Behavioural Pharmacological Characteristics of Honokiol,an Anxiolytic Agent Present in Extracts of Magnolia Bark,Evaluated by an Elevated Plus-maze Test in Mice

Honokiol, a neolignane derivative of Magnolia bark, has central depressant action and, at much lower doses, anxiolytic activity. We have investigated the characteristics of the behavioural effects of honokiol by means of an elevated plus-maze test. In the plus-maze test a single oral dose of 20 mg kg^?1 honokiol significantly prolonged the time spent in the open arms of the maze, suggesting anxiolytic effect. Moreover, when honokiol was administered daily for seven days and the plus-maze test was conducted 3 or 24 h after the last administration, significant prolongation of the time in the open arms was manifested even for doses of 0.2 mg kg^?1. The maximum effect was observed for doses of 0.5 mg kg^?1. Honokiol at any dose in both single and repeated administration schedules caused neither change in motor activity nor disruption of traction performance. Orally administered diazepam, 0.5–2 mg kg^?1, caused dose-dependent prolongation of the time spent in the open arms of the maze with a significant increase in motor activity at 1 mg kg^?1, and dose-dependent disruption of traction performance. The changes in the plus-maze performance after treatment for seven days with 0.2 mg kg^?1 honokiol and after a single treatment with 1 mg kg^?1 diazepam were almost equivalent. The effect of honokiol (0.2 mg kg^?1, treatment for seven days) was inhibited by subcutaneous flumazenil (0.3 mg kg^?1) and (+)-bicuculline (0.1 mg kg^?1) and by intraperitoneal CCK-4 (50 μg kg^?1) and caffeine (30 mg kg^?1). The anxiolytic effect of diazepam (1 mg kg^?1) was also inhibited by flumazenil and bicuculline. However, the combined administration of diazepam with caffeine enhanced the effect, and diazepam completely reversed the effect of CCK-4. These results suggest that, in contrast with diazepam, honokiol selectively induces an anxiolytic effect with less liability of eliciting motor dysfunction and sedation or dis-inhibition. The combined effects of the drug also revealed that the mechanism of anxiolytic effect of honokiol is partially different from that of diazepam.     

Multiple Hypersonographic Spots in Basal Cell Carcinoma

BACKGROUND: High-frequency ultrasound is a useful method to obtain preoperative information regarding extension of basal cell carcinoma. Its contribution to diagnosis is generally limited, however. Recently, we observed hypersonographic spots in some cases of basal cell carcinoma. OBJECTIVE: The present study was performed to determine the diagnostic value of this finding in this type of tumor. MATERIALS AND METHODS: We conducted a retrospective study of archived sonographic images with a 30- or 15-MHz scanner and histology specimens of a total of 85 lesions, consisting of 29 basal cell carcinomas and 56 melanomas. RESULTS: The findings were classified into four patterns as follows: Type A, multiple (more than five spots/lesion) hypersonographic spots (14 cases, 48%); Type B, sparse (3-5 spots/lesion) hypersonographic spots (7 cases, 24%); Type C, multiple moderate sonographic spots (3 cases, 10%); and Type D, sparse moderate sonographic spots (5 cases, 17%). Three of 56 melanoma lesions examined as controls showed the Type D pattern, but none showed Type A, B, or C patterns. Histopathologically, these hypersonographic spots in BCCs seemed to correspond to calcification, horn cysts, or clusters of apoptotic cells in the centers of nests of basal cell carcinoma. CONCLUSION: Multiple hypersonographic spots might become a useful finding for differential diagnosis between basal cell carcinoma and melanoma.     

Age-dependent induction and maintenance of sensitization to methamphetamine-induced hyperactivity in mice

Abstract Repeated administrations of methamphetamine (2 mg/kg, s.c), 10 times at 3-day intervals, induced ambulatory sensitization in all groups of mice that were 13-, 15-, 19-, 23- and 36-weeks-old at the start of methamphetamine administration. The most prominent sensitization was observed in the 19-week-old mice. Among five groups of mice, even though the mice of 36 weeks old showed the highest sensitivity to methamphetamine at the first administration, they exhibited the lowest sensitization during the latter stage of repeated methamphetamine administration. Methamphetamine sensitization once established was well reproduced by the post-sensitization period of 8 weeks. Furthermore, the group of mice given methamphetamine with post-sensitization interval of 8 weeks (19-week-old mice) exhibited further enhancement of the sensitization. In contrast, the groups of mice given methamphetamine with post-sensitization intervals of 12 and 25 weeks (the 23- and 36-week-old, respectively) showed a significant reduced sensitization, and the latter group failed to reach the level of sensitization previously established. These results suggest that the induction of and maintenance of methamphetamine sensitization are dependent on the age of the mice, and that methamphetamine sensitization once established completely persists for up to 8 weeks.     

A case of leiomyosarcoma of the penis

A case of leiomyosarcoma of the penis is reported. A 27-year-old-man presented to our department with a mass at the root of the penis. Biopsy of the tumor showed that the tumor was leiomyosarcoma. The tumor was clinically and pathologically categorized into the deep type. Despite total penectomy and adjuvant chemotherapy, the patient died from disseminated disease 14 months after surgery. This is the 45th case of penile leiomyosarcoma.     

Neural substrates of emotional habituation: A PET study using film stimuli

Abstract  While external stimuli are given repeatedly, the level of emotional response gradually decreases. This study aims to reveal the neural substrates of such emotional habituation. Fifteen healthy male volunteers were examined using [¹⁵O]-H₂O-PET scanning. Subjects were required to watch two film clips, a horror scene (emotional task) and a calm scene (non-emotional task). Each film clip was repeatedly presented six times during 12 PET scans. The regional cerebral blood flow (rCBF) in the first two scans of each task was compared with that in the last two scans. On the emotional task, the right retrosplenial cortex (Brodmann's areas 30 and 23) was activated during the former scans, and the bilateral occipital cortices (BA19 and 37) were activated during the latter scans. As for the non-emotional task, the bilateral occipital cortices (BA19 and 37) were activated during the first two scans, and the bilateral prefrontal cortices (BA10) were activated during the last two scans. The activated cerebral region by emotional experience reciprocally transferred from the paralimbic region (the retrosplenial cortex) to the neocortical region (the bilateral occipital cortices) as the experience was repeated. This finding is consistent with the theory that the process of emotional habituation is promoted by the process of conceptualization.     

Diffuse xanthogranulomatous pyelonephritis in a patient with myotonic dystrophy and cerebral palsy

Xanthogranulomatous pyelonephritis (XGP), a morphological and clinical variant of chronic pyelonephritis, is an uncommon disease in children. It is characterized by the destruction of the renal parenchyma and replacement by granulomatous tissue containing foamy lipid-laden macrophages and is classified into diffuse and focal XGP. We present a case of diffuse XGP in a child with myotonic dystrophy complicated by cerebral palsy and discuss the importance of correct diagnosis and preoperative management to reduce inflammation and improve malnutrition associated with the disease.     

Allogeneic Bone Marrow Transplantation for the Treatment of Acute Leukemia: The Kanazawa Experience

Twelve patients with acute leukemia (7 with nonlymphoblasticleukemia and 5 with lymphoblastic leukemia) were treated withhigh-dose cyclophosphamide and 1,000 rad total body irradiationfollowed by allogeneic bone marrow transplantation from theirHLA-identical sibling donors. Of eight patients given transplantsat relapse, only one patient has become a long-term survivor;he is alive in disease-free complete remission (CR) 4 yr afterthe transplantation. A cure is probable in this patient. Offour patients given transplants during remission, two have survivedin unmaintained CR for almost 1 yr or more. Recurrent leukemiawas observed in two patients whose disease was resistant toconventional therapy at the time of transplantation. Major causesof treatment failure were interstitial pneumonia, hepatic failuredue to veno-occlusive disease, severe infection and relapse.Transplantation-related complications were more frequent andserious in patients who received transplants at relapse thanin those receiving them during remission. The incidence of graft-versus-hostdisease was relatively high but the disease was neither primarynor leading cause of death. These preliminary but relativelyencouraging data suggest that transplantation during remissionmay reduce posttransplant morbidity and mortality. This approachwill contribute to producing long-term survival or cure in patientswith adult acute leukemia if a suitable donor is available.     

一种新的合成salacinol衍生物的方法及其对α-糖苷酶的抑制活性

目的探索更有效的合成salacinol及其衍生物的方法，以研发新的糖尿病治疗药。方法以d-葡萄糖为原料，经7步反应制得 salacinol及其衍生物合成的关键中间体 2,4-o-异丙亚基-l-赤藓糖醇-1,3-环硫酸酯(2a)；此方法成本明显低于文献报道的以l-葡萄糖为原料的合成方法。以此方法，制备salacinol的含氮衍生物4，并与salacinol进行了体外抑制α-葡糖苷酶活性的比较研究。结果采用此种新的路线，顺利制得salacinol的含氮衍生物(4)及结构简化物(13)。结论以d-葡萄糖为原料的新的合成路线优于文献方法，salacinol分子结构中的硫原子用氮原子替代时，其活性明显降低。     

Protective effects of cyclodextrin sulphates against gentamicin-induced nephrotoxicity in the rat

Abstract— The effects of cyclodextrin sulphates on the development of rat renal dysfunction induced with gentamicin, an aminoglycoside antibiotic, were studied. Daily subcutaneous injection of gentamicin (100 mg kg^?1, 14 days) developed nephrotoxicity in the rat as assessed by an increase in serum urea nitrogen and histopathological changes in the renal cortex. When cyclodextrin sulphates were given intraperitoneally at 300 mg kg^?1 at 6 h intervals after gentamicin administration, they protected the rat against the drug-induced renal impairment, while the parent cyclodextrins were ineffective. Since post-administration of cyclodextrin sulphates did not reduce the total amount of gentamicin accumulated in the kidney, the protection may occur through interference with intracellular events leading from the drug accumulation to nephrotoxicity. These results suggest that cyclodextrin sulphates are particularly effective in preventing renal failure associated with aminoglycoside treatment.