Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrolysis of acetylsalicylic acid (ASA, aspirin), an antiplatelet drug commonly used in the prevention of stroke and myocardial infarction, seems to play a crucial role in its pharmacological action. Thirty-eight healthy volunteers and 38 type 2 diabetic patients were enrolled to test the hypothesis that the enhanced plasma degradation and lowered bioavailability of ASA in diabetic patients is associated with the attenuation of platelet response. Aspirin esterase activities were tested at pH 7.4 and 5.5. A significantly higher overall aspirin esterase activity was noted at pH 7.4 in the diabetic patients (P<0.003), corresponding to faster ASA hydrolysis (P<0.006). This increased activity was attributable to butyrylcholinesterase and probably to albumin, because it was effectively inhibited by eserine and 4-bis-nitrophenyl phosphate (P<0.01). No significant differences between control and diabetic subjects were found at pH 5.5 in either enzymatic activities or ASA hydrolysis rates. The enhanced plasma ASA degradation in diabetic subjects was significantly associated with the refractoriness of blood platelets to ASA (P<0.05) and modulated by plasma cholesterol (P<0.01). No direct effects of plasma pH or albumin were observed. In conclusion, higher aspirin esterase activity contributes to the lowered response of diabetic platelets to ASA-mediated antiplatelet therapy.
 ...
PMID:Increased blood plasma hydrolysis of acetylsalicylic acid in type 2 diabetic patients: a role of plasma esterases. 1644 34

Increasing interest has been directed to role of pharmaceuticals in the recovery of cerebrovascular events. However, only few scientific studies are available to date, and further research is needed. Amphetamine is the most extensively studied drug shown to promote recovery of function, although clinical data have lead to conflicting results. Other psychostimulants drugs have been proposed, as levodopa or methylphenidate, even if published data are still few. Recently, two studies have been published about the positive role of cholinesterase inhibitor donepezil on stroke recovery. However, such data must still be confirmed by randomized controlled trials. Antidepressant drugs have shown to be effective not only in improving depressive symptoms in stroke patients, but also in decreasing, although partially, the negative impact of poststroke depression on functional outcome. Serotoninergic agents may have a role in improving stroke recovery, in a fashion that is not dependent on their primary antidepressant activity. Last, it is important to be aware that certain drugs as clonidine, prazosin, dopamine receptor antagonists, benzodiazepines, phenytoin, and phenobarbital could have a detrimental effect on the poststroke recovery.
 ...
PMID:New developments on drug treatment rehabilitation. 1683 44

Vascular dementia (VaD) is the second leading cause of dementia and is often underdiagnosed. Stroke is the leading cause of VaD, although it may also develop secondary to a variety of other cerebrovascular or cardiovascular conditions. Currently, no drugs are approved for the treatment of VaD. However, because cholinergic deficits have been found in patients with VaD, similar to those found in patients with Alzheimer disease (AD), it is believed that cholinesterase inhibitors, which are indicated for the treatment of mild to moderate AD, may also provide benefit for patients with VaD. Clinical trials of donepezil, galantamine, and rivastigmine have supported this idea, although as yet, large-scale, prospective studies in VaD have only been reported for donepezil. Donepezil was shown to provide benefits in cognition, global function, and activities of daily living compared with placebo. The N-methyl-D-aspartate receptor antagonist memantine may also provide some cognitive benefit in VaD, particularly in patients with more advanced disease. These data suggest that antidementia drugs currently used for treatment of AD should be considered for treatment of VaD as well.
 ...
PMID:Use of antidementia agents in vascular dementia: beyond Alzheimer disease. 1703 61

Cognitive impairment of any severity associated with cerebrovascular damage is defined as vascular cognitive impairment as proposed by O'Brien. This is a heterogeneous syndrome with many subtypes, the most prevalent being vascular cognitive impairment without dementia. Neuropathological studies confirm that cerebrovascular disease and Alzheimer's disease frequently coexist. Diagnosis depends on criteria for dementia and vascular pathologies. Brain imaging is an important diagnostic tool. Although there is no approved intervention specifically for vascular cognitive impairment, general treatments (such as antiplatelet and antihypertensives) aimed at the prevention and management of stroke are used. Evidence from randomised, placebo-controlled studies of cholinesterase inhibitors for vascular dementia suggests that there may be beneficial effects for cognitive function, and clinical global impression is more favourable for the cholinesterase inhibitors compared with placebo. The effect of memantine also seems to be modest and similar to the effect that is demonstrated in patients with Alzheimer's disease. The accumulated evidence is not as comprehensive as that which exists for Alzheimer's disease. The cholinesterase inhibitors and memantine have not been extensively studied in vascular cognitive impairment without dementia. For the purposes of this review, the authors focus on interventions that have been evaluated by randomised controlled trials.
 ...
PMID:Investigational treatment for vascular cognitive impairment. 1746 38

Alzheimer's disease (AD) is characterized by an extensive loss of cholinergic neurons, and their cortical projections, from the basal forebrain area. The resulting reduction in cholinergic activity is associated with decreased levels of the neurotransmitter acetylcholine (ACh), decreased activity of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and increased butyrylcholinesterase (BChE) activity. In the present study, we investigated whether the BCHE, ACHE, and CHAT genes were associated with AD and the possibility of a synergistic effect with APOE-epsilon4 in a Sardinian sample. AD patients (n = 158), exclusively of Sardinian ancestry, were recruited from the Division of Geriatrics Local Health Agency 8 and Unit of Clinical Pharmacology, Department of Neurosciences, University of Cagliari. Patients were diagnosed according to DSM-IV, and National Institute of Neurologic and Communicative Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) criteria for possible or probable AD. Cognitive screening was performed by means of Mini-Mental State Examination (MMSE). Healthy controls (n = 118) of Sardinian ancestry were recruited from religious and sport associations. All patients and control subjects gave informed consent for participation in the study. Single nucleotide polymorphism (SNP) analysis was performed by PCR/RFLP or the TaqMan 5' exonuclease method. Our study confirms the association between APOE epsilon4 allele and AD (P < 0.000). No significant differences were observed in allele and genotype frequencies of BCHE, ACHE, and CHAT between AD and controls. Haplotype analysis of ACHE SNPs did not reveal a significant association between ACHE and AD. Our results suggest that the AChE, ChAT, and BChE polymorphisms do not constitute a major genetic risk factor for susceptibility to AD in a Sardinian population.
 ...
PMID:Alzheimer's disease: case-control association study of polymorphisms in ACHE, CHAT, and BCHE genes in a Sardinian sample. 1750 75

The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimer's disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain.
 ...
PMID:The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. 1806 9

The human sweating response is subject to the influence of diverse classes of drugs. Some act centrally at the hypothalamus or at spinal thermoregulatory centres, while others act at sympathetic ganglia or at the eccrine-neuroeffector junction. Pharmacological disturbances of sweating have broad clinical implications. Drugs that induce hyperhidrosis, or sweating in excess of that needed to maintain thermoregulation, can cause patient discomfort and embarrassment, and include cholinesterase inhibitors, selective serotonin reuptake inhibitors, opioids and tricyclic antidepressants. Drugs that induce hypohidrosis, or deficient sweating, can increase the risk of heat exhaustion or heat stroke and include antimuscarinic anticholinergic agents, carbonic anhydrase inhibitors and tricyclic antidepressants. As acetylcholine is the principal neuroeccrine mediator, anhidrosis is one of the clinical hallmarks by which acute anticholinergic toxicity may be recognized. The symptom of dry mouth often accompanies the less apparent symptom of hypohidrosis because the muscarinic M(3) acetylcholine receptor type predominates at both sweat and salivary glands. Management options include dose reduction, drug substitution or discontinuation. When compelling medical indications require continuation of a drug causing hyperhidrosis, the addition of a pharmacological agent to suppress sweating can help to reduce symptoms. When hypohidrotic drugs must be continued, deficient sweating can be managed by avoiding situations of heat stress and cooling the skin with externally applied water. The availability of clinical tests for the assessment of sudomotor dysfunction in neurological disease has enhanced recognition of the complex effects of drugs on sweating. Advances in the understanding of drug-induced anhidrosis have also enlarged the therapeutic repertoire of effective treatments for hyperhidrosis.
 ...
PMID:Drug-induced hyperhidrosis and hypohidrosis: incidence, prevention and management. 1821 88

Mitochondrial disorders, in particular respiratory chain diseases (RCDs), present either as single organ problem or as multi-system disease. One of the most frequently affected organs in RCDs, in addition to the skeletal muscle, is the central nervous system (CNS). CNS manifestations of RCDs include epilepsy, stroke-like episodes, migraine-like headache, ataxia, spasticity, movement disorders, psychosis, demyelination, calcification, but also dementia. Cognitive impairment may be a feature of syndromic as well as non-syndromic RCDs. Syndromic RCDs associated with cognitive impairment include MELAS, KSS, Leigh syndrome, and many others. RCDs with cognitive decline not only result from mtDNA mutations but also from mutations in nuclear genes. At onset there is often no general intellectual deterioration in these patients but specific cognitive deficits, particularly in the visual construction, attention, abstraction, or flexibility. Diagnosis of cognitive impairment from RCDs is based on neuropsychological testing, imaging studies, including MRI, PET, SPECT, or MR-spectroscopy, CSF investigations, or electroencephalography. Therapeutic strategies for dementia in RCDs rely on symptomatic measures. Only single patients may profit from cholinesterase inhibitors or memantine, antioxidants, vitamins, or other substitutes. Overall, cognitive decline in RCDs (mitochondrial dementia) needs to be included in the differentials of dementia.
 ...
PMID:Cognitive decline as a manifestation of mitochondrial disorders (mitochondrial dementia). 1857 95

Randomized controlled trials of primary and secondary prevention of vascular dementia demonstrate real effects on the cause or progression of disease (disease-modifying treatment). These strategies lead to a reduction in all cerebrovascular risk factors, in particular hypertension. Such treatment may prevent dementia by reducing stroke and possibly by other mechanisms that remain undetermined,such as those involved in neurodegeneration and cell death. Curative treatment of vascular dementia, particularly given recent studies on cholinesterase inhibitors (rivastigmine, donepezil and galantamine) and memantine, is still ineffective. There is insufficient evidence to support widespread use of these drugs in vascular dementia. Particular considerations should be taken into account in clinical trials. Vascular dementia is a heterogeneous disease with different subtypes and mechanisms.Therefore, well-designed, adequately powered trials accounting for this heterogeneity, with better clinical definitions and an assessment and detection of cognitive and global changes specific to vascular dementia, are needed.
 ...
PMID:Is it possible to treat vascular dementia? 1918 67

The organ most frequently affected in mitochondrial disorders, particularly respiratory chain diseases (RCDs), in addition to the skeletal muscle, is the central nervous system (CNS). CNS manifestations of RCDs comprise stroke-like episodes, epilepsy, migraine, ataxia, spasticity, movement disorders, psychiatric disorders, cognitive decline, or even dementia (mitochondrial dementia). So far mitochondrial dementia has been reported in MELAS, MERRF, LHON, CPEO, KSS, MNGIE, NARP, Leigh syndrome, and Alpers-Huttenlocher disease. Mitochondrial dementia not only results from mutations in the mitochondrial genome but also from mutations in nuclear genes, such as POLG, thymidine kinase 2, or DDP1. Often mitochondrial dementia starts with specific cognitive deficits, particularly in visual construction, attention, abstraction, or flexibility but without a general intellectual deterioration. Cognitive impairment in RCDs is diagnosed upon neuropsychological testing, imaging studies, such as MRI, PET, or MR-spectroscopy, CSF-investigations, or electroencephalography. Therapy of mitochondrial dementia relies on symptomatic measures. Only single patients profit from cholinesterase inhibitors or memantine, antioxidants, vitamins, coenzyme-Q, or other substitutes. Overall, mitochondrial dementia is an important differential of dementias and should be considered in patients with multi-system disease.
 ...
PMID:Mitochondrial disorders, cognitive impairment and dementia. 1926 75


<< Previous 1 2 3 4 5 Next >>