2.832), TNF-,- 863 A (OR, 1.863; 95% CI, 1.118,3.107) and TNF-, -1031 C (OR 2.074; 95% CI, 1.244,3.457) was also associated with increased risk of gastric cancer development. There was no relationship between the development of H. pylori -related diseases and polymorphisms of IL-1, -511/-31 and TNF-, -308. The simultaneous carriage of three different high-producer alleles of TNF-, -857/-863/-1031 significantly increased the risk of gastric ulcer (OR, 6.57; 95% CI, 2.34,18.40) and gastric cancer (OR, 5.20; 95% CI, 1.83,14.78). Conclusions:, Polymorphisms in TNF-, rather than IL-1, are associated with increased risk for gastric ulcers and gastric cancer in Japan. The simultaneous carriage of more than one high-producer allele of TNF-, further increased the risks for gastric ulcer and cancer. [source] Clinical and histopathological evaluation of 13 cases of adenocarcinoma in aged rhesus macaques (Macaca mulatta)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2002N.A. Rodriguez In recent years, the emphasis on aging research, has led to an increase in the number of aged macaques being maintained in some research facilities with a subsequent increase in the occurrence of age-related diseases. One of the most commonly reported age related diseases is intestinal adenocarcinoma. At the University of Illinois at Chicago (UIC), which maintains a colony of approximately 55 aged rhesus macaques 13 cases of intestinal adenocarcinoma were diagnosed within a 25-month period. This report provides a comprehensive description of the clinical findings for intestinal adenocarcinoma in aged rhesus macaques, including results from physical examinations, laboratory tests, radiographic evaluations, gross and histopathologic findings as well as a comparison with the disease condition in humans. The use of carcinoembryonic antigen as a potential tumor marker was evaluated by immunohistochemical analysis of tissue specimens in 10 cases. Intestinal adenocarcinoma is a disease condition that should be of concern to individuals responsible for the care of aged rhesus macaques. [source] HIF prolyl hydroxylase inhibition increases cell viability and potentiates dopamine release in dopaminergic cellsJOURNAL OF NEUROCHEMISTRY, Issue 1 2010Jens Leander Johansen J. Neurochem. (2010) 115, 209,219. Abstract Hypoxia-inducible factor (HIF) controls the expression of genes that adapts the cellular condition to accommodate oxidative stress. The potential beneficial effect of HIF up-regulation in ischemia has recently gained interest substantiated by the known HIF-regulation of erythropoietin and other hypoxia accommodating genes. So far the perspectives for HIF up-regulation has been focused on anemia and ischemia related diseases but little information is available about the relevance of HIF biology for neurodegenerative disease like Parkinson's disease. We therefore sought out to characterize the effect of HIF-up-regulation on survival and dopamine homeostasis in dopaminergic cells. We used a low molecular weight HIF prolyl hydroxylase (HPH) inhibitor and lentiviral based shRNA knockdown of HPH subtypes as molecular tools to increase HIF protein level and downstream HIF-regulated genes. We show that HIF induction results in protection against oxidative stress in cellular models based on PC12 cells and LUHMES cells. In addition, HPH inhibition elevates tyrosine hydroxylase expression and activity, which causes increased dopamine synthesis and release in both PC12 cells and a primary rat ventral mesencephalic cell culture. All together these findings suggest that prolyl hydroxylases may represent novel targets for therapeutic intervention in disorders characterized by dopamine homeostasis dysregulation like Parkinson's disease. [source] Controlling the mass action of ,-synuclein in Parkinson's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Changyoun Kim Abstract Parkinson's disease (PD) is an age-related neurodegenerative disease with unknown etiology. Growing evidence from genetic, pathologic, animal modeling, and biochemical studies strongly support the theory that abnormal aggregation of ,-synuclein plays a critical role in the pathogenesis of PD. Protein aggregation is an alternative folding process that competes with the native folding pathway. Whether or not a protein is subject to the aggregation process is determined by the concentration of the protein as well as thermodynamic properties inherent to each polypeptide. An increase in cellular concentration of ,-synuclein has been associated with the disease in both familial and sporadic forms of PD. Thus, maintenance of the intraneuronal steady state levels of ,-synuclein below the critical concentration is a key challenge neuronal cells are facing. Expression of the ,-synuclein gene is under the control of environmental factors and aging, the two best-established risk factors for PD. Studies also suggest that the degradation of this protein is mediated by proteasomal and autophagic pathways, which are two mechanisms that are related to the pathogenesis of PD. Recently, vesicle-mediated exocytosis has been suggested as a novel mechanism for disposal of neuronal ,-synuclein. Relocalization of the protein to specific compartments may be another method for increasing its local concentration. Regulation of the neuronal steady state levels of ,-synuclein has significant implications in the development of PD, and understanding the mechanism may disclose potential therapeutic targets for PD and other related diseases. [source] Thermodynamic and kinetic origins of Alzheimer's and related diseases: A chemical engineer's perspective ,AICHE JOURNAL, Issue 8 2008Carol K. Hall First page of article [source] Changes in calcium absorption and subsequent tissue distribution induced by Maillard reaction products: in vitro and in vivo assays,JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 2 2006Cristina Delgado-Andrade Abstract The effects of Maillard reaction products (MRP) from glucose,lysine and glucose,methionine on calcium bioavailability were studied by in vivo (rats) and in vitro (Caco-2 cells) assays. Equimolar glucose/lysine and glucose/methionine mixtures (40% moisture) were heated (150 °C, 30 min) to prepare samples (GL30 and GM30, respectively). For 21 days, rats were fed a control diet (control group) or diets containing separately 3% of the heated mixtures (GL30 and GM30 groups, respectively). In the last week a calcium balance was performed, after which the animals were sacrificed and some organs and serum were removed to analyze calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention (retained calcium during the entire 21 days). Unheated and heated samples were used for calcium transport experiments in Caco-2 cells. Food intake and final body weight were lower in the GM30 group. Calcium fecal excretion decreased and digestibility increased in this group. Accordingly, increased calcium transport in Caco-2 cells was found in the presence of the GM30 sample, when compared with the unheated sample. However, global calcium retention tended to decrease in the GM30 group, mainly owing to the lower food intake. Bone calcium concentrations decreased in the animals fed the MRP diets. The possible long-term effects of MRP intake on calcium digestibility and bone calcium should be taken into account to avoid related diseases. Copyright © 2005 Society of Chemical Industry [source] Inherited defects of coagulation Factor V: the thrombotic sideJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2006H. L. VOS Summary., DNA variations in the Factor V gene have played a major role in thrombosis research ever since the discovery of Factor V Leiden. Here, all relatively common DNA variations in the coding regions of the Factor V gene are discussed. Many of them have been associated with venous thrombosis or related diseases. However, most variations have been studied separately, without taking the presence of other variations in the same gene into account. This means that their association with disease should be interpreted with caution, as it may reflect linkage with another variation. An approach in which a haplotype-based analysis of the Factor V gene is combined with in vitro assays of recombinant proteins is advocated. Finally, a possible reason for the relatively polymorphic nature of the Factor V protein is discussed. [source] Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2aLIVER INTERNATIONAL, Issue 4 2008Patrick Marcellin Abstract Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 ,g peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88,89 vs 96,100%), serious AEs (4,5 vs 7,16%) and treatment withdrawals (6,8 vs 17,33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression. [source] Development and implementation of guidelines in allergic rhinitis , an ARIA-GA2LEN paperALLERGY, Issue 10 2010J. Bousquet To cite this article: Bousquet J, Schünemann HJ, Zuberbier T, Bachert C, Baena-Cagnani CE, Bousquet PJ, Brozek J, Canonica GW, Casale TB, Demoly P, Gerth van Wijk R, Ohta K, Bateman ED, Calderon M, Cruz AA, Dolen WK, Haughney J, Lockey RF, Lötvall J, O'Byrne P, Spranger O, Togias A, Bonini S, Boulet LP, Camargos P, Carlsen KH, Chavannes NH, Delgado L, Durham SR, Fokkens WJ, Fonseca J, Haahtela T, Kalayci O, Kowalski ML, Larenas-Linnemann D, Li J, Mohammad Y, Mullol J, Naclerio R, O'Hehir RE, Papadopoulos N, Passalacqua G, Rabe KF, Pawankar R, Ryan D, Samolinski B, Simons FER, Valovirta E, Yorgancioglu A, Yusuf OM, Agache I, Aït-Khaled N, Annesi-Maesano I, Beghe B, Ben Kheder A, Blaiss MS, Boakye DA, Bouchard J, Burney PG, Busse WW, Chan-Yeung M, Chen Y, Chuchalin AG, Costa DJ, Custovic A, Dahl R, Denburg J, Douagui H, Emuzyte R, Grouse L, Humbert M, Jackson C, Johnston SL, Kaliner MA, Keith PK, Kim YY, Klossek JM, Kuna P, Le LT, Lemiere C, Lipworth B, Mahboub B, Malo JL, Marshall GD, M vale-Manuel S, Meltzer EO, Morais-Almeida M, Motala C, Naspitz C, Nekam K, Niggemann B, Nizankowska-Mogilnicka E, Okamoto Y, Orru MP, Ouedraogo S, Palkonen S, Popov TA, Price D, Rosado-Pinto J, Scadding GK, Sooronbaev TM, Stoloff SW, Toskala E, van Cauwenberge P, Vandenplas O, van Weel C, Viegi G, Virchow JC, Wang DY, Wickman M, Williams D, Yawn BP, Zar HJ, Zernotti M, Zhong N, In collaboration with the WHO Collaborating Center of Asthma and Rhinitis (Montpellier). Development and implementation of guidelines in allergic rhinitis , an ARIA-GA2LEN paper. Allergy 2010; 65: 1212,1221. Abstract The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved. [source] Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis , a GA2LEN studyALLERGY, Issue 4 2009C. Bachert Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA2LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets. [source] The distribution of oral mucosal pH values in healthy saliva secretorsORAL DISEASES, Issue 4 2006DJ Aframian Objectives:, To establish the normal range of oral mucosal pH and to correlate these measurements to salivary flow rate in healthy individuals according to age and gender. Subjects and methods:, Measurements of pH levels using a flat pH meter and salivary secretion rates were established in eight mucosal sites from a total of 50 healthy individuals. Results:, The mean pH (±s.d.) of all sites was 6.78 ± 0.04 with significant differences between mean pH values in the palate (7.34 ± 0.38), the floor of the mouth (6.5 ± 0.3), the buccal mucosa (6.28 ± 0.36) and the tongue (6.8 ± 0.26). A significant correlation was found between age and pH at palatal and tongue sites but no gender effects were noted. Conclusions:, This method is easy and relatively quick to manipulate, and may offer many diagnostic possibilities for oral related diseases and disorders such as oral malodour, mouth breathing, dysgeusia, acidic diet consumption and gastrointestinal disorders affecting the mouth. [source] Novel recombinant congenic mouse strain developing arthritis with enthesopathyPATHOLOGY INTERNATIONAL, Issue 7 2008Shiro Mori Based on the hypothesis that the complex pathological and immunological manifestations of rheumatoid arthritis (RA) and the related diseases are under the control of multiple gene loci with allelic polymorphism, a recombinant congenic mouse strain was prepared between an MRL/Mp- lpr/lpr (MRL/lpr) strain, which develops arthritis resembling RA, and a non-arthritic strain C3H/HeJ- lpr/lpr (C3H/lpr). In MRL/lpr × (MRL/lpr × C3H/lpr) F1 mice, the mice developing severe arthritis were selected based on joint swelling to further continue intercrosses, and then an McH- lpr/lpr -RA1 (McH/lpr-RA1) strain was established and its histopathological phenotypes of joints and autoimmune traits were analyzed. Arthritis in McH/lpr-RA1 mice developed at a higher incidence by 20 weeks of age, compared with that in the MRL/lpr mice, who had severe synovitis (ankle, 60.3%; knee, 65.1%), and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy (ankle, 79.4%; knee, 38.1%), resulting in ankylosis. The lymphoproliferative disorder was less, and serum levels of IgG and IgG autoantibodies including anti-dsDNA and rheumatoid factor were lower than those of both MRL/lpr and C3H/lpr strains. McH/lpr-RA1 mice may provide a new insight into the study of RA regarding the common genomic spectrum of seronegative RA and enthesopathy. [source] Management and outcome in prenatally diagnosed sacrococcygeal teratomasPEDIATRICS INTERNATIONAL, Issue 4 2008Tadao Okada Abstract Background: The aim of the present study was to retrospectively determine the clinical factors affecting the outcome after birth in prenatally diagnosed sacrococcygeal teratomas (SCT). Methods: Six cases of prenatal SCT were identified from January 1985 until August 2005. A retrospective review of case-notes and pathological reports was carried out. Clinical data during the perinatal period, operative findings, postoperative complications and follow up were evaluated in the patients with prenatally diagnosed SCT. Results: SCT presented as type I in two neonates and type III in four between 22 and 33 weeks' gestation. Fetal intervention was not performed for any fetus. Five of six were delivered by cesarean section and the other was delivered vaginally due to small tumor size. Patients were born at between 29 and 39 weeks' gestation and weighed from 1840 to 3500 g. All patients with type III SCT presented with related diseases, including bilateral hydronephrosis, neurological deficit of the communicating peroneal nerve such as paralytic talipes equines, bladder or bowel dysfunction, high-output cardiac failure, or fetal hydrops in one of a set of fraternal twins. A baby with high-output cardiac failure and fetal hydrops underwent urgent cesarean section at 29 weeks' gestation and died 8 days after birth despite intensive care due to multi-organ failure. In five cases, surgery was successful with good outcomes maintained at follow-up of between 8 months and 14 years. Conclusions: Detailed ultrasound should be performed to rule out associated anomalies, and determine the presence or absence of hydrops in prenatally diagnosed SCT. Fetal hydrops, orthopedic impairment such as lower extremity weakness and swelling, and urinary incontinence are important clinical factors affecting the outcome after birth in prenatally diagnosed SCT. In particular, the present study indicated that the association of a fraternal twin and fetal hydrops makes it very difficult to treat SCT perinatally. [source] New criteria of normal serum lipid levels in Japanese children: The nationwide studyPEDIATRICS INTERNATIONAL, Issue 6 2002Tomoo Okada Abstract Aim: To make new criteria of serum lipid levels in current Japanese children using the large nationwide data provided from Japan Association of Health Service for the analysis. Methods: The subjects were schoolchildren who received screening and care programs for lifestyle related diseases since 1993,1999. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and triglyceride (TG) levels were measured, and low-density lipoprotein cholesterol (LDLC) levels were calculated. Serum lipid levels were analyzed by age and sex. For each serum lipid, we extracted age- and sex-specific group which the mean value was not statistically different from that in 1999 by Student's t -test analysis. Results: The level below the 75th percentile was defined to be acceptable, from the 75th to 95th to be borderline and over the 95th to be high in TC/LDLC. The level below the fifth percentile in HDLC was defined to be low and the level over the 95th percentile in TG to be high. Therefore, TC level was categorized as follows: acceptable < 190 mg/dL; borderline 190,219 mg/dL; and high > 220 mg/dL. The LDLC level was also categorized into: acceptable < 110 mg/dL; borderline 110,139 mg/dL; and high > 140 mg/dL. The cut-off value in TG was determined to be 140 mg/dL and in HDLC was 40 mg/dL. Conclusions: This new criteria should prove valuable in health strategies for rational prevention and intervention in children. It should be emphasized to provide some intervention for Japanese children immediately. [source] Hypolipidaemic activity of aqueous ocimum basilicum extract in acute hyperlipidaemia induced by triton WR-1339 in rats and its antioxidant propertyPHYTOTHERAPY RESEARCH, Issue 12 2006Souliman Amrani Abstract Hyperlipidaemia, atherosclerosis and related diseases are becoming a major health problem in developing countries. Ocimum basilicum is one of the medicinal plants widely used in Morocco to reduce plasma cholesterol and to reduce the risk of atherosclerosis-related diseases. However, mechanisms underlying the reported hypolipidaemic effect of this plant have not been investigated. This study evaluates the lipid lowering effect of aqueous Ocimum basilicum extract in Triton WR-1339-induced hyperlipidaemic rats. Hyperlipidaemia was developed in animals by intraperitoneal injection of Triton (200 mg/kg). After injection of Triton the animals were divided into three treatment groups: hyperlipidaemic, hyperlipidaemic plus herb extract and hyperlipidaemic plus fenofibrate treated rats. At 7 h after the Triton injection, levels of plasma cholesterol, triglycerides and LDL-cholesterol in rats treated also with the Ocimum basilicum extract (0.5 g/100 g body weight) were, respectively, 50%, 83% and 79% lower than Triton-treated rats and HDL-cholesterol was 129% higher than in rats given Triton alone. At 24 h following Ocimum basilicum administration, total cholesterol, triglycerides and LDL-cholesterol levels decreased by 56%, 63% and 68%, respectively, in comparison with the Triton treated group and HDL-cholesterol was not increased significantly. The hypolipidaemic effect exerted by Ocimum basilicum extract was markedly stronger than the effect induced by fenofibrate treatments. Further it was demonstrated that Ocimum basilicum aqueous extract displayed a very high antioxidant power. These results indicate that Ocimum basilicum extract may contain hypolipidaemic and antioxidant substances and its use as a therapeutic tool in hyperlipidaemic subjects may be of benefit and encourage further investigation in this field. Copyright © 2006 John Wiley & Sons, Ltd. [source] Photodynamic therapy: a targeted therapy in periodonticsAUSTRALIAN DENTAL JOURNAL, Issue 2009M Raghavendra Abstract The oral cavity is colonized by a large number and highly diversified communities of micro-organisms. Bacterial biofilm present on tooth or root surface is a major cause of gingivitis and periodontitis. Chemical antimicrobial agents are widely used in prophylactic and therapeutic regimens for dental plaque related diseases, which are among the most common human infections. As these agents are difficult to maintain at therapeutic concentrations in the oral cavity and can be rendered ineffective by resistance development in target organisms, there is a need for an alternative antimicrobial approach. A novel approach, photodynamic therapy (PDT), could be a solution to these problems. Lethal photosensitization of many bacteria, both Gram positive and Gram negative was found in many studies. The advantage of this new approach includes rapid bacterial elimination, minimal chance of resistance development and safety of adjacent host tissue and normal microflora. Thus, the available knowledge of photodynamic therapy should encourage a more clinically oriented application of this technique. [source] | ||||||||||||||||||||||||||||||||||