Pathogenesis

Source: www.ncbi.nlm.nih.gov --- 1 day ago
Related Articles [Recent advances in molecular Pathogenesis and polycystic kidney disease treatment] Rev Med Chir Soc Med Nat Iasi. 2008 Jan-Mar;112(1):11-20 Authors: Covic M, Covic M Polycystic kidney diseases (PKD) are common genetic disorders characterized by formation and progressive enlargement of cysts kidney, liver and other organs, leading to end stage renal disease. Regardless of the genetic defect underlying PKD, cystic epithelia seem to display common abnormalities: increased proliferation and apoptosis, loss of cellular differentiation and polarity, hypersecretion. The localization of multiples proteins, whose function are disrupted in PKD, in the primary cilium or at basal body at the base of the cilium highlight this neglected organelle as a common trigger of cystic diseases. Significant progresses have been made over the last few years towards a greater understanding of the molecular Pathogenesis of cysts formation, particularly in the signaling pathways involved in cytogenesis: cAMP, mTOR, Wnt, Ras/MAPK. These advances have already brought several potential therapies targeting several key pathways of cystogenesis. PMID: 18677899 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 5 days ago
Related Articles Renal disease in patients with HIV infection: epidemiology, Pathogenesis and management. Drugs. 2008;68(7):963-80 Authors: Fine DM, Perazella MA, Lucas GM, Atta MG With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirals and other medications. Therefore, the differential diagnosis is vast.Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better ou ...

Source: www.ncbi.nlm.nih.gov --- 3 days ago
Related Articles Pathogenesis of Paget's disease of bone. Bone. 2008 Jul 11; Authors: Ralston SH Paget's disease of bone is a common condition characterised by increased and disorganised bone turnover which can affect one or several bones throughout the skeleton. These abnormalities disrupt normal bone architecture and lead to various complications such as bone pain osteoarthritis, pathological fracture, bone deformity, deafness, and nerve compression syndromes. Genetic factors play an important role in PDB and mutations or polymorphisms have been identified in four genes that cause classical Paget's disease and related syndromes. These include TNFRSF11A, which encodes RANK, TNFRSF11B which encodes osteoprotegerin, VCP which encodes p97, and SQSTM1 which encodes p62. All of these genes play a role in the RANK-NFkappaB signalling pathway and it is likely that the mutations predispose to PDB by disrupting normal signalling, leading to osteoclast activation. Although Paget's has traditionally be considered a disease of the osteoclast there is evidence that stromal cell function and osteoblast function are also abnormal, which might account for the fact that the disease is associated with increased bone formation as well as resorption. Environmental factors also contribute to Paget's disease. Most research has focused on paramyxovirus infection as a possible environmental trigger but evidence in favour of the involvement of viruses in the ...

Source: www.ncbi.nlm.nih.gov --- 6 days ago
Related Articles Pathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis: current understanding and future directions. Med Mycol. 2008 Jul 30;:1-7 Authors: Rapaka RR, Kolls JK Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disease characterized clinically by wheezing, pulmonary infiltrates, bronchiectasis, and fibrosis that affects patients with asthma and cystic fibrosis (CF). Although this disease has been characterized by a Th2 immune response to Aspergillus, the disease has some features such as central bronchiectasis which is not seen in other Th2 driven lung diseases such as atopic asthma. Here we will review the current pathophysiology of ABPA in CF and highlight new molecules that may influence immune responses against Aspergillus and affect disease Pathogenesis. PMID: 18668399 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 1 day ago
Related Articles Tissue Plasminogen Activator (tPA) and Matrix Metalloproteinases in the Pathogenesis of Stroke: Therapeutic Strategies. CNS Neurol Disord Drug Targets. 2008 Jul;7(3):243-53 Authors: Adibhatla RM, Hatcher JF Today there exists only one FDA-approved treatment for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA). In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? Is the animal research truly translational in identifying new agents for stroke treatment? This review summarizes the current state of affairs with plasminogen activators in thrombolytic therapy. In addition to therapeutic value, potential side effects of tPA also exist that aggravate stroke injury and offset the benefits provided by reperfusion of the occluded artery. Thus, combinational options (ultrasound alone or with microspheres/nanobubbles, mechanical dissociation of clot, activated protein C (APC), plasminogen activator inhibitor-1 (PAI-1), neuroserpin and CDP-choline) that could offset tPA toxic side effects and improve efficacy are also discussed here. Desmoteplase, a plasminogen activator derived from the saliva of Desmodus rotundus vampire bat, antagonizes vascular tPA-induced neurotoxicity by competitively binding to low-density lipoprotein related-receptors (LPR) at the blood-brain barrie ...

Source: www.ncbi.nlm.nih.gov --- 3 days ago
Related Articles Pleural effusions in patients with chronic myeloid leukaemia treated with dasatinib may have an immune-mediated Pathogenesis. Br J Haematol. 2008 May;141(5):745-7 Authors: de Lavallade H, Punnialingam S, Milojkovic D, Bua M, Khorashad JS, Gabriel IH, Chaidos A, Olavarria E, Goldman JM, Apperley JF, Marin D PMID: 18331365 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 25 days ago
Related Articles [Diagnosis and Pathogenesis in functional dyspepsia] Nippon Rinsho. 2008 Jul;66(7):1379-84 Authors: Haruma K, Imamura H, Kusunoki H, Manabe N, Hata J Functional gastrointestinal disorders (FGID) such as functional dyspepsia (FD) and irritable bowel syndrome are common gastrointestinal diseases in clinical practice. FGID is not life-threatened disease, but it is an important disease because the patients with FGID have a poor QOL. Recently the Rome criteria for the diagnosis of FGID has been established in Western countries, however, whether the criteria is suitable for clinical practice in Japan or not has not fully discussed. Many factors including gastrointestinal dysmotility, abnormality of acid secretion, visceral hypersensitivity, Helicobacter pylori infection or stress might play in the Pathogenesis of FD. Our previous studies using ultrasonography indicate the decrease in gastric emptying and antral motility and the increase in duodenogastric reflux in patients with FD. In the treatment of FD, prokinetic agents, acid-suppressive drugs and antidepressants have been widely used. PMID: 18616131 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 18 days ago
Related Articles Pathogenesis and treatment of secondary hyperparathyroidism in dialysis patients: the role of paricalcitol. Curr Vasc Pharmacol. 2008 Apr;6(2):148-53 Authors: Cozzolino M, Galassi A, Gallieni M, Brancaccio D Hemodialysis (HD) patients are commonly affected by secondary hyperparathyroidism (SHPT), in which 3 well-known factors are usually involved: hypocalcemia, hyperphosphatemia and calcitriol deficiency. Classically, high parathyroid hormone (PTH) levels cause bone-associated diseases, such as osteitis fibrosa and renal osteodystrophy, but more recently it has been demonstrated the link between SHPT and a systemic toxicity, with a major role in determining cardio-vascular disease, including arterial calcification, endocrine disturbances, compromised immune system, neurobehavioral changes, and altered erythropoiesis. Treatment with calcitriol (CT), the active form of vitamin D, reduces parathyroid hormone (PTH) levels, but may result in elevations in serum calcium (Ca) and phosphorus (P), increasing the risk of cardio-vascular calcification in the HD population. Several new vitamin D analogs have been developed and investigated with the rationale to treat SHPT with a reduced risk of hypercalcemia and hyperphosphatemia in HD patients. Paricalcitol (1,25-dihydroxy-19-nor-vitamin D(2), 19-Nor-D(2)) is a vitamin D analog that suppresses PTH secretion with minimal increases on serum calcium and phosphate levels. It was dem ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles NPY and brain monoamines in the Pathogenesis of cancer anorexia. Nutrition. 2008 Jul 26; Authors: Laviano A, Inui A, Meguid MM, Molfino A, Conte C, Rossi Fanelli F Cancer anorexia frequently characterizes the clinical journey of patients with cancer and affects patients' morbidity, mortality, and quality of life. A constellation of symptoms concur to the diagnosis of anorexia, and early satiety, changes in taste/smell, and nausea are the more frequently reported. The Pathogenesis of cancer anorexia is multifactorial, but accumulating evidence indicates that the hypothalamic melanocortin and neuropeptide Y systems become resistant to peripheral inputs. This results in increased melanocortin activity and reduced neuropeptide Y function, thereby leading to the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Interestingly, hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. In the clinical setting, cancer anorexia develops with heterogeneous presenting symptoms (i.e., early satiety and/or nausea and/or changes of taste) and varying degrees of severity. Available evidence suggests that the constellation of symptoms characterizing this syndrome should be considered, at least in part, as different phenotypes of common neurochemical/metabolic alteratio ...

Source: www.ncbi.nlm.nih.gov --- 32 days ago
Related Articles The Damage Signals Hypothesis of Alzheimer's Disease Pathogenesis. J Alzheimers Dis. 2008;14(3):329-333 Authors: Fernández JA, Rojo L, Kuljis RO, Maccioni RB Virtually none of the hypotheses on Alzheimer's disease (AD) Pathogenesis address the earliest events that trigger the molecular alterations that precede cerebral degeneration and account for the diversity of risk factors that converge on a well-defined disease phenotype. We propose that long-term activation of the innate immune system by an individual array of risk factors constitutes a unifying mechanism leading to the triggering of an inflammatory cascade that converges in cytoskeletal alterations (tau aggregation, paired helical filament formation) as a previously hypothesized final common pathway in AD. The key pathogenic phenomena consist in the long-term, maladaptive activation of innate immunity-triggering receptors - such as the toll-like and advanced glycation end-products receptors, and others located in the microglial membrane - by seemingly heterogeneous risk factors such as hyperlipidemia, hyperglycemia, oxidative stress, head injury, amyloid oligomers, etc. Our hypothesis provides a unifying mechanism that explains both the diversity of risk factors acting over long periods of time and the individual response to such insults. This formulation is amenable to both empirical testing and implementation into therapeutic strategies that may lead to effect ...

Source: www.ncbi.nlm.nih.gov --- 21 days ago
Related Articles The lymph node in HIV Pathogenesis. Semin Immunol. 2008 Jul 10; Authors: Lederman MM, Margolis L Since the earliest days of the AIDS epidemic, clinicians and researchers have recognized the importance of lymphoid tissue both in the clinical manifestations of disease and in its Pathogenesis. Generalized lymphadenopathy was one of the earliest harbingers of AIDS in the United States and over the past 27 years an increasing body of evidence has implicated the lymphoid organs as central to the Pathogenesis of immune deficiency in chronic HIV-1 infection. In this essay, we will review some of the data that have been accumulated and propose a testable model that may reconcile them. PMID: 18620868 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 15 days ago
Related Articles Metagenomic approaches for defining the Pathogenesis of inflammatory bowel diseases. Cell Host Microbe. 2008 Jun 12;3(6):417-27 Authors: Peterson DA, Frank DN, Pace NR, Gordon JI The human gastrointestinal tract is home to immense and complex populations of microorganisms. Using recent technical innovations, the diversity present in this human body habitat is now being analyzed in detail. This review focuses on the microbial ecology of the gut in inflammatory bowel diseases and on how recent studies provide an impetus for using carefully designed, comparative metagenomic approaches to delve into the structure and activities of the gut microbial community and its interrelationship with the immune system. PMID: 18541218 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Insulin: a novel agent in the Pathogenesis of prostate cancer. Int Urol Nephrol. 2008 Jul 30; Authors: Nandeesha H Prostate cancer, the most frequent non-cutaneous malignancy in aging men, is a growing medical problem, representing the second leading cause of male cancer deaths. Despite its high morbidity, the etiology of prostate cancer remains largely unknown. Several studies have documented hormonal imbalance, such as alteration in androgens and estrogens, obesity, family history and growth factors, as risk factors in the Pathogenesis of prostate cancer. Insulin is a growth-promoting hormone that is reported to be involved in the Pathogenesis of various malignancies, such as breast and bladder cancers. Insulin is known to increase cancer risk through its effect on cell proliferation, differentiation and apoptosis. In the last decade, converging evidence from epidemiological and clinical studies suggests that the insulin is involved in the tumorigenesis and neoplastic growth of the prostate. Several mechanisms have been suggested to explain the possible causal relationship between insulin and prostate cancer, such as the sympathoexcitatory effect of insulin, alteration of sex hormone metabolism, insulin-like growth factor pathway, signal transduction mechanism and dyslipidemia. The present paper reviews relevant existing studies related to the role of insulin in the Pathogenesis of prostate carcinoma. PMID: 18665451 [PubMed - as supp ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles The mast cell and allergic diseases: role in Pathogenesis and implications for therapy. Clin Exp Allergy. 2008 Jun;38(6):1063-4; author reply 1064-5 Authors: Edwards A PMID: 18498546 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 13 days ago
Genetics. Insights into the Pathogenesis of autism. Science. 2008 Jul 11;321(5886):208-9 Authors: Sutcliffe JS PMID: 18621658 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 21 days ago
Related Articles Evidence for a role of epithelial mesenchymal transition during Pathogenesis of fistulae in Crohn's disease. Inflamm Bowel Dis. 2008 Jul 14; Authors: Bataille F, Rohrmeier C, Bates R, Weber A, Rieder F, Brenmoehl J, Strauch U, Farkas S, Fürst A, Hofstädter F, Schölmerich J, Herfarth H, Rogler G Background: The Pathogenesis of fistulae in Crohn's disease (CD) patients is barely understood. We recently showed that more than two-thirds of CD fistulae are covered with flat, mesenchymal-like cells (transitional cells [TC]) forming a patchy basement membrane. Epithelial-to-mesenchymal transition (EMT) is a process of reprogramming epithelial cells, allowing them to migrate more effectively and giving epithelial cells an "invasive" potential. EMT has been suggested to be crucial in fibrosis found in different tissues and diseases. We therefore investigated whether EMT could be involved in the Pathogenesis of fistulae formation in CD.Methods: In all, 18 perianal fistulae, 2 enteroenteric, and 1 enterovesical fistulae from 17 CD patients were analyzed. In addition 2 perianal fistulae of non-CD patients were studied. Hematoxylin and eosin staining, immunohistochemistry for the expression of cytokeratins 8 and 20, beta6-integrin, E-cadherin, beta-catenin, vimentin, and TGF-beta1 and 2 were performed according to standard techniques.Results: The TC covering perianal or enteroenteric fistulae were strongly positive for cytokeratins ...

Source: www.ncbi.nlm.nih.gov --- 27 days ago
Related Articles Penile cancer: epidemiology, Pathogenesis and prevention. World J Urol. 2008 Jul 8; Authors: Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ OBJECTIVES: Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. Insight into its precursor lesions, Pathogenesis and risk factors offers options to prevent this potentially mutilating disease. This review presents an overview of the different histologically and clinically identified precursor lesions of penile cancer and discusses the molecular Pathogenesis, including the role of HPV in penile cancer development. METHODS: A systematic review of the literature evaluating penile carcinogenesis, risk factors and molecular mechanisms involved. RESULTS: Careful monitoring of men with lichen sclerosis, genital Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. Special attention is given to flat penile lesions, which contain high numbers of HPV. Their role in HPV transmission to sexual partners is highlighted, but their potential to transform as a precursor lesion into penile cancer has been unsatisfactorily explored. CONCLUSIONS: Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecu ...

Source: www.ncbi.nlm.nih.gov --- 21 days ago
Related Articles Pathogenesis and management of Paget's disease of bone. Lancet. 2008 Jul 12;372(9633):155-163 Authors: Ralston SH, Langston AL, Reid IR Paget's disease of bone is a common disease characterised by focal areas of increased bone turnover, affecting one or several bones throughout the skeleton. Paget's disease is often asymptomatic but can be associated with bone pain and other complications such as osteoarthritis, pathological fracture, bone deformity, deafness, and nerve compression syndromes. Genetic factors have an important role in this disease, and mutations have been identified in four genes that cause Paget's disease and related syndromes. The most important of these is Sequestosome 1 (SQSTM1), which is a scaffold protein in the nuclear factor kappaB (NFkappaB) signalling pathway. Patients with SQSTM1 mutations have severe Paget's disease of bone and a high degree of penetrance with increasing age. Environmental factors also contribute. Most research has focused on paramyxovirus infection as a possible trigger, but evidence for this notion is conflicting. Other potential triggers include deficiency of dietary calcium and repetitive mechanical loading of the skeleton. Medical management of Paget's disease of bone is based on giving inhibitors of osteoclastic bone resorption, and bisphosphonates are the treatment of first choice. Bisphosphonate therapy is primarily indicated for patients who have bone pain arising ...

Source: www.ncbi.nlm.nih.gov --- 31 days ago
Related Articles High-mobility group box protein 1 (HMGB1): an alarmin mediating the Pathogenesis of rheumatic disease. Arthritis Res Ther. 2008 Jun 30;10(3):209 Authors: Pisetsky DS, Erlandsson-Harris H, Andersson U ABSTRACT: High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 can serve as an alarmin to activate the innate system and mediate a wide range of physiological and pathological responses. To function as an alarmin, HMGB1 translocates from the nucleus of the cell to the extra-cellular milieu, a process that can take place with cell activation as well as cell death. HMGB1 can interact with receptors that include RAGE (receptor for advanced glycation endproducts) as well as Toll-like receptor-2 (TLR-2) and TLR-4 and function in a synergistic fashion with other proinflammatory mediators to induce responses. As shown in studies on patients as well as animal models, HMGB1 can play an important role in the Pathogenesis of rheumatic disease, including rheumatoid arthritis, systemic lupus erythematosus, and polymyositis among others. New approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling. PMID: 18598385 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 31 days ago
Related Articles Ischemic injury underlies the Pathogenesis of aristolochic acid-induced acute kidney injury. Transl Res. 2008 Jul;152(1):38-46 Authors: Wen YJ, Qu L, Li XM Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial renal disease caused by aristolochic acid intake. To determine the contribution of renal ischemia to the Pathogenesis of AAN, we characterized changes in the expression of angiogenic factors and vasoactive substances, and then we evaluated the expression of a marker of hypoxia in an acute AAN rat model. Rats were orally administrated either a decoction of Aristolochiae manshuriensis that contained 20 mg/kg of aristolochic acid-I or an equal volume of distilled water (control group) once daily for 4 days or 7 days. Renal histology and serum creatinine were assessed. Expression of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1alpha) mRNA within renal cortex were determined by semiquantitative reverse-transcription polymerase chain reaction. Levels of ET-1, nitric oxide (NO), vascular endothelial growth factor (VEGF), and HIF-1alpha in kidneys were determined by radioimmunoassay, Griess method, Western blot, and immunohistochemistry, respectively. Tubular injury scores and ET-1 mRNA expression were increased in the AA-treated rats at both days 4 and 8, whereas serum creatinine level and ET-1 protein expression was increased only at day 4. In contrast, NO production in AA-treated ra ...