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Protection against dopaminergic nigrostriatal cell death by excitatory input ablation (2000)

Takada, M. ; Matsumura, M. ; Kojima, J. ; [et al.]

Oxford, UK : Blackwell Science Ltd

European journal of neuroscience 12 (2000), S. 0

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ISSN: 1460-9568

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: The importance of enhanced glutamatergic neurotransmission in the basal ganglia and related structures has recently been highlighted in the development of Parkinson's disease. The pedunculopontine tegmental nucleus (PPN) is the major origin of excitatory, glutamatergic input to dopaminergic nigrostriatal neurons of which degeneration is well known to cause Parkinson's disease. Based on the concept that an excitatory mechanism mediated by glutamatergic neurotransmission underlies the pathogenesis of neurodegenerative disorders, we made an attempt to test the hypothesis that removal of the glutamatergic input to the nigrostriatal neurons by PPN lesions might prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the macaque monkey. The PPN was lesioned unilaterally with microinjection of kainic acid, and, then, MPTP was administered systemically. In these monkeys, the degree of parkinsonian motor signs was behaviourally evaluated, and the histological changes in the dopaminergic nigrostriatal system were analysed by means of tyrosine hydroxylase immunohistochemistry. The present results revealed that nigrostriatal cell loss and parkinsonian motor deficits were largely attenuated in the MPTP-treated monkey group whose PPN had been lesioned, compared with the control, MPTP-treated monkey group with the PPN intact. This clearly indicates that the onset of MPTP neurotoxicity is suppressed or delayed by experimental ablation of the glutamatergic input to the nigrostriatal neurons. Such a protective action of excitatory input ablation against nigrostriatal cell death defines evidence that nigral excitation driven by the PPN may be implicated in the pathophysiology of Parkinson's disease.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00062.x

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The relationship between risk of hypoglycemia and use of cibenzoline and disopyramide (2000)

Takada, M. ; Fujita, S. ; Katayama, Y. ; [et al.]

Springer

European journal of clinical pharmacology 56 (2000), S. 335-342

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ISSN: 1432-1041

Keywords: Key words Hypoglycemia ; ATP-sensitive K+ channel ; Cibenzoline

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract Objective: A case-control study was carried out to compare the risks of hypoglycemia caused by disopyramide and cibenzoline. Methods: We selected 91 subjects with hypoglycemia from among 14,156 outpatients who consulted the National Cardiovascular Center (NCVC) and received drug therapy between September 1997 and February 1998. We used the fasting blood sugar (FBS) level of 75 mg/dl or less as the cut-off level to screen for hypoglycemia. For each case, five controls matched for gender and age were selected from the clinical division consulted by relevant subjects. Results: Ninety-one cases and 455 controls were enrolled in this study. Of 91 cases with hypoglycemia, 8 (8.8%) were treated with cibenzoline and 3 (3.3%) with disopyramide. The percentage of cases treated with cibenzoline was greater than that in the controls (1.5%), and the prescription frequency of cibenzoline during the study period was 2%. With adjustment for potential confounding factors using conditional logistic regression, hypoglycemia was significantly correlated with the use of cibenzoline [OR 8.0 (95% CI 1.7–36.8)], insulin [OR 48.4 (95% CI 8.8–267.2)], and thyroid agents [OR 13.0 (95% CI 1.1–160.4)]. An increased risk of hypoglycemia associated with the use of sulfonylureas was not detected. In additional logistic regression analysis, including the variables with individual sulfonylureas, glibenclamide but not gliclazide significantly increased the risk of hypoglycemia. The use of disopyramide did not affect the risk of hypoglycemia. In separate analyses for diabetic and non-diabetic patients, the risks of hypoglycemia associated with the use of drugs other than β-blocking agents in non-diabetic patients were estimated to be lower than those in diabetic patients. Conclusion: The use of cibenzoline was significantly correlated with an increased risk of hypoglycemia.