Calcium/calmodulin protein kinase (CaMK)-dependent nitric oxide (NO) and the downstream intracellular messenger cGMP, which is activated by soluble guanylate cyclase (sGC), are believed to induce long-term changes in efficacy of synapses through the activation of protein kinase G (PKG). The aim of this study was to examine the involvement of the CaMKII-dependent NO/sGC/PKG pathway in a novel form of repetitive stimulation-induced spinal reflex potentiation (SRP). A single-pulse test stimulation (TS; 1/30 Hz) on the afferent nerve evoked a single action potential, while repetitive stimulation (RS; 1 Hz) induced a long-lasting SRP that was abolished by a selective Ca 2ϩ /CaMKII inhibitor, autocamtide 2-related inhibitory peptide (AIP). Such an inhibitory effect was reversed by a relative excess of nitric oxide synthase (NOS) substrate, L-arginine. In addition, the RS-induced SRP was abolished by pretreatment with the NOS inhibitor, N G -nitro-L-arginine-methyl ester (L-NAME). The sGC activator, protoporphyrin IX (PPIX), reversed the blocking effect caused by L-NAME. On the other hand, a sGC blocker, 1H-[1, 2, 4]oxadiazolo[4, 3-␣]quinoxalin-1-one (ODQ), abolished the RS-induced SRP. Intrathecal applications of the membrane-permeable cGMP analog, 8-bromoguanosine 3Ј,5Ј-cyclic monophosphate sodium salt monohydrate (8-Br-cGMP), reversed the blocking effect on the RS-induced SRP elicited by the ODQ. Our findings suggest that a CaMKII-dependent NO/sGC/PKG pathway is involved in the RSinduced SRP, which has pathological relevance to hyperalgesia and allodynia.spinal reflex potentiation; soluble guanylate cyclase; cyclic monophosphate sodium salt monohydrate; spinal cord; windup ACTIVITY-DEPENDENT REFLEX plasticity, the dynamic regulation of reflex strength by ongoing neural activities, is a fundamental component of normal CNS functions. Long-term potentiation (LTP), a form of well-known activity-dependent reflex potentiation in synaptic responses that occurs in the CA1 area of the hippocampus, is considered the base for some forms of learning and memory (45). In the hippocampal CA1 region, LTP is induced by brief tetanic stimulation of afferent glutamatergic fibers and is typically dependent on activation of postsynaptic N-methyl-D-aspartate (NMDA) receptors (3).A key-initiating event in LTP induction is the activation of Ca 2ϩ /calmodulin protein kinase II (CaMKII) (14, 44, 30; 54). An increase in the intracellular Ca 2ϩ concentration, partly by the influx through NMDA receptor channels, activates calmodulin, which in turn triggers the activation of CaMKII, causing it to bind to the postsynaptic density. It is a well-known fact that nitric oxide (NO) stimulates soluble guanylyl cyclase, and, in turn, produces intracellular cGMP and subsequently activates the protein kinase G (PKG) to induced activity-dependent reflex potentiation (53). Brenman and Bredt (6) reported that NO can be activated by CaMKII. Several investigators revealed that NO plays a role in LTP as indicated by experiments showing that LTP is eliminated or...

Context. Stroke is the second leading cause of death and the primary cause of disability worldwide. It is uncertain what care patients with stroke receive in their end of life and what trends in care are in recent years. Objectives. The objective of this study was to investigate the changes in the use of intensive and supportive procedures for Taiwanese patients with stroke in their last month of life during 2000e2010. Methods. Analysis of claims data of 55,930 patients with stroke obtained from the National Health Insurance Research Database was performed to investigate the changes in the use of intensive and supportive procedures for Taiwanese patients with stroke in their last month of life during 2000e2010. Results. Over the whole study period, 25.4% of patients with stroke were admitted to intensive care units in their last month of life. The percentages of patients receiving mechanical ventilation (77.4%e67.9%), cardiopulmonary resuscitation (53.8%e35.8%), and inotropic agents (73.5%e64.3%) decreased over time. The percentages of patients receiving artificial hydration and nutrition (65.9%e73.3%) and sedative or analgesic agents (34.7%e38.6%) increased over time. Patients under 85 years old were more likely to be admitted to intensive care units. Men were more likely to receive mechanical ventilation and cardiopulmonary resuscitation than women. Conclusion. Over time, the use of supportive procedures increased, and the use of intensive procedures decreased in patients with stroke in the last month of life. This study highlights a need for research, guidelines, and training in how to provide palliative care for end-stage patients with stroke.

Five classrooms in a Primary School in Xuanwu District of Beijing were chosen for investigation of indoor air quality. In the autumn measurement period and in the winter measurement period, various dust particle fractions (PM10 and PM2.5) were monitored indoors and outdoors continuously by portable monitors and samplers. Applying statistical software, the impact of different parameters on particulate matter (PM10 and PM2.5) mass concentration was then quantitatively analyzed. The main conclusions were included as follows: (1) Exposure to PM10 and PM2.5 in the indoor air of classrooms in autumn and in winter was high, especially that of PM2.5 in autumn. (2) The indoor PM10 and PM2.5 mass concentrations were related to different parameters including relative humidity, temperature, carbon dioxide, area of opened windows or louver windows, number of students and room volume/student and so on. (3) No marked differences in indoor PM10 and PM2.5 mass concentrations were observed between autumn and winter (p>0.05). However, a statistically significant influence of class level on the indoor PM10 and PM2.5 mass concentrations was apparent in both measurement periods (p<0.05).

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