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)

Diabetic encephalopathy is characterized by impaired cognitive functions that involve neuronal damage triggered by glucose driven oxidative stress. The objective of the present study was to determine whether N-acetylcysteine (NAC) supplementation ameliorates learning and memory deficits caused by hyperglycemia-induced oxidative stress in experimental diabetes. Male Wistar rats (200-250 g) were rendered diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). Cognitive deficits were observed in diabetic animals assessed using elevated plus maze test after 8 weeks of induction of diabetes. Acetylcholinesterase activity, a marker of cholinergic function, was decreased by 15.6% in the cerebral cortex, 20.9% in cerebellum and 14.9% in brain stem of diabetic rats compared to control rats. There was an increase in lipid peroxidation in cerebral cortex (21.97%), cerebellum (20.4%) and brain stem (25.5%) of diabetic rats. This was accompanied by decrease in glutathione and total thiol content along with decrease in the activities of superoxide dismutase, catalase and glutathione reductase. However, glutathione peroxidase activity increased by 11.2%, 13.6% and 23.1% in cerebral cortex, cerebellum and brain stem respectively, while the activity of glutathione-s-transferase decreased only in cerebral cortex (21.7%). Supplementation with NAC (1.4 g/kg/day in drinking water) significantly attenuated cognitive deficits and oxidative stress in diabetic rats. Our results emphasize the involvement of increased oxidative stress in cognitive impairment in diabetic animals and point towards the potential beneficial role of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.
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PMID:Neuroprotective effect of N-acetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes. 1880 43

Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L: -cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase. Thirty-eight male Wistar rats were divided into six groups: C(A) (8-week-control), C(B) (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), D(A) (8-week-diabetic), D(B) (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated). All diabetic rats were once treated with an intraperitoneal (i.p.) STZ injection (50 mg/kg body weight) at the beginning of the experiment, while all Cys-treated groups received i.p. injections of Cys 7 mg/kg body weight (daily, for 1-week, during the 9th-week). Whole rat brain parameters were measured spectrophotometrically. In vitro incubation with 0.83 mM of Cys or 10 mM of STZ for 3 h was performed on brain homogenate samples from groups C(B) and D(B), in order to study the enzymes' activities. Diabetic rats exhibited a statistically significant reduction in brain TAS (-28%, D(A) vs C(A);-30%, D(B) vs C(B)) that was reversed after 1-week-Cys-administration into basal levels. Diabetes caused a significant increase in AChE activity (+27%, D(A) vs C(A); +15%, D(B) vs C(B)), that was further enhanced by Cys-administration (+57%, D + Cys vs C(B)). The C + Cys group exhibited no significant difference compared to the C(B) group in TAS (+2%), but showed a significantly increased AChE activity (+66%, C + Cys vs C(B)). Diabetic rats exhibited a significant reduction in the activity of Na(+),K(+)-ATPase (-36%, D(A) vs C(A);-48%, D(B) vs C(B)) that was not reversed after 1-week Cys administration. However, in vitro incubation with Cys partially reversed the diabetes-induced Na(+),K(+)-ATPase inhibition. Mg(2+)-ATPase activity was not affected by STZ-induced diabetes, while Cys caused a significant inhibition of the enzyme, both in vivo (-14%, C + Cys vs C(B);-17%, D + Cys vs C(B)) and in vitro (-16%, D(B) + in vitro Cys vs C(B)). In vitro incubation with STZ had no effect on the studied enzymes. The present data revealed a protective role for Cys towards the oxidative effect of diabetes on the adult rat brain. Moreover, an increase in whole brain AChE activity due to diabetes was recorded (not repeatedly established in the literature, since contradictory findings exist), that was further increased by Cys. The inhibition of Na(+),K(+)-ATPase reflects a possible mechanism through which untreated diabetes could affect neuronal excitability, metabolic energy production and certain systems of neurotransmission. As concerns the use of Cys as a neuroprotective agent against diabetes, our in vitro findings could be indicative of a possible protective role of Cys under different in vivo experimental conditions.
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PMID:Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na(+),K (+))- and Mg(2+)-ATPase: modulation by L-cysteine. 1929 11

The objective of the present study was to investigate the effect of the administration of resveratrol (RV) on memory and on acetylcholinesterase (AChE) activity in the cerebral cortex, hippocampus, striatum, hypothalamus, cerebellum and blood in streptozotocin-induced diabetic rats. The animals were divided into six groups (n=6-13): Control/saline; Control/RV 10 mg/kg; Control/RV 20 mg/kg; Diabetic/saline; Diabetic/RV 10 mg/kg; Diabetic/RV 20 mg/kg. One day after 30 days of treatment with resveratrol the animals were submitted to behavioral tests and then submitted to euthanasia and the brain structures and blood were collected. The results showed a decrease in step-down latency in diabetic/saline group. Resveratrol (10 and 20 mg/kg) prevented the impairment of memory induced by diabetes. In the open field test, no significant differences were observed between the groups. In relation to AChE activity, a significant increase in diabetic/saline group (P<0.05) was observed in all brain structures compared to control/saline group. However, AChE activity decreased significantly in control/RV10 and control/RV20 (P<0.05) groups in cerebral cortex, hippocampus and striatum, while no significant differences were observed in diabetic/RV10 and diabetic/RV20 groups in all brain structures compared to control/saline group. Blood AChE activity increased significantly in diabetic/saline group (P<0.05) decreased in control/RV10, control/RV20 and diabetic/RV20 groups (P<0.05) compared to control/saline group. In conclusion, the present findings showed that treatment with resveratrol prevents the increase in AChE activity and consequently memory impairment in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and consequently improve cognition.
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PMID:Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. 1930 6

Neuronal malfunction is a characteristic feature of diabetic mellitus. Hence, the present study therefore sought to evaluate the effect of diphenyl diselenide (DPDS) on the antioxidant status, sodium pump, cholinergic and glutamatergic system in the rat brain of streptozotocin (STZ) induced diabetes. The results show that although STZ evoke a significant diminution on the antioxidant status and activity of Na(+)/K(+)-ATPase, the activity of acetylcholinesterase and glutamate uptake and release was not altered. However, DPDS was able to markedly restore the observed imbalance in cerebral antioxidant status and also relieve the inhibition of Na(+)/K(+)-ATPase caused by streptozotocin. Hence, we conclude that DPDS is a potential candidate in the management of neuronal dysfunction that often accompanied complications associated with diabetic hyperglycemia.
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PMID:Diphenyl diselenide and streptozotocin did not alter cerebral glutamatergic and cholinergic systems but modulate antioxidant status and sodium pump in diabetic rats. 1936 73

The effect of white matter lesions in magnetic resonance imaging or vascular atherosclerosis on cognitive function is not fully understood in Alzheimer disease (AD). In this investigation, we examined the influence of white matter lesions on cognitive decline in AD. A total of 142 patients with AD (44 men, mean age 65.7 + 7.6 years; mean education period 7.8 + 5.0 years) were included. Patients were divided into 4 groups based on the severities of white matter hyperintensities (WMH) in brain magnetic resonance images (MRI) using Fazekas scale. Cognitive functions were determined using the Korean version of the Mini-Mental State Examination (K-MMSE) and the Clinical Dementia Rating (CDR) scale before acetylcholinesterase inhibitors were administered. Of the 142 patients, 30% (43/142) had no white matter signal abnormality (grade 0). Fourteen percentage (20/142) were grade 1, 42% (59/142) grade 2, and 14% (20/142) were grade 3. Mean K-MMSE scores declined as MRI grades increased to grade 2 and 3 compared to grade 0 (P < .01). Clinical Dementia Ratings were also aggravated by MRI grade. These results remained significant after adjusting for compounding factors affecting cognitive functions; sex, age, number of years in full-time education, hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation. The presence of WMHs were associated with score of MMSE and CDR impairment in patients with AD. These features could be a correctable factor hastening cognitive decline in AD.
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PMID:White matter hyperintensities and cognitive dysfunction in Alzheimer disease. 1943 63

The aim of the present study was to investigate the effects of resveratrol (RV), an important neuroprotective compound on NTPDase, 5'-nucleotidase and acetylcholinesterase (AChE) activities in cerebral cortex synaptosomes of streptozotocin (STZ)-induced diabetic rats. The animals were divided into six groups (n=8): control/saline; control/RV 10mg/kg; control/RV 20mg/kg; diabetic/saline; diabetic/RV 10mg/kg; diabetic/RV 20mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the cerebral cortex was removed for synaptosomes preparation and enzymatic assays. The results demonstrated that NTPDase and 5'-nucleotidase activities were significantly increased in the diabetic/saline group (p<0.05) compared to control/saline group. Treatment with resveratrol significantly increased NTPDase, 5'-nucleotidase activities in the diabetic/RV10 and diabetic/RV20 groups (p<0.05) compared to diabetic/saline group. When resveratrol was administered per se there was also an increase in the activities of these enzymes in the control/RV10 and control/RV20 groups (p<0.05) compared to control/saline group. AChE activity was significantly increased in the diabetic/saline group (p<0.05) compared to control/saline group. The treatment with resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups. In conclusion, this study demonstrated that the resveratrol interfere with the purinergic and cholinergic neurotransmission by altering NTPDase, 5'-nucleotidase and AChE activities in cerebral cortex synaptosomes of diabetic rats. In this context, we can suggest that resveratrol should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with the diabetes.
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PMID:Ectonucleotidase and acetylcholinesterase activities in synaptosomes from the cerebral cortex of streptozotocin-induced diabetic rats and treated with resveratrol. 1972 69

Diabetes mellitus (DM) is clinically associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism remains unclear. We hypothesized that neural remodeling enhances AF vulnerability in diabetic hearts. Eight weeks after creating streptozotocin-induced diabetic rats (DM rats) or control rats, the hearts were perfused according to the Langendorff method. Inducibility of AF was evaluated by 5 times burst pacing from the right atrium and the atrial effective refractory period (AERP) was measured. The protocol was repeated during sympathetic nerve stimulation (SNS) or parasympathetic nerve stimulation (PNS). In tissue samples taken from the right atrium, the density of nerves positive for tyrosine hydroxylase (TH) and acetylcholinesterase (AChE) were determined. SNS significantly increased the incidence of AF in DM rats (14 +/- 6 to 30 +/- 8%, P < 0.01), but not in control rats (11 +/- 4 to 14 +/- 6%, NS). Although AERP was significantly decreased by SNS in both rats (each P < 0.01), increased heterogeneity of AERP by SNS was seen only in DM rats. PNS significantly decreased AERP and increased the incidence of AF (9 +/- 5 to 30 +/- 5% in control rats, 12 +/- 6 to 27 +/- 6% in DM rats, each P < 0.01) in both rats. The density of TH-positive nerves was heterogeneous in DM rats compared with control rats, whereas the heterogeneity of AChE-positive nerves was not different in the rats. The prevalence of AF was enhanced by adrenergic activation in diabetic hearts, in which heterogeneous sympathetic innervation was evident. These results suggest that neural remodeling may play a crucial role for increased AF vulnerability in DM.
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PMID:Influences of autonomic nervous system on atrial arrhythmogenic substrates and the incidence of atrial fibrillation in diabetic heart. 1980 11

Cognitive speed, inhibitory function, and memory decline with age while crystallised, particularly verbal, abilities remain largely intact. Poor health, fewer years of education, lower activity, the presence of the APOE E4 allele, and high BP appear to predict faster cognitive decline. Dementia is diagnosed in the presence of objective cognitive impairment, both long- and short-term memory, plus at least one additional (cortical) cognitive deficit, such as dysphasia, dyspraxia, agnosia, or disturbance in executive functioning. In addition, patients have to show significant impairment in social or occupational functioning and a significant decline from previous levels. Both smoking and diabetes increase the risk of all types of dementia, not smoking or even stopping smoking reduces this risk, but better control of type 2 diabetes does not appear to have a measurable effect. Drinking small to moderate amounts of alcohol appears to confer some benefit in ameliorating cognitive decline. There is some evidence that HRT, DHEA, BP lowering in patients without prior cerebrovascular disease, statins, vitamin B6 and procaine are NOT helpful. There is insufficient evidence to establish or refute a beneficial effect for exercise, treatment of type 2 diabetes, omega-3 fatty acids, folic acid with/without vitamin B12, antioxidant vitamins, or ginkgo biloba. Depressive symptoms are more prevalent than dementia. Clinical (major) depression can present with cognitive deterioration, often associated with subjective complaints. Patients with subjective or objective memory impairment, but without functional deterioration, can be referred to the local memory clinic, while demented patients eligible for acetylcholinesterase inhibitor treatment, patients whose diagnosis is unclear and who may need some specific investigations, as well as patients who may benefit from a combined approach with psychotropic drugs and behavioural support should be referred to the local mental health team.
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PMID:Normal cognitive decline or dementia? 2019 32

In this era, major community worldwide is suffering from diabetes type II, cancer and neurodegenerative disorders. To overcome these diseases, in the screening of Korean medicinal plants, we studied the whole plant of Boehmeria nivea (B. nivea). The methanolic leaf, stem and root extracts of B. nivea and their respective n-hexane, methylene chloride (CH(2)Cl(2)), ethyl acetate (EtOAc), n-butanol (BuOH) and aqueous fractions were investigated for their total phenolic content (TPC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, alpha-glucosidase, beta-glucosidase, alpha-galactosidase, beta-galactosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activities. Profound TPC and DPPH free radical scavenging activities were observed in the EtOAc and BuOH fractions of root, where the BuOH fraction showed high-pitched alpha-glucosidase inhibition and the EtOAc layer showed the maximum beta-glucosidase inhibition. Furthermore, the leaf extract demonstrated the highest beta-galactosidase inhibitory activity, but no alpha-galactosidase inhibition was seen in any of the plant parts. Notable BChE and moderate AChE inhibitory activity was found in whole plant. It can be suggested that whole plant of B. nivea provides a strong biochemical rationale as one of the good choices for the treatment of diabetes type II, cancer and neurodegenerative diseases (AD, etc).
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PMID:Evaluation of antiglycosidase and anticholinesterase activities of Boehmeria nivea. 2036 6

Diabetes has been found to increase the probability of vascular dementia in humans. We have investigated the effect of 4'-hydroxy-3'-methoxyacetophenone (HMAP), a NADPH oxidase inhibitor and Pitavastatin, HMG Co-A reductase inhibitor, on Streptozotocin (STZ) diabetes induced vascular dementia in rats. Donepezil served as a positive control. The rats were administered with single dose of STZ for the induction of diabetes. Drug treatment was started after one month of STZ administration and treatment was continued till the end of the study (i.e. 56th day). On 52nd day onwards, the animals were exposed to Morris water-maze (MWM) for testing learning & memory. Serum glucose, bodyweight, vascular endothelial function, serum nitrite / nitrate levels, aortic & brain oxidative stress levels and brain acetylcholinesterase activity were also tested. STZ treated animals performed poorly on MWM hence reflecting impairment of learning & memory. Further STZ treatment also produced a reduction in body weight, impairment of vascular endothelial function, decrease in serum nitrite / nitrate levels, along with increase in serum glucose, aortic & brain oxidative stress levels and brain acetylcholinesterase activity. Treatment of HMAP, Pitavastatin and Donepezil significantly reversed diabetes induced learning and memory, endothelial dysfunction, and changes in various biochemical levels. It may be concluded that STZ induces vascular dementia. 4'hydroxy-3'-methoxy acetophenone and Pitavastatin may be considered as potential pharmacological agents for the management of diabetes induced vascular dementia.
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PMID:Pitavastatin and 4'-hydroxy-3'-methoxyacetophenone (HMAP) reduce cognitive dysfunction in vascular dementia during experimental diabetes. 2056 Aug 81


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