다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Fish bioaccumulation and biomarkers in environmental risk assessment: a review

Population-based epidemiologic studies have uncovered the high prevalence and wide severity spectrum of undiagnosed obstructive sleep apnea, and have consistently found that even mild obstructive sleep apnea is associated with significant morbidity. Evidence from methodologically strong cohort studies indicates that undiagnosed obstructive sleep apnea, with or without symptoms, is independently associated with increased likelihood of hypertension, cardiovascular disease, stroke, daytime sleepiness, motor vehicle accidents, and diminished quality of life. Strategies to decrease the high prevalence and associated morbidity of obstructive sleep apnea are critically needed. The reduction or elimination of risk factors through public health initiatives with clinical support holds promise. Potentially modifiable risk factors considered in this review include overweight and obesity, alcohol, smoking, nasal congestion, and estrogen depletion in menopause. Data suggest that obstructive sleep apnea is associated with all these factors, but at present the only intervention strategy supported with adequate evidence is weight loss. A focus on weight control is especially important given the expanding epidemic of overweight and obesity in the United States. Primary care providers will be central to clinical approaches for addressing the burden and the development of cost-effective case-finding strategies and feasible treatment for mild obstructive sleep apnea warrants high priority.

Epidemiology of obstructive sleep apnea: a population health perspective.

Obesity increases the risk of cardiovascular disease and premature death. Adipose tissue releases a large number of bioactive mediators that influence not only body weight homeostasis but also insulin resistance - the core feature of type 2 diabetes - as well as alterations in lipids, blood pressure, coagulation, fibrinolysis and inflammation, leading to endothelial dysfunction and atherosclerosis. We are now beginning to understand the underlying mechanisms as well as the ways in which smoking and dyslipidaemia increase, and physical activity attenuates, the adverse effects of obesity on cardiovascular health.

Mechanisms linking obesity with cardiovascular disease

Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC's survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.

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The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers. During apoptosis, FOXOs are involved in mitochondria-dependent and -independent processes triggering the expression of death receptor ligands like Fas ligand, TNF apoptosis ligand and Bcl‑XL, bNIP3, Bim from Bcl-2 family members. Different types of growth factors like insulin play a vital role in the regulation of FOXOs. The most important pathway interacting with FOXO in different types of cancers is the PI3K/AKT pathway. Some other important pathways such as the Ras-MEK-ERK, IKK and AMPK pathways are also associated with FOXOs in tumorigenesis. Therapeutically targeting the FOXO signaling pathway(s) could lead to the discovery and development of efficacious agents against some cancers, but this requires an enhanced understanding and knowledge of FOXO transcription factors and their regulation and functioning. This review focused on the current understanding of cell biology of FOXO transcription factors which relates to their potential role as targets for the treatment and prevention of human cancers. We also discuss drugs which are currently being used for cancer treatment along with their target pathways and also point out some potential drawbacks of those drugs, which further signifies the need for development of new drug strategies in the field of cancer treatment.

/pdf/foxo-signaling-pathways-as-therapeutic-targets-in-cancer-1xig5w7khs.pdf

FOXO Signaling Pathways as Therapeutic Targets in Cancer.

The epidemic of obesity in the developed world over the last two decades is driving a large increase in type 2 diabetes and consequentially setting the scene for an impending wave of cardiovascular morbidity and mortality. It is only now being recognized that the major antecedent of type 2 diabetes, insulin resistance with its attendant syndrome, is the major underlying cause of the susceptibility to type 2 diabetes and cardiovascular disease. In metabolic tissues, insulin signaling via the phosphatidylinositol-3-kinase pathway leads to glucose uptake so that in insulin resistance a state of hyperglycemia occurs; other factors such as dyslipidemia and hypertension also arise. In cardiovascular tissues there are two pathways of insulin receptor signaling, one that is predominant in metabolic tissues (mediated by phosphatidylinositol-3-kinase) and another being a growth factor-like pathway (mediated by MAPK); the down-regulation of the former and continued activity of the latter pathway leads to atherosclerosis. This review addresses the metabolic consequences of the insulin resistance syndrome, its relationship with atherosclerosis, and the impact of insulin resistance on processes of atherosclerosis including insulin signaling in cells of the vasculature.

Insulin resistance and atherosclerosis

Cardiovascular actions and therapeutic potential of tanshinone IIA.

Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis.

/pdf/lox-1-in-atherosclerosis-biological-functions-and-4rmrle50h2.pdf

Peter J. Little

Papers

The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

FOXO Signaling Pathways as Therapeutic Targets in Cancer.

Insulin resistance and atherosclerosis

Cardiovascular actions and therapeutic potential of tanshinone IIA.

LOX-1 in atherosclerosis: biological functions and pharmacological modifiers