Modules in the brain stem and spinal cord underlying motor behaviors

Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous system (CNS). However, which CNS regions are responsible for expressing muscle synergies remains an open question. We address whether the brain stem and spinal cord are involved in expressing muscle synergies used for executing a range of natural movements. We analyzed the electromyographic (EMG) data recorded from frog leg muscles before and after transection at different levels of the neuraxis-rostral midbrain (brain stem preparations), rostral medulla (medullary preparations), and the spinal-medullary junction (spinal preparations). Brain stem frogs could jump, swim, kick, and step, while medullary frogs could perform only a partial repertoire of movements. In spinal frogs, cutaneous reflexes could be elicited. Systematic EMG analysis found two different synergy types: 1) synergies shared between pre- and posttransection states and 2) synergies specific to individual states. Almost all synergies found in natural movements persisted after transection at rostral midbrain or medulla but not at the spinal-medullary junction for swim and step. Some pretransection- and posttransection-specific synergies for a certain behavior appeared as shared synergies for other motor behaviors of the same animal. These results suggest that the medulla and spinal cord are sufficient for the expression of most muscle synergies in frog behaviors. Overall, this study provides further evidence supporting the idea that motor behaviors may be constructed by muscle synergies organized within the brain stem and spinal cord and activated by descending commands from supraspinal areas.     

Antinociceptive Effect of Cyperi rhizoma and Corydalis tuber Extracts on Neuropathic Pain in Rats

In this study, we examined the antinociceptive effect of Cyperi rhizoma (CR) and Corydalis tuber (CT) extracts using a chronic constriction injury-induced neuropathic pain rat model. After the ligation of sciatic nerve, neuropathic pain behavior such as mechanical allodynia and thermal hyperalgesia were rapidly induced and maintained for 1 month. Repeated treatment of CR or CT (per oral, 10 or 30 mg/kg, twice a day) was performed either in induction (day 0~5) or maintenance (day 14~19) period of neuropathic pain state. Treatment of CR or CT at doses of 30 mg/kg in the induction and maintenance periods significantly decreased the nerve injury-induced mechanical allodynia. In addition, CR and CT at doses of 10 or 30 mg/kg alleviated thermal heat hyperalgesia when they were treated in the maintenance period. Finally, CR or CT (30 mg/kg) treated during the induction period remarkably reduced the nerve injury-induced phosphorylation of NMDA receptor NR1 subunit (pNR1) in the spinal dorsal horn. Results of this study suggest that extracts from CR and CT may be useful to alleviate neuropathic pain.     

Autophagy regulates embryonic survival during delayed implantation

Delayed implantation, considered a state of suspended animation, is widespread in mammals. Blastocysts under this condition remain dormant for an extended period but resume implantation competence upon favorable conditions. The underlying mechanism by which extended longevity of dormant blastocysts is maintained is not clearly understood. Using autophagy markers and the well-defined delayed implantation model in mice, we show that autophagy is important for the extended longevity of dormant blastocysts in utero during delayed implantation. However, prolonged dormancy leads to reduced developmental competency of blastocysts and cellular damage with compromised pregnancy outcome. Estrogen supplementation, which activates implantation of dormant blastocysts, induces the formation of multivesicular bodies in the trophectoderm in vivo. Collectively, our results suggest that autophagy is a critical cellular mechanism that is utilized for the prolonged survival of dormant blastocysts.     

Paramedics as decision makers on the activation of the catheterization laboratory in the presence of acute ST-elevation myocardial infarction

Materials and Methods

To minimize delays in time to reperfusion in an urban-suburban North Carolina County, Guilford County Emergency Medical Services (EMS) and Moses Cone Hospital, Greensboro, NC, have collaborated to use the acquisition of 12-lead electrocardiographs and their paramedic interpretation to initiate the catheterization laboratory team and cardiologist; independent of over read by a physician. The study population of 91 patients was divided into the catheterization laboratory activation by EMS and catheterization laboratory activation by the emergency department physician (ED-MD) groups, and also by EMS and self-transported groups.

Results

The EMS group had shorter median time intervals from hospital door to percutaneous coronary intervention (PCI) with balloon inflation than those patients who self-transported to the hospital. Also, patients who were treated during the EMS activation of the catheterization laboratory phase had shorter median hospital door to PCI times than those who were treated during ED-MD activation of the catheterization laboratory.

Conclusion

The time from hospital arrival to PCI with balloon inflation was significantly shorter during the period in which EMS activated the catheterization laboratory than during the period the laboratory was activated by hospital staff. Thus, paramedics with quality electrocardiogram interpretation training and education can identify patients with acute ST-elevation myocardial infarction and properly activate the catheterization laboratory.     

Adaptation of aerobic respiration to low O2 environments

Aerobic respiration in bacteria, Archaea, and mitochondria is performed by oxygen reductase members of the heme-copper oxidoreductase superfamily. These enzymes are redox-driven proton pumps which conserve part of the free energy released from oxygen reduction to generate a proton motive force. The oxygen reductases can be divided into three main families based on evolutionary and structural analyses (A-, B- and C-families), with the B- and C-families evolving after the A-family. The A-family utilizes two proton input channels to transfer protons for pumping and chemistry, whereas the B- and C-families require only one. Generally, the B- and C-families also have higher apparent oxygen affinities than the A-family. Here we use whole cell proton pumping measurements to demonstrate differential proton pumping efficiencies between representatives of the A-, B-, and C-oxygen reductase families. The A-family has a coupling stoichiometry of 1 H⁺/e^-, whereas the B- and C-families have coupling stoichiometries of 0.5 H⁺/e^-. The differential proton pumping stoichiometries, along with differences in the structures of the proton-conducting channels, place critical constraints on models of the mechanism of proton pumping. Most significantly, it is proposed that the adaptation of aerobic respiration to low oxygen environments resulted in a concomitant reduction in energy conservation efficiency, with important physiological and ecological consequences.     

Prevalence of asymptomatic carotid stenosis in Korea based on health screening population

We attempted to investigate the prevalence and risk factors of carotid artery stenosis in Korea. Twenty thousand seven hundred twelve individuals who underwent carotid artery ultrasonography for health screening between March 2005 and March 2010 were retrospectively evaluated. The population was divided into four groups, according to the degree of stenosis, as Group A, below 29%; Group B, 30% to 49%; Group C, 50% to 74%; Group D, above 75%. The medical records of the individuals were investigated, and Fisher's exact test, chi-square tests, Kruskal-Wallis tests and a binary logistic regression model were used for statistical analysis. The prevalence of carotid stenosis was Group B, 5.5%; Group C, 0.9%; Group D, 0.1%. Old age, male gender, hypertension, diabetes mellitus and ischemic heart disease were significantly higher in Groups C and D (P = 0.001, 0.001, 0.001, 0.048, and 0.001, respectively). Among the males aged over 65 yr, the prevalence of carotid stenosis ≥ 50% and ≥ 30% were 4.0% and 18.2%, respectively. Asymptomatic carotid stenosis is not uncommon in Korea. Carotid ultrasonography is necessary for people with above-listed risk factors.     

Prolonged use of aspirin alters human and rat intestinal cells and thereby limits the absorption of clopidogrel

Clopidogrel therapy to prevent atherothrombosis faces the challenge of reduced responsiveness. The absorption of clopidogrel is regulated by multidrug-resistance protein 1 (MDR1) in the intestinal epithelium. Given that aspirin induces MDR1 in cancer cells and peripheral blood cells, it may induce MDR1 in intestinal epithelial cells as well, thereby affecting the absorption of clopidogrel. In this study, aspirin treatment induced the expression of MDR1 in human epithelial colorectal (Caco-2) cells in vitro and in rat intestine in vivo, as evidenced by dose-dependent increases in gene, protein, and efflux function. Along with the upregulation of MDR1 proteins by aspirin, clopidogrel absorption was significantly decreased in the aspirin-treated Caco-2 cells and in rat intestine. Our data provide evidence that prolonged use of aspirin may reduce the intestinal absorption of clopidogrel. Further human studies would be necessary to clarify whether these data have any relevance to prevention of stroke or myocardial infarction.     

Neuronal activity regulates the regional vulnerability to amyloid-β deposition

Amyloid-β (Aβ) plaque deposition in specific brain regions is a pathological hallmark of Alzheimer's disease. However, the mechanism underlying the regional vulnerability to Aβ deposition in Alzheimer's disease is unknown. Herein, we provide evidence that endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF) Aβ, which drives local Aβ aggregation. Using in vivo microdialysis, we show that ISF Aβ concentrations in several brain regions of APP transgenic mice before plaque deposition were commensurate with the degree of subsequent plaque deposition and with the concentration of lactate, a marker of neuronal activity. Furthermore, unilateral vibrissal stimulation increased ISF Aβ, and unilateral vibrissal deprivation decreased ISF Aβ and lactate, in contralateral barrel cortex. Long-term unilateral vibrissal deprivation decreased amyloid plaque formation and growth. Our results suggest a mechanism to account for the vulnerability of specific brain regions to Aβ deposition in Alzheimer's disease.