Dietary supplementation with sodium nitrite can exert neuroprotective effects on global cerebral ischemia/reperfusion in mice.

BACKGROUND: Nitrite-derived NO protects against middle cerebral artery occlusion in mice. We developed a new mouse model of global cerebral ischemia and reperfusion (GCI/R) involving reversible occlusion of the major vessels from the aortic arch supplying the brain, and investigated neuroprotection with dietary sodium nitrite supplementation against GCI/R injury. METHODS: Mice received drinking water with (nitrite group) or without (control group) sodium nitrite (2 mM) for 5 days and underwent 3-min GCI/R by reversible occlusion of major vessels from the aortic arch (i.e., brachiocephalic, left common carotid, and left subclavian artery). Survival rates and neurological function scores were evaluated for up to 5 days after GCI/R. Histopathological studies were performed to detect neurological degeneration and caspase-3 activation in serial hippocampal sections. RESULTS: In the control group, 17/30 mice (57 %) survived 5 days after 3-min GCI/R, whereas in the nitrite group 25/30 mice (83 %) survived (p < 0.05). The neurological score at 5 days after GCI in control group was significantly higher than in the nitrite group. Cerebral blood flow (CBF) during GCI was significantly higher in the nitrite group than in the control group, while MABP did not differ significantly between groups. Degenerative changes and caspase-3 activation in hippocampal sections after GCI were observed in the control group but not in the nitrite group. Pretreatment with the NO scavenger c-PTIO abolished the neuroprotective effects of sodium nitrite. CONCLUSIONS: Sodium nitrite supplementation attenuated mortality and neurological impairment after 3-min GCI in mice; an effect likely mediated via vascular mechanisms involving NO.

Desensitization by different strategies of epidermal growth factor receptor and ErbB4.

Four transmembrane tyrosine kinases constitute the ErbB protein family: epidermal growth factor receptor (EGFR) or ErbB1, ErbB2, ErbB3, and ErbB4. In general, the structure and mechanism of the activation of these members are similar. However, significant differences in homologous desensitization are known between EGFR and ErbB4. Desensitization of ligand-occupied EGFR occurs by endocytosis, while that of ErbB4 occurs by selective cleavage at the cell surface. Because ErbB4 is abundantly expressed in neurons from fetal to adult brains, elucidation of the desensitization mechanism is important to understand neuronal development and synaptic functions. Recently, it has become clear that heterologous desensitization of EGFR and ErbB4 are induced by endocytosis and cleavage, respectively, similar to homologous desensitization. It has been reported that heterologous desensitization of EGFR is induced by serine phosphorylation of EGFR via the p38 mitogen-activated protein kinase (p38 MAP kinase) pathway in various cell lines, including alveolar epithelial cells. In contrast, the protein kinase C pathway is involved in ErbB4 cleavage. In this review, we will describe recent advances in the desensitization mechanisms of EGFR and ErbB4, mainly in alveolar epithelial cells and hypothalamic neurons, respectively.

[Anesthetic management of intra-aortic balloon occlusion (IABO) for seven cases of placenta accreta--a six year experience at our institute].

We studied retrospectively amount of bleeding, clamping time, and the presence or absence of ischemia-reperfusion injury in all seven cases of IABO performed for placenta accreta from 2007 to 2012 at our hospital. We also examined rSO2 change before and after clamping in four cases in which lower-limb rSO2 monitoring was performed with NIRS (near-infrared spectroscopy). There was no case suspected of ischemia-reperfusion injury during and after clamping with the amount of bleeding around 1,580-10,973 ml (mean 4,536 ml) and clamping time of 10-83 min (mean 44 min). No significant decrease was observed in lower-limb rSO2 with 73.5 ± 5.9% before clamping and 70.8 ± 5.6% (mean ± SD) after clamping.

Long-term treatment with san'o-shashin-to, a kampo medicine, markedly ameliorates cardiac ischemia-reperfusion injury in ovariectomized rats via the redox-dependent mechanism.

BACKGROUND: Hormone replacement therapy has failed to reduce ischemic cardiovascular events in climacteric women. To explore alternative therapy, we examined whether san'o-shashin-to (TJ-113), a kampo medicine, ameliorates cardiac ischemia-reperfusion (IR) injury in a climacteric rat model. METHODS AND RESULTS: Cardiac function and infarct size after IR were significantly exacerbated in ovariectomized rats as compared with sham-operated rats, whereas long-term treatment with a clinical dosage of TJ-113 for 4 weeks markedly improved these functional and morphological changes. Myocardial inducible nitric oxide synthase (iNOS) expression and peroxynitrite levels were significantly higher in ovariectomized rats compared with sham-operated rats, and long-term TJ-113 treatment significantly reduced these oxidative changes. Furthermore, myocardial manganese superoxide dismutase (Mn-SOD) activity was significantly lower in ovariectomized than in sham-operated rats, and long-term TJ-113 treatment significantly restored antioxidant activity. Importantly, those beneficial actions of TJ-113 were significantly inhibited by the estrogen receptor antagonist, fulvestrant, and the phytoestrogen, emodin, a TJ-113 ingredient, mimicked the actions of TJ-113, suggesting involvement of emodin in the effects of TJ-113. CONCLUSIONS: These results provide the first evidence that long-term treatment with a clinical dosage of TJ-113 markedly ameliorates cardiac IR injury in ovariectomized rats via inhibition of iNOS expression, suppression of peroxynitrite formation, and restoration of Mn-SOD activity. TJ-113 may be a novel therapeutic option in the treatment of ischemic heart disease in climacteric women.

Neuroprotective effect of epidural electrical stimulation against ischemic spinal cord injury in rats: electrical preconditioning.

BACKGROUND: Electroconvulsion therapy is likely to serve as an effective preconditioning stimulus for inducing tolerance to ischemic brain injury. The current study examines whether electrical stimuli on the spinal cord is also capable of inducing tolerance to ischemic spinal cord injury by transient aortic occlusion. METHODS: Spinal cord ischemia was induced by occlusion of the descending thoracic aorta in combination with maintaining systemic hypotension (40 mmHg) during the procedure. Animals implanted with epidural electrodes were divided into four groups according to electrical stimulation and sham. Two groups consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion 24 h after either pretreatment with epidural electrical stimulation (DE group, n = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or sham stimulation. The group P50 represents the duration of spinal cord ischemia associated with 50% probability of resultant paraplegia. RESULTS: Pretreatment with electrical stimulation in the DE group but not the RE group protected the spinal cord against ischemia, and this stimulation prolonged the P50 by approximately 15.0% in the DE group compared with the DC group. CONCLUSIONS: Although the optimal setting for this electrical preconditioning should be determined in future studies, the results suggest that epidural electrical stimulation will be a useful approach to provide spinal protection against ischemia.

[Sivelestat sodium hydrate was effective for ARDS in a patient suffering from chronic rheumatoid arthritis with acute exacerbation after failing to respond to high dose steroid pulse therapy].

Sivelestat sodium hydrate (ELASPOL) was effective for ARDS in a fifty-year-old female patient suffering from chronic rheumatoid arthritis with acute exacerbation, after failing to respond to high dose steroid pulse therapy. In ICU, the patient had bilateral lung opacities, especially of the upper lobes, respiratory acidosis, hypercapnea (PaCO2 89 mmHg), and poor oxygenation (P/F ratio 193). High dose steroid pulse therapy had been performed, but oxygenation was not improved, and a low level of oxygenation (P/F ratio 155) persisted. Sivelestat was started two days after finishing the steroid pulse therapy. The butterfly shadow on chest X ray and impaired oxygenation were markedly improved from the third day of sivelestat administration. Respiratory support was terminated with P/F ratio 300. Plasma concentrations of SP-A and SP-D decreased after sivelestat administration, but concentration of KL-6 was still elevated. In this case, sivelestat was effective for ARDS in the patient not responding to steroid pulse therapy, and clinical finding and plasma concentrations of SP-A and SP-D were correlated well.