Influences of histamine H1 receptor antagonists on maximal electroshock seizure in infant rats

The influences of histamine H1 receptor antagonists on maximal electroshock seizure were studied using infant rats. In this study, electroconvulsion was induced by stimulating rats using ear-clip electrodes, and the durations of electroencephalogram (EEG) seizure, tonic extensor (TE) seizure and clonic (CL) seizure induced by maximal electroshock were measured. Diphenhydramine, chlorpheniramine, cyproheptadine and ketotifen caused a dose-dependent and significant prolongation of both EEG seizure and TE seizure induced by maximal electroshock. On the other hand, epinastine and fexofenadine caused no such effects, even at a dose of 50 mg/kg. All drugs used in this study showed no significant effect on CL seizure induced by maximal electroshock. From these findings, it is suggested that epinastine and fexofenadine may cause no harmful influence on epilepsy, even when used in a little child.     

Anti-herpes simplex virus target of an acidic polysaccharide, nostoflan, from the edible blue-green alga Nostoc flagelliforme

The acidic polysaccharide nostoflan was previously isolated as an antiviral component from the terrestrial alga Nostoc flagelliforme. In the present study, we examined the target for its anti-herpes simplex virus type 1 action. In time-of-addition experiments, the most sensitive stage of viral replication to nostoflan was found to be early events, including the virus binding and/or penetration processes. In order to determine what extent nostoflan may be involved in these processes, virus binding and penetration assays were separately performed. The results indicated that the inhibition of virus binding to but not penetration into host cells was responsible for the antiherpetic effect induced by nostoflan. Our study suggests that nostoflan may be a potential antiherpes agent.     

Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting

Background

Although the aetiology of moyamoya disease (MMD) has not been fully clarified, genetic analysis of familial MMD (F‐MMD) has considerable potential to disclose it.

Objective

To determine the inheritance pattern and clinical characteristics of F‐MMD to enable precise genetic analyses of the disease.

Methods

15 highly aggregated Japanese families (52 patients; 38 women and 14 men) with three or more affected members were examined. The difference in categories of age at onset (child onset, adult onset and asymptomatic) between paternal and maternal transmission was compared by χ² statistics.

Results

In all families there had been three or more generations without consanguinity, and all types of transmission, including father‐to‐son, were observed. Among a total of 135 offspring of affected people, 59 (43.7%) were patients with MMD or obligatory carriers. Affected mothers were more likely to produce late‐onset (adult‐onset or asymptomatic) female offspring (p = 0.007).

Conclusions

The mode of inheritance of F‐MMD is autosomal dominant with incomplete penetrance. Thus, in future genetic studies on F‐MMD, parametric linkage analyses using large families with an autosomal dominant mode of inheritance are recommended. Genomic imprinting may be associated with the disease.Moyamoya disease (MMD) is an idiopathic progressive angiopathy characterised by progressive stenosis or occlusion and affecting the terminal portions of the bilateral internal carotid artery and the circle of Willis. Collateral vessels develop at the base of the brain to compensate for the progressive stenosis. These enlarged collaterals appear as a puff of smoke on angiography, which gives the disease its name.MMD is predominantly found in East Asian populations, with most reported cases originating from Japan, Korea and China. The estimated annual incidence in Japan in 1994 was 0.35 per 100 000 population,¹ whereas that in Europe was one tenth of this.² It is well known that MMD has been observed predominantly in women, with a female‐to‐male ratio of 1.8.^1,3 Recently, MMD has been diagnosed by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA),^4,5 which makes it possible to detect asymptomatic patients. Accordingly, familial occurrence has been increasing; it was observed in 12.1% of the patients in 2004.³ The female predominance, East Asian distribution and familial occurrence of the disease imply the existence of genetic risk factors.To clarify the genetic background of MMD, several non‐parametric linkage analyses using mainly affected sibling pairs have been carried out, showing linkages to 3p24.2–p26, 6q25, 8q23, 12p12 and 17q25.^6,7,8,9 The association analysis of tissue inhibitor of metalloproteinase 2 in 17q25 showed that a polymorphism in the promoter region was markedly associated with familial MMD (F‐MMD).¹⁰To make further progress in genetic analysis of the disease, it is important to enrol highly aggregated families with MMD to characterise the clinical features and inheritance patterns in F‐MMD. Some unresolved issues are as follows:

1. The mode of inheritance has not yet been determined.
2. Some reports mention that paternal transmission led to earlier onset than maternal transmission.¹¹ However, the difference between maternal and paternal transmission has not been proved by a statistical analysis.

The aim of this study is to resolve these issues, to enable precise genetic analyses of F‐MMD.     

Surgical technique in endoscopic posterior septoplasty for an adult patient with choanal stenosis

The technique in endoscopic posterior septoplasty for the case of a female aged 49 with bilateral choanal stenosis is presented. This female had undergone endoscopic nasal surgery for stenosis twice before the posterior septoplasty. However, restenosis of the choanae had arisen within 2 weeks after each surgery. This patient underwent the endoscopic posterior septoplasty under general anesthesia. After removal of the cartilage and bony structures of the nasal septum, the posterior one-third of bilateral septal membranes was excised. This technique is to enlarge the choanal opening obliquely. Excellent visualization for the septoplasty using the endoscope was obtained. Sufficient patency of the choanae was achieved using this technique. There still is no restenosis of the choanae observed and the rhinomanometry shows extreme decrease of nasal airway resistance 1 year after this surgery. It is considered that endoscopic posterior septoplasty for choanal stenosis is an effective procedure with low morbidity and long-term patency.     

Colorimetric lactate dehydrogenase (LDH) assay for evaluation of antiviral activity against bovine viral diarrhoea virus (BVDV) in vitro

A rapid and sensitive screening assay has been established for in vitro evaluation of antiviral compounds against bovine viral diarrhoea virus (BVDV), which is widely used as a surrogate for hepatitis C virus (HCV). The procedure is based on photospectrometrical assessment for the viability of virus-infected cells via extracellular leakage of lactic dehydrogenase (LDH). The level of LDH in culture supernatants of BVDV-infected Madin-Darby bovine kidney (MDBK) cells was significantly higher than those of mock-infected MDBK cells. Under optimized assay conditions, the LDH level was found to correlate well with the degree of viral replication. When the 50% effective concentrations (EC50s) of ribavirin, cyclosporine A and human interferon-alpha for BVDV replication were determined by the established LDH method and compared with those obtained by a conventional tetrazolium colorimetric (MTT) method, there was a complete correlation in EC50s between the two methods. Furthermore, a much higher ratio of background activity (noise) to sample activity (signal) could be achieved with the LDH method than with the MTT method, indicating that the present LDH assay permits a sensitive, rapid and reliable screening of compounds for their anti-BVDV activity and may be useful for the discovery of novel anti-HCV agents.     

Relationship between bone mineral density and urine level of NTx in rheumatoid arthritis

We analyzed the relationship between the level of type-I collagen N-telopeptide (NTx) in urine (U-NTx) and bone mineral density (BMD) in patients with rheumatoid arthritis (RA). The subjects were 62 female patients with RA who had experienced the menopause 5 years or more before the study commenced, and who had not been treated for osteoporosis. The mean age of the subjects was 61.6 years and the mean disease duration was 13.3 years. They were classified for global functional status (classes I to IV), and then grouped based on the presence or absence of corticosteroid administration. Bone mineral density (BMD) and U-NTx levels were measured. In the presence of corticosteroid administration (CS group; n = 40), the mean level of U-NTx/creatinine (Cr) was 88.8 nM and the percent young adult mean (%YAM) for BMD was 71.2%. In the no corticosteroid (nCS group; n = 22), the values were 72.1 nM and 78.2%, respectively. The U-NTx/Cr value and %YAM were not significantly different between the CS group and the nCS group. A negative correlation was observed between the U-NTx/Cr value and %YAM in both groups (P = 0.005 and P = 0.0265). No significant difference was observed for the U-NTx/Cr value or %YAM between the CS and nCS groups, in any class. In the CS group, a positive correlation was observed between the U-NTx/Cr value and the total dose of corticosteroid (P = 0.001), and a negative correlation was observed between the %YAM and the total dose of corticosteroid (P = 0.003). These results suggested that preventive medical treatment for osteoporosis is required for RA patients in class III, irrespective of whether they have had corticosteroid administration.     

Identification of a protanomalous chimpanzee by molecular genetic and electroretinogram analyses

We determined the structures of long (L)-wavelength-sensitive and middle (M)-wavelength-sensitive opsin gene array of 58 male chimpanzees and we investigated relative sensitivity to red and green lights by electroretinogram flicker photometry. One subject had protanomalous color vision, while others had normal color vision. Unlike in humans, a polymorphic difference in the copy number of the genes and a polymorphic base substitution at amino acid position 180 were not frequently observed in chimpanzees.     

Inhibitory effects of hyssop (Hyssopus officinalis) extracts on intestinal alpha-glucosidase activity and postprandial hyperglycemia

It has been known that Hyssopus officinalis (hyssop) is a herb that grows in the wild and is a source of natural antioxidants. We previously reported that a-glucosidase inhibitors, (2S, 3S)1-O-beta-D-6'-O-cinnamoylglucopyranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol and (2S, 3S)1-O-beta-D-glucopranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol, from the dry leaves of hyssop, were isolated. This study examined the alpha-glucosidase inhibitory effects of hyssop extracts on intestinal carbohydrate absorption in rat everted gut sac and carbohydrate-loaded hyperglycemia in mice. In the everted gut sac experiment, 10 mM sucrose- and 5 mM maltose-treated increases in glucose concentration in the serosal compartment were inhibited in the presence of 0.5 and 1.0 mg/ mL hyssop extracts, although a 10 mM glucose-induced increase in serosal glucose was not inhibited by the extracts. Additionally, hyperglycemia in sucrose- and maltose-loaded mice was significantly suppressed at an early stage, within 30 to 60 min by oral pre-administration of 300 and 100 mg/kg hyssop extracts, respectively. These findings suggest that hyssop extracts inhibited the digestion of complex carbohydrates, but not that of absorbable monosaccharide, and might be a useful supplemental food for hyperglycemia.