The inhibitory effects of Asparagus cochinchinensis against inflammatory response induced by lipopolysaccharide (LPS), substance P and phthalic anhydride (PA) treatment were recently reported for some cell lines and animal models. To evaluate the hepatotoxicity and nephrotoxicity of A. cochinchinensis toward the livers and kidneys of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed in male and female ICR mice after oral administration of 150, 300 and 600 mg/kg body weight/day saponin-enriched extract of A. cochinchinensis (SEAC) for 14 days. The saponin, total flavonoid and total phenol levels were found to be 57.2, 88.5 and 102.1 mg/g in SEAC, respectively, and the scavenging activity of SEAC gradually increased in a dose-dependent manner. Moreover, body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ between the vehicle and SEAC treated group. Furthermore, no significant alterations were measured in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the SEAC treated group relative to the vehicle treated group. Moreover, the specific pathological features induced by most toxic compounds were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that SEAC does not induce any specific toxicity in the livers and kidneys of male and female ICR mice at doses of 600 mg/kg body weight/day.
Administration, Oral ; Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Aspartate Aminotransferases ; Blood Urea Nitrogen ; Body Weight ; Cell Line ; Creatinine ; Female ; Humans ; Kidney ; L-Lactate Dehydrogenase ; Liver ; Male ; Mice ; Mice, Inbred ICR* ; Models, Animal ; Mortality ; Organ Size ; Pathology ; Phenol ; Phenotype ; Saponins ; Substance P

Asparagus cochinchinensis has been used to treat various diseases including fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease, while IL-4 cytokine has been considered as key regulator on the skin homeostasis and the predisposition toward allergic skin inflammation. However, few studies have investigated its effects and IL-4 correlation on skin inflammation to date. To quantitatively evaluate the suppressive effects of ethyl acetate extracts of A. cochinchinensis (EaEAC) on phthalic anhydride (PA)-induced skin inflammation and investigate the role of IL-4 during their action mechanism, alterations in general phenotype biomarkers and luciferase-derived signals were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice with PA-induced skin inflammation after treatment with EaEAC for 2 weeks. Key phenotype markers including lymph node weight, immunoglobulin E (IgE) concentration, epidermis thickness and number of infiltrated mast cells were significantly decreased in the PA+EaEAC treated group compared with the PA+Vehicle treated group. In addition, expression of IL-1β and TNF-α was also decreased in the PA+EaEAC cotreated group, compared to PA+Vehicle treated group. Furthermore, a significant decrease in the luciferase signal derived from IL-4 promoter was detected in the abdominal region, submandibular lymph node and mesenteric lymph node of the PA+EaEAC treated group, compared to PA+Vehicle treated group. Taken together, these results suggest that EaEAC treatment could successfully improve PA-induced skin inflammation of IL-4/Luc/CNS-1 Tg mice, and that IL-4 cytokine plays a key role in the therapeutic process of EaEAC.
Animals ; Biomarkers ; Brain Diseases ; Cough ; Epidermis ; Fever ; Homeostasis ; Immunoglobulin E ; Immunoglobulins ; Inflammation* ; Inflammatory Breast Neoplasms ; Interleukin-4 ; Kidney Diseases ; Luciferases ; Lymph Nodes ; Mast Cells ; Mice ; Phenotype ; Skin*

BACKGROUND: The evaluation of anesthetic depth using electroencephalography showed reduction in recovery time from anesthesia and decrease in the amount of anesthesia used. This research compared the dosage of propofol and the recovery characteristics when anesthesia was controlled using spectral entropy monitoring and when it was controlled by hemodynamic changes. METHODS: Seventy children of the American Society of Anesthesiologists physical class I-II, ages 3-10, that were scheduled for general anesthesia were randomly distributed into two groups. The children were sedated with midazolam (0.15 mg/kg), and anesthesia was induced with fentanyl (2.0 microg/kg), propofol (2.5 mg/kg), and rocuronium (0.6 mg/kg). Anesthesia was maintained with propofol continuous IV infusion under N2O in O2. For the Entropy Group, the state entropy (SE) was maintained at 40-60, and for the Standard Group, anesthesia was maintained so that the heart rate and systolic blood pressure were at 20% of the standard value. RESULTS: Last 10 minutes of the surgery, the SE and RE (Response entropy) were significantly higher for the Entropy Group when compared to the Standard Group (P < 0.05). The maintenance dose of propofol was significantly lower for the Entropy Group when compared to the Standard Group (P < 0.05). The times taken for recovery were all significantly shorter for the Entropy Group than the Standard Group (P < 0.05). CONCLUSIONS: Entropy guided anesthetic administration was associated with reduced propofol use and faster recovery in children compared to standard practice.
Anesthesia ; Anesthesia, General ; Anesthesia, Intravenous ; Blood Pressure ; Child* ; Electroencephalography ; Entropy* ; Fentanyl ; Heart Rate ; Hemodynamics ; Humans ; Midazolam ; Propofol*

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular Ca2+ ([Ca2+]i) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-HT2B, 3, 4, and 7 receptors in ICC. However, SDZ 205557 (a 5-HT4 receptor antagonist), SB 269970 (a 5-HT7 receptor antagonist), 3-tropanylindole - 3 - carboxylate methiodide (3-TCM; a 5-HT3 antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-HT2B receptor antagonist). Based on [Ca2+]i analysis, we found that 5-HT increased the intensity of [Ca2+]i. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-HT3, 4, and 7 receptors via [Ca2+]i mobilization and regulation of mitogen-activated protein kinases.
Animals ; Flavonoids ; Gastrointestinal Motility ; Imidazoles ; Interstitial Cells of Cajal ; Intestine, Small ; Mice ; Mitogen-Activated Protein Kinases ; para-Aminobenzoates ; Patch-Clamp Techniques ; Phenols ; Pyridines ; Receptor, Serotonin, 5-HT2B ; Receptors, Serotonin ; Receptors, Serotonin, 5-HT4 ; Serotonin ; Sulfonamides

We studied whether nitric oxide (NO) and hydrogen sulfide (H2S) have an interaction on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of NO and H2S on pacemaker activities were investigated by using the whole-cell patch-clamp technique and intracellular Ca2+ analysis at 30degrees C in cultured mouse ICC. Exogenously applied (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, or sodium hydrogen sulfide (NaHS), a donor of H2S, showed no influence on pacemaker activity (potentials and currents) in ICC at low concentrations (10 microM SNAP and 100 microM NaHS), but SNAP or NaHS completely inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction at high concentrations (SNAP 100 microM and NaHS 1 mM). Co-treatment with 10 microM SNAP plus 100 microM NaHS also inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction. ODQ, a guanylate cyclase inhibitor, or glibenclamide, an ATP-sensitive K+ channel inhibitor, blocked the SNAP+NaHS-induced inhibition of pacemaker currents in ICC. Also, we found that SNAP+NaHS inhibited the spontaneous intracellular Ca2+ ([Ca2+]i) oscillations in cultured ICC. In conclusion, this study describes the enhanced inhibitory effects of NO plus H2S on ICC in the mouse small intestine. NO+H2S inhibited the pacemaker activity of ICC by modulating intracellular Ca2+. These results may be evidence of a physiological interaction of NO and H2S in ICC for modulating gastrointestinal motility.
Animals ; Gastrointestinal Motility ; Glyburide ; Guanylate Cyclase ; Humans ; Hydrogen ; Hydrogen Sulfide ; Interstitial Cells of Cajal ; Intestine, Small ; Mice ; Nitric Oxide ; Patch-Clamp Techniques ; Sodium ; Sulfides ; Tissue Donors

PURPOSE: To assess the characteristics and treatments of ocular surface squamous neoplasms (OSSN). METHODS: We analyzed four representative cases of squamous neoplasms present on the ocular surface and discussed a new paradigm for the diagnosis and management of such lesions. CONCLUSIONS: Conjunctival and corneal tumors differentiated to squamous cells are rare. OSSN has various clinical appearances, and because OSSN itself is either malignant or has potential to become malignancy, precise discrimination and adequate treatment methods are necessary. We hope that the results from this study provide a basic source of information for diagnosing and treating OSSN.
Carcinoma, Squamous Cell ; Diagnosis ; Discrimination (Psychology) ; Hope

BACKGROUND/AIMS: Tamoxifen is a widely used anticancer drug for breast cancer with frequent gastrointestinal side effects. Changes in gastrointestinal motility is associated with altered activities of membrane ion channels. Ion channels have important role in regulating membrane potential and cell excitability. This study was performed to investigate the effects of tamoxifen on the membrane ionic currents in colonic smooth muscle cells. METHODS: Murine colonic smooth muscle cells were isolated from the proximal colon using collagenase, and the membrane currents were recorded using a whole-cell patch clamp technique. RESULTS: Two types of voltage-dependent K+ currents were recorded (A-type and delayed rectifier K+ currents). Tamoxifen inhibited both types of voltage-dependent K+ currents in a dose-dependent manner. However, tamoxifen did not change the half-inactivation potential and the recovery time of voltage-dependent K+ currents. Chelerythrine, a protein kinase C inhibitor or phorbol 12, 13-dibutyrate, a protein kinase C activator did not affect the voltage-dependent K+ currents. Guanosine 5'-O-(2-thio-diphosphate) did not affect the tamoxifen-induced inhibition of voltage-dependent K+ currents. Tamoxifen inhibited voltage-dependent Ca2+ currents completely in whole-test ranges. CONCLUSIONS: These results suggest that tamoxifen can alter various membrane ionic currents in smooth muscle cells and cause some adverse effects on the gastrointestinal motility.
Animals ; Antineoplastic Agents, Hormonal/*pharmacology ; Calcium Channels/drug effects ; Colon/*drug effects/physiology ; English Abstract ; In Vitro ; Membrane Potentials ; Mice ; Myocytes, Smooth Muscle/*drug effects/physiology ; Potassium Channels/*drug effects ; Tamoxifen/*pharmacology

BACKGROUND: This study is to demonstrate that the estimates of effective concentration (EC) inferred by logit, probit, and sigmoid Emax can be declared to be similar. METHODS: The estimates of EC (5, 25, 50, 75, 95 [%]) of 24 vecuronium concentration-single twitch response data were obtained with three pharmacodynamic methods. A paired t-test with Bonferroni's correction was used. RESULTS: The distribution of estimates by probit were narrower than that of those by logit and sigmoid Emax. The estimates of logit and sigmoid Emax were closely similar. CONCLUSIONS: It suggests that the EC estimates of other paper analysed by the different pharmacodynamic method could be lower or higher.
Colon, Sigmoid* ; Vecuronium Bromide

The facial nerve is mainly composed of motor fibers and is distributed to the muscles of facial expressions. In ophthalmology clinics, orbicularis oculi muscle innervated by the facial nerve is involved in spontaneous and voluntary blinking, winking, and more forceful eyelid closure. To understand pathophysiogy of facial nerve palsy due to brain stem lesion involving nucleus, 50% Horseradish Peroxidase (HRP) was injected into nerve stump innervating orbicularis oculi muscle of cat and serial sections of midbrain were studied with light and dark field of light microscope to examine morphology and distribution of the facial nuclei. The HRP-labelled motor neurons were located exclusively within the intermediate division of the ipsilateral facial nuclei and no labelled neurons were found in the contralateral facial nuclei, in the nuclei of the trigeminal nerve, or any other brain stem nuclei. The mean diameter of HRP-labelled motor neurons was 45 micrometer. Most of them were multipolar in shape containing many dendrites. These result suggest that the intermediate division of ipsilateral facial nuclei play an important role in innervating orbicularis oculi muscle.
Animals ; Armoracia* ; Blinking ; Brain Stem ; Cats* ; Dendrites ; Eyelids ; Facial Expression ; Facial Nerve ; Horseradish Peroxidase* ; Mesencephalon ; Motor Neurons* ; Muscles ; Neurons ; Ophthalmology ; Paralysis ; Trigeminal Nerve

The authors investigated the effects of amniotic membrane ointment on inflammatory cell infiltration into corneal stroma, early keratocyte and inflammatory cell apoptosis and lipid peroxidation of cell membrane after photorefractive keratectomy (PRK) in rabbits. PRK was performed on both eye of 10 white rabbits, then we applied amniotic membrane ointment on one eye and ointment base on the other eye, three times a day, respectively. All corneas were harvested after 24 hours. Hematoxylineosin (H&E) stains for polymorphonuclear cells (PMNs) infiltration, terminal deozyribonucleotidyl transferase mediated dUTP-digoxigenin nick end labeling (TUNEL) stains for keratocyte apoptosis and malondialdehyde (MDA) immunohistochemical stains for lipid peroxidation were performed. In amniotic membrane ointment applicated group, PMNs in corneal stroma, TUNEL stain positive cells and degree of lipid peroxidation were significantly less than those of base ointment applicated group (P<0.05). Therefore, those findings may be able to utilize as basic data for clinical use of amniotic membrane ointment.
Amnion* ; Apoptosis ; Cell Membrane ; Coloring Agents ; Cornea* ; Corneal Stroma ; In Situ Nick-End Labeling ; Inflammation ; Lipid Peroxidation ; Malondialdehyde ; Photorefractive Keratectomy ; Rabbits* ; Transferases