Effect of Ghrelin on catecholamine secretion in rat pheochromocytoma PC12 cells

A novel peptide Ghrelin, found to be a ligand to growth hormone (GH) secretagogue receptor (GHS-R), exeterts to stimulates GH release from pituitary gland. Recently, it has been shown that ghrelin and its receptor are existed in a adrenal ground. At concentrations of 10 nM and over (10 nM, 100 nM, and 1 microM), ghrelin significantly inhibited basal dopamine release by 30, 32 and 34%, respectively (P < 0.05) in PC12 cells, suggesting that ghrelin may be involved in the mechanism of catecholamine regulation in chromaffin cells.     

Implementation of the immunological method for improvement on accurate platelet counts

Rapid and accurate platelet counting is clinically required in severe thrombocytopenia. Prophylactic platelet transfusions are usually indicated in thrombocytopenia with platelet counts less than 20,000/microliter. It was recently reported that the confidence lower limit of platelet counts by automated blood cell counter is about 14,000/microliter. Clinical blood samples occasionally contain red-cell fragments or large platelets. In these cases, platelets should be counted by the phase-contrast microscopy. However, this manual operation is accurate but not precise and needs complicated technique. Abbott has developed an immunological platelet counting method by CELL-DYN 4000. We measured platelet counts in 137 blood samples from thrombocytopenic patients. These samples included red-cell fragmentation and large platelets on blood smears. We compared platelet counts with the immunological method(PLTimm) to those with Brecher-Cronkite, the optical(PLTo) and the impedance method(PLTi). PLTimm correlated more closely with the phase-contrast microscopy counts than PLTo or PLTi. In patients with microangiopathic hemolytic anemia, PLTo or PLTi could not exclude red-cell fragments, but PLTimm absolutely excluded red-cell fragments. In patients with giant platelets, PLTo or PLTi could not include large platelets but PLTimm included them and coincided well with platelet counts by the phase-contrast microscopy. These results indicate that the immunological method by CELL-DYN 4000 appears to be accurate and a very useful method for accurate platelet counts in severe thrombotybopenia.     

Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer

Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). III. Secular changes in susceptibility

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from 565 patients diagnosed as urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of these bacteria to various antimicrobial agents were examined. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1994 and 2002. The drug sensitivity of S. aureus in this year was similar to those in up to the previous years and S. aureus showed the best susceptibility to vancomycin. The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous years. The drug sensitivity of E. coli in this year was generally good except penicillins and was similar to those in up to the previous years. Among cephems, cefozopran (CZOP) and cefpirome (CPR) showed the highest potency activity (MIC90: < or = 0.125 microg/mL). An antibacterial activity of cefotiam (CTM) was stable for 10 years and was fine (MIC0: < or = 0.5 microg/mL). The sensitivity of E. coli to carbapenems and carumonam (CRMN) also was good like to CZOP. The sensitivity of the complicated UTIs group to quinolones, however, has decreased after 2000 and it was suggested that the resistance to the drug has developed. Kiebsiella spp. showed a decrease in the susceptibility to some of cephems. The drugs indicating a big decrease in the sensitivity were cefazolin, CTM, cefaclor, and cefpodoxime. Imipenem, carbapenems, also indicated a decrease in the sensitivity. The susceptibility of the strain to the other drugs was similar to that in up to the previous years. Among them, CZOP maintained good susceptibility (MIC90: > or = 0.125 microg/mL against uncomplicated UTIs, 0.25 microg/mL against complicated UTIs) like meropenem. The drug sensitivity of P. aeruginosa was generally low and was not much different from that in up to the previous years.     

Chronological changes of sympathetic outflow to muscles in amyotrophic lateral sclerosis

To confirm correlations between muscle sympathetic nerve activity (MSNA) and patients' chronological data, we selected 40 consecutive patients with sporadic amyotrophic lateral sclerosis (ALS) recorded by similar methods. MSNA at rest was quantified as the number of sympathetic bursts per 100 heartbeats and as the value expressed as a percentage of the predicted value based on control data. Twelve patients who underwent recordings of MSNA twice at intervals of 6 months or more showed marked decreases in MSNA amplitudes and frequencies between examinations. There was a slightly positive correlation between the frequency of MSNA and age, though younger patients exhibited higher values of MSNA than older patients. The standardized value of MSNA correlated negatively with disease duration and disability levels (p<0.01, 0.05, respectively), but several patients with duration shorter than 12 months showed low values of MSNA. Twelve patients who underwent repeated recordings of MSNA showed a significant decrease in the mean standardized value of MSNA (102.6+/-24.9%) at the second examination, compared to the value (114.3+/-18.9%) at the first one. In ALS, sympathetic outflow to muscles tends to increase initially and then decrease with increasing age and duration. This pattern may be similar to chronological changes at motor neurons.     

Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery: is a differential diagnosis possible?

OBJECT: In this study the authors examined how to differentiate radiation necrosis from recurrent metastatic brain tumor following stereotactic radiosurgery by using positron emission tomography (PET) with L-[methyl-11C]methionine (MET). METHODS: In 21 adult patients with suspected recurrent metastatic brain tumor or radiation injury, MET-PET scans were obtained. These patients had previously undergone stereotactic radiosurgery and subsequent contrast-enhanced magnetic resonance (MR) examinations before nuclear medicine imaging. Positron emission tomography images were obtained as a static scan of 10 minutes performed 20 minutes after injection of 370 MBq of MET. On MET-PET scans, the portion of the tumor with the highest accumulation of MET was selected as the region of interest (ROI), and the ratio of tumor tissue to normal tissue (T/N) was defined as the mean counts of radioisotope per pixel in the tumor divided by the mean counts per pixel in normal gray matter. The standardized uptake value (SUV) was calculated using the same ROI in the tumor. The accuracy of the MET-PET scan was evaluated by correlating findings with results of subsequent histological analysis (11 cases) or, in cases in which surgery or biopsy was not performed, with subsequent clinical course and MR imaging findings (10 cases). Histological examinations performed in 11 cases showed viable tumor cells with necrosis in nine and necrosis with no viable tumor cells in two. Another 10 cases were characterized as radiation necrosis because the patients exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR images after 5 months. The mean T/N was 1.15 in the radiation necrosis group (12 cases) and 1.62 in the tumor recurrence group (nine cases). The mean SUV was 1.78 in the necrosis group and 2.5 in the recurrence group. There were statistically significant differences between the recurrence and necrosis groups in T/N and SUV. Furthermore, the borderline T/N value was 1,42 according to a 2 x 2 factorial table (high T/N or low T/N, recurrence or necrosis). From this result, the sensitivity and specificity of MET-PET scanning in detecting tumor recurrence were determined to be 77.8 and 100%, respectively. CONCLUSIONS: The use of MET-PET scanning is a sensitive and accurate technique for differentiating between metastatic brain tumor recurrence and radiation necrosis following stereotactic radiosurgery. This study reveals important information for creating strategies to treat postradiation reactions.     

Effects of Homologous Plasma Cross-Circulation on Liver Function in Galactosamine-Induced Hepatic Necrosis in Rats

Plasma cross-circulation that resembles clinical plasma exchange was carried out in rats with galactosamine (GalN)-treated hepatic failure to investigate its effect on the damaged liver function. Twenty-four hours after the injection of GalN, plasma cross-circulation was performed at a plasma flow rate of 0.1 ml/min for 6 h. At 48 h after the injection of GalN, survival was obtained in 6 of 8 GalN-injected rats treated with plasma cross-circulation as compared with 4 of 10 GalN-injected rats treated with sham circulation. State 3 oxygen consumption and ATP synthesis (mitochondrial respiratory function) and ATP, ADP, and total adenine nucleotide contents in the liver were significantly higher in the former group than in the latter group at that period, as determined by sacrificing the surviving animals. Although the survival rate was not significantly improved, evidence suggests that plasma cross-circulation enhanced mitochondrial phosphorylative activity and produced an augmented high-energy state of the liver, which had been markedly reduced by GalN administration. An efficient removal of toxic metabolites as well as an influx of a large amount of fresh plasma by plasma cross-circulation would be beneficial for the regenerative process of the necrosing liver tissues.     

EFFECTS OF INTRACAROTID ADMINISTRATION OF β-PHENYL-γ-AMINOBUTYRIC ACID ON THE PERFUSED CAT BRAIN

An investigation was carried out on the effects of intracarotid administration of β-phenyl-γ-aminobutyric acid (β-phenyl-GABA) on the functions of a perfused cat brain. After injecting one ml, each of containing 1, 5, 10, 20, 25, or 35mg/ml of β-phenyl-GABA into the tubes perfusing the carotid arteries with standard artificial blood, the acute effects of the drug on EEG, cerebral blood flow, and oxygen consumption were observed. The results may be briefly summarized as follows.

• 1). EEG is inhibited shortly after the drug reaches the brain. The extent of inhibition rises and the duration of the inhibition is longer as the dose is increased.
• 2). β-phenyl-GABA increases the cerebral blood flow in the cat brain and the increase reaches its maximum with a dose of 5 mg. Above this dose it declines.
• 3). This drug increases the oxygen consumption of the brain slightly.
• 4). It has no effect on the systemic blood pressure.