Emphysematous Salmonella-Infected Aneurysm of the Aortic Arch: Case Report.

BACKGROUND: Infected aortic aneurysm is a relatively rare disease with significant morbidity and mortality. Because of its deeper position, patients with infected aortic arch aneurysms may present with only fever and other vague symptoms, such as weakness, fatigue, dizziness, anorexia, and functional decline. It is difficult confirm a diagnosis that is based solely on history or physical examination, and it may only be apparent on imaging studies. CASE REPORT: We present a brief case report of a patient presenting to the emergency department with unexplained fever who was diagnosed with emphysematous salmonella-infected aneurysm of the aortic arch. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Infected aortic arch aneurysm is an extremely unusual disease entity that emergency physicians encounter. Because of the high mortality and morbidity of this catastrophic disease, an infected aortic aneurysm should be considered as a possible diagnosis in patients with persistent fever and vague symptoms without a specific infection focus. To avoid delayed diagnosis, emergency physicians should be aware of infected aortic arch aneurysm.

Co-existing "spear-and-shield" air filter: Anchoring proteinaceous pathogen and self-sterilized nanocoating for combating viral pandemic.

Infectious pollutants bioaerosols can threaten human public health. In particular, the indoor environment provides a unique exposure situation to induce infection through airborne transmission like SARS-CoV-2. To prevent the infection from spreading, personal protective equipment or indoor air purification is necessary. However, it has been discovered that the conventional filter can become contaminated by pathogen-containing aerosols, meaning that advanced filtering and self-sterilization systems are required. Here, we fabricate a multilayered nanocoating around the fabric using laponite (LAP) with Cu2+ ions (LAP-Cu2+ nanocoating) two contradictory functions in one system: trapping proteinaceous pathogens and antibacterial effect. Due to the strong LAP-protein interaction, albumin and spike protein (S-protein) are trapped into the fabric when proteins are sprayed using a nebulizer. The protein-blocking performance of the nanocoated fabric is 9.55-fold higher than bare fabric. These trapping capacities are retained after rinsing and repeated adsorption cycles, showing reproducibility for air filtration. Even though the protein-binding occurred, the LAP-Cu2+ fabric indicates antibacterial effect. LAP-Cu2+ fabric has an equivalent air and water transmittance rate to that of bare fabric with a stability under physiological environment. Therefore, given its excellent "Spear-and-shield" functions, the proposed LAP-Cu2+ fabric shows great potential for use in filter and masks during the viral pandemic.

UiO-66-NH2 and Zeolite-Templated Carbon Composites for the Degradation and Adsorption of Nerve Agents.

Composites of metal-organic frameworks and carbon materials have been suggested to be effective materials for the decomposition of chemical warfare agents. In this study, we synthesized UiO-66-NH2/zeolite-templated carbon (ZTC) composites for the adsorption and decomposition of the nerve agents sarin and soman. UiO-66-NH2/ZTC composites with good dispersion were prepared via a solvothermal method. Characterization studies showed that the composites had higher specific surface areas than pristine UiO-66-NH2, with broad pore size distributions centered at 1-2 nm. Owing to their porous nature, the UiO-66-NH2/ZTC composites could adsorb more water at 80% relative humidity. Among the UiO-66-NH2/ZTC composites, U0.8Z0.2 showed the best degradation performance. Characterization and gas adsorption studies revealed that beta-ZTC in U0.8Z0.2 provided additional adsorption and degradation sites for nerve agents. Among the investigated materials, including the pristine materials, U0.8Z0.2 also exhibited the best protection performance against the nerve agents. These results demonstrate that U0.8Z0.2 has the optimal composition for exploiting the degradation performance of pristine UiO-66-NH2 and the adsorption performance of pristine beta-ZTC.

Extreme field confinement in zigzag plasmonic crystals.

We propose extreme field confinement in a zigzag plasmonic crystal that can produce a wide plasmonic bandgap near the visible frequency range. By applying a periodic zigzag structure to a metal-insulator-metal plasmonic waveguide, the lowest three plasmonic crystal bands are flattened, creating a high-quality broadband plasmonic mirror over a wavelength range of 526-909 nm. Utilizing zigzag plasmonic crystals in a three-dimensional tapered metal-insulator-metal plasmonic cavity, extreme field confinement with a modal volume of less than 0.00005 λ 3 can be achieved even at resonances over a wide frequency range. In addition, by selecting the number of zigzag periods in the plasmonic crystal, critical coupling between the cavity and the waveguide can be achieved, thereby maximizing the field intensity with an enhancement factor of 105 or more. We believe that zigzag plasmonic crystals will provide a powerful platform for implementing broadband on-chip plasmonic devices.

Factors for modifying the termination of resuscitation rule in out-of-hospital cardiac arrest.

BACKGROUND: False positive rate (FPR) of the current basic life support (BLS) termination of resuscitation (TOR) rule in out-of-hospital cardiac arrest (OHCA) patients (not witnessed; no return of spontaneous circulation prior to transport; and no shocks were delivered) has been ethically challenging. We validated the current BLS TOR rule with using nationwide Korean Cardiac Arrest Research Consortium (KoCARC) registry and identified the factors for modifying the rules. METHODS: This prospective, multicenter, registry-based study was performed using the nontraumatic OHCA registry data between October 2015 and June 2017. Independent factors associated with poor neurologic outcome were identified to propose new KoCARC TOR rules by using multivariable analysis. The diagnostic performances of the TOR rules were calculated respectively. RESULTS: Among 4,360 OHCA patients, 2,801 (64.2%) satisfied all 3 criteria of the BLS TOR rule. The FPR and positive predictive value of the BLS TOR rule were 5.9% and 99.3%. Asystole as initial rhythm and age > 60 years were found as new factors for modifying the TOR rule. New KoCARC TOR rules, combination of asystole and age > 60 years with current TOR rule, showed lower FPR (0.3%-2.1%) and higher positive predictive value (99.7%-99.9%) for predicting poor neurologic outcome at discharge. CONCLUSIONS: In this recent nationwide cohort, the current BLS TOR rule showed high FPR (5.9%) for predicting poor neurologic outcome. We anticipate that our new KoCARC TOR rules, application of 2 new factors (asystole as initial rhythm and age > 60 years) with BLS TOR rule, could reduce unwarranted death.

Nanolayer-embedded pseudo-photonic crystals.

In recent years, novel high-performance nanophotonic devices have been realized by applying ultrathin two-dimensional nanolayer materials to nanophotonics. In this paper, we propose nanolayer-embedded compact pseudo-photonic crystals (PPCs) that enable strong interaction between ultrathin nanolayers and photonic crystal modes. In typical two-dimensional slab photonic crystals, the transverse-magnetic (TM) photonic crystal bandgap is not well formed, making it difficult to operate the TM photonic crystal waveguide modes. However, by utilizing the low-frequency TM PPC bands, a long propagation TM waveguide mode, a slow TM waveguide mode, and a TM photonic bandgap are all readily available. In particular, the insertion of a nanometer-thick low-refractive-index layer in the vertical center of TM PPC waveguide can localize the electric fields tightly in nanometer space, causing strong field interaction with the inserted nanolayer material. Using the TM slow light near PPC band edges, field interaction with the nanolayer is significantly enhanced. We can also realize nanolayer-embedded high-quality-factor (Q-factor > 104) PPC cavities using the TM PPC bandgap. We believe that the proposed TM PPCs will play an important role in the strong interaction of ultrathin nanolayer materials with photonic crystal modes.

Incidence of bacteremia and antimicrobial resistance, and associated factors among patients transferred from long-term care hospital.

OBJECTIVE: To evaluate the prevalence of bacteremia and antimicrobial resistance, and associated factors among infectious patients transferred from long-term care hospitals (LTCHs). METHODS: Consecutive adult patients who were transferred for suspected infection from affiliated LTCH's to study hospital emergency department (ED) over a 12 month period from January to December 2016 were included retrospectively. Patients with positive blood cultures (excluding contaminants as clinically determined) were defined as primary measure and subjected to further analysis according to antimicrobial resistance pattern. The latter was categorized into 4 subgroups based on groups of antimicrobial choices for empiric choices of suspected bloodstream infections. R-Group 0: bacteria susceptible to penicillin and amoxicillin; R-Group 1: bacteria resistant to penicillin/amoxicillin, first, second, or third generation cephalosporins. R-Group 2: ESBL-producing bacteria or bacteria resistant methicillin, fourth generation cephalosporin, or fluoroquinolone. R-Group 3: highly resistant pathogens including vancomycin resistant enterococci, carbapenem or colistin resistant Gram negatives. Blood culture isolate could therefore be included in >1 group. RESULTS: Among 756 patients who were transferred from LTCHs, we excluded 278 patients who were not suspicious of infection and 65 patients who were not checked blood culture at ED. In total, 422 patients were enrolled. The incidence of bacteremia was 20.4% (n = 86). The most frequent pathogen was E. coli (n = 25) followed by S. aureus (n = 10), S. epidermidis (n = 8), and K. pneumonia (n = 6). The incidences of the R-Group 1, 2, and 3 groups were 16.8% (n = 71), 14.4% (n = 61), and 1.4% (n = 6), respectively. Of the Gram-positive pathogens (n = 44), the R-Group 1, 2, and 3 groups were 84.1% (n = 37), 75.0% (n = 33), and 9.1% (n = 4), respectively. Of the Gram-negative pathogens (n = 46), the R-Group 1, 2, and 3 groups were 82.6% (n = 38), 69.6% (n = 32), and 4.3% (n = 2), respectively. Among tested variables, initial serum procalcitonin level was significantly associated with the presence of bacteremia (AOR 1.03, 95% confidence interval 1.00-1.05), R-Group 1 (1.04, 1.01-1.07) and the R-Group 2 (1.04, 1.00-1.06). CONCLUSIONS: The prevalence of bloodstream infections in patients admitted from LTCH was high (20.4%) with majority of these infections from resistant bacteria. Procalcitonin levels were significantly higher in bacteremic patients with an increasing trend towards bacteria in the antimicrobial resistant groups.

Parapheromones Suppress Chemotherapy Side Effects.

The cytotoxic drugs used in chemotherapy are often accompanied by nausea and vomiting. Despite the use of antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) remain significant side effects for cancer patients and are associated with serotonin type 3 receptor (5-HT3R) activation in the brainstem. Farnesol and nerolidol are sesquiterpene alcohols found in essential oils of plants such as roses, citronella, and lemon grass and are used as antiemetic parapheromones. Medicinal plants often are effective in treating gastrointestinal disorders, including CINV, although the mechanism of action remains unclear. In the current work, the antiemetic efficacy of the naturally occurring racemic mixture of farnesol (m-farnesol) and nerolidol (m-nerolidol) against cisplatin CINV was tested using the pica behavior (consumption of nonnutritive substances) of rats. Animals treated with m-farnesol or m-nerolidol consumed a smaller amount of kaolin than of saline-treated control animals. This result is consistent with the antiemetic efficacy of farnesol and nerolidol. Compared with controls, m-farnesol- but not m-nerolidol-treated animals consumed more food and lost less body weight. Thus, farnesol effectively reduced appetite suppression and weight loss induced by cisplatin. In separate experiments, isomers of farnesol and nerolidol were tested on 5-HT-induced responses of acutely isolated nodose neurons using patch-clamp methods. All the tested constituents inhibited 5-HT3R-mediated current in a noncompetitive manner. Thus, both farnesol and nerolidol may exert antiemetic efficacy by inhibiting 5-HT signaling in cranial visceral afferents, resulting in interruption of emetogenic signaling; however, nerolidol failed to suppress cisplatin-induced anorexia and weight loss, suggesting that additional mechanisms may contribute.

GAREM1 regulates the PR interval on electrocardiograms.

PR interval is the period from the onset of P wave to the start of the QRS complex on electrocardiograms. A recent genomewide association study (GWAS) suggested that GAREM1 was linked to the PR interval on electrocardiograms. This study was designed to validate this correlation using additional subjects and examined the function of Garem1 in a mouse model. We analyzed the association of rs17744182, a variant in the GAREM1 locus, with the PR interval in 5646 subjects who were recruited from 2 Korean replication sets, Yangpyeong (n = 2471) and Yonsei (n = 3175), and noted a significant genomewide association by meta-analysis (P = 2.39 × 10-8). To confirm the function of Garem1 in mice, Garem1 siRNA was injected into mouse tail veins to reduce the expression of Garem1. Garem1 transcript levels declined by 53% in the atrium of the heart (P = 0.029), and Garem1-siRNA injected mice experienced a significant decrease in PR interval (43.27 ms vs. 44.89 ms in control, P = 0.007). We analyzed the expression pattern of Garem1 in the heart by immunohistology and observed specific expression of Garem1 in intracardiac ganglia. Garem1 was expressed in most neurons of the ganglion, including cholinergic and adrenergic cells. We have provided evidence that GAREM1 is involved in the PR interval of ECGs. These findings increase our understanding of the regulatory signals of heart rhythm through intracardiac ganglia of the autonomic nervous system and can be used to guide the development of a therapeutic target for heart conditions, such as atrial fibrillation.

Diagnostic performance of initial serum albumin level for predicting in-hospital mortality among aspiration pneumonia patients.

PURPOSE: The predictive value of serum albumin in adult aspiration pneumonia patients remains unknown. METHODS: Using data collected during a 3-year retrospective cohort of hospitalized adult patients with aspiration pneumonia, we evaluated the predictive value of serum albumin level at ED presentation for in-hospital mortality. RESULTS: 248 Patients were enrolled; of these, 51 cases died (20.6%). The mean serum albumin level was 3.4±0.7g/dL and serum albumin levels were significantly lower in the non-survivor group than in the survivor group (3.0±0.6g/dL vs. 3.5±0.6g/dL). In the multivariable logistic regression model, albumin was associated with in-hospital mortality significantly (adjusted odds ratio 0.30, 95% confidential interval (CI) 0.16-0.57). The area under the receiver operating characteristics (AUROC) for in-hospital survival was 0.72 (95% CI 0.64-0.80). The Youden index was 3.2g/dL and corresponding sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio were 68.6%, 66.5%, 34.7%, 89.1%, 2.05 and 0.47, respectively. High sensitivity (98.0%) was shown at albumin level of 4.0g/dL and high specificity (94.9%) was shown at level of 2.5g/dL. CONCLUSION: Initial serum albumin levels were independently associated with in-hospital mortality among adult patients hospitalized with aspiration pneumonia and demonstrated fair discriminative performance in the prediction of in-hospital mortality.

Extreme field enhancement in nano-gap plasmonic cavity via 90% efficient coupling with silicon waveguide.

We propose a novel design for a sub-5-nm-gap plasmonic cavity to couple it efficiently with an integrated low loss silicon waveguide. We numerically obtain over 90% efficient coupling between a nano-gap plasmonic cavity with a modal volume of less than 10-7λ3 and a conventional silicon-on-insulator (SOI) waveguide by utilizing the anti-symmetric second-order resonance mode of the cavity and engineering its geometry to reduce the modal size to less than 5 nm. The electromagnetic field efficiently coupled to the small cavity, leading to extreme enhancement of the field intensity. For a 2-nm-gap cavity, the intensity enhancement was calculated to be more than 100,000,000 compared to that of light in an SOI waveguide.

In vivo AAV1 transduction with hRheb(S16H) protects hippocampal neurons by BDNF production.

Recent evidence has shown that Ras homolog enriched in brain (Rheb) is dysregulated in Alzheimer's disease (AD) brains. However, it is still unclear whether Rheb activation contributes to the survival and protection of hippocampal neurons in the adult brain. To assess the effects of active Rheb in hippocampal neurons in vivo, we transfected neurons in the cornu ammonis 1 (CA1) region in normal adult rats with an adeno-associated virus containing the constitutively active human Rheb (hRheb(S16H)) and evaluated the effects on thrombin-induced neurotoxicity. Transduction with hRheb(S16H) significantly induced neurotrophic effects in hippocampal neurons through activation of mammalian target of rapamycin complex 1 (mTORC1) without side effects such as long-term potentiation impairment and seizures from the alteration of cytoarchitecture, and the expression of hRheb(S16H) prevented thrombin-induced neurodegeneration in vivo, an effect that was diminished by treatment with specific neutralizing antibodies against brain-derived neurotrophic factor (BDNF). In addition, our results showed that the basal mTORC1 activity might be insufficient to mediate the level of BDNF expression, but hRheb(S16H)-activated mTORC1 stimulated BDNF production in hippocampal neurons. These results suggest that viral vector transduction with hRheb(S16H) may have therapeutic value in the treatment of neurodegenerative diseases such as AD.

Validation of modified early warning score using serum lactate level in community-acquired pneumonia patients. The National Early Warning Score-Lactate score.

STUDY OBJECTIVE: The aim of this study was to investigate the prognostic prediction power of a newly introduced early warning score modified by serum lactate level, the National Early Warning Score-Lactate (NEWS-L) score, among community-acquired pneumonia (CAP) patients. We also compared the NEWS-L score with the pneumonia severity index (PSI) and CURB-65. METHODS: We designed a retrospective observational study and collected data on confirmed adult CAP patients who visited the study hospital between October 2013 and September 2014. Variables relevant to, the NEWS-L score, PSI, and CURB-65 were extracted from electronic medical records. Survival status at hospital discharge was determined in the same manner. The NEWS-L score was calculated as NEWS-L=NEWS+serum lactate level (mmol/L). The NEWS-L was divided into quartiles. The ability to predict mortality was assessed through area under the receiver operating characteristic curve analysis and calibration analysis. RESULTS: A total of 553 patients were enrolled, and the inpatient mortality rate was 10.8% (n=60). Mortality rates increased incrementally in conjunction with the NEWS-L quartiles: first quartile, 2.2%; second quartile, 7.9%; third quartile, 9.6%; and fourth quartile, 23.9%. The area under the receiver operating characteristic curve of the NEWS-L score was 0.73 (95% confidence interval [CI], 0.66-0.80), which showed no significant difference from that of the PSI (0.68; 95% CI, 0.61-0.76; P=.28) and CURB-65 (0.66; 95% CI, 0.59-0.73; P=.06). CONCLUSIONS: The newly introduced early warning score modified by serum lactate level, NEWS-L score, was comparable to PSI and CURB-65, for predicting inpatient mortality among adult CAP patients.

Comprehensive interpretation of hyperglycemia and hyperosmolality on the clinical outcomes among ischemic stroke patients.

BACKGROUND: Hyperglycemia and hyperosmolality are associated with poor outcomes among acute ischemic stroke (AIS) patients. OBJECTIVES: We evaluated the association between hyperglycemia and hyperosmolality, as a combination measure, with poor outcome among AIS patients. METHODS: We conducted a retrospective study of AIS patients admitted to the study hospital emergency department between January and December 2014. Hyperglycemia was defined as serum glucose >144 mg/dL, and hyperosmolality was defined as a serum osmolality >295 mOsm/kg. After excluding hypoglycemia and hypoosmolality, the enrolled patients were classified into the following 4 subgroups: normoglycemia-normoosmolality, hyperglycemia-normoosmolality (HGNO), normoglycemia-hyperosmolality (NGHO), and hyperglycemia-normoosmolality (HGHO). The primary outcome was poor neurological status at 6 months, which was defined as a modified Rankin scale score ≥2. RESULTS: Six hundred seven patients were included. The primary outcome was 336 (55.4%), and it was highest in the HGNO group (69.6%, 103/148), followed by the HGHO group (67.9%, 53/78), the NGHO group (57.3%, 43/75) and the normoglycemia-normoosmolality group (44.7%, 137/306). The multivariable logistic regression analysis revealed that HGNO and HGHO remained significant factors, with primary outcomes (adjusted odds ratio, 2.08; 95% confidence interval, 1.16-3.71) and 2.93 (1.45-5.91), respectively), whereas NGHO was not a significant factor. Cases of extremely high sodium levels were few in the NGHO and HGHO groups, whereas considerable cases of extremely high glucose level were observed in the HGHO group. CONCLUSION: Hyperglycemia was associated with poor outcome, even after excluding the effect of hyperosmolality. However, hyperosmolality without hyperglycemia was not associated with poor outcome. An additive effect, likely reflecting severe hyperglycemia, was observed.

Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons.

Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.

Production and applications of rosmarinic acid and structurally related compounds.

Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid; RA) is a naturally occurring hydroxylated compound commonly found in species of the subfamily Nepetoideae of the Lamiaceae and Boraginaceae, such as Rosmarinus officinalis, Salvia officinalis, and Perilla frutescens. RA is biosynthesized from the amino acids L-phenylalanine and L-tyrosine by eight enzymes that include phenylalanine ammonia lyase and cinnamic acid 4-hydroxylase. RA can also be chemically produced by the esterification of caffeic acid and 3,4-dihydroxyphenyllactic acid. RA and its numerous derivatives containing one or two RA with other aromatic moieties are well known and include lithospermic acid, yunnaneic acid, salvianolic acid, and melitric acid. Recently, RA and its derivatives have attracted interest for their biological activities, which include anti-inflammatory, anti-oxidant, anti-angiogenic, anti-tumor, and anti-microbial functions. Clinically, RA attenuates T cell receptor-mediated signaling, attenuates allergic diseases like allergic rhinitis and asthma, and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like symptoms, protects from neurotoxicity, and slows the development of Alzheimer's disease. These attributes have increased the demand for the biotechnological production and application of RA and its derivatives. The present review discusses the function and application of RA and its derivatives including the molecular mechanisms underlying clinical efficacy.

Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression.

The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease.

Ginger and its pungent constituents non-competitively inhibit serotonin currents on visceral afferent neurons.

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.

Potentiating effect of glabridin on GABAA receptor-mediated responses in dorsal raphe neurons.

Flavonoid-rich ethanol extracts of licorice root have sedative and anxiolytic effects. Glabridin is a major flavonoid component from licorice which we evaluated by examining GABA responses in acutely isolated dorsal raphe neurons of the rat. Neurons were recorded with patch-clamp methods at a holding potential of - 50 mV. Glabridin potentiated GABA-induced responses by positively modulating GABAA receptor responses with different concentration range. GABA (2 × 10(-6) M)-evoked currents were potentiated in a stepwise pattern increasing glabridin concentration. Between 10(-12) and 10(-8) M glabridin increased GABA responses by about 140 % of the control. At concentrations above 10(-7) M, a much larger, dose-dependent potentiation occurred before reaching a plateau at 3 × 10-6 M glabridin. A hypnotic drug, zolpidem, also induced biphasic concentration-potentiation relationship. The glabridin potentiation ratio was 2.2 times larger than the maximum potentiation to the benzodiazepine receptor full agonist diazepam. Benzodiazepine receptor antagonist, flumazenil (3 × 10(-7) M), failed to inhibit glabridin (3 × 10(-7) M)-induced potentiation. This result implies that glabridin may exhibit sedative and hypnotic effects by potentiating GABAergic inhibition in dorsal raphe neurons by GABAA receptor actions.

Effect of endogenous substance P on visceral afferent signal integration in the nucleus tractus solitaries of rat brainstem slices.

In the first synapse of the blood-pressure-regulating pathway, a neurokinin (NK) family peptide substance P (SP) is release with an excitatory neurotransmitter, glutamate, to enhance the sensitivity of the baroreflex responses. However, the underlying mechanisms of action are not yet well understood. The effects of NK receptor antagonists and agonists on solitary tract stimulation-evoked excitatory postsynaptic responses were recorded using whole-cell patch-clamp recordings of neurons in the medial portion of the nucleus tractus solitarius (mNTS) in the brainstem. SP reduced the amplitude of the evoked excitatory postsynaptic currents (eEPSCs) and shifted the holding current inward, in a dose-dependent manner. The concentrations of SP needed to induce such responses were different between capsaicin-sensitive unmyelinated (C-type) and capsaicin-resistant myelinated (A-type) neurons. The perfusion of a NK1 receptor antagonist, sendide, reduced the amplitude of eEPSCs in all tested neurons but did not affect the levels of the holding current. A Neurokinin type 1 receptor (NK1 receptor) agonist, [Sar9, Met(O2)11]-SP, reduced the amplitude of the eEPSCs and shifted the holding current inward in capsaicin-resistant neurons; however, it failed to induce any significant changes in the capsaicin-sensitive neurons. Furthermore, a selective Neurokinin type 3 receptor (NK3 receptor) antagonist, SB223412, failed to induce any changes in any tested neuron. In current-clamp experiments, sendide reduced solitary tract (ST)-stimulation evoked firing of action potentials in both A- and C-type neurons. [Sar9, Met(O2)11]-SP suppressed the firing of the action potentials in C-type but not A-type neurons. In spontaneous synaptic recordings, SP reduced frequency of the sEPSCs in CAP sensitive neuron but NK1 agonist reduced at capsaicin resistant neurons. Taken together, the findings show that ST activation leads to the co-transmission of SP and glutamate and enhances baroreflex sensitivity by potentiating the amplitude of eEPSC in an NK1 receptor activity-dependent manner.