Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test

Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40 mg/kg i.p. significantly reduced immobility. At 40 mg/kg i.p., it increased climbing behavior. Even at 40 mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect.     

Prognostic significance of the DNA ploidy of the early glottic cancer

The stage classification is most frequently used at the present in predicting the outcome of laryngeal carcinoma. Recently, DNA ploidy pattern as detected by DNA flow cytometry and cytofluorometry has been also shown to be predictive. In this study, DNA cytofluorometry was performed on formalin-fixed paraffin-embedded tissues from 18 patients with T1 and T2 glottic squamous cell carcinoma for whom long-term follow-up data were available. The DNA ploidy pattern was classified into three types, diploid, diploid + tetraploid and aneuploid according to the DNA content of Go/G1 cells and mitotic cells. In these 18 cases, 8 cases (44%) had diploid pattern, 3 cases (17%) had the diploid + tetraploid pattern and 7 cases (39%) had the aneuploid pattern. The ploidy pattern was significantly associated with the relapse-free rate, but did not correlate with the stage of the carcinoma and differentiation of the cancer cells. Distribution of the patients by histology, stage and therapy was almost equal among the diploid, diploid + tetraploid and aneuploid groups. All the patients were treated with irradiation (60Gy). In the group as a whole, no patient died of glottic carcinoma. Relapse-free survival rates for diploid, diploid + tetraploid and aneupoid were 88%, 33% and 29% respectively. This retrospective study of glottic cancer treated with radiation therapy suggests the possibility that the DNA ploidy pattern would significantly predict patient outcome and would be useful for selecting patients whose poor prognosis demands more aggressive therapy.     

Precursor-product relationship between oval cells and hepatocytes: comparison between tritiated thymidine and bromodeoxyuridine as tracers

The expansion and differentiation of oval cells in the acetylaminofluorene(AAF)/partial hepatectomy (PH) model was studied utilizing pulse-chaselabeling with both tritiated thymidine ([³H]TdR) and bromodeoxyuridine(BUdR). Animals in which a significant decrease in serum albuminand increase in alanine aminotransferase and bilirubin wereobserved demonstrated the most prominent differentiation ofoval cells into hepatocytes. Administration of [³H]TdR or BUdR,either individually or together, to the animals on day 6 afterpartial hepatectomy resulted in labeling of the majority ofthe oval cells by days 7 and 9 after PH. A striking differencein the distribution of [³H]TdR- and BUdR-labeled cells in thedouble labeling experiments was observed on day 11, at whichtime the number of [³H]TdR-labeled cells increased 6-fold andthat of double labeled cells decreased 2-fold. Furthermore,on day 11 the basophilic foci were weakly positive for BUdRand negative at later time points in animals receiving BUdRalone or together with [³H]TdR. In contrast, the cells in basophilicfoci as well as transitional cells were positive for [³H]TdR.Cells heavily labeled with both [³H]TdR and BUdR were presentat all time points, indicating an inhibition of the proliferativeactivity. Pulse labeling of rat liver epithelial cells withBUdR in vitro demonstrated that immunodetection of BUdR waslost after three or more cell divisions. We conclude that theBUdR tagging method is particularly sensitive to label dilutionduring cell cycling and may not be suitable for establishmentof a precursor-product relationship between cell lineages whenthe progenitor population proliferates more than three times.     

Characterization and effects of methyl-2- (4-aminophenyl)-1, 2-dihydro-1-oxo-7- (2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), a novel potent inhibitor of cGMP-binding cGMP-specific phosphodiesterase (PDE5)

An isoquinolone derivative, methyl-2-(4-aminophenyl)-1, 2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), was found to be a novel potent inhibitor of cyclic GMP (cGMP)-binding cGMP-specific phosphodiesterase (PDE5). We investigated the inhibitory effects of T-1032 on six PDE isozymes isolated from canine tissues. T-1032 specifically inhibited the hydrolysis of cGMP by PDE5 partially purified from canine lung, at a low concentration (IC(50) = 1.0 nM, K(i) = 1.2 nM), in a competitive manner. In contrast, the IC(50) values of T-1032 for PDE1, PDE2, PDE3, and PDE4 were more than 1 microM. T-1032 also inhibited PDE6 from canine retina with an IC(50) of 28 nM, which is of the same order of magnitude as the IC(50) of sildenafil. cGMP hydrolytic activities of two alternative splice variants of canine PDE5 expressed in COS-7 cells were inhibited by this compound to a similar extent. T-1032 increased the intracellular concentration of cGMP in cultured rat vascular smooth muscle cells in the presence and absence of C-type natriuretic peptide, an activator of membrane-bound guanylate cyclase, whereas the compound did not change cyclic AMP levels. These data indicated that T-1032, which belongs to a new structural class of PDE5 inhibitors, is a potent and selective PDE5 inhibitor. This compound may be useful in pharmacological studies to examine the role of a cGMP/PDE5 pathway in tissues.     

Devices for facial aesthetic improvement in the treatment of skeletal mandibular protrusion

Some techniques for the treatment of mandibular protrusion with consideration for aesthetic improvement of the face as a whole are described. The aesthetic inferiority complex in the mind of patients with masticatory disorders as the chief complaint should not be underestimated. Three techniques were used in this study; preoperative orthodontic treatment, preservation of the patient's self-image, and maintenance of beautiful relationship between the midfacial line and the nasolabial fold as well as the nasal ala.     

Direct in vivo evidence of a vascular statin: a single dose of cerivastatin rapidly increases vascular endothelial responsiveness in healthy normocholesterolaemic subjects

AIMS: HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect. METHODS: We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group (n = 15) or cerivastatin group (n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin. RESULTS: There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h (P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endothelium--independent dilatation of brachial artery was not altered. CONCLUSIONS: A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.     

The consult is real,the visit is virtual

A web-based service was developed through which patients can obtain second opinions from physicians. Factors addressed included incorporating e-appointments into a medical practice, consolidating different approaches to second opinions, complying with disparate state licensing regulations, and communicating the program's features to providers and patients.     

Bilateral vocal fold paralysis and adhesion in anterior spinal artery syndrome

The purpose of this report is to present a rare case of anterior spinal artery syndrome (ASAS) in which there proved to be a combined lesion of paralysis and adhesion. A 26-year-old woman with a history of ASAS complained of difficulty of tracheal decannulation. In 1988, she was intubated and underwent tracheotomy because of respiratory muscle weakness, and she was decannulated in 1990. In 1998, she had cesarean delivery under general anesthesia, and postdelivery dyspnea necessitated tracheotomy again. On her first visit to us, endoscopic examination revealed bilateral vocal fold immobility at the midline without an apparent web. Direct laryngoscopy under general anesthesia revealed a posterior glottic adhesion and scarring, which were treated by excision of the scar and local steroid injection. The left vocal fold gradually regained mobility, permitting decannulation 3 months after treatment. This complicated vocal fold immobility was found to be due to adhesion and partial paralysis combined.     

Targeting of post-ischemic cerebral endothelium in rat by liposomes bearing polyethylene glycol-coupled transferrin

To achieve an efficient delivery targeting to post-ischemic cerebral vascular endothelium, PEG-liposome conjugated with transferrin (Tf) (Tf-PEG-liposome) was intravenously administered to the rats after 90 min of transient middle cerebral occlusion. The expression of Tf receptor (TfR) in the cerebral endothelium increased with a peak at 1 day after the reperfusion and returned to the control level by 6 days. The Tf-PEG fluorescence was marginally detectable in sham control brain, but remarkably increased with a peak at 2 days, showing about 70% of TfR positive vascular endothelium double-labeled with Tf-PEG. These results indicate that the Tf-PEG-liposome could be utilized as an efficient drug delivery tool to the brain after stroke.     

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion.