Hypothalamic histamine release by taste stimuli in freely moving rats: possible implication of palatability

Our previous study indicated that taste information via the chorda tympani (CT) activates the central histaminergic system in anesthetized rats. However, the physiological roles of taste-induced histamine release remain unknown, thus to further investigate the relationship between histamine release and gustatory information, in the present study we investigated the effect of taste stimuli infused intraorally on histamine release using in vivo microdialysis in free moving rats. Consistent with findings from our previous study, application of NaCl and HCl caused significant increases in histamine levels further supporting the suggestion that this phenomenon is attributed to the excitation of the CT. When rats were intraorally infused with quinine HCl (QHCl) solution, a significant increase in hypothalamic histamine release was observed. On the other hand, histamine release was decreased by sucrose and saccharin solutions. When rats were conditioned to acquire taste aversion to sucrose solution or saccharin solution, instead of the histamine decrease seen by the palatable solutions, the pattern of histamine release was similar to that seen by QHCl solution. From these observations, it is concluded that the histamine release by the infusion of these tastants may be explained by two mechanisms-by causing a transient increase after taste stimulation and by causing a decrease relative to the tastant's palatability.     

Feasibility study of neoadjuvant chemotherapy followed by interval cytoreductive surgery for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206

A feasibility study was started in January 2003 on neoadjuvant chemotherapy (NAC) followed by interval cytoreductive surgery (ICS) and postoperative chemotherapy for stage III/IV müllerian carcinomas such as ovarian, tubal and peritoneal carcinomas. The purpose is to assess the safety and efficacy of the treatment starting with NAC and also to know whether we can accurately diagnose these advanced carcinomas by imaging studies, cytologic findings and tumor markers without staging laparotomy or laparoscopy. Fifty-six patients with advanced müllerian carcinomas will be recruited to the study. After confirmation of diagnosis by laparoscopic inspection and biopsies, patients undergo four cycles of chemotherapy as NAC, followed by ICS and an additional four cycles of post-surgical chemotherapy. The primary endpoint is proportion of clinical complete remission after accomplishment of the protocol treatment, while the major secondary endpoint is positive predictive value of diagnosis before laparoscopy regarding tumor origin, histology and stage. Based on the results of this study, we will conduct a phase III study to compare the treatment starting with NAC and primary cytoreductive surgery followed by post-surgical chemotherapy.     

Extremely rapid formation of mitral valve ring abscess in infective endocarditis

A patient with infective endocarditis (IE) due to methicillin-resistant staphylococcus aureus (MRSA) was found to have conversion of the hypoechoic region of the posterior mitral valve ring apparatus into a clearly delineated echolucent space by repeating transthoracic echocardiography at an interval of 1 week. Color Doppler showed features of blood entry into this space. Abscess formation in IE due to MRSA may be quick and repeated echocardiography may help detect the complications of IE. Semiurgent mitral valve plasty was performed for the associated prolapse of the posterior mitral leaflet using a hand-made, rolled, twisted autologous pericardial ring.     

Interference of (1 --> 3)-beta-D-glucan administration in the measurement of plasma (1 --> 3)-beta-D-glucan

OBJECTIVE: Blood (1 --> 3)-beta-D-glucan (betaG) measurement is widely used as an effective sero-diagnostic method for deep-seated mycosis. Antitumor betaG (lentinan, schizophyllan) administration is known as one of the false-positive factors of blood betaG measurement. To understand the influence of administered betaG preparation to betaG measurement in blood, we compared the interfering effect of betaG administration in different betaG measuring methods. METHODS: betaG concentration in plasma was measured by three different methods. MATERIALS: betaG concentration was measured in plasma of 18 samples of 7 cases with betaG administration and 86 samples without betaG administration. The period after last betaG administration was three days to three years. RESULTS: In the cases for which betaG was administered, blood betaG level drastically increased using the method which employs alkaline pretreatment. Even in the cases for which betaG was administered three years previously; betaG value measured by alkaline pretreatment was significantly high. Thus, interference of betaG administration in blood betaG measurement continued for years after the last administration. CONCLUSION: Disparity in betaG values measured by different methods for betaG administered cases is due to differences among sample pretreatment methods. Conformation of administered betaG seemed to be transformed into a sensitive form to factor G by alkaline pretreatment. Especially in the case of the alkaline pretreatment method, betaG administration disturbance was much stronger than for dilution-heating pretreatment. Therefore, in suspected cases, it is important to pay attention to betaG administration during the previous few years.     

Pharmacological dissection of calcium channel subtype-related components of strontium inflow in large mossy fiber boutons of mouse hippocampus

Several subtypes of voltage-dependent calcium channels (VDCCs) are present in the presynaptic terminals. In the mammalian hippocampus, P/Q-, N-, and R- but not L-type VDCCs are involved in the fast transmitter release from large mossy fiber (MF) boutons, which are associated with CA3 pyramidal cell dendrites. We investigated whether L-type VDCCs are indeed absent in these large MF boutons. With the use of Sr2+ as the Ca2+ substitute, the stimulus-evoked Sr2+ increment (delta[Sr2+]pre) was evaluated fluorometrically. Delta[Sr2+]pre appeared to be proportional to Sr2+ inflow through VDCCs and was specifically attenuated by conventional VDCC subtype-selective antagonists. The P/Q-type selective omega-agatoxin IVA (AgTx(IVA)) blocked delta[Sr2+]pre with an IC50 of 28 nM and by 30-35% at its maximum effective concentration of 0.5 microM. The N-type selective omega-conotoxin GVIA (CgTx(GVIA)) blocked delta[Sr2+]pre with an IC50 of 15 nM and by 20-25% at its maximum effective concentration of 1 microM. The R-type selective SNX-482 blocked delta[Sr2+]pre with an IC50 of 79 nM and by 20-25% at its maximum effective concentration of 1 microM. The effects of these toxins did not overlap at their maximum effective concentrations and about 70-80% of delta[Sr +]pre was blocked by the simultaneous exposure to these toxins. delta[Sr2+]pre component that is resistant to AgTx(IVA), CgTx(IVA), and SNX-482 was significantly potentiated by an L-type agonist, (S)-(-)-Bay K8644, and attenuated by an L-type antagonist, nimodipine, suggesting that L-type VDCCs are present in large MF terminals. The L-type agonist, (+/-)-Bay K8644, also potentiated Sr2+ inflow into individual boutons identified as large MF boutons under confocal microscopy. Almost similar results were observed for Ca2+ inflow-dependent fluorescence increments. L-type VDCCs appear to be present in large MF boutons and mediate a substantial Ca2+ inflow into presynaptic terminals during action potentials.     

PPARα-dependent modulation of hepatic CYP1A by clofibric acid in rats

Fibrates, hypolipidemic drugs, have been reported to suppress the metabolic activities of cytochrome P450 1A1 and 1A2 in rats but the mechanism has not been elucidated. In the present study we tested the hypothesis that the inhibitory effect of fibrates on arylhydrocarbon receptor (AhR) function may be due to their stimulatory effects on PPAR. Sudan III (S.III) treatment induced CYP 1A1 and CYP 1A2 protein expression, mRNA and their metabolic activities, methoxyresorufin-O-demethylase (MROD) and ethoxyresorufin-O-deethylase (EROD), in Wistar rats higher than those in the control. Co-treatment of rats with S.III and clofibric acid (CA) caused a 40–50% decrease in the induced levels of CYP1A1 and CYP1A2 protein, mRNA expression and their metabolic activities and reduced AhR protein expression. When we treated HepG2 cells with S.III and/or CA, no suppressive effect on S.III-induced CYP1A1 protein expression due to CA was found. HepG2 cells were transiently transfected with increasing concentrations of PPAR mammalian expression vector and exposed to the same treatment. CA co-treatment with S.III decreased AhR protein and S.III-induced CYP1A1 protein expression with increasing dose of PPAR transfected into HepG2 cells. Our results demonstrate that the suppressive effect of fibrates on CYP1A is PPAR-dependent and suggest that PPARhas an inhibitory effect on AhR function.Abbreviations AhR Arylhydrocarbon receptor - CA Clofibric acid - CYP1A1 Cytochrome P450 1A1 - CYP1A2 Cytochrome P450 1A2 - EROD Ethoxyresorufin-O-deethylase - MROD Methoxyresorufin-O-demethylase - PPAR Peroxisome proliferator activated receptor alpha - PPRE Peroxisome proliferator response element - RXR Retinoid-X receptor - S.III Sudan III - TCDD 2,3,7,8-tetrachlorodibenzo-p-dioxin - TNF Tumor necrosis factor-alpha - XAP2 Hepatitis B virus X-associated protein     

Method of detecting beta-lactam antibiotic induced vancomycin resistant MRSA (BIVR)

Despite the fact that the combination of vancomycin and a beta-lactam antibiotic are known to act synergistically on vancomycin-susceptible Staphylococcus aureus (VSSA), some MRSA have emerged showing antagonism to the combination of vancomycin and a beta-lactam antibiotic. These MRSA are called beta-lactam antibiotic-induced vancomycin resistant MRSA (BIVR). A method based on this antagonistic phenomenon has been devised to detect BIVR strains. The method inhibits the VSSA strain but allows the BIVR strain to grow. Forty-six commercially available beta-lactam antibiotics induced the vancomycin-resistance. Using this detection method, 717 MRSA clinical isolates obtained from eight institutes throughout Japan were thus screened and 6.3% of these were detected as BIVR when judged at 48 h.