Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It remains controversial as to whether mitral annular calcification (MAC) is an independent predictor of stroke. The aim of this study was to investigate whether there is an association between the presence of MAC and stroke or whether MAC is one of the predictive factors of carotid atheroma and therefore is a secondary risk for stroke. Fifty-six patients who had MAC demonstrated by echocardiography underwent carotid artery duplex sonography and computed brain tomography with various causes were enrolled in the study. They were compared with 58 control patients without MAC. MAC was defined as a dense, localized, highly reflective area larger than 5 mm at the junction of the atrioventricular groove and posterior mitral valve leaflet. Carotid artery stenosis was defined as lumen diameter narrowing exceeding 60%. Cerebral ischemia was detected by spiral tomography and was classified as infarction and lacunae. A significant association was found between the presence of MAC and carotid atheroma (P = 0.011), MAC and hyperechogen plaque (P = 0.034), and MAC and stenosis (P = 0.008). There was an association between the presence of carotid atheroma and cerebral infarction (P = 0.007). Logistic regression analysis revealed hypertension and diabetes mellitus were independent risk factors (P = 0.030, P = 0.034, respectively) for developing carotid atheroma. MAC was an independent factor for carotid stenosis (P = 0.029). MAC may not be a significant causative factor for stroke, but may be a secondary risk factor. A significant association between the presence of MAC and carotid artery atherosclerotic disease may explain the high prevalence of stroke in patients with MAC.
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PMID:Association between mitral annular calcification and stroke. 1565 75

Diabetes with hypertension is characterized by increased cerebrovascular pathology and poorer outcomes following stroke. In this study we evaluated the effect of global brain ischemia on brain metabolic parameters in normal and diabetic rats treated with a dihydropyridine calcium antagonist, felodipine. Normal and diabetic rats were treated daily with felodipine (5 mg/kg) or saline. After 4 wk global ischemia was produced by occluding the carotid arteries for 1 h. In other groups the occlusion was removed and the animals were allowed to reperfuse for an additional 2 h. Following 1 h global ischemia, with or without reperfusion, the animals and controls were killed by decapitation. Cerebral water, lactate, ATP, and glutamate were measured. Glo-bal ischemia with or without reperfusion increased cerebral water and lactate, but decreased ATP. Treatment with felodipine decreased lactate, but increased water content. Ischemia in diabetics with or without reperfusion decreased water and lactate. Treated diabetics had higher ATP levels after reperfusion. Glutamate levels were increased in diabetics and were further increased by treatment. We conclude that the enhanced CNS damage following cerebral ischemia in diabetes is not correlated with ATP or lactate levels and may be mediated in part by increased glutamate. Calcium channel antagonist may augment this process.
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PMID:The effect of global brain ischemia in normal and diabetic animals: the influence of calcium channel blockers. 1571 Oct 20

Reactive oxygen species (ROS) are implicated in reperfusion injury after transient focal cerebral ischemia. The antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD), is one of the major means by which cells counteract the deleterious effects of ROS after ischemia. Recently, we reported that when Tat-SOD fusion protein is transduced into pancreatic beta cells it protects the beta cells from destruction by relieving oxidative stress in ROS-implicated diabetes (Eum et al., 2004). In the present study, we investigated the protective effects of Tat-SOD fusion protein against neuronal cell death and ischemic insults. When Tat-SOD was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Immunohistochemical analysis revealed that Tat-SOD injected intraperitoneally (i.p.) into mice has access to various tissues including brain neurons. When i.p. injected into gerbils, Tat-SOD prevented neuronal cell death in the hippocampus in response to transient fore-brain ischemia. These results suggest that Tat-SOD provides a strategy for therapeutic delivery in various hu-man diseases, including stroke, related to this anti-oxidant enzyme or to ROS.
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PMID:Transduced Tat-SOD fusion protein protects against ischemic brain injury. 2044 45

Hyperglycemia, even if mild, is known to aggravate neuronal damage from cerebral ischemia. In order better to define the influence of currently used anesthetic techniques on plasma glucose levels during cerebrovascular surgery, we examined serial plasma glucose values during 43 carotid endarterectomies (CEA) and 19 intracranial arteriovenous malformation (AVM) resections. CEA patients (aged 67.6 +/- 1.4 years and weighing 76.4 +/- 2.3 kg, mean +/- SEM) received N2O in O2 and either isoflurane (ISO) (n = 14), halothane (n = 8), fentanyl (n = 10), or sufentanil (n = 11). Plasma glucose was compared at 1.12 +/- 0.05 h (stage 1), 2.08 +/- 0.07 h (stage 2), and 3.12 +/- 0.1 h (stage 3) after induction of anesthesia. AVM patients received ISO and N2O in O2. Plasma glucose was compared 2.32 +/- 0.14 h (stage 1) and 6.25 +/- 0.34 h (stage 2) after induction of anesthesia (surgical stage). Glucose was determined by the hexokinase method. In the CEA cases, progressively elevated plasma glucose levels were associated with successive surgical stage (114 +/- 6, 122 +/- 6, and 138 +/- 6 mg/dl). The seven CEA patients that carried the diagnosis of diabetes mellitus tended to have higher glucose levels but they did not differ significantly from nondiabetic patients. The AVM patients (aged 35.7 +/- 2.3 years and weighing 71.1 +/- 2.9 kg) were all nondiabetic. They were significantly younger than the CEA patients and each received dexamethasone intraoperatively. In these patients, there was a significant effect (p <0.04) of surgical stage to increase plasma glucose (115 +/- 10 vs. 126 +/- 10 mg/dl). For CEA, the anesthetic techniques examined do not differ significantly in their influence on plasma glucose levels, but all techniques were associated with a gradual increase in plasma glucose levels intraoperatively, even in nondiabetic patients. Compared to the group of younger AVM patients, glucose elevation was more pronounced in the elderly CEA patients. We conclude that intraoperative monitoring of plasma glucose may be useful in elderly patients during prolonged neurovascular procedures.
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PMID:The equivalence of anesthetic regimens with respect to plasma glucose elevation during cerebrovascular surgery. 1581 13

PARP-1 is a nuclear enzyme activated by DNA breaks. Activated PARP-1 cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to nuclear acceptor proteins. Poly(ADP-ribosyl)ation has been implicated in the regulation of a diverse array of cellular processes ranging from DNA repair, chromatin organization, transcription, replication to protein degradation. On the 'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia reperfusion and various forms of inflammation, as proven by pharmacological studies as well as experiments utilizing PARP-1 knockout animals. To our current knowledge, two mechanisms are responsible for the beneficial effects of PARP inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii) inhibition of inflammatory signal transduction and production of inflammatory mediators. Here we review the possible regulatory mechanisms (e.g. calcium signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP-1-mediated cell death pathway and discuss recent developments shedding new light on the complex role of PARP-1 in the regulation of the expression of inflammatory mediators.
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PMID:Pathophysiologic role of oxidative stress-induced poly(ADP-ribose) polymerase-1 activation: focus on cell death and transcriptional regulation. 1586

Lung transplantation is currently the most effective means of improving survival and quality of life in patients with end-stage cystic fibrosis. In reviewing our 6-year experience we sought to evaluate complications and survival after sequential bilateral lung transplantation. Between October 1996 and October 2002, 114 patients with cystic fibrosis were referred to us from 15 Italian regional centers and 2 support centers for cystic fibrosis as possible candidates for lung transplantation. Of these 114 patients, 99 were included in the waiting list and 15 were refused. The mean time spent on the waiting list was 6.8+/-5.2 months (range 1 day-21 months) for those patients receiving lung transplantation, and 5.4+/-4.5 months (range 10 days-18 months) for those 35 patients who died while on the waiting list. A total 55 patients (6 children and 49 adults), mean age 25.6+/-6.6 years (range 9-52 years), 29 males, underwent bilateral sequential lung transplantation. One patient had a second transplantation 14 months after the first. The most frequent medical non-infective complications after transplantation were chronic renal failure (n=27 patients), diabetes (n=31), osteoporosis (n=17), arterial hypertension (n=14), seizures (n=4), transient cerebral ischaemia (n=1), and transient bilateral blindness (n=1). Bacterial lower airways respiratory infections with the organisms that colonized patients' airways before lung transplantation developed in 42 patients; cytomegalovirus (CMV) infection in 41; and opportunistic infections of the lung with Pneumocystis carinii in 3 patients. Cultures of sputum or bronchoalveolar lavage fluid grew Aspergillus fumigatus in nine patients; aspergillosis of right bronchial anastomosis developed in one patient and a lung infection in another. Another patient had a pulmonary infection secondary to Aspergillus niger. An average of 1.3 episodes of acute rejection developed per patient in the first 6 months after lung transplantation. Freedom from bronchiolitis obliterans syndrome was 95% at 1 year, 82.5% at 2 years, 70% at 3 years, and 65% at 4, 5 and 6 years. Actuarial survival rates were 80% at 1 month, 79% at 1 year, 74% at 2 years, 70% at 3 years and 58% at 4, 5 and 6 years. Ten patients (17.8%) died in the early postoperative period (1-30 days) for the following reasons: primary graft failure (n=4), multiorgan failure (n=3), Burkholderia cepacia sepsis (n=1), myocardial infarction (n=1), and pulmonary embolism (n=1). Mortality was accounted for by 9 patients (16%) who died from 9 to 43 months after lung transplantation, for the following reasons: P. carinii infection (n=2), bronchiolitis obliterans syndrome (n=4), A. fumigatus pulmonary infection (n=1), unknown cause (n=1) and suicide (n=1). In conclusion, the leading causes of morbidity after lung transplantation for cystic fibrosis are pulmonary bacterial infection and opportunistic infections. Bronchiolitis obliterans develops in more than half of lung transplant recipients who survive for more than 3 years and is an important cause of death in the late post transplantation period.
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PMID:Lung transplantation for cystic fibrosis: 6-year follow-up. 1591 93

Insulin resistance (IR) impairs endothelium-mediated vasodilation in cerebral arteries as well as K+ channel function in vascular smooth muscle. Peripheral arteries also show an impaired endothelium-dependent vasodilation in IR and concomitantly show an enhanced contractile response to endothelin-1 (ET-1). However, the contractile responses of the cerebral arteries in IR have not been examined systematically. This study examined the contractile responses of pressurized isolated middle cerebral arteries (MCAs) in fructose-fed IR and control rats. IR MCAs showed no difference in pressure-mediated (80 mmHg) vasoconstriction compared to controls, either in time to develop spontaneous tone (control: 61+/-3 min, n=30; IR: 63+/-2 min, n=26) or in the degree of that tone (control: 60 min: 33+/-2%, n=22 vs. IR 60 min: 34+/-3%, n=17). MCAs treated with ET-1 (10(-8.5) M) constrict similarly in control (53+/-3%, n=14) and IR (53+/-3%, n=14) arteries. Constrictor responses to U46619 (10(-6) M) are also similar in control (48+/-9%, n=8) and IR (42+/-5%, n=6) MCAs as are responses to extraluminal uridine 5'-triphosphate (UTP; 10(-4.5) M) (control: 35+/-7%, n=11 vs. IR: 38+/-3%, n=10). These findings demonstrate that constrictor responses remain intact in IR despite a selective impairment of dilator responses and endothelial and vascular smooth muscle K+ channel function in cerebral arteries. Thus, it appears that the increased susceptibility to cerebrovascular abnormalities associated with IR and diabetes (including cerebral ischemia, stroke, vertebrobasilar transient ischemic attacks) is not due to an enhanced vasoreactivity to constrictor agents.
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PMID:Insulin resistance does not impair contractile responses of cerebral arteries. 1595 70

Nontraumatic arterial dissection of the anterior cerebral artery (NAD-ACA) is a relatively rare disease entity, although case reports have recently been increased. We treated 6 patients suffering from NAD-ACA from January 1996 to December 2003, and the neuroradiological findings together with the clinical courses were reviewed. There were 3 males and 3 females with a mean age of 57.7-year-old, ranging from 41 to 65. Five patients had a past history of hypertension and one diabetes mellitus. At the onset, all patients presented with clinical manifestations of cerebral ischemia. Among them, all exhibited contralateral hemiparesis with greater weakness of the lower extremity, and two patients exhibited headache. Initial angiography revealed the pearl and string sign in four patients and string sign, tapered occlusion in each one. Follow-up angiographies revealed sequential changes in all patients; four improved and two progressed. Main anatomic site of the lesion was as follows; five in the A2 and one in the A1 portion, in addition, one patient was complicated by saccular aneurysm, one by PCA dissection, and two had with saccular aneurysm contralateral ACA & MCA and VA dissection each other. Four patients were treated conservatively by intravenous administration of argatroban, one by intravenous administration of Dextrane and one by anti-platelet agent in the acute stage. All patients were treated by anti-platelet agents in the chronic stage. Good recovery was achieved in five patients, but one who suffered from severe subarachnoid hemorrhage in the chronic stage died. Our experience suggests that hypertension and/or the succeeding abnormal structural changes in the arterial wall may contribute to the occurrence of this disease. NAD-ACA showing clinical manifestations of cerebral ischemia could result in a relatively good prognosis; however, attention should be paid to patients treated conservatively with a very closed follow-up angiography to prevent a possibility of severe hemorrhage.
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PMID:[Nontraumatic arterial dissection of the anterior cerebral artery: six cases report]. 1602 47

Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.
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PMID:Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health. 1641 45

Diabetes exacerbates neuronal cell death induced by cerebral ischemia. One contributing factor is enhanced acidosis during ischemia. Astrocytes are vulnerable to hypoxia under acidic conditions in vitro and may be targets of ischemia under diabetic conditions. The objective of this study was to determine whether diabetes would cause damage to astrocytes after an ischemic brain injury in vivo. Diabetic and nondiabetic rats were subjected to 5 min of forebrain ischemia and followed by 30 min, 6 h, or 1 or 3 days of recovery. The results showed that ischemia caused activation of astrocytes in nondiabetic rats. In contrast, diabetes caused astrocyte activation in early stage of reperfusion and astrocyte death in late stage of reperfusion. Remarkable astrocyte death was preceded by increased DNA oxidation. Further studies revealed that increased astrocyte damage coincided with enhanced production of free radicals. These data suggest that hyperglycemic ischemia worsens outcome in astrocytes, as it does in neurons.
Diabetes 2006 Feb
PMID:Streptozotocin-induced diabetes causes astrocyte death after ischemia and reperfusion injury. 1644 67


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