Ejaculatory response induced by a 5-HT2 receptor agonist m-CPP in rats: differential roles of 5-HT2 receptor subtypes

It has been reported that systemic administration of m-CPP (1-[3-chlorophenyl] piperazine hydrochloride), a 5-HT(2) receptor agonist, produces a 5-HT(2C) receptor-mediated penile erections and self-grooming in rats. In the present study, we examined the ability of m-CPP to induce ejaculation in rats and determined which 5-HT(2) receptor subtypes may be involved in the m-CPP-induced ejaculation. The ejaculatory response was assessed by weighing the seminal materials accumulated over 30 min. In Experiment 1, systemic administration of m-CPP (0.1-3.0 mg/kg, i.p.) produced a dose-dependent increase in both the incidence of ejaculation and the weight of the seminal materials. The inverted U-shaped dose-response effects of m-CPP on penile erection and genital grooming were also observed, with maximum effects at 0.6 mg/kg. Pretreatment with SB242084 (0.1 and 0.3 mg/kg, i.p.), a selective 5-HT(2C) receptor antagonist, dose-dependently attenuated the ejaculatory response induced by m-CPP (3.0 mg/kg). The proejaculatory effect of m-CPP was also attenuated by ketanserin (0.3 and 1.0 mg/kg, i.p.), a 5-HT(2A) receptor antagonist, whereas SB204741 (0.1 and 0.3 mg/kg, i.p.), a selective 5-HT(2B) receptor antagonist, significantly potentiated the m-CPP-induced ejaculatory response. Penile erection and genital grooming induced by m-CPP (0.3 mg/kg, i.p.) was only blocked by SB242084. In Experiment 2 (termed as corset test), in rats fitted with a corset at the thoracic level to prevent the loss of seminal materials by genital grooming, the proejaculatory effect of m-CPP was more efficiently detected than in the non-fitted animals: the ED(50) value for inducing ejaculation was reduced to less than 50% of the ED(50) in non-fitted animals. In this test, the proejaculatory effect of m-CPP (0.6 mg/kg, i.p.) was completely blocked by SB242084 (0.3 mg/kg, i.p.), whereas ketanserin (0.3 mg/kg, i.p.) or SB204741 (0.3 mg/kg, i.p.) did not affect the m-CPP -induced ejaculation. From these observations, it is suggested that the 5-HT(2) receptor agonist m-CPP at low doses (0.3-1.0 mg/kg) possesses the proejaculatory as well as proerectile effects in rats that are primarily associated with the activation of 5-HT(2C) receptors, and that the activation of 5-HT2B receptors may produce an inhibitory effect on ejaculation induced by a high dose (3.0 mg/kg) of m-CPP. Furthermore, the results of the present study also indicate that the corset test employed in this study may be useful for detecting the proejaculatory effect of the compounds.     

Methamphetamine sensitization in nociceptin receptor knockout mice: locomotor and c-fos expression

The role of endogenous nociceptin in the development and expression of sensitization to repeated methamphetamine administration in a novel environment was studied in nociceptin receptor knockout mice. No differences in acute or sensitized locomotor responses were found in nociceptin receptor knockout mice. However, analysis of c-fos expression revealed significant interactions between chronic methamphetamine treatment and genotype in the nucleus accumbens and lateral septum. This was due to increased c-fos expression in chronically methamphetamine-treated nociceptin receptor knockout mice contrasted with reduced c-fos expression in chronically vehicle-treated nociceptin receptor knockout mice. Two further regions (nucleus accumbens core and ventromedial caudate putamen) showed significant interactions between genotype, chronic, and acute methamphetamine treatment due to accentuated c-fos expression in nociceptin receptor knockout mice sensitized and challenged with methamphetamine. These findings suggest endogenous nociceptin modulates the response of the central nervous system to repeated psychostimulant administration, although this is little reflected in locomotion.     

High efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2-ASP) in two patients with hematological malignancies

Two patients with hematological malignancies were successfully treated with monomethoxypolyethylene glycol-conjugated Escherichia coli L-asparaginase (PEG2-ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to L-asparaginase (L-ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100-200 IU/day dose of PEG2-ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG2-ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG2-ASP. Thus, PEG2-ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of L-ASP.     

Clinical utility of doppler ultrasonography in evaluation of early therapeutic efficacy after transcatheter arterial embolization in patients with hepatocellular carcinoma

This study was undertaken to determine the value of Doppler ultrasonography in the early evaluation of therapeutic efficacy of hepatocellular carcinoma after transcatheter arterial embolization (TAE). Fifty-two nodules in which tumor vascularity had been detected by Doppler ultrasonography before TAE were examined in 41 patients. Doppler signals were evaluated 1 week after TAE, and the results were compared with tumor vascularity as determined by dynamic magnetic resonance imaging (dynamic MRI), which was used as the gold standard. The sonographic signal disappeared in 41 (79%) of the 52 nodules and remained in 11 (21%). All nodules in which intratumor vascularity had been detected showed positive stain to dynamic MRI. Four of 41 nodules in which the sonographic signal disappeard showed positive stain on dynamic MRI. The Sensitivity of Doppler ultrasonography was 73%; specificity, 100%; and accuracy, 92%. Flow signal in deeply (≥5 cm) located small (<3 cm) nodules tended to be more difficult to detect. We conclude that Doppler ultrasonography warrants use after TAE in the early evaluation as a specific and noninvasive imaging technique.     

Cluster Headache Like Symptoms Due to Sinusitis: Evidence for Neuronal Pathogenesis of Cluster Headache Syndrome

SYNOPSIS
Two patients with paranasal sinusitis, who showed cluster headache like symptoms rather than typical sinusitis symptoms, are reported. A possible mechanism of the cluster headache like symptoms is discussed. The importance of paranasal radiological study of patients with cluster headache like symptoms is emphasized. These cases seem to support a neuronal pathogenesis of the cluster headache syndrome.     

Comparison of the microbicidal activities of superoxidized and ozonated water in the disinfection of endoscopes

The microbicidal activities of superoxidized water (electrolysed strong acid water [ESAW] or electrolysed weak acid water [EWAW]), ozonated water, 0.05% chlorhexidine and 2% glutaraldehyde were tested against seven strains of clinical micro-organism isolates. Following incubation of bacterial suspensions in ESAW and EWAW for 10 s, the number of micro-organisms was reduced below the detection limit. The microbicidal activities of ESAW and EWAW were similar to that of glutaraldehyde, and superior to ozonated water and 0.05% chlorhexidine. The microbicidal activities of ESAW, EWAW and ozonated water were markedly diminished in the presence of albumin. Microbial contamination of upper gastrointestinal endoscopes was detected after 90 endoscopic procedures, but treatment of the endoscope with ESAW, EWAW or ozonated water eradicated the microbes. These results indicate that ESAW and EWAW are effective disinfectants after mechanical cleaning of upper gastrointestinal endoscopes, and can, therefore, be used in the endoscopy unit.     

Intercostal venous hemangioma presenting as a chest wall tumor

Chest wall tumors are uncommon, but intercostal hemangioma is even more so: There have been only a handful of reports on it to date. We report on a 32-year-old man with a left-side chest wall mass detected on a chest roentgenogram and computed tomography scans. The tumor was completely resected by means of video-assisted thoracic surgery. Two years after the surgery, the patient is doing well with no evidence of recurrence.