Quantification of nicotinic acetylcholine receptors in Parkinson's disease with (123)I-5IA SPECT

We quantified in vivo brain nicotinic acetylcholine receptor (nAChR) distributions in patients with Parkinson's disease (PD) and evaluated correlations between nAChR distributions and clinical variables of the patients, especially dopaminergic medications. Ten patients with PD without dementia underwent 5-(123)I-iodo-3-(2(S)-azetidinylmethoxy)pyridine ((123)I-5IA) single photon emission computed tomography (SPECT) and the data were compared with those of 10 age-matched healthy volunteers. Correlation analyses between (123)I-5IA distribution volumes (DVs) in each brain region and clinical variables of the patients were also performed. The PD group showed a statistically significant decrease (20-25%) in the brainstem and frontal cortex as compared with the control group. Although age, duration of disease, daily dose of levodopa, duration of PD medication use, and scores on the motor section of Unified Parkinson's Disease Rating Scale were not significantly correlated with DV values in any brain regions, high daily doses of dopamine agonist showed a significant negative correlation with DVs in the cerebellum, and temporal, parietal and occipital cortices. These findings suggest that patients with PD without dementia can show reductions especially in the brainstem and frontal cortex. They also suggest that dopamine agonists can have a negative influence on the distribution of nAChRs.     

Radiographic features of Mycoplasma pneumoniae pneumonia: differential diagnosis and performance timing

Background  

The Japanese Respiratory Society guidelines propose a differential diagnosis for atypical pneumonia and bacterial pneumonia using a scoring system for the selection of appropriate antibiotic. In order to improve this scoring system, the guidelines are seeking new specific parameter. The purpose of this study was to clarify the pattern of abnormalities with Mycoplasma pneumoniae pneumonia on chest computed tomography (CT) and whether the radiographic findings could distinguish M. pneumoniae pneumonia from Streptococcus pneumoniae pneumonia.     

Acute pulmonary edema associated with naphazoline ingestion

In published reports of naphazoline ingestion, clinical effects are hypertension, bradycardia, pallor, diaphoresis, and respiratory distress. We report three cases of acute pulmonary edema after the intentional ingestion of naphazoline-containing antiseptic first aid liquid. These cases presented with altered mental status, hypertension, bradycardia, and diaphoresis. Chest x-ray on admission revealed acute pulmonary edema. Two cases required mechanical ventilation. All of these clinical effects resolved within 24 hours and the patients were discharged with no sequelae. Since naphazoline stimulates the peripheral alpha-2 adrenergic receptor, we speculate that intense vasoconstriction may have elevated cardiac afterload and left atrial-ventricular blood volume and caused acute pulmonary edema.     

The prevalence of metabolic syndrome in Japanese renal transplant recipients

BACKGROUND: The prevalence of metabolic syndrome (MS) after renal transplantation has yet to be elucidated. In the present study, we investigated the prevalence of MS in Japanese renal transplant recipients. METHODS: A cross-sectional study was conducted to determine the prevalence of MS in 101 renal transplant recipients at Osaka City University Hospital. The prevalence of MS was determined using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria (modified and original) and the International Diabetes Federation (IDF) criteria. RESULTS: Using the modified (Japanese) NCEP criteria, a total of 24 out of 101 patients (23.8%) had MS including 21 out of 64 male patients (32.8%) and three out of 37 female patients (8.1%). Using the modified (Asian) NCEP criteria, MS was diagnosed in 23 patients (22.8%); 19 male (29.7%) and four female (10.8%). Using the original NCEP criteria, MS was diagnosed in 15 patients (14.9%); 12 male (18.8%) and three female (8.1%). Using the IDF criteria, MS was diagnosed in 16 patients (15.8%); 15 male (23.4%) and one female (2.7%). CONCLUSION: The prevalence of MS differed according to the NCEP criteria used, which had different cut-off points for waist circumference (14.9-23.8%). By the IDF criteria, which cites central obesity as an essential component, the prevalence of MS was slightly lower. Furthermore, in our study, MS was more prevalent in male renal transplant recipients.     

7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one is a novel competitive and selective inhibitor of dipeptidyl peptidase IV with an antihyperglycemic activity

7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one (ER-319711) is a novel dipeptidyl peptidase (DPP)-IV inhibitor discovered in our laboratories. In this study, we have characterized this DPP-IV inhibitor in vitro and in vivo as an antidiabetic agent. The trifluoroacetate salt form of ER-319711, ER-319711-15, inhibited human DPP-IV with an IC(50) value of 0.089 microM, whereas its IC(50) values toward human DPP8 and DPP9 were >100 microM. Inhibition kinetic pattern analysis indicated that ER-319711-15 inhibited DPP-IV in a competitive manner. ER-319711-15 (1 mg/kg) reduced glucose excursion in an oral glucose tolerance test (OGTT) using Zucker fa/fa rats, with significant increases in plasma insulin and active glucagon-like peptide-1 levels. In an OGTT using mice fed a high-fat diet in which ER-319711-15 (0.1-10 mg/kg) was orally administered at 0 h, and glucose was loaded at 0 and 5 h, this compound improved glucose tolerance dose dependently at both 0- and 5-h glucose loading. Next, we compared efficacy of ER-319711-15, E3024, a competitive DPP-IV inhibitor having an imidazopyridazinone structure, or vildagliptin, a slow-binding and long-acting DPP-IV inhibitor, at the same dose, 10 mg/kg, in the same procedures. At the first glucose challenge, all compounds lowered area under the curve (AUC) values of delta blood glucose between 0 and 2 h significantly to the same degree. At the second glucose load, the AUC values between 5 and 7 h were significantly decreased by ER-319711-15 and vildagliptin, but not by E3024. Therefore, ER-319711 might be a potent, competitive, and selective DPP-IV inhibitor with an antihyperglycemic activity.     

Persistent sympathetic activation during chronic antihypertensive therapy: a potential mechanism for long term morbidity?

Previous studies have demonstrated that antihypertensive treatment resets baroreflex control of heart rate (HR) and increases cardiac vagal baroreflex sensitivity. However, it is uncertain whether baroreflex control of muscle sympathetic nerve activity (MSNA) also resets after treatment. We tested the hypothesis that chronic antihypertensive therapy alters baroreflex regulation of MSNA in patients with untreated moderate hypertension. Seven newly diagnosed patients with systolic blood pressure (BP) of 159+/-5 mm Hg (mean+/-SE) and diastolic BP of 103+/-4 mm Hg were studied before and after 1 to 2 weeks ' and 3 months (chronic) of antihypertensive treatment with losartan-hydrochlorothiazide (Hyzaar). MSNA and hemodynamics were measured supine, during a Valsalva maneuver (VM), and at 70 degrees head-up tilt (HUT) for 10 minutes. Data were compared with those obtained in 7 age-matched healthy controls. We found that Hyzaar lowered mean BP acutely and chronically by 20+/-4 and 23+/-3 mm Hg (both P<0.01) but did not change HR. Supine MSNA increased by 43+/-11% and 34+/-11% after acute and chronic treatment (both P<0.01). However, MSNA responses to VM and HUT did not differ after treatment compared with before treatment, indicating unchanged reflex control. These data indicate that sympathetic neural activity was augmented substantially by antihypertensive treatment with Hyzaar, consistent with an ongoing baroreflex unloading, and did not return to baseline or "reset" after 3 months of therapy. We speculate that persistent and marked sympathetic activation by the baroreflex may be a potential mechanism for hypertension that is refractory to antihypertensive therapy and may provide a target mechanism for persistent morbidity despite adequate BP control.