Nitric oxide directly activates calcium-activated potassium channels from rat brain reconstituted into planar lipid bilayer

AbstractUsing the planar lipid bilayer technique, we tested whether NO directly activates calcium-activated potassium (Maxi-K) channels isolated from rat brain. We used streptozotocin (STZ) as NO donor, and the NO release was controlled with light. In the presence of 100–800 μM STZ, the Maxi-K channel activity increased up to 3-fold within several tens of seconds after the light was on, and reversed to the control level several minutes after shutting off the light. Similar activation was observed with other NO donors such as S-nitroso-N-acetylpenicillamine and sodium nitroprusside. The degree of activity increase was dependent upon the initial open probability (Pinit). When the Pinit was lower, the activity increase was greater. These results demonstrate that NO can directly affect the Maxi-K channel activity, and suggest that the Maxi-K channel might be one of the physiological targets of NO in brain

Striatal neuroinflammation promotes parkinsonism in rats

The specific role of neuroinflammation in the pathogenesis of Parkinson's disease remains to be fully elucidated. By infusing lipopolysaccharide (LPS) into the striatum, we investigated the effect of neuroinflammation on the dopamine nigrostriatal pathway. Here, we report that LPS-induced neuroinflammation in the striatum causes progressive degeneration of the dopamine nigrostriatal system, which is accompanied by motor impairments resembling parkinsonism. Our results indicate that neurodegeneration is associated with defects in the mitochondrial respiratory chain related to extensive S-nitrosylation/nitration of mitochondrial proteins. Mitochondrial injury was prevented by treatment of L-N^6^-(l-iminoethyl)-lysine, an inducible nitric oxide synthase (iNOS) inhibitor, suggesting that iNOS-derived NO is responsible for mitochondrial dysfunction. Furthermore, the nigral dopamine neurons exhibited intracytoplasmic [alpha]-synuclein and ubiquitin accumulation. These results demonstrate that degeneration of nigral dopamine neurons by neuroinflammation is associated with mitochondrial malfunction induced by NO-mediated S-nitrosylation/nitration of mitochondrial proteins

Cancer Statistics in Korea: Incidence, Mortality and Survival in 2006-2007

Cancer has been the leading cause of death in Korea. Korea is facing a very rapid change and increase in cancer incidence, which draws much attention in public health. This paper overviews the nationwide cancer statistics, including incidence, mortality, and survival rates, and their trends in Korea based on the cancer incidence data from The Korea Central Cancer Registry (KCCR) in year 2006 and 2007. In Korea, there were 153,237 cancer cases and 65,519, cancer deaths observed in 2006, and 161,920 cancer cases and 67,561 cancer deaths in 2007, respectively. The incidence rate for all cancer combined showed an annual increase of 2.8% from 1999 to 2007. Specifically, there was significant increase in the incidence of colorectal, thyroid, female breast, and prostate cancers. The number of cancer deaths has increased over the past two decades, due mostly to population aging, while the age-standardized mortality rates have decreased in both men and women since 2002. Notable improvement has been observed in the 5-yr relative survival rates for most major cancers and for all cancer combined, with the exception of pancreatic cancer. The nationwide cancer statistics in this paper will provide essential data for cancer research and evidence-based health policy in Korea

Small-cell neuroendocrine carcinoma of the breast

A small-cell carcinoma is one of the histologic subtypes of primary neuroendocrine carcinomas of the breast. A small-cell carcinoma is a rare entity of the breast and exhibits similar morphologic features as neuroendocrine tumors of the gastrointestinal tract and lung. We present the imaging and pathologic findings of a primary small-cell neuroendocrine carcinoma of the breast. This is the first report of a primary small-cell carcinoma arising from the breast in Korea

Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration.

Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of Id2, or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration

Abdominal Ultrasonography Findings in Patients with Spinal Cord Injury in Korea

This is a retrospective study of 500 patients with spinal cord injury who underwent abdominal ultrasonography as a routine screening test from 2000 to 2003. We analyzed the results according to the different abdominal organ systems. Among the 500 cases, 226 (45.2%) showed abnormal findings. 98 cases of abnormal findings in the liver included 75 of fatty liver and 13 of mass. The 88 cases of abnormal findings in the bladder included 56 of bladder wall thickening, 14 of cystitis and 10 of urinary stone. The 35 cases of abnormal findings in the kidney included 19 of renal cyst and 6 of pelvic dilatation. The 35 cases with gallbladder abnormalities included 19 with gallstones and 11 with biliary sludge. Excluding the cases with bladder wall thickening, there were still 170 cases with abnormal ultrasonographic findings. Abdominal sonography seems to be a useful tool in detecting hidden intraabdominal pathologies in patients with spinal cord injury

Quercetin, the active phenolic component in kiwifruit, prevents hydrogen peroxide-induced inhibition of gap-junction intercellular communication

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2-Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2-Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJI

17β-Estradiol strongly inhibits azoxymethane/dextran sulfate sodium-induced colorectal cancer development in Nrf2 knockout male mice

© 2020 The Author(s)Nuclear factor erythroid 2-related factor 2 (Nrf2) has dual effects on inflammation and cancer progression depending on the microenvironment. Estrogens have a protective effect on colorectal cancer (CRC) development. The aim of this study was to investigate CRC development in Nrf2 knockout (KO) mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO male mice were sacrificed at weeks 2 and 16 after AOM injection with/without 17β-estradiol (E2) treatment during week 1. Disease activity index and colon tissue damage at week 2 showed strong attenuation following E2 administration in WT mice but to a lesser extent in Nrf2 KO male mice. At week 16, E2 significantly diminished AOM/DSS-induced adenoma/cancer incidence at distal colon in the Nrf2 KO group, but not in the WT. Furthermore, mRNA or protein levels of NF-κB-related mediators (i.e., iNOS, TNF-α, and IL-1β) and Nrf2-related antioxidants (i.e., NQO1 and HO-1) were significantly lower in the Nrf2 KO group regardless of E2 treatment compared to the WT. The expression of estrogen receptor beta (ERβ) was higher in the Nrf2 KO group than in the WT. In conclusion, estrogen further inhibits CRC by upregulating ERβ-related alternate pathways in the absence of Nrf2.

Successful management of heterotopic cornual pregnancy with laparoscopic cornual resection

AbstractObjectiveTo examine the feasibility of laparoscopic cornual resection for the treatment of heterotopic cornual pregnancy.Study designWomen who underwent laparoscopic cornual resection for heterotopic cornual pregnancy at our hospital between January 2003 and March 2015 were retrospectively analyzed. We evaluated significant parameters such as operative complications and postoperative pregnancy outcomes of concomitant pregnancy.ResultsThirteen patients with heterotopic cornual pregnancy were included in the study. All were pregnant through assisted reproductive technology, and the diagnosis was made at a median of 6+6 weeks (range 5+4–10+0). They were successfully treated with laparoscopic cornual resection and admitted for a median of 4 days (range, 2–7) postoperatively. The median operative time was 65min (range, 35–145min) and estimated blood loss was 200mL (range, 10–3000mL). There was a spontaneous abortion at 7+6 gestational weeks in a patient who received bilateral cornual resection. Seven patients delivered babies at term and 3 at preterm. All 10 women delivered without any maternal or neonatal complications. Two were lost to follow-up.ConclusionsLaparoscopic cornual resection is a feasible primary approach for the management of heterotopic cornual pregnancy