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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery ectasia (CAE) is well-recognized, angiographic finding of abnormal coronary dilatation, and detected in 0.3-5.3% of angiographic studies. The gold standard for diagnosis this type of aneurysm is coronary angiography, which provides information about the size, sample, location and number of aneurysms. Despite growing prevalence in recent years, controversy still exists as to the pathogenetic mechanisms that underlie this entity. An increased incidence of CAE has been reported in several disorders. Examples include atherosclerotic vascular disease, heterozygous familial hypercholesterolemia, usage of substances including herbicide spray, acetylcholinesterase inhibitors and nitrates, previous arterial balloon angioplasty, polyarteritis nodosa and Kawasaki syndrome. In addition, possible factors contributing to CAE are imbalance between matrix metalloproteinase and tissue inhibitor of metalloproteinase, angiotensin converting enzyme genotype, elevated homocysteine levels, cocaine user, smoking, vascular trauma, nitrate use and diabetes. Emerging investigations have pinpointed inflammation as a central process in all stages of atherosclerosis. This inflammatory process culminates in acute thrombotic complications and clinical events, which is involved in different clinical settings of atherosclerotic diseases. Recent data have also showed that CAE is associated with inflammatory response presented as elevated inflammatory cytokines and C-reactive protein. Accordingly, more complete understanding of the pro- and anti-inflammatory circuits that operate during CAE in particular may foster the development of novel therapeutic approaches.
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PMID:Is any link between inflammation and coronary artery ectasia? 1722 19

Palmoplantar pustulosis (PPP) is probably the inflammatory skin disease most strongly associated to smoking. The disease is common in middle-aged, smoking women, and is chronic, sometimes disabling and characterized by pustules, erythema and scaling on the soles and palms. It is often treatment-resistant. PPP patients have a co-morbidity with an increased risk of autoimmune thyroid disease, celiac disease/gluten intolerance, abnormal calcium homeostasis, diabetes type 2, and depression. The sweat gland apparatus is involved in the pathogenesis of PPP since a) the normal structure of the acrosyringium is abolished so the keratin pattern differs to that in normal palmar skin; b) granulocytes migrate outwards in the acrosyringium forming the pustule in the stratum corneum. Acetylcholine (ACh) is the main inducer of sweating. With immunohistochemistry the ACh synthesizing enzyme choline acetyltransferase (ChAT) and the ACh-degrading enzyme acetylcholinesterase (AChE) were found to be strongly expressed in the gland and duct as were the alpha-3 and alpha-7 nicotinic acetylcholine receptors (nAChRs). Smoking influenced the staining intensity of the enzymes and the alpha-3 nAChR in healthy subjects. In involved PPP skin there was a massive infiltration of granulocytes expressing ChAT and alpha-3 nAChR, and mast cells expressing AChE indicating a role for acetylcholine in inflammation. Cessation of smoking resulted in fewer pustules, and less scaling and erythema. The mechanisms for the effect of nicotine/smoking in PPP are still unknown but nicotine may lead to enhanced inflammation in consideration of the properties of the sweat duct and/or nicotine might facilitate autoimmune reactions.
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PMID:The cutaneous non-neuronal cholinergic system and smoking related dermatoses: studies of the psoriasis variant palmoplantar pustulosis. 1734 25

Anastomoses between the jejunum and the bile duct are an important component of many surgical procedures; however, risk factors for clinically relevant bile leaks have not yet been adequately defined. The objective of this study was to describe the incidence of bile leaks after hepaticojejunostomy and to define predictive factors associated with this risk and with surgical morbidity. Between October 2001 and April 2004, hepaticojejunostomies were performed in 519 patients in a standardized way. Patient- and treatment-related data were documented prospectively. A bile leak was defined as bilirubin concentration in the drains exceeding serum bilirubin with a consecutive change of clinical management or occurrence of a bilioma necessitating drainage. Surgical morbidity occurred in 15% of patients, the incidence of a bile leak was 5.6%. Multivariate analysis confirmed preoperative radiochemotherapy, preoperative low cholinesterase levels, biliary complications after liver transplantation necessitating a hepaticojejunostomy, and simultaneous liver resection as risk factors for bile leakages, whereas biliary complications after liver transplantation necessitating hepaticojejunostomy, simultaneous liver resection, and diabetes mellitus were significantly associated with postoperative surgical morbidity. Our results demonstrate that hepaticojejunostomy is a safe procedure if performed in a standardized fashion. The above found factors may help to better predict the risk for complications after hepaticojejunostomy.
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PMID:Hepaticojejunostomy--analysis of risk factors for postoperative bile leaks and surgical complications. 1739 45

Emerging epidemiologic data indicates that diabetes is a potential predisposing factor for neuropsychiatric deficits as stroke, cerebrovascular diseases, diabetes-associated cognitive decline, depression and anxiety. Diabetes-associated cognitive decline, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of sesamol (3,4-methylenedioxyphenol), a phenolic antioxidant and anti-inflammatory molecule, on cognitive functions, oxidative stress and inflammation in diabetic rats. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 80% in the cerebral cortex of diabetic rats. There was 107 and 121% rise in thiobarbituric acid reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in cerebral cortex and hippocampus was increased by 138 and 109%, respectively. Serum tumor necrosis factor-alpha, a marker for inflammation, was found to increase by 1,100% in diabetic rats. Chronic treatment with sesamol (2, 4 and 8 mg/kg; p.o.) significantly and dose-dependently attenuated cognitive deficit, reduced acetylcholinesterase, oxidative stress and inflammation in diabetic rats. The results emphasize the involvement of oxidative stress and inflammation in the development of cognitive impairment in diabetic animals and point towards the therapeutic potential of sesamol in diabetes-associated cognitive decline.
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PMID:Effect of sesamol on diabetes-associated cognitive decline in rats. 1795 23

Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and lipid peroxides are high whereas those of endothelial nitric oxide are low in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that these diseases are characterized by low-grade systemic inflammation. Recent studies showed that the plasma and tissue activities of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in patients with Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia. As a result of this increase in the activities of enzymes acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway" mediated by acetylcholine acts by inhibiting the production of tumor necrosis factor, interleukin-1, macrophage migration inhibitory factor, and high mobility group box-1 and suppresses the activation of nuclear factor-kappa B expression. ACh is a neurotransmitter and regulates the levels and activities of serotonin, dopamine and other neuropeptides and thus, modulates both immune response and neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by inactivating acetylcholine may enhance inflammation. This suggests that increased plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase seen in various clinical conditions could serve as a marker of low-grade systemic inflammation.
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PMID:Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. 1804 45

Animal models of liver cirrhosis (LC) display a reduced hypothalamic somatostatinergic tone. To test whether a similar mechanism could explain the enhanced Growth Hormone (GH) secretory response to GH-Releasing Hormone (GHRH), which is seen in human LC, we studied the effect of the cholinesterase inhibitor pyridostigmine (PD), which is able to reduce the release of hypothalamic somatostatin (SS), on the GHRH-stimulated GH secretion. We considered that if PD were unable to increase GH secretion, this would constitute evidence of an already inhibited endogenous somatostatinergic tone. If proved, this in turn could explain the enhanced GH response to GHRH seen in LC. Ten LC patients and nine controls were given GHRH (100 microg, intravenously), or PD (120 mg, orally) plus GHRH. After GHRH alone, the GH peak was four times higher in LC than in controls (40.85+/-15.7 ng/ml in LC and 9.35+/-2.5 ng/ml in controls). In LC, PD administration markedly increased the GH response to GHRH (GH peak: 98.0+/-19.7 ng/ml; +240% vs. GHRH alone). The ability of PD to increase the GH response in patients with LC suggests that in this condition the enhanced GH response to GHRH is not due to a completely inhibited endogenous somatostatinergic tone. SS appears instead to maintain its modulator role on GH secretion in human LC, in contrast with what observed in animal models.
Exp Clin Endocrinol Diabetes 2008 Mar
PMID:An inhibition of the hypothalamic somatostatinergic tone is not the cause of the enhanced growth hormone response to growth hormone-releasing hormone in patients with liver cirrhosis. 1809 39

The present study is designed to screen the possible effects of sodium orthovanadate therapy on the kinetic parameters of brain membrane-bound and soluble acetylcholinesterase (AChE) forms in alloxan-induced diabetic rats. The diabetic rats were treated with 300 mg/kg sodium orthovanadate orally for 45 days. While diabetes significantly decreased the brain specific activity (V(max)) of AChE soluble form by 42%, it caused a fivefold increase of the K(m) of the membrane-bound form. Furthermore, the activity of brain glutathione-S-transferase (GST) was significantly decreased and this was associated with a remarkable increase in brain lipid peroxidative parameter, thiobarbituric acid reactive substances (TBARS), as compared to sham control. The alterations of both AChE forms observed in diabetic state could be attributed to hyperglycemia and lipid peroxidation that triggered brain dysfunction by disturbing the neurotransmitter acetylcholine level. Administration of sodium orthovanadate reversed the diabetic conditions by lowering the blood glucose level and normalized the blood Hb(A1C) level. It also normalized the levels of brain AChE, GST and TBARS as compared to diabetic state and control. Therefore, vanadate administration could protect against direct action of lipid peroxidation on brain AChE and in this way, it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes.
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PMID:Vanadium improves brain acetylcholinesterase activity on early stage alloxan-diabetic rats. 1837 83

Diabetes-induced learning and memory impairment, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involve direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of lycopene, a potent anti-oxidant and anti-inflammatory molecule, on cognitive functions, oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. Cognitive functions were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 1.8 fold in the cerebral cortex of diabetic rats. There was about 2 fold and 2.2 fold rise in thiobarbituric acid-reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Total nitric oxide levels in cerebral cortex and hippocampus was increased by 2.4 fold and 2 fold respectively. Serum tumor necrosis factor-alpha, an inflammatory marker, was found to increase by 8 fold in diabetic rats. Chronic treatment with lycopene (1, 2 and 4 mg/kg; p.o.) significantly and dose dependently attenuated cognitive deficit, increased acetylcholinesterase activity, oxidative-nitrosative stress and inflammation in diabetic rats. The results emphasize the involvement of oxidative-nitrosative stress and peripheral inflammation in the development of cognitive impairment in diabetic animals and point towards the therapeutic potential of lycopene in diabetes-induced learning and memory impairment.
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PMID:Lycopene attenuates diabetes-associated cognitive decline in rats. 1858 96

There is increasing interest in the potential of transdermal drug delivery systems for the treatment of neurological disorders, especially in the elderly. In this population, the higher incidence of chronic diseases, such as diabetes mellitus, cardiovascular disease, neurological disease and chronic pain, has dramatically increased the need for long-term medications. Additionally, elderly patients often have a combination of several chronic diseases, meaning drug delivery, drug-drug interactions, absorption/blood concentrations, toxicity and compliance are of concern for patients as well as for their caregivers and physicians. Recent efforts have focused on developing pharmaceutical preparations that overcome these issues. For example, rate-controlled drug delivery systems have been under active development. Transdermal drug delivery systems have been developed to deliver phenserine, rivastigmine, nicotine and estradiol for the management of cognitive and behavioural dysfunctions in patients with Alzheimer's disease because this form of administration has several advantages, including maintenance of sustained therapeutic plasma concentrations of drugs, easy application and reduced systemic adverse effects. Thus, transdermal drug delivery for elderly patients offers promise as the ideal therapeutic approach to treating Alzheimer's disease.This article reviews the technical principles underlying the development of transdermal drug delivery systems, focusing on cholinesterase inhibitors, and the prospects for future development. The clinical performance of transdermal patches, again with emphasis on cholinesterase inhibitors, is also reviewed.
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PMID:Transdermal delivery of treatment for Alzheimer's disease: development, clinical performance and future prospects. 1872 47

Pharmacological treatment of dementia addresses two main clinical features of the disease: cognitive deterioration with predominantly memory loss and behavioural and psychological symptoms (BPSD). While cholinesterase inhibitors are recommended in an attempt to delay memory loss and disability, what should be considered the most appropriate pharmacological treatment for BPSD has remained questionable. Antipsychotic medications, conventional and atypical agents, have been increasingly utilized in clinical practice but only a small number of clinical studies have investigated their relative cost-benefit ratio. This review focuses on the safety of atypical and conventional antipsychotics when used in patients with BPSD. Overall, atypical and conventional antipsychotics are associated with a similarly increased risk for all-cause mortality and cerebrovascular events. Relative to atypical agents users, patients being treated with conventional antipsychotics have an increased incidence of cardiac arrhythmias and extrapyramidal symptoms. Conversely, users of atypical antipsychotics are exposed to an increased risk of venous thromboembolism and aspiration pneumonia. Also, metabolic effects (i.e. increased risk of diabetes, weight gain) have consistently been documented in clinical studies with atypical antipsychotics, although this effect tends to be attenuated with advancing age and in elderly patients with dementia. Antipsychotics, both conventional and atypical, should be used with caution only when nonpharmacologic approaches have failed to adequately control BPSD. More effective interventions are necessary to improve postmarket drug safety in vulnerable populations.
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PMID:Use of antipsychotics in elderly patients with dementia: do atypical and conventional agents have a similar safety profile? 1897 43


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