Journal of biomedical science
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Heart ischemia can rapidly induce apoptosis and mitochondrial dysfunction via mitochondrial permeability transition-induced cytochrome c release. We tested whether nitric oxide (NO) can block this damage in isolated rat heart, and, if so, by what mechanisms. ⋯ The results indicate that NO rapidly protects the ischemic heart from apoptosis and mitochondrial dysfunction via PKG-mediated blockage of mitochondrial permeability transition and cytochrome c release.
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Case Reports
Characterization of a novel Nav1.5 channel mutation, A551T, associated with Brugada syndrome.
Brugada syndrome is a life-threatening, inherited arrhythmia disorder associated with autosomal dominant mutations in SCN5A, the gene encoding the human cardiac Na+ channel alpha subunit (Nav1.5). Here, we characterized the biophysical properties of a novel Brugada syndrome-associated Nav1.5 mutation, A551T, identified in a proband who was successfully resuscitated from an episode of ventricular fibrillation with sudden collapse. Whole-cell currents through wild-type (WT) Nav1.5 and mutant (A551T) channels were recorded and compared in the human embryonic kidney cell line HEK293T transfected with SCN5A cDNA and SCN1B cDNA, using the patch-clamp technique. ⋯ These results suggest that the DI-DII linker may be involved in the stability of inactivation gating process. This study supports the notion that a reduction in Nav1.5 channel function is involved in the pathogenesis of Brugada syndrome. The structural-functional study of the Nav1.5 channel advances our understanding of its pathophysiolgocial function.
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Gender difference in the antinociceptive effect of tramadol and gabapentin (alone or in combination) were investigated in mice. For investigation of acute antinociceptive effect, tramadol and gabapentin were administered to mice by intraperitoneal injection and per os, respectively, and antinociceptive activity was measured by the tail-flick test 30 min after drug administration. For investigation of the development of antinociceptive tolerance to analgesics, mice were injected with tramadol (60 mg/kg), alone or in combination with gabapentin (75 mg/kg), twice daily for seven consecutive days and the tail-flicks were tested on experimental days 1, 3, 5 and 7. ⋯ Repeated administration of tramadol produced antinociceptive tolerance in both genders. Gabapentin produced synergistic effect in tramadol-tolerant mice and repeated administration of gabapentin did not alter the synergistic effect in tramadol-tolerant mice. Because females show a higher overall prevalence of pain and less sensitivity to opioids, our finding may suggest a clinical significance of combined use of the two drugs.
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Comparative Study
Serum total sialic acid levels in smokers and users of smokeless tobacco in form of oral powder (Maraş powder).
Smokeless tobacco (ST) is widely used as chewing tobacco and as oral snuff in the world. Also, in Kahramanmaraş, a city in Southern Turkey, ST used as 'oral powder' or 'Maraş Powder' is consumed widely instead of cigarette smoking. The aim of this study was to search the effect of ST use on serum total sialic acid (TSA) and to compare the serum TSA levels in smokers and ST users. ⋯ But, there was no significant difference in serum TSA levels between smokers and Maraş powder users (p > 0.05). We can conclude from the results obtained that serum TSA was affected by ST use as seen in smokers. This finding may be an indication of harmful effects of ST use as Maraş powder as well as cigarette smoking.
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Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant for monocytes, is thought to play a major role in atherosclerosis, but whether its atherogenic effects involve the direct modulation of vascular smooth muscle cell (SMC) functions remains unclear. This study examined the effects of MCP-1 on the migration of cultured A7r5 SMCs and the signaling pathways involved. Addition of recombinant MCP-1 stimulated SMC migration in modified Boyden chambers coated with type I collagen in a concentration-dependent manner, with 10(-9) M being maximally effective. ⋯ Furthermore, transfection of an active mutant of MEK1 (ERK 1/2 kinase) markedly increased superoxide production in rat aortic smooth muscle cells, as detected by dihydroethydium staining, suggesting that ERK 1/2 activation stimulates ROS generation. ERK 1/2 activation was increased for at least 30 min in cells incubated with MCP-1, and this effect was abolished by U0126 or DPI pretreatment. These results demonstrate that MCP-1 is a chemoattractant for SMCs and that MCP-1-stimulated migration requires both ROS production and ERK 1/2 activation in a positive activation loop, which may contribute to the atherogenic effects of MCP-1.