736,933 research outputs found

    Acromegaly: pathogenesis & treatment

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    Acromegaly is a multi-system disorder whose etiology is most often traced back to a growth hormone-secreting pituitary adenoma (PA). Growth hormone (GH) secretion promotes insulin-like growth factor 1 (IGF-1) release from peripheral tissues, leading to the clinical manifestations of acromegaly. Current treatment methods for acromegaly include surgery, medical therapy, and radiation therapy. The goals of acromegaly treatment are to reduce GH levels and IGF-1 levels to age/sex-normalized levels, relieve comorbidities, normalize mortality rate, and to remove the pituitary mass causing high hormone levels. This study aims to provide a comprehensive review of current treatment methods and an analysis of novel therapies for treatment of acromegaly. The primary treatment method of acromegaly is surgery due to limited complications, relatively low cost, and remission in the majority of cases. However, surgery is not an effective treatment method for invasive macroadenomas with extension into the intracranial space. Medical therapies such as dopamine agonists (DAs) and somatostatin receptor ligands (SRLs) are effective at reducing GH and IGF-1 levels and may have anti-tumor effects. However, DAs are only effective at treating minor elevations in GH and IGF-1 levels and SRLs may cause hyperglycemia after prolonged treatment. In contrast to DAs and SRLs, Pegvisomant does not have anti-tumor effects, but it is more effective at reducing GH and IGF-1 levels. The disadvantages of Pegvisomant are the possibility of irreversible liver damage and the overwhelming cost of treatment. Stereotactic radiosurgery (SRS) is another mode of treatment for acromegaly, however, there are many disadvantages to SRS including prolonged latency period, hypopituitarism, radio-necrosis of normal brain tissue, and secondary tumor formation. Novel therapies for acromegaly include antisense drugs and modified botulin neurotoxins. Despite the success of antisense drugs and modified botulin neurotoxins in animal models, greater research is required prior to application in human clinical trials. Gene therapy is an emerging treatment method for acromegaly and proper manipulation of viral immunogenic effects could prove as a successful treatment for large macroadenomas, invasive PAs, and recurrent PAs. Despite the success of surgery in treating microadenomas and noninvasive macroadenomas, therapeutic alternatives must be explored to treat invasive PAs, macroadenomas, and recurrent PAs. Future research in immunotherapies and gene therapies may provide greater insight into the development of more effective and less invasive treatment methods for acromegaly

    Pathogenesis of polymyalgia rheumatica

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    Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause, almost exclusively occurring in people aged over 50 and often associated with giant cell arteritis. The evidence that PMR occurs almost exclusively in individuals aged over 50 may indicate that age-related immune alterations in genetically predisposed subjects contribute to development of the disease. Several infectious agents have been investigated as possible triggers of PMR even though the results are inconclusive. Activation of the innate and adaptive immune systems has been proved in PMR patients as demonstrated by the activation of dendritic cells and monocytes/macrophages and the altered balance between Th17 and Treg cells. Disturbed B cell distribution and function have been also demonstrated in PMR patients suggesting a pathogenesis more complex than previously imagined. In this review we will discuss the recent findings regarding the pathogenesis of PMR

    Pathogenesis of endocrine thyroid cancer

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    This review aims to discuss the different genetic alterations that may come about and thus give rise to thyroid cancer. The importance of understanding the pathogenesis of this disease is in the use of these genetic alterations as prognostic markers and as targets in treatment. Principal alterations to these central pathways, namely the MAPK pathway and PI3K/AKT pathway, are mutations, increase in gene number, methylations and translocations. The effects of the environment on the progression of thyroid cancer, such as the effects of the microenvironment and exposure to endocrine disruptors, will also be discussed.peer-reviewe

    RPB4 and pathogenesis of diabetes

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    Obesity is an important risk factor for a number of chronic diseases that impose a huge burden on individuals and society. Recently it has become clear that adipose tissue-secreted products may play a significant role in mediating many obesity-related diseases including diabetes. Thus, in addition to being an energy depot, the adipocyte is a highly active cell, secreting a plethora of factors with profound effects on a number of organs and systems. The study of these factors and their endocrine effects has become a rapidly evolving and dynamic area of endocrinology. One paradigm for explaining the deleterious effects of adipokines is related to the sheer increase in adipose tissue mass in obesity. When preadipocytes differentiate to become mature adipocytes, they acquire the ability to synthesize numerous proteins, including cytokines, growth factors, and hormones that are involved in overall energy homeostasis and various paracrine effects. In health, these proteins do not spill over significantly into the circulation. In obesity, the massive increase in fat mass leads to a significant increase in circulation of many adipose tissue secreted factors that may have pathogenic effects. For example, the increase in circulating angiotensin II in obesity is related at least in part due to excess adiposity and may mediate hypertension (1). In recent years, adipose tissue has been found to be a major source of many proteins that may directly contribute to vascular injury, diabetes, and atherogenesis (2). These proinflammatory adipokines include TNF-α, IL-6, leptin, plasminogen activator inhibitor-1, angiotensinogen, and resistin, among many others. In contrast, the adipokine adiponectin confers protection against inflammation, atherogenesis, and obesity-linked insulin resistance

    Colonization of Intestinal Pathogen Changes the Gut Microbiota

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    Enterohemorrhagic Escherechia coli is a serious human pathogen causing bloody diarrhea and hemolytic uremic syndrome. It is difficult to study in animal models, but pathogenesis may be modeled in mice with the similar murine pathogen, Citrobacter rodentium. C. rodentium does not cause disease in streptomycin-treated mice, suggesting that it is competition with other facultative anaerobes that triggers pathogenesis. Streptomycin-treated mice were co-colonized with C. rodentium and a commensal E. coli strain. The intestinal microbiota of each group was observed over a 15-day period using quantitative PCR. Colon weights were also measured over the same period. Results indicate that the disease caused by competition is not similar to normal C. rodentium pathogenesis. Further research is necessary to determine the precise mechanism of pathogenesis in this experimental model. The outcome may provide new insight into enterohemorrhagic E. coli prevention and treatment

    An Investigation of the Efficacy of Curcumin for Treatment of Alzheimer\u27s Disease

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    Curcumin is the primary curcuminoid found in the rhizome of the turmeric plant (Curcuma longa), responsible for the spice’s distinctive yellow color. Research conducted within the past two decades suggests that the compound may be an effective treatment for Alzheimer’s disease, the most prevalent form of dementia affecting nearly 5.2 million Americans. This paper investigates the efficacy of curcumin as treatment for the pathogenesis and symptoms of Alzheimer’s. Research was conducted pertaining to the pathogenesis of Alzheimer’s, the in vitro applications of curcumin, the chemical properties of curcumin, and the in vivo clinical applications of curcumin. The pathogenesis of Alzheimer’s is defined by the aggregation of amyloid-beta plaques, dissociation of tau protein, propagation of reactive oxygen species, and neuroinflammation. Alzheimer’s is also characterized by symptoms of cognitive decline and memory loss. The physiochemical nature of curcumin enables it to interact with multiple biochemical pathways in the central nervous system (CNS), inhibiting the pathogenesis of the disease. In vitro applications of curcumin show much promise to this end. In vivo studies of curcumin on living subjects provide mixed results for the substance’s efficacy on symptoms and pathogenesis. Furthermore, the complex chemical properties of curcumin make drug development very difficult. Curcumin shows much promise in inhibiting the pathogenesis of Alzheimer’s, according to in vitro studies. However, the lack of definitive conclusions from in vivo applications and difficulty in overcoming curcumin’s complex chemical properties for drug development show that the substance cannot yet be designated as an effective treatment for the disease

    TSE pathogenesis in cattle and sheep

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    Many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (TSE). Only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (BSE) and scrapie in their natural hosts. In this review, we summarize the most recent insights into the pathogenesis of BSE and scrapie starting from the initial uptake of TSE agents and crossing of the gut epithelium. Following replication in the gut-associated lymphoid tissues (GALT), TSE agents spread to the enteric nervous system (ENS) of the gut. Infection is then carried through the efferent fibers of the post-ganglionic neurons of the parasympathetic and sympathetic nervous system to the pre-ganglionic neurons in the medulla oblongata of the brain and the thoracic segments of the spinal cord. The differences between the pathogenesis of BSE in cattle and scrapie in sheep are discussed as well as the possible existence of additional pathogenetic routes

    Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis.

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    BACKGROUND: Gastrointestinal tract (GIT) involvement is a common cause of debilitating symptoms in patients with systemic sclerosis (SSc). There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. AIMS: To investigate novel aspects of the pathogenesis of gastrointestinal involvement in SSc. To summarise existing knowledge regarding the cardinal clinical gastrointestinal manifestations of SSc and its pathogenesis, emphasising recent investigations that may be valuable in identifying potentially novel therapeutic targets. METHODS: Electronic (PubMed/Medline) and manual Google search. RESULTS: The GIT is the most common internal organ involved in SSc. Any part of the GIT from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are nonspecific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the absence of cutaneous disease. Up to 8% of SSc patients develop severe GIT symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the GIT causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of GIT dysmotility mediated by functional anti-muscarinic receptor autoantibodies. CONCLUSIONS: Despite extensive investigation, the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions
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