Synthesis and central nervous system actions of thyrotropin-releasing hormone analogs containing a 1-substituted 2-oxoimadazolidine moiety*

A series of thyrotropin-releasing hormone (TRH) analogs in which the pyroglutamic acid residue was replaced by (S)-2-oxoimidazolidine-4-carboxylic acid (Oic-OH) and the related derivatives was prepared, and the central nervous system (CNS) actions were examined. Of these, 1-benzyl-Oic-His-Pro-NH₂ (2c) showed the most potent activities, which were 1.5-8 times greater than those of TRH. Moreover, the thyrotropin (TSH)-releasing activity of 2c was about 1/16 times weaker than that of TRH.     

Depleted intestinal goblet cells and severe pathological changes in SCID mice infected with Heligmosomoides polygyrus

To determine the role of T cells and mast cells in intestinal pathology and immune expulsion of intestinal nematodes, worm burdens, goblet cell responses and villus structures were analysed in T- and B-cell-deficient severe combined immunodeficiency (SCID) mice, athymic nu/nu mice and mast cell deficient W/W^v mice after infection with the nematode Heligmosomoides polygyrus. SCID and nu/nu mice showed significantly higher worm burdens at week 9 post-infection compared with the wild-type controls. SCID and nu/nu mice showed compromised goblet cell hyperplasia and/or Muc 2 expression, indicating that both events are T-cell dependant. On the other hand, the SCID mice showed increased pathology (villus atrophy and crypt hyperplasia) and increased numbers of proliferating cell nuclear antigen positive cells compared to the wild-type controls. W/W^v mice, conversely, were able to expel the worms normally, had normal goblet cell hyperplasia, and did not demonstrate the changes in mucosal architecture seen in SCID mice, confirming that a normal mast cell response is not necessarily required for these changes. These results suggest that a functional T-cell response, but not a mast cell response, is necessary for anti-parasite responses, goblet cell function, and maintaining normal mucosal architecture.     

Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and its treatment with sildenafil

BACKGROUND: We retrospectively evaluated the erectile function after nerve-sparing radical retropubic prostatectomy (RRP) and the efficacy of sildenafil for erectile dysfunction (ED) following RRP according to the preoperative erectile function. METHODS: We evaluated 48 Japanese patients who underwent nerve-sparing RRP at the Sapporo Medical University School of Medicine, Sapporo, Japan, between January 1996 and December 2001. Erectile function following nerve-sparing RRP was assessed by a simple mailed questionnaire that was constructed for the study. RESULTS: Of the 48 patients, 36 had normal erectile function preoperatively, but for 12, function was not sufficient to penetrate. The overall estimated recovery rates of any degree of erection were 50.6% at 36 months and 94.3% at 60 months. However, that of erection sufficient to penetrate was only 17.7% at 36 months and was only seen in bilateral nerve-sparing patients. Sildenafil was effective in 9 of 13 ED patients (69.2%) in both nerve-sparing groups. When patients were divided according to preoperative erectile function, no difference was found in the efficacy rate between patients with normal function and those with ED. CONCLUSIONS: Even bilateral nerve-sparing RRP can not always guarantee a sufficient erection. However, sildenafil is effective for ED following nerve-sparing RRP regardless of the nerve-sparing procedure or preoperative erectile function. Thus, preoperative function alone, although depending on its severity, may not necessarily be a reason for exclusion from receiving nerve-sparing RRP if patients want to have the operation.     

Effects of turpentine oil pretreatment on β-blocker pharmacokinetic parameters in rats

Abstract— Turpentine oil treatment (0·2 mL kg^?1, s.c.) was used to increase the plasma concentration of α₁-acid glycoprotein (0·13 mg mL^?1 in control rats) to 1·72 mg mL^?1 after 2 days, and allow assessment of its effects on the pharmacokinetics and stereoselective binding of three β-blockers. Racemates (5 mg kg^?1) were administered intravenously to control and turpentine oil-pretreated rats and the plasma concentrations were determined up to 90 min. Stereoselective analysis showed the apparent distribution volume and the area under plasma concentration-time curves (AUC) of R-(+)-propranolol to be, respectively, one-quarter and twice those of the S-(–)-enantiomer and differences in pharmacokinetic parameters between the two were magnified by turpentine oil pretreatment. Pharmacokinetic parameters of oxprenolol enantiomers were essentially similar for the controls but after turpentine oil pretreatment, a higher affinity of the R-(+)-enantiomer for plasma was observed. Acebutolol enantiomers behaved non-stereospecifically throughout. These results were consistent with predictions from the in-vitro stereospecific binding properties of these agents to purified rat α₁-acid glycoprotein.     

Outcome analysis for conservative management of Peyronie''s disease

BACKGROUND: We retrospectively analysed the outcomes of conservative management of Peyronie's disease and determined the factors predicting successful outcome. METHODS: The study involved 31 patients with Peyronie's disease who were treated at our institute between 1985 and 2003. We assessed the efficacy of vitamin E for the improvement of the symptoms, and the factors which contributed to successful outcome with conservative management using multivariate analysis. RESULTS: There was no statistically significant difference in the relief rate between the vitamin E and no-medication groups. The overall estimated relief rate was 67.5% at 2 years from presentation. The multivariate analysis revealed plaque size to be the only significant factor predicting the relief from all symptoms in patients with conservative management. The rate was 100% in patients having a plaque size of 20 mm or smaller and 20.0% in those having a size of larger than 20 mm (P=0.005). CONCLUSIONS: We could not confirm the benefit of vitamin E for Peyronie's disease. Plaque size was the only significant factor predicting the relief from all symptoms. Patients with larger plaque might fail to respond to the conservative management.     

Some sensory stimuli generate spontaneous K-complexes

Abstract The present study was performed in order to determine whether spontaneous K-complex are induced by sensory stimuli. Electroencephalogram (EEG) segments in stage 2 sleep containing an evoked K-complex or spontaneous K-complex were separately averaged with respect to the peak of N300, one of the main components constituting the K-complex. Small negative and positive components were found immediately before the main components of spontaneous K-complex in averaged EEG. These two components were judged to correspond to N100 and P200 induced by the sound stimulus. The present findings suggest that the spontaneous K-complex is not a spontaneous phenomenon but that it is induced by sensory stimuli.     

EFFECT OF FUSARIC ACID (A DOPAMINE β-HYDROXYLASE INHIBITOR) ON PHAEOCHROMOCYTOMA

Fusaric acid, an inhibitor of dopamine beta-hydroxylase, which converts dopamine to noradrenaline, lowered the blood pressure and induced a subjective improvement in patients with phaeochromocytoma. These effects may be due either to an impairment of catecholamine biosynthesis or to a direct action on the blood vessels. The use of this drug in the treatment of patients with inoperable malignant phaeochromocytoma or neuroblastoma may improve symptoms and prolong survival.     

A case of pelvic malignant paraganglioma

We report a rare case of pelvic malignant paraganglioma that was treated with surgery, combination chemotherapy and radiation. A 47-year-old man was diagnosed with pelvic malignant paraganglioma that had metastasised to the thoracic vertebrae. The pelvic mass, which was 6 cm in size, was on the posterior side of the bladder and had invaded the prostate, seminal vesicle and bladder neck. We resected the intrapelvic tumor and lymph nodes using cystoprostatectomy. Metastases to bilateral obturator lymph nodes and the right internal iliac lymph node were shown by pathology. Adjuvant therapies included six courses of the combination chemotherapy (cyclophosphamide, vincristine and dacarbazine), and 12 courses of VP-16 therapy. Radiation therapy was done for metastasis of the thoracic vertebrae. Local recurrence, progression of bone metastasis and new metastasis have not been detected since these treatments. The patient has been clinically stable during 20 months of follow-up. Chemotherapy of cyclophosphamide, vincristine and dacarbazine and VP-16 with radiation appears to be effective in treating advanced malignant paraganglioma.     

A negative component on event related potential recorded in the drowsy state

Abstract Behavior of event related potential (ERP) components in the drowsy state was examined in nine subjects using oddball paradigm. A component with peak latency of 300 msec, N300, was superimposed on ERP in the drowsy state. N300 appeared also in stage 1 of NREM sleep and closely resembled vertex sharp wave evoked by sound stimulation in both scalp distribution and peak latency. It was suggested that N300 recorded in the drowsy state and vertex sharp wave recorded in stage 1 of NREM sleep are generated by the identical synchronizing mechanism in the brain.