ACCUMULATED ENDOGENOUS NITRIC OXIDE SYNTHASE INHIBITORS IN INHIBITING URETHRAL RELAXATION FOLLOWING ESTROGEN SUPPLEMENTATION IN OVARIECTOMIZED RABBITS

PURPOSE: We investigated the possible role of the endogenous nitric oxide (NO) synthase (NOS) inhibitors N-monomethyl-L-arginine (L-NMMA) and asymmetrical N, N-dimethyl-L-arginine (ADMA) in inhibiting urethral relaxation following estrogen supplementation in ovariectomized rabbits. MATERIALS AND METHODS: A total of 16 mature Japanese White female rabbits were divided into 2 groups. In the control group rabbits were sacrificed 2 weeks after bilateral ovariectomy. In the estrogen group estradiol was administered subcutaneously for 2 weeks with the aid of sustained release pellet from 2 weeks after ovariectomy until sacrifice. Isolated urethra was cut into transverse strips for functional study and processed to determine endogenous NOS inhibitors, NOS activity, dimethylarginine dimethylaminohydrolase (DDAH) activity as a metabolizing enzyme of endogenous NOS inhibitors and cyclic guanosine monophosphate production. RESULTS: Electrical field stimulation produced NO mediated and neurogenic relaxation of the urethral strip in the presence of guanethidine and atropine under contraction with phenylephrine. Relaxation was significantly decreased in the estrogen group and accompanied by decreased cyclic guanosine monophosphate production. Sodium nitroprusside induced relaxation was not different between the 2 groups. The content of L-NMMA plus ADMA in the urethra was significantly increased in the estrogen group. Ca dependent NOS activity in the urethra remained unaffected. DDAH activity was significantly lower in the estrogen group. CONCLUSIONS: Estrogen supplementation leads to decreased NO mediated and neurogenic urethral relaxation through the accumulation of L-NMMA and ADMA in the urethra. The accumulation of NOS inhibitors is possibly brought about by impaired DDAH activity.     

HSP-derived Peptides Inducing Uveitis and IgG and IgA Antibodies

Heat shock protein (HSP) 65 kD-derived peptides, which specifically stimulate T cells from patients with Behçet's disease (BD), are capable of inducing uveitis in rats. Mycobacterial HSP 65 kD and BD-specific peptides were injected into Lewis rats and the development of uveitis was monitored clinically and histologically, and IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Rats immunized with HSP peptides that developed uveitis showed significantly higher serum IgG antibody levels to peptide 311–326 (P<0.05) and the corresponding homologous human peptide 336–351 (P<0.01) than rats without uveitis. Significant increases in serum IgA antibodies in rats with uveitis were also observed in those immunized with peptides 111–125, 311–326 and 336–351 (P<0.05). Rats injected with HSP 65 kD showed a rise in IgG antibody levels to peptides 111–125, 154–172 and 311–326 and to a lesser extent, a rise in IgA antibody level to peptide 311–326. HSP showed almost complete inhibition of binding of IgG antibodies to HSP 65 kD, but peptides 111–125, 154–172, 311–326 and 336–351 showed inhibition to a lesser extent in a competitive assay. These results suggest that increases in IgG and IgA antibody levels to specific peptides within HSP, develop in rats with uveitis. The T and B cell epitopes responsible for the development of ocular disease in rats immunized with HSP-derived peptides, appear to be similar or identical to those found in patients with the ocular type of BD.     

Trigeminal Neuralgia in a Patient with Marfan Syndrome: Case Report

Marfan syndrome can demonstrate tortuous and elongated intracranial arteries. However, these arteries rarely cause neurovascular compression resulting in hemifacial spasm or trigeminal neuralgia. The authors report a 33-year-old woman who was diagnosed as Marfan syndrome, suffered from trigeminal neuralgia. Magnetic resonance (MR) angiography showed tortuous and elongated left vertebral artery (VA). The coronal section of three dimensional (3D) MR cisternography with contrast enhancement showed that the left trigeminal nerve was compressed from underneath by the tortuous and elongated left VA. After successful surgery of microvascular decompression, the patient’s symptom resolved and no recurrence was encountered. Neurosurgeons should not only be aware of hemifacial spasm but also of trigeminal neuralgia caused by elongated vessels in a patient with Marfan syndrome, although it is an extremely rare condition. In addition, offending vessel is not atherosclerotic in younger patients unlike usual cases of trigeminal neuralgia. Thus, microvascular decompression can be easier than usual cases. Care should be taken to prevent arterial dissection during transposition by using some technical tips.     

Stereoselective N-Demethylation of Chlorpheniramine by Rat-liver Microsomes and the Involvement of Cytochrome P450 Isozymes

Previous studies have suggested that degradation of the two stereoisomers of chlorpheniramine in the liver might be catalysed by different types of cytochrome P450. Stereoselective N-demethylation of chlorpheniramine and the involvement of cytochrome P450 (CYP) isozymes have, therefore, been investigated in the liver microsomes of eight-week-old male rats. Incubation of racemic chlorpheniramine with liver microsomes from the male rat resulted in the formation of both enantiomers of monodesmethylchlorpheniramine (DMChp). Further metabolism of DMChp to didesmethylchlorpheniramine (DDMChp) did not, however, occur. The S/R enantiomeric ratio for intrinsic clearance (V_max/K_m) was approximately 2.0, suggesting that the N-demethylation was stereoselective for S-(+)-chlorpheniramine. On the other hand, although the V_max/K_m value for the formation of S-(+)- and R-(–)-DMChp increased with phenobarbitone-inducible rat-liver microsomes, there was no difference between the rates of N-demethylation of the enantiomers. In contrast, 3-methylcholanthrene reduced the intrinsic clearance of S-(+)-chlorpheniramine by N-demethylation and increased its value for R-(–)-chlorpheniramine, showing no stereoselectivity for the N-demethylation of chlorpheniramine. The difference between the intrinsic clearance of the two enantiomers by N-demethylation was because of differences in affinity for the catalysing enzyme. This is indicative of stereoselective involvement of the main enzyme concerned in the N-demethylation of the enantiomers, considered to be CYP 2C11. Anti-CYP 2C11 also partially inhibited the N-demethylation of racemic chlorpheniramine in rat-liver microsomes exposed to phenobarbitone and 3-methylcholanthrene. That CYP 2B1 was involved in the N-demethylation of both enantiomers was also supported by results from an experiment using phenobarbitone-inducible rat-liver microsomes. CYP1A1 did not, however, catalyse the N-demethylation of either enantiomer. These results indicate that N-demethylation of the S-(+)-enantiomer of chlorpheniramine occurs preferentially in the microsomes, demonstrating the stereoselective contribution of CYP2C11. Immunoinhibition studies suggest, moreover, that the N-demethylation of both chlorpheniramine enantiomers is catalysed by CYP2B1, but not by CYP1A1.     

Local spread of HDV infection transiently occurring in Japan

Hepatitis B virus (HBV) carriers and patients with acute hepatitis B living in the Kamigoto islands, a part of Japan with a high incidence of HBV carriage, were retrospectively tested for serum anti-hepatitis D virus (anti-HDV) and they were compared with the inhabitants of Oita City (an area with an average HBV carriage rate). The prevalence of anti-HDV in HBV-infected individuals was 8.3% (42/507) in Kamigoto and 0% (0/101) in Oita City. With one exception, all of the positive serum samples in Kamigoto were collected before 1986, and the mean age of the positive individuals was significantly younger than that of the negative individuals (P < 0.005). Among the 42 anti-HDV-positive patients, nine (21%) had definite liver disease. The route of infection was uncertain in most cases (i.e. sporadic), but two pairs of mothers and children were detected. Although the prevalence of anti-HDV positivity in Japan has been reported to be very low (about 1% or less), the present investigation showed that the local spread of HDV infection in Kamigoto occurred on a minor scale up to 1986. The infections presumably resulted from the closed environment and the high incidence of HBV carriage in these islands. Accordingly, there could be a considerable risk of the outbreak of HDV infection in the future under similar conditions, even in countries where the disease has never been detected previously.     

CASE REPORT: Metachronous early gastric carcinoma in a reconstructed gastric tube after radical operation for oesophageal carcinoma

The incidence of double cancer has increased as a result of the signi?cant advances in both diagnostic procedures and anti-cancer therapy, and as the outcome of oesophageal squamous cell carcinoma (ESCC) has improved, the number of cases of double cancer of the oesophagus and stomach has also increased. Two patients with metachronous early gastric carcinoma in a reconstructed gastric tube were successfully treated after subtotal oesophagectomy for ESCC. These cases have shown that early diagnosis of second cancer is very important for curative therapy.     

A case of possessive state with onset influenced by 'door-to-door' sales

Abstract Recently in Japan, 'door-to-door sales' has become of concern because it has created numerous legal and social problems. In this paper, a 47 year old dissociative trance disorder case who presented with possession by God is discussed. Specific types of door-to-door sales is known to use superstition and folk beliefs as tools to lure customers. In this particular case, these religious factors seemed to have played an important role in the precipitation of the disorder and its presentation. In addition, the brain-washing environment observed in video lectures used in door-to-door sales seemed to play an important role in the development of the possessive state. We also performed social psychiatric analysis of the occurrence of the possessive state in a city area, which has been considered to develop within traditional culture. Phenomenological classification by one of the authors was useful for diagnosing underlying disorders in the possessive state.     

Consecutive cerebral MRI findings of acute relapsing disseminated encephalomyelitis

A seven year old girl with acute relapsing disseminated encephalomyelitis (ARDEM) was observed with serial magnetic resonance imaging (MRI) examination. She had the first encephalomyelitis episode at the age of 2 years 9 months. She entered remission with steroid therapy. She suffered a recurrence at the age of 7. Steroid therapy was instituted and consecutive magnetic resonance imaging (MRI) was performed. In spite of rapid improvement of neurological abnormality with steroid and steroid pulse therapy, disseminated high intensity lesions in T₂-weighted imaging which were considered as demyelination remained for a long time. Magnetic resonance imaging seems to be most suitable for evaluating the clinical condition and long-term follow-up of ARDEM.