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The prognostic assessment of an ICU patient involves assessing the severity of their condition, interventions, and length of ICU stay. Over the past 30 years, researchers have proposed numerous predictive models and severity assessment scales for ICU patients in specific regions, including APACHE II and SAPS II. However, most existing methods rely heavily on curve fitting which do not account for misclassifications caused by false negatives and positives. Specificity and sensitivity must be provided as an indicator of model performance. The primary aim in this study is to develop a machine-learning model to formulate a prognosis for MICU and SICU patients by using data from the MIMIC-IV for training. The predictive models developed in this study facilitate the prediction of mortality and other outcomes across various treatment regimens.

Background: Surrogates often do not accurately predict older people's preferences about end-of-life (EOL) care. Few studies have examined the impact of advance care planning (ACP) on EOL decision-making consistency between older people and their surrogates, and these studies have yielded conflicting results. Objectives: To evaluate the effectiveness of ACP in improving EOL decision-making consistency between older people and their surrogates. Design: The intervention in this pre-post quasi-experimental design included an informative video, a brochure about ACP, and a guided discussion about EOL wishes. Setting: Two geriatric wards in a medical center in northern Taiwan. Subjects: One hundred eight participants, as 54 pairs of older people and their surrogates, were randomly assigned to either the experimental or control group. The experimental group received an intervention, while the control group received usual care. Measurements: Life-Support Preferences Questionnaire. Results: The intervention did not improve decision-making consistency between older people and their surrogates. This was the first time that most pairs discussed specific EOL decisions, so additional preparation may improve comfort with this topic. This study also found that some older people had difficulty concentrating on the educational brochure or understanding the related terms. Conclusions: Preparation for ACP discussion is needed for older people and their surrogates. Longer-term effects of ACP should be monitored because ACP interventions may have enhanced empathy between older people and their surrogates. Additionally, a culturally sensitive illustrated questionnaire that explains life-support preferences and ACP topics may improve communication between older people and their surrogates.

Importance: Due to the evolving variants of coronavirus disease 2019 (COVID-19), it is important to understand the relationship between the disease condition and socioeconomic, demographic, and health indicators across regions. Background: Studies examining the relationships between infectious disease and socioeconomic variables are not yet well established. Design: A total of 3042 counties in the United States are included as the observation unit in the study. Two outcome variables employed in the study are the control of disease spread and infection prevalence rates in each county. Method: Data are submitted to quantile regression, hierarchical regression, and random forest analyses to understand the extent to which health outcomes are affected by demographics, socioeconomics, and health indicators. Results: Counties with better control of the disease spread tend to have lower infection rates, and vice versa. When measuring different outcome variables, the common risk factors for COVID-19 with a 5% level of statistical significance include employment ratio, female labor ratio, young population ratio, and residents’ average health risk factors, while protective factors include land size, housing value, travel time to work, female population ratio, and ratio of residents who identify themselves as mixed race. Conclusions: The implications of the findings are that the ability to maintain social distancing and personal hygiene habits are crucial in deterring disease transmission and lowering incidence rates, especially in the early stage of disease formation. Relevant authorities should identify preventive factors and take early actions to fight infectious diseases in the future.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

In this article, a performance evaluation of the Chinese Professional Baseball League (CPBL) was conducted from a human resources (HR) perspective. Two important aspects were included: (1) a comprehensive evaluation of the competition performance of the professional baseball teams in international games and regular season games; and (2) the data envelopment analysis (DEA) and “two-stage” methodologies, which were employed to process truncated data to resolve the factors that affect the efficiency of the decision-making unit (DMU). By applying DEA and truncated regression analysis with bootstrapping, the performances of CPBL teams in games of different intensities were investigated. The number of foreign coaches and native players both were the key factors to affect the competitive efficiency of CPBL teams, and the Uni President 7-ELEVEN Lions had the best performance efficiency team. This interdisciplinary investigation provided the most appropriate references and recommendations for professional baseball teams on HR management so that baseball fans' expectations are met.

This study provides a systematic analysis of sports promotion efficiency in 22 administrative districts in Taiwan from 2011 to 2018. We first considered sports behavior and sports information promotion and connected the multiple intermediate products using network DEA, used the public performance and outputs to measure the total efficiency of sports promotion in the 22 administrative districts, and then established the final input–output indicators. The long-term tracking of sports promotion efficiency shows that, while Taipei and Taoyuan experienced upward trends, the other 20 administrative districts saw declining trends. We also used truncated regression to identify 14 environmental variables that affected the efficiency of sports promotion in the 22 administrative districts from 2016 to 2018, with the results showing that funding, satisfaction with life, and average BMI in each administrative district were significant factors, revealing the latest trends in and measurements of governance in terms of government accessibility.

The prevalence of metabolic syndrome and its components continue to increase among patients with serious mental illness. This cross-sectional study investigated whether metabolic syndrome prevalence and risk factors differ between male and female patients with serious mental illness. In total, 260 eligible patients were recruited from two hospitals. The data on demographic characteristics, lifestyle behaviour factors, biochemistry, and anthropometry were collected. Analyses were performed using multivariate logistic regression. Metabolic syndrome prevalence was 40.8% (35.1% in men and 46.8% in women). Among patients aged 40-49 years, metabolic syndrome prevalence was higher in men; however, the trend was reversed among patients aged 50 years or older. Notably, gender-specific metabolic syndrome risk factors were observed. In men, they included low education level, high body mass index (BMI), prolonged illness, comorbid physical illness, and diagnosis of bipolar disorder, whereas they included being married, old age, and high BMI in women. Our findings suggest that mental health professionals should consider the gender- and age-based metabolic syndrome prevalence trend in patients with serious mental illness when designing interventions for the study population to minimize metabolic syndrome prevalence.

Summary Aim The aim of the study was to develop and validate an instrument to evaluate nurses' knowledge and to understand the obstacles that they encounter when administering resuscitation medications. Background Insufficient knowledge is a major factor in nurses' drug administration errors. Resuscitation involves situations in which doctors issue oral orders, and is inherently highly stressful. Sufficient knowledge is vital for nurses if they are to respond quickly and accurately when administering resuscitation medications. Methods A cross-sectional study was conducted. A questionnaire (20 true-false questions) developed from literature and expert input, and validated by subject experts and one pilot study, was used to evaluate nurses' knowledge of resuscitation medications. Stratified sampling and descriptive statistics were applied. Results A total of 188 nurses participated. The overall correct answer rate was 70.5% and the greater the nurse's work experience the higher the score. Only 8% of nurses considered themselves to have sufficient knowledge and 73.9% hoped to gain more training about resuscitation medications. The leading obstacle reported was “interruption of the drug administration procedure on resuscitation” (62.8%). Seventeen out of 20 questions achieved a discriminatory power of over 0.36, indicating good to excellent questions. In the study, a total of 16 resuscitation medication errors were reported by the participants, in which the errors involved atropine (five cases), epinephrine (three cases) and others (eight cases). The errors mainly involved misinterpretation of orders, insufficient knowledge and confusing certain drugs for other look-alike drugs. Conclusion Evidence-based results strongly suggest that nurses have insufficient knowledge and could benefit from longer working experience and additional training about resuscitation medications. Further research to validate the instrument is needed and the education of nurses regarding resuscitation medications is recommended.

Background/Aims Antispasmodics including otilonium bromide (OB) are recommended to treat irritable bowel syndrome (IBS). However, reports about OB experience in Asia is sparse. The purpose of present study was to provide the efficacy of OB in treating Asian IBS patients. Methods Overall, 117 IBS patients meeting Rome II criteria were enrolled in an 8-week, double-blind, active-controlled and single center trial. Randomized participants received either OB 40 mg or mebeverine 100 mg 3 doses daily. The primary endpoints were to evaluate the net changes of abdominal pain/discomfort frequency score (APDFS) and safety profile, while the secondary endpoints were to assess the changes in abdominal pain/discomfort intensity, flatulence, abdominal bloating, satisfied stool frequency etc. Results Finally, 49 OB and 52 mebeverine subjects were eligible for efficacy analysis. Compared to baselines in per protocol populations, the reduced APDFSs in OB and mebeverine were 0.55 ± 1.20 (P = 0.011) and 0.37 ± 1.11 (P = 0.042), respectively, to show similarly reduced scores. The most reported side effects included dry mouth, nausea and dizziness. Besides, the improved APDFSs at 4th week visit, final alleviations in abdominal pain intensity, flatulence, abdominal bloating and satisfied stool frequency with global assessments filled by both patients and investigators were significantly achieved by both treatments, and OB was not inferior to mebeverine in treating these parameters. Conclusions In Orientals, OB is as effective as mebeverine for alleviating IBS symptoms in terms of abdominal pain, flatulence, abdominal bloating etc. However, obvious side effects are also observed. A large-scaled trial and post-marketing surveillance are recommended to confirm its efficacy and safety.

Flavonoids are natural phenolic substances widely found in fruit, vegetables, grains, and wine. Most of these compounds exert health-promoting effects seem to attribute to their antioxidant activity. Metallothioneins (MT) has been suggested to protect against acute heavy metal toxicity in the liver, and the proteins of MT can be induced by various stimuli including antioxidant. Measuring the induction of MT genes may provide an efficient approach to understand the chemopreventive mechanisms of flavonoids. The antioxidant activity of eight flavonoids was determined by TEAC and ORAC assays and their effects on MT protein were also measured. HepG2 cells were employed to explore the mechanisms underlying flavonoid-induced MT induction. Statistical analysis revealed a positive correlation between the antioxidant activity of flavonoids and MT expression. Quercetin-induced MT expression may function by activating the phosphorylation of JNK, p38 and PI3K/Akt as well as by enhancing Nrf2 DNA-binding activity. Moreover, quercetin exhibited a potential protective effect on t-BHP-caused injury in hepatocytes through the induction of MT. These results suggest that quercetin is a natural antioxidant in the diet and the consumption of foods that are rich in quercetin could be beneficial for the prevention of environmental oxidant-induced liver damage.

Background: Critical thinking is essential in nursing practice. Promoting critical thinking competence in clinical nurses is an important way to improve problem solving and decision-making competence to further improve the quality of patient care. However, using an adequate tool to test nurses' critical thinking competence and disposition may provide the reference criteria for clinical nurse characterization, training planning, and resource allocation for human resource management. Purpose: The purpose of this study was to measure the critical thinking competence and critical thinking disposition of clinical nurses as well as to explore the related factors of critical thinking competence. Methods: Clinical nurses from four different clinical ladders selected from one medical center were stratified randomly. All qualified subjects who submitted valid questionnaires were included in the study. A Taiwan version of the modified Watson-Glaser Critical Thinking Appraisal and Critical Thinking Disposition Inventory was developed to measure the critical thinking competence and critical thinking disposition of clinical nurses. Validity was evaluated using the professional content test (content validity index=.93). Reliability was assessed with a Cronbach's alpha coefficient of .85. Data were analyzed using the SPSS for Windows (Version 12.0; SPSS Inc., Chicago, IL). Results: Results showed that competence of interpretation was the highest critical thinking competence factor. Inference was the lowest, and reflective thinking as a critical thinking disposition was more positive. In addition, age, years of nursing experience, and experiences in other hospitals significantly influenced critical thinking competence (p＜.05). Factors of age, years of experience, and nurses clinical ladder were shown to affect critical thinking disposition scores. Clinical ladder N4 nurses had the highest scores in both competence and disposition. A significant relationship was found between critical thinking competence and disposition scores, with 29.3% of the variance in critical thinking competence potentially explained by total years of nurse hospital experience. Clinical ladder and age were predictive factors for critical thinking disposition. Commonality was 27.9%. Conclusions and Implications for Practice: Nursing experience and clinical ladders positively affect critical thinking competence and disposition. Issues of critical thinking competence increasingly need to be measured. Therefore, appropriate tools for nursing professions should be further developed and explored for specific areas of practice.

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 Ca2+/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, NG-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-α]quinoxalin-1-one (ODQ), abolished the RS-induced SRP. Intrathecal applications of the membrane-permeable cGMP analog, 8-bromoguanosine 3′,5′-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 RS-induced SRP, which has pathological relevance to hyperalgesia and allodynia.

This study was conducted to investigate whether dorsolateral pontine tegmentum stimulation modulates spinal reflex potentiation (SRP) and whether serotonergic neurotransmission is involved in such a modulation. Reflex activities of the external urethra sphincter (EUS) electromyogram in response to a test stimulation (TS; 1/30 Hz) or repetitive stimulation (RS; 1 Hz) on the pelvic afferent nerve in 35 anesthetized rats were recorded with/without synchronized train pontine stimulation (PS; 300 Hz, 30 ms) and/or intrathecal administrations of 10 microl of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (NBQX; 100 microM), d-2-amino-5-phosphonovalerate (APV; 100 microM), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY 100635; 100 microM), and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT; 100 microM). The TS evoked a single action potential (1.00 +/- 0.00 spikes/stimulation), while the RS produced a long-lasting SRP (16.12 +/- 1.59 spikes/stimulation) that was abolished by APV (1.57 +/- 0.29 spikes/stimulation) and was attenuated by NBQX (7.42 +/- 0.57 spikes/stimulation). Synchronized train PS with RS (PS+RS) produced facilitation in RS-induced SRP (25.17 +/- 2.21 spikes/stimulation). Intrathecal WAY 100635 abolished the facilitation in SRP as a result of the synchronized PS (14.66 +/- 1.58 spikes/stimulation). On the other hand, intrathecal 8-OH-DPAT elicited facilitation in the RS-induced SRP (25.16 +/- 1.05 spikes/stimulation) without synchronized PS. Our findings suggest that dorsolateral pontine tegmentum may modulate N-methyl-d-aspartic acid-dependent SRP via descending serotonergic neurotransmission. This descending modulation may have physiological/pharmacological relevance in the neural controls of urethral closure.

The purposes of this study were to investigate whether the pelvic nerve-to-external urethra sphincter (EUS) reflex potentiation can be induced under physiological conditions and to determine whether glutamatergic neurotransmission is involved in the reflex potentiation. Stimulation-evoked reflex activities, during rhythmic bladder contractions caused by a continuous saline infusion, in 21 anesthetized rats were recorded with/without the intrathecal administration of 10 microl of CNQX (a glutamatergic AMPA receptor antagonist; 100 microM) and APV( a glutamatergic NMDA receptor antagonist; 100 microM). Reflex activities became potentiated following the increment of intravesical pressure (IVP) during the storage phase (2.39 +/- 0.28 spikes/mmHg, n = 21) and the ascending period of the voiding phase (1.46 +/- 0.35 spikes/mmHg, n = 21) and decreased following the decrement of IVP during the descending period of the voiding phase (1.50 +/- 0.33 spikes/mmHg, n = 21). Although it is characterized by a low IVP, a postvoiding reflex potentiation in stimulation-evoked activities was elicited at the critical period after a voiding contraction had just finished (23.95 +/- 8.96 spikes/mmHg, n = 21). The slope of the regression line of evoked activities vs. the IVP during the storage phase was significantly (P0.01) higher than that of the ascending and descending periods of the voiding phase, but there was no statistical difference between the ascending and the descending periods (P0.05). In addition, the slope of the regression line of posttetanic reflex potentiation was significantly higher than that of the storage phase (P0.01). All the slopes of the regression lines decreased after intrathecal CNQX administration (from 3.15 +/- 0.44, 2.10 +/- 0.57, 2.13 +/- 0.53, and 21.30 +/- 3.41 to 0.83 +/- 0.31, 0.74 +/- 0.12, 0.76 +/- 0.12, and 4.31 +/- 3.71 spikes/mmHg in storage, ascending and descending period of the voiding phase, and postvoiding potentiation, respectively; all P0.01, n = 10). The slopes of the regression lines became almost horizontal after intrathecal APV administration (from 3.15 +/- 0.44, 2.10 +/- 0.57, 2.13 +/- 0.53, and 21.30 +/- 3.41 to 0.16 +/- 0.12, 0.21 +/- 0.07, 0.18 +/- 0.05, and 0.23 +/- 0.76 spikes/mmHg in storage, ascending and descending period of voiding phase, and postvoiding potentiation, respectively; all P0.01, n = 10). Our results suggest that a potentiation in the pelvic nerve-to-EUS reflex can be induced under physiological conditions and the glutamatergic mechanism appears to be involved in this reflex potentiation.

The purpose of this study was to develop kinds of multi-walled carbon nanotubes (MWCNT)-based materials, which could replace current autografts for neuron regeneration. The alternative MWCNT films was developed by encapsulated chitosan. To evaluate the characteristics of MWCNT films after modification, the measurements of electrical conductivity, contact angle and the degree of degradation were carried out. Two kinds of chitosan film preparation were designed, one was the dish film and the other was microscope slide film. The microscope slide film was exterior, however, the dish film was wrinkling. Comparing the thickness by micrometer caliper, the thickness of the dish film was 0.1950 to 0.0425 mm, and the microscope slide film was 0.0584 to 0.0109 mm. This result indicated the microscope slide film was more suitable for the following experiment because of less error value. The contact angle of the chitosan film was measured between 60~90 deg, it indicated the film was more hydrophobic. In order to achieve better biocompatibility, adding MWCNT significantly increased hydrophilicity of chitosan film.

Purpose: To clarify the contributions of sensory inputs and glutamate transmissions to the spinal micturition reflex. Materials and Methods: Cystometrogram and external urethral sphincter electromyogram activities evaluated the L6 and/or S1 levels. Results: Changes in intravesicular pressure (IVP) in response to saline infusion (0.1 ml/min) were found after unilateral dorsal root rhizotomy at the L6 level, which showed significant increases in threshold pressure (rhizotomized vs. control: 14.25 ± 0.82 vs. 8.40 ± 0.69 cmH2O, P

Purpose To clarify the contributions of parasympathetic inputs and outputs to the micturition reflex. Materials and Methods Intra-vesical pressure (IVP), external urethral sphincter electromyogram (EMG), pelvic afferent nerve activities (PANA), and pelvic efferent nerve activities (PENA) as well as the time-derived IVP (dIVP, an index of bladder contractility) were evaluated in intact and acute dorsal or ventral root(s) rhizotomized (DRX and VRX, respectively) rats. Results In DRX rats, when compared with that in intact stage, the voiding frequency was decreased (75 ± 15% of intact, P

We showed previously that lipopolysaccharide (LPS) induces noncholinergic airway hyperreactivity to capsaicin via an upregulation of tachykinin synthesis. This study was designed to test whether double-stranded preprotachykinin (ds PPT) RNA, RNA interference (RNAi), prevents the LPS-induced alterations. First, cultured primary nodose ganglial cells of newborn Brown-Norway rats were divided into four groups: control; LPS; LPS+RNAi; and LPS+RNAi+liposome. Second, young Brown-Norway rats for the in vivo study were divided into three groups (control; LPS; and LPS+RNAi), and ds PPT RNA was microinjected bilaterally into the nodose ganglia in the LPS+RNAi group. Then, ganglial cells were collected from the culture whereas the nodose ganglia and lungs were sampled from the animals, and PPT mRNA and substance P (SP) levels were analyzed. Also, airway reactivity to capsaicin was performed in vivo. LPS induced significant increases in PPT mRNA and SP levels in vitro and in vivo and an increase in airway reactivity to capsaicin in vivo. However, ds PPT RNA, but not scrambled RNA, prevented all LPS-induced alterations. The effect of ds PPT RNA was not enhanced by liposome in vitro. Therefore, we demonstrated that the local application of RNAi prevents effectively the activation of the noncholinergic system modulating the lungs/airways.

We explored the dysfunction of tachykinins on monocrotaline (MCT)-induced pulmonary hypertension by using double-stranded preprotachykinin (ds PPT) RNA and neurokinin receptor (NK) antagonists. Here, we showed the possibility to attenuate the PPT gene expression by ds RNA, RNA interference (RNAi), in fully developed tissue of rats. We designed four groups (control, MCT, RNAi + MCT, and solvent + MCT) of experiments in series 1 and seven groups (control, MCT, MCT + CP-96345-3.4, MCT + CP-96345-10, MCT + CP-96344-10, MCT + SR-48968, and MCT + SR-48965) of experiments in series 2. Rats in the control groups received saline injection. MCT-treated rats received a single MCT injection (60 mg/kg sc). One day prior to MCT, bilateral nodose ganglia were microinjected with ds PPT RNA in rats of the RNAi + MCT group or with solvent in the solvent + MCT group. Beginning from 1 day post-MCT, MCT-treated rats received a daily injection of the NK1 receptor antagonist, CP-96345 (3.4 or 10 mg/kg ip) or its inactive enantiomer CP-96344 (10 mg/kg ip). The NK2 receptor antagonist SR-48968 (3 mg/kg ip) or its inactive enantiomer SR-48965 (3 mg/kg ip) was injected to MCT-treated rats every other day starting 1 day post-MCT. Functional study was carried out 2 weeks (series 1) or 3 weeks (series 2) after MCT. MCT induced right ventricular hypertrophy, as well as increases in pulmonary arterial pressure, PPT mRNA (nodose ganglia and lung tissue), and lung tissue substance P level. All of the above MCT-induced alterations were attenuated by either RNAi or NK receptor antagonists. We conclude that tachykinins play an important role in MCT-induced pulmonary hypertension.

The purpose of this study was to investigate if PPARγplays a role in the melanogenesis. B16/F10 cells were divided into five groups: control, melanin stimulating hormone (α-MSH),α-MSH+retinol,α-MSH+GW9662 (PPARγantagonist), and GW9662. Cells in the control group were cultured in the Dulbecco’s modified Eagle’s medium (DMEM) for 48 hrs. To initiate the melanogenesis, cells in allα-MSH groups were cultured in medium containingα-MSH (10 nM) for 48 hrs. Cells were treated simultaneously with retinol (5 μM) in theα-MSH+retinol group. Instead of retinol, GW9662 (10 μM) was cocultured in theα-MSH+GW9662 group. Cells in the final group were cultured in the DMEM with GW9662. All the analyses were carried out 48 hours after treatments. Theα-MSH was able to increase cell number, melanin production, and the activity of tyrosinase, the limiting enzyme in melanogenesis. Theseα-MSH-induced changes were prevented either by retinol or by GW9662. Further analyses of the activities of antioxidant enzymes including glutathione, catalase, and the superoxide dismutase (SOD) showed thatα-MSH treatment raised the activity of SOD which was dependent on PPARγlevel. According to our results, theα-MSH-induced melanogenesis was PPARγdependent, which also modulated the expression of SOD.

In this article, a nanoporous chitosan polymer membrane was successfully produced and applied as microdialysis membrane forin vitrosampling of biomolecules. With the use of nanoparticle leaching technique, porogenic gelatin nanoparticles formed nanopores in the chitosan-based membrane to create a secure implantable nanoporous membrane for biomolecule sampling. The gelatin nanoparticles size was in the range of 45 to 70 nm, and the pore size of the chitosan membrane was around 40 to 100 nm. The porosity of membrane was found to be dependent on the mixing ratio of chitosan solution and gelatin nanoparticles solution. The results of diffusion study showed that we can alter the mixing ratio of porogen to achieve size-selective molecular diffusion, which means that the porosity and cut-off size of porous membrane can be controlled. The recoveries of the probe fabricated from the chitosan-based membrane were examined for four different model compounds of different molecular weights: 2-NBDG, substance P, TNF-α, and FITC-BSA. The microdialysis probes showed linear responses and substantial recovery to various concentrations of biomolecules. These results indicated that the microdialysis probe constructed by chitosan nanoporous membrane could sample and monitor the biomoleculesin vitroand has the potential for the applicationin vivo.

We attempted to evaluate whether the antioxidants 1,3-dimethyl-2-thiourea (DMTU) and hexa(sulfobutyl)fullerenes (FC 4 S) attenuate monocrotaline (MCT)-induced pulmonary hypertension (PH) by lowering lung substance P (SP) in Wistar rats. Sixty-three rats weighing 297 ± 8 g were divided into six groups: control; MCT; capsaicin + MCT; MCT + DMTU-1; MCT + DMTU-2; and MCT + FC 4 S. Three weeks before the functional study, saline was injected into each control rat, whereas each MCT rat received 60 mg/kg sc MCT. Rats in the third group received capsaicin pretreatment followed by MCT. A 3-day injection of DMTU was performed during the early (DMTU-1) or the late (DMTU-2) post-MCT period. For the last group, each MCT-treated rat received a daily FC 4 S injection until the commencement of the functional study. Compared to the control group, MCT caused significant increases in pulmonary arterial pressure (Ppa), right ventricular hypertropy, pulmonary arterial medial thickness, lung SP level, and luminol-enhanced chemiluminescence counts in bronchoalveolar lavage. Both capsaicin and antioxidants significantly attenuated the above MCT-induced alterations. SP-induced acute increase in Ppa was exaggerated in MCT-treated rats. These results suggest that oxygen radicals play an important role in MCT-induced PH via elevating lung SP level.

Taiwan's Department of Health (DOH) promotes a standardized 2-year training program to raise the competence of newly certified nurses in the realms of patient care, nursing professionalism and communication skills as well as to ensure professional nurse training program quality.This study evaluated training program participants' self-perception of nursing competency.We used a cross-sectional approach and structured questionnaire to evaluate the nursing competency of 128 nurse trainees at a medical center. Questionnaires were filled out independently by participants and thus reflect participant self-assessments of questionnaire items. Descriptive and correlation analyses further explored data.Results showed: mean scores were 3.80 ± .60 for clinical technique; 3.78 ± .67 for administrative skill; and 3.21 ± .88 for educational and research skills . Nursing ability correlated significantly with age, seniority, nursing grade, and courses taken. The relationship between participant total score and program completion ratio formed a "V"-shaped distribution.The DOH training program was has a positive effect on nursing competency in nurse trainees. Results also provide valuable information and suggestions for revising the DOH's nurse training program in the future.

Acute bacterial meningitis (ABM) is a serious disease with severe neurological sequelae. The intense calcium-mediated microglial activation and subsequently pro-inflammatory cytokine release plays an important role in eliciting ABM-related oxidative damage. Considering resveratrol possesses significant anti-inflammatory and anti-oxidative properties, the present study aims to determine whether resveratrol would exert beneficial effects on hippocampal neurons following ABM. ABM was induced by inoculating Klebsiella pneumoniae into adult rats intraventricularly. The time-of-flight secondary ion mass spectrometry (TOF-SIMS), Griffonia simplicifolia isolectin-B4 (GSA-IB4) and ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry, enzyme-linked immunosorbent assay as well as malondialdehyde (MDA) measurement were used to examine the calcium expression, microglial activation, pro-inflammatory cytokine level, and extent of oxidative stress, respectively. In ABM rats, strong calcium signaling associated with enhanced microglial activation was observed in hippocampus. Increased microglial expression was coincided with intense production of pro-inflammatory cytokines and oxidative damage. However, in rats receiving resveratrol after ABM, the calcium intensity, microglial activation, pro-inflammatory cytokine and MDA levels were all significantly decreased. Quantitative data showed that much more hippocampal neurons were survived in resveratrol-treated rats following ABM. As resveratrol successfully rescues hippocampal neurons from ABM by suppressing the calcium-mediated microglial activation, therapeutic use of resveratrol may act as a promising strategy to counteract the ABM-induced neurological damage.

The purpose of this study was to determine the effects of an extract from Moringa oleifera (MO) on the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) in Wistar rats. An ethanol extraction was performed on dried MO leaves, and HPLC analysis identified niaziridin and niazirin in the extract. PH was induced with a single subcutaneous injection of MCT (60 mg/kg) which resulted in increases in pulmonary arterial blood pressure (Ppa) and in thickening of the pulmonary arterial medial layer in the rats. Three weeks after induction, acute administration of the MO extract to the rats decreased Ppa in a dose-dependent manner that reached statistical significance at a dose of 4.5 mg of freeze-dried extract per kg body weight. The reduction in Ppa suggested that the extract directly relaxed the pulmonary arteries. To assay the effects of chronic administration of the MO extract on PH, control, MCT and MCT+MO groups were designated. Rats in the control group received a saline injection; the MCT and MCT+MO groups received MCT to induce PH. During the third week after MCT treatment, the MCT+MO group received daily i.p. injections of the MO extract (4.5 mg of freeze-dried extract/kg of body weight). Compared to the control group, the MCT group had higher Ppa and thicker medial layers in the pulmonary arteries. Chronic treatments with the MO extract reversed the MCT-induced changes. Additionally, the MCT group had a significant elevation in superoxide dismutase activity when normalized by the MO extract treatments. In conclusion, the MO extract successfully attenuated the development of PH via direct vasodilatation and a potential increase in antioxidant activity.

Perinatal hypoxia has been observed to cause more aggressive pulmonary hypertension in human. Several mediators such as reactive oxygen species (ROS) and substance P are believed to be crucial in the mechanism of inducing pulmonary hypertension. This study was designed to test whether substance P and ROS play a role in perinatal hypoxia-exaggerated, monocrotaline (MCT)-induced pulmonary hypertension. Normoxic Wistar rats (weighing 258 ±9 g, n = 31) were divided into two groups: control (n = 16) and MCT (n = 15). Perinatal hypoxia Wistar rats (weighing 260 ±19 g, n = 49) were divided into six groups: Hypoxia (n = 8), Hypoxia+MCT (n = 8), Hypoxia+capsaicin (CP)+MCT (n = 7), Hypoxia+MCT+1,3-dimethyl-2- thiourea (DMTU)E (n = 10), Hypoxia+MCT+DMTU(subscript L) (n = 9), and Hypoxia+MCT+ hexa(sulfobutyl) fullerenes (HSF) (n = 7). Rats in the control group received saline injections. MCT (60 mg/kg, s.c.) was given three weeks prior to the functional examination. Chronic capsaicin pretreatment was performed to deplete substance P. Hydroxyl radical scavenger DMTU (500 mg/kg) was intraperitoneally (i.p.) injected early (DMTU(subscript E)) or late (DMTU(subscript L)) after MCT. Antioxidant HSF (10 mg/kg, i.p.) was given once daily for three weeks following MCT. MCT treatment caused significant increases in pulmonary arterial pressure (Ppa) and substance P level in lung tissue in normoxic rats. The MCT-induced increase in pulmonary arterial blood pressure was exaggerated by perinatal hypoxia, but this exaggeration was attenuated by either capsaicin pretreatment or antioxidant administrations. These results suggest that both ROS and substance P are involved in perinatal hypoxia-augmented, MCT-induced pulmonary hypertension.

The purpose of this study was to investigate the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the development of the monocrotaline (MCT)- induced pulmonary hypertension. Rosiglitazone (TZD) was used to activate the PPARγin this study. Sixty-four Wistar rats (BW = 114.1 ±1.2 g) were divided into five groups: control, MCT, MCT+vehicle (VEH, 15% alcohol), MCT+TZD, and TZD. Rats in the control group received injection of 0.5 ml saline intraperitoneally. Pulmonary hypertension was induced by one bolus injection of MCT (60 mg/kg, sc). Two weeks after MCT treatment, rats were daily treated with either 0.5 ml of 15% alcohol in the MCT+VEH group or TZD (10 mg/kg, ip) in the MCT+TZD group. In the TZD group, the same doses of TZD were given in the saline-treated rats on the corresponding days of the MCT+TZD group. Pulmonary arterial blood pressures were measured on the 22nd day post MCT. Comparing to the control group, the MCT administration caused significant increases in the pulmonary arterial pressure as well as the weight ratio of right ventricle (RV) to the sum of left ventricle and septum (LV+S), and the thickness of the vessel walls, indicating the development of pulmonary hypertension. The TZD treatment significantly attenuated the severity of pulmonary hypertension. However, the endogenous antioxidant enzymes in lung tissues, including superoxide dismutase, glutathione and catalase, were in similar levels among all groups. Therefore, the PPARγattenuated pulmonary hypertension may not be related to the antioxidant pathway.

Selection of a qualified pitcher has relied previously on qualitative indices; here, both quantitative and qualitative indices including pitching statistics, defense, mental skills, experience, and managers' recognition were collected, and an analytic hierarchy process was used to rank baseball pitchers. The participants were 8 experts who ranked characteristics and statistics of 15 baseball pitchers who comprised the first round of potential representatives for the Chinese Taipei National Baseball team. The results indicated a selection rate that was 91% consistent with the official national team roster, as 11 pitchers with the highest scores who were recommended as optimal choices to be official members of the Chinese Taipei National Baseball team actually participated in the 2009 Baseball World Cup. An analytic hierarchy can aid in selection of qualified pitchers, depending on situational and practical needs; the method could be extended to other sports and team-selection situations.

The inadequate infrastructure makes healthcare resources unbalance between rural and city. The telemedicine might be a solution. Patient's information sharing is the prerequisite in telemedicine, and the medical image communication is another critical issue. DICOM is one of the most popular medical image standards. In rural clinics, the ultrasonography is well seen for its non-radical, but usually is early models, which is not DICOM compatible. This situation obstructs the sharing of ultrasonography, and prevents the implement of telemedicine. This research developed a telemedicine counselling structure, which integrated the ultrasonography into modern DICOM system.

Recently, we demonstrated a chronic neurosteroid-dependent inhibition of activity-dependent spinal reflex potentiation (SRP), but it remains unclear whether neurosteroids acutely modulate SRP induction. This study shows progesterone as well as two of its 3α,5α-derivatives, allopregnalonone and 3α,5α-tetrahydrodeoxycorticosterone (THDOC), to be capable of producing acute GABAA receptor (GABAAR)-dependent inhibition of SRP. When compared with test simulation (1 stimulation/30 s) of pelvic afferent nerves that evoked a baseline reflex activity in an external urethra sphincter electromyogram, repetitive stimulation (RS; 1 stimulation/1 s) induced SRP characterized by an increase in the evoked activity. Intrathecal progesterone (3–30 μM, 10 μl) at 10 min before stimulation onset dose dependently prevented RS induction. Intrathecal allopregnalonone (10 μM, 10 μl it) and THDOC (10 μM, 10 μl it) also prevented the SRP caused by RS. Pretreatment with the GABAAR antagonist bicuculline (10 μM, 10 μl it) at 1 min before progesterone/neurosteroid injection attenuated the inhibition of SRP caused by progesterone, allopregnanolone, and THDOC. Results suggest that progesterone and its neurosteroid metabolites may be crucial to the development of pelvic visceral neuropathic/postinflammatory pain and imply clinical use of neurosteroids, such as allopregnanolone and THDOC, for visceral pain treatment.

The pressor effects on blood pressure (BP) elicited by electro-acupuncture (Ea) stimulations and vesico-vascular reflex (VVR) were investigated in anesthetized rats. Twenty adult female Sprague-Dawley rats were used throughout this study. Two acupoints, the Hoku (Li-4) and the Tsusanli (St-36), were tested by a low frequency Ea (LFEa, 2 Hz) and a high frequency Ea (HFEa, 20 Hz) with intensities 20 times that of the motor threshold. Ea at Tsusanli elicited no pressor effects (98.15 +/- 4.10% and 101.43 +/- 3.96% of pre-stimulation control in LFEa and HFEa, respectively) whereas pressor effects could be induced by Ea stimulations at Hoku (126.3 +/- 3.3% and 136.3 +/- 3.8% of pre-stimulation control in LFEa and HFEa, respectively, P < 0.01, n=10). In addition, the patterns of pressor effects elicited by LFEa and HFEa at Hoku were different, i.e., LFEa at Hoku elicited a tonic pressor effect, while HFEa elicited a phasic one. The VVR induced by bladder isovolumic saline distension also elicited a pressor effect on BP (119.2 +/- 2.2%, P < 0.01, n=10) in the same preparations during bladder contractions. The VVR did not modify the Ea-induced pressor responses, and vice versa, when both of them were superimposed. All the results suggested that the pressor effects elicited by the VVR and the Ea stimulation were additive responses. In addition, for future clinical application, our findings may imply that patients should be carefully monitored for signs and symptoms of autonomic dysfunction during clinical acupuncture treatments.

This study was conducted to investigate the possible neurotransmitter that activates the descending pathways coming from the dorsolateral pontine tegmentum (DPT) to modulate spinal pelvic-urethra reflex potentiation. External urethra sphincter electromyogram (EUSE) activity in response to test stimulation (TS, 1/30 Hz) and repetitive stimulation (RS, 1 Hz) on the pelvic afferent nerve of 63 anesthetized rats were recorded with or without microinjection of nicotinic cholinergic receptor (nAChR) agonists, ACh and nicotine, to the DPT. TS evoked a baseline reflex activity with a single action potential (1.00 ± 0.00 spikes/stimulation, n = 40), whereas RS produced a long-lasting reflex potentiation (16.14 ± 0.96 spikes/stimulation, n = 40) that was abolished by d-2-amino-5-phosphonovaleric acid (1.60 ± 0.89 spikes/stimulation, n = 40) and was attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (7.10 ± 0.84 spikes/stimulation, n = 40). ACh and nicotine microinjections to DPT both produced facilitation on the RS-induced reflex potentiation (23.57 ± 2.23 and 28.29 ± 2.36 spikes/stimulation, P < 0.01, n = 10 and 20, respectively). Pretreatment of selective nicotinic receptor antagonist, chlorisondamine, reversed the facilitation on RS-induced reflex potentiation caused by nicotine (19.41 ± 1.21 spikes/stimulation, P < 0.01, n = 10) Intrathecal WAY-100635 and spinal transection at the T1level both abolished the facilitation on reflex potentiation resulting from the DPT nicotine injection (12.86 ± 3.13 and 15.57 ± 1.72 spikes/stimulation, P < 0.01, n = 10 each). Our findings suggest that activation of nAChR at DPT may modulate N-methyl-d-aspartic acid-dependent reflex potentiation via descending serotonergic neurotransmission. This descending modulation may have physiological/pathological relevance in the neural controls of urethral closure.

The current study investigates whether the spinal pelvic nerve-to-external urethra sphincter (EUS) reflex potentiation can be induced by a mechanical stimulation and whether the glutamatergic mechanism is involved in yielding such a reflex potentiation. The external urethra sphincter electromyogram (EUSE) activity, evoked by a single or by repetitive pelvic nerve stimulation, in 30 anesthetized rats was recorded with/without bladder saline distension. Without saline distension (0 cmH(2)O), a single pulse nerve stimulation evoked a single action potential in the reflex activity, whereas repetitive pelvic stimulation and saline distension (6 approximately 20 cmH(2)O) both elicited a long-lasting reflex potentiation (20.05 +/- 3.21 and 75.01 +/- 9.87 spikes/stimulation, respectively). The saline distension-induced pelvic nerve-to-EUS reflex potentiation was abolished by D-2-amino-5-phosphonovalerate [APV; a glutamatergic N -methyl-D-aspartic acid (NMDA) receptor antagonist; 100 microM, 10 microl, 1.72 +/- 0.31 spikes/stimulation] and attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline [NBQX; a glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptor antagonist; 100 microM, 10 microl, 26.16 +/- 7.27 spikes/stimulation], but was not affected by bicuculline (a GABAergic antagonist; 100 microM, 10 microl, 53.62 +/- 15.54 spikes/stimulation). Intrathecal administration of glutamate (31.12 +/- 8.25 spikes/stimulation, 100 microM, 10 microl) and NMDA (26.25 +/- 4.12 spikes/stimulation, 100 microM, 10 microl) both induced a long-lasting pelvic nerve-to-EUS reflex potentiation without saline distension, which was similar to the findings observed from saline distension only. The duration of the contraction wave of the urethra was elongated by the saline distension-induced pelvic nerve-to-EUS reflex potentiation, whereas the peak pressure of the contraction wave was not affected. Our findings suggest that saline distension in the bladder elicits a pelvic nerve-to-EUS reflex potentiation and the glutamatergic mechanism contributes to the presence of such a reflex potentiation.

Although catatonia is a well defined syndrome, the treatment of chronic catatonia remains an unresolved issue. Here, we report a successful treatment of a 30-year-old patient with treatment-resistant catatonic schizophrenia in 10 years by augmentation of selective serotonin reuptake inhibitors (SSRIs). We present a 30-year-old man with treatment-resistant catatonic schizophrenia who failed to respond to the treatment of benzodiazepines and antipsychotics for 10 years. He markedly improved after taking SSRIs. Now, he does not hold odd postures and begins to talk and show more facial expressions. We postulate that the therapeutic effect is related to the enhancement of 5-HT neurotransmission. SSRIs can be a considerable choice to treat chronic catatonia.

To clarify the contributions of sensory inputs and glutamate transmissions to the spinal micturition reflex.Cystometrogram and external urethral sphincter electromyogram activities evaluated the L6 and/or S1 levels.Changes in intravesicular pressure (IVP) in response to saline infusion (0.1 ml/min) were found after unilateral dorsal root rhizotomy at the L6 level, which showed significant increases in threshold pressure (rhizotomized vs. control: 14.25 +/- 0.82 vs. 8.40 +/- 0.69 cmH(2)O, P0.01, n = 28), post-voiding pressure (7.66 +/- 0.56 vs. 5.42 +/- 0.52 cmH(2)O, P0.01, n = 28), holding duration (135.06 +/- 23.6 vs. 77.73 +/- 13.56 sec, P0.05, n = 28), and inter-contraction interval (140.62 +/- 23.29 vs. 82.40 +/- 13.57 sec, P0.05, n = 28). Several (mean = 2.32 +/- 1.31 vs. 0.12 +/- 0.21, P0.01, n = 28, P0.01, n = 28) non-voiding contractions with gradual increase in IVP were found ahead of voiding contraction after rhizotomy. An additional dorsal root rhizotomy at the ipsilateral S1 level caused further increases in urodynamic parameters (threshold pressure, 18.18 +/- 1.67 cmH(2)O, P0.01; post-voiding pressure 8.07 +/- 0.96 cmH(2)O, P0.01; holding duration, 211.44 +/- 42.54 sec, P0.01; inter-contraction interval, 264.2 +/- 59.99 sec, P0.05; non-voiding contractions, 4.41 +/- 2.12, P0.01, n = 7). Intrathecal glutamate (100 microM, 10 microl) ameliorated all the pathological conditions induced by unilateral dorsal root rhizotomy at the L6 level in a dose dependent manner (ED(50) = 1.25 +/- 10(-5)). Intrathecal CNQX (6-cyano-7-nitroquinoxaline-2,3-dione; 100 microM, 10 microl) and APV (D-2-amino-5-phosphonovaleric acid; 100 microM, 10 microl) injections after rhizotomy at the L6 level induced disturbances similar to that caused by an additional rhizotomy at ipsilateral S1 level. Wherease, glutamate (100 microM, 10 microl) reversed the disturbances caused by CNQX but showed no effect on that by APV.Acute partial sensory deprivation caused acute impaired micturition reflex in rat models. In addition, glutamatergic NMDA and AMPA receptors are important for mediating these impairments in micturition reflex.

The effects of gonadal steroids on glutamate-mediated pelvic nerve-to-urethra reflex (PUR) plasticity were investigated in rats, which received a sham operation (Sham), ovariectomy (OVX), or ovariectomy with daily supplemental estrogen (50 microg/kg, OVX + E2). The magnitude of the repetitive stimulation (RS, 1 Hz)-induced potentiation in PUR activity decreased significantly in the OVX group when compared with the Sham groups (18.09 +/- 3.91 and 7.40 +/- 1.03 spikes/stimulation in Sham and OVX group; respectively, P < 0.01, n = 21). Supplemental estrogen (OVX + E2, 12.60 +/- 1.49 spikes/stimulation) significantly reversed the decrease in RS-induced PUR potentiation caused by OVX (P < 0.01, n = 21). The magnitude of the RS-induced potentiation in PUR activity decreased significantly after intrathecal 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline [(20 microm, 10 microl), from 18.09 +/- 3.91 to 10.40 +/- 0.81, from 7.40 +/- 1.03 to 3.20 +/- 0.94, and from 12.60 +/- 1.49 to 8.06 +/- 0.32 spikes/stimulation in Sham, OVX, and OVX + E2, respectively, P < 0.01, n = 18] and D-2-amino-5-phosphonoraleric acid [(100 microm, 10 microl), from 18.09 +/- 3.91 to 1.04 +/- 0.12, from 7.40 +/- 1.03 to 1.06 +/- 0.22, and from 12.60 +/- 1.49 to 0.98 +/- 0.25 spikes/stimulation in Sham, OVX, and OVX + E2, respectively, P < 0.01, n = 18]. In addition, potentiation in PUR activities was induced by intrathecal l-glutamate (0.1 mm, 10 microl, from 1.04 +/- 0.02 to 21.60 +/- 0.93, from 1.10 +/- 0.06 to 8.40 +/- 1.50, and from 1.03 +/- 0.03 to 18.04 +/- 0.84 spikes/stimulation in Sham, OVX, and OVX + E2, respectively, P < 0.01, n = 18) and N-methyl-D-aspartic acid (0.1 mm, 10 microl, from 1.04 +/- 0.02 to 14.80 +/- 0.97, from 1.10 +/- 0.06 to 4.60 +/- 0.48, and from 1.03 +/- 0.03 to 9.09 +/- 0.63 spikes/stimulation in Sham, OVX, and OVX + E2); N-methyl-D-aspartic acid-mediated PUR plasticity in female rats and may contribute to alterations in urinary dysfunction after menopause.

To clarify the contributions of parasympathetic inputs and outputs to the micturition reflex.Intra-vesical pressure (IVP), external urethral sphincter electromyogram (EMG), pelvic afferent nerve activities (PANA), and pelvic efferent nerve activities (PENA) as well as the time-derived IVP (dIVP, an index of bladder contractility) were evaluated in intact and acute dorsal or ventral root(s) rhizotomized (DRX and VRX, respectively) rats.In DRX rats, when compared with that in intact stage, the voiding frequency was decreased (75 +/- 15% of intact, P0.05, n = 8), while the threshold pressure to trigger voiding contractions was significantly increased (187 +/- 75% of intact, P0.05, n = 8). In addition, several insufficient contractions (5.3 +/- 3.5 contractions/voiding, P0.05, n = 8) occurred in ahead of each voiding contraction. On the other hand, in VRX rats, the peak and rebound IVP were significantly decreased (90 +/- 3.5% and 75 +/- 11.3% of intact, P0.01, n = 8), while the threshold pressure was not affected (102 +/- 11% of intact, P = NS, n = 8). The time-derived parameters were significantly decreased in VRX (peak dIVP, 78 +/- 10.2%, rebound dIVP, 75 +/- 15.6%, minimal dIVP, 68 +/- 14% of intact, P0.01, n = 8) but only peak dIVP was decreased (85 +/- 11% of intact, P0.01, n = 8) in DRX rats.Acute selective DRX and VRX rat can be an animal model to investigate peripheral neural control in micturition functions.

The pharmacological activity of CL-065 (trans-3-acetamido-2, 2-dimethyl-4-hydroxy-3, 4-dihydro-2H-1-benzopyran-6-carbonitrite) was investigated in anaesthetized spontaneously hypertensive rats (SHR) and isolated thoracic aorta of Sprague-Dawley rats. The intravenous administration of CL-065 (0.1–2.0 mg kg−1) to anaesthetized SHR induced a dose-dependent reduction of mean arterial pressure (MAP) with maximum effect approximately 5 min after injection and which persisted for over 3 h. CL-065 also induced a reflex tachycardia which seemed to parallel the time course of the hypotensive effect. The hypotensive effect of CL-065 was blocked by pretreatment with glibenclamide (5 mg kg−1, i.v.), a specific ATP-sensitive potassium (KATP) channel blocker. Moreover, CL-065 (0.01–10 μM) resulted in dose-dependent vasodilatory effects on phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. The vasorelaxation elicited by CL-065 was antagonized competitively by pretreatment with glibenclamide (0.1–1.0 μM; pA2 = 6.90 ± 0.09; slope = 1.03 ± 0.18). Similarly, the other two KATP-channel openers cromakalim (1.0 nM–1.0 μM) and nicorandil (0.1–30 μM) also induced vasorelaxation in thoracic aorta. The EC50 of cromakalim, CL-065 and nicorandil (i.e. the doses having half the maximum effect) were approximately 0.083, 0.17, and 4.5 μM, respectively, for phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. Moreover, increased extracellular potassium levels (20–60 mM) resulted in concentration-dependent attenuation of the vasodilator effect of CL-065. In conclusion, CL-065 induces a depressor effect via activation of KATP channels.