肠溶性瑞巴派特壳聚糖胶囊的制备及大鼠口服给药吸收评价

目的评价肠溶性瑞巴派特壳聚糖胶囊的释药作用,考察其结肠定位效果。方法将瑞巴派特1 mg装入壳聚糖胶囊中,并用羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)包裹胶囊,观察胶囊的体外释药性能。在乙醚麻醉下通过聚乙烯管大鼠口服给予瑞巴派特壳聚糖胶囊4 mg,对照组口服同剂量的明胶胶囊和羧甲基纤维素溶液。于给定的时间间隔取血,取出结肠组织,分离提取药物,用HPLC法测定大鼠血液及结肠中药物浓度。结果在6 h体外溶出试验中,即人工胃液2 h和人工肠液4 h中,瑞巴派特从壳聚糖胶囊中的释药量的质量分数小于10%。大鼠口服瑞巴派特壳聚糖胶囊时,在结肠黏膜中的药物含量-时间曲线下面积(AUCLI0-9,16.01 mg.h.L-1)分别是明胶胶囊和羧甲基纤维素溶液的2.5倍和4.4倍。口服瑞巴派特壳聚糖胶囊,大鼠血浆药物含量-时间曲线下面积(AUCPL0-9)为1.02 mg.h.L-1,同剂量的明胶胶囊和羧甲基纤维素溶液分别是2.16 mg.h.L-1和1.89 mg.h.L-1,表明在壳聚糖的作用下,与明胶胶囊或羧甲基纤维素溶液比较,瑞巴派特从胃肠道吸收进入血液循环的量较少。结论在HPMCP的保护下,壳聚糖是瑞巴派特在结肠释药的一种有效的载体。     

A case with dicentric translocation between chromosome 9 and 18: Confirmation by fluorescent in situ hybridization on metaphase spread

A female child with dicentric translocation between chromosome 9 and chromosome 18 presented non-specific minor anomalies with laryngomalacia. Chromosomal analyses were performed by the G-banding method and a fluorescence in situ hybridization (FISH) technique with a specific probe for the centromeric region of chromosome 18 and the painting probe for the chromosomes 9 and 18. Her full karyotype was confirmed as 45, XX, tdic (9;18)(p24;p11). This is the first case of dicentric translocation between chromosomes 9 and 18. The FISH technique is an important tool in chromosome diagnostics.     

Anti-neutrophil cytoplasmic antibodies in Japanese children with ulcerative colitis

Objective: To investigate the diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of ulcerative colitis (UC) in Japanese children.
Methodology Serum samples from 23 children with UC (17 Japanese, 6 non-Japanese), 27 children with Crohn's disease (CD) (10 Japanese, 17 non-Japanese), 10 children with other diarrhoeal diseases, and 33 normal, healthy adult volunteers were assayed for ANCA using an indirect immunofluorescence technique.
Results ANCA were detected in 6/17 (35%) UC patients and 0/10 (0%) CD patients in Japanese children, and in 3/6 (50%) UC patients and 3/17 (18%) CD patients in non-Japanese children. The difference in prevalence between Japanese and non-Japanese children with UC was not statistically significant ( P >0.05). ANCA were not found in other diarrhoeal patients and volunteers.
Conclusions Although ANCA have been reported to be useful in the diagnosis of UC in adults, they may be of limited use in Japanese children. This might reflect the heterogeneity of UC.     

Inflammatory esophagogastric polyp and fold in an adolescent

The case of a 13 year old boy with an inflammatory esophagogastric polyp and ulcerative colitis is described. Endoscopy revealed a typical polyp and gastric fold complex at the esophagogastric junction and a hiatal hernia. Histology of a biopsy specimen confirmed an inflammatory polyp covered by hyperplastic squamous and gastric foveolar epithelium. Continuous 24 hour esophageal manometry suggested gastroesophageal reflux, which may be related to the pathogenesis of the lesion. Follow-up endoscopy showed marked regression of the polyp with medication for reflux eosphagitis. This clinical entity is rare in childhood and adolescence, and the manifestations may not be readily recognized. Therefore, endoscopic biopsy is important in children with esophageal polyps. However, polypectomy is unnecessary except when malignancy is suspected or when symptoms persist.     

Acute childhood leukemia in a patient with hemophilia: First report in Japan

This study reports an unusual case of acute leukemia which was diagnosed as hemophilia A on initial admission for leukemia. A 3 year old boy was admitted to Kagoshima University Hospital with anemia. He was diagnosed as acute lymphoblastic leukemia. At the same time he was revealed to have severe hemophilia A⁻ without any previous episodes of severe bleeding tendency or family history of this disease. The laboratory investigation showed his mother to be a carrier of hemophilia A. Although there are many cases of hemophilia which have developed malignant tumors, most of them were caused by association with human immunodeficiency virus (HIV) infection. Only five cases with coexistence of leukemia and hemophilia without HIV infection have been reported and the present case is the first one in Japan. At this stage, hemophiliacs are not necessarily regarded to be a population at risk for the development of leukemia. Furthermore, no particular subtype of leukemia was characterized among these patients in the literature.     

Effect of Sairei-to on irreversible glomerular sclerotic lesions in rats

The effects of Sairei-to and its active components on a model of irreversible mesangial proliferative glomerulonephritis induced by injecting monoclonal antibody (MoAb) 1-22-3 into uninephrectomized rats were examined. The significant suppressive effects of Sairei-to and its active components on proteinuria were demonstrated on days 7, 14, 21 after MoAb 1-22-3 injection compared with phosphate-buffered saline (PBS)-treated controls. On day 21, light microscopy revealed that the drugs reduced mesangial cell proliferation, mesangial matrix expansion (matrix score: 84.5±41.6 for Sairei-to, 76.1±31.9 for Syo-saiko-to, 66.7±46.3 for its three components vs 162.4±26.1 for PBS, P<0.005) and crescent formation (mean percentage: 2.25% for Sairei-to, 1.71% for Syo-saiko-to, 1.43% for its three components vs 18.86% for PBS, P<0.005). The kidney weights of the groups given the drugs were significantly lower than the PBS group value (1.03±0.08 g with Sairei-to, 1.11±0.12 g with Syo-saiko-to, 1.06±0.12 g with its three components vs 1.39±0.20 g with PBS, P<0.01 or P<0.05). Immunofluorescence analysis revealed that the drugs suppressed the expression of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and collagen type I in the glomeruli, and reduced the numbers of ED1-positive cells in the glomeruli and OX8-positive cells in the glomeruli and in the tubular interstitium. The blood biochemistry results revealed significant differences between the total cholesterol levels (70.0±5.9 mg/dL with Sairei-to, 66.0±6.4 mg/dL with Syo-saiko-to, 76.6±8.4 mg/dL with its three components vs 104.3±26.6 mg/dL with PBS, P<0.05). We conclude that Sairei-to and its active components have suppressive effects on proteinuria and mesangial matrix expansion in rats with irreversible renal sclerosis. Transforming growth factor-β, collagen type I and α-SMA expression and infiltration by ED1- and OX8-positive cells were also suppressed by these drug preparations.     

Intraspinal Metastasis of Neuroblastoma -- Report of a Case Detected at Autopsy --

Metastasis to the brain or spinal cord parenchyma is extremelyrare in cases of neuroblastoma. We present a 3-year-7-month-old boy with neuroblastoma, stageIV, with intraspinal metastasis. He had no neurologic manifestationexcept incontinentia urinae and ataxia at the terminal stage.His cranial computed tomography scan showed high density areasin both cerebellar hemispheres which seemed to be distant metastaticmasses. At autopsy, the metastases in the cerebellum were foundto be due to dural infiltration but in the spinal cord parenchymaof the lumbar spine metastases were detected macroscopically.There were multiple distant metastatic areas near the roots,anterior and posterior. The neuroblastoma seemed to have spreadalong the roots by direct invasion from the meninges. In the future, the number of patients with metastasis into thebrain or spinal cord parenchyma will increase because patientswith progressive disease could live for a long time as a resultof intensive chemotherapy. Observation of these cases will behelpful to clarify the routes of metastasis to these areas.     

Acute Effects of Different Atrial Pacing Sites in Patients with Atrial Fibrillation: Comparison of Single Site and Biatrial Pacing

It has been reported that a trial single site or biatrial pacing can suppress the occurrence of AF. However, its mechanism remains unclear. The study population included 32 patients with AF (n = 20: AF group), or without paroxysmal AF (n = 12: control group). The mechanism and efficacy of atrial pacing were investigated by electrophysiological studies to determine which was more effective for suppressing AF induction; single site pacing of the right atrial appendage (RAA) or distal coronary sinus (CS-d), or biatrial (simultaneous BAA and CS-d) pacing. In the AF group, AF inducibility was significantly higher with BAA extrastimulus during RAA (12/20; P < 0.0001) or biatrial paced drive (7/20; P < 0.01) than during CS-d paced drive (0/20). In the control group, AF was not induced at any site paced. In the AF group, the conduction delay and other parameters of atrial vulnerability significantly improved during CS-d paced drive. The atrial recovery time (ART) at RAA and CS-d was measured during each basic pacing mode. ART was defined as the sum of the activation time and refractory period, and the difference between ARTs at RAA and CS-d was calculated as the ART difference (ARTD). The ARTD was significantly longer during BAA pacing in the AF group than in control group (155.0 +/- 32.8 vs 128.8 +/- 32.9 ms, P < 0.05). In the AFgroup, ARTDs during biatrial (52.0 +/- 24.2 ms) and CS-d pacing (51.7 +/- 26.0 ms) were significantly shorter than ARTD during RAA pacing. The CS-d paced drive was more effective for suppressing AF induction than biatrial or RAA paced drive by alleviating conduction delay. CS-d and biatrial pacing significantly reduced ARTD compared with RAA pacing.     

A case of linear IgA buUous dermatosis with IgA anti-type VII collagen autoantibodies

Summary In this study we present a patient with the sublamina densa type of linear IgA bullous dermatosis (LABD). with IgA autoantibodies reactive with the 290-kDa type VII collagen (the epidermolysis bullosa acquisita (EBA) antigen) and with immunoblotting of normal human dermal extracts. The clinical and histological features of the present case were compatible with those of LABI) but quite different from those of RBA. Although EBA sera reacted with the bacterial fusion protein of the N-terminal globular (NC1) domain of type VII collagen, this patient's serum did not show reactivity. Furthermore, ultrastructural localization of target epitopes on the anchoring fibrils in this patient was considerably different from EBA. These results indicate that, whereas EBA antibodies react with the NC1 domain of type VII collagen, the epitope in this case is different from that of EBA (and is most likely on the central triple helical domain). This difference may be responsible for the clinical presentation in this patient being distinct from that of EBA.     

GENOTYPES OF ALDH2 RELATED TO LIVER AND PULMONARY DISEASES AND OTHER GENETIC FACTORS RELATED TO ALCOHOLIC LIVER DISEASE

Genetic factors related to the development of alcoholic liverand pancreatic diseases (ALD and APD) and of alcohol-inducedasthma were analyzed. The development of ALD is geneticallycontrolled and is directly associated with the polymorphismsof the genes of acetaldehyde (Ac-CHO) and ethanol-metabolizingenzymes, aldehyde dehydrogenase-2 (ALDH2) and cytochrome P4502E1.The development of ALD and APD may also be genetically linkedwith the induction of gamma-glutamyl transferase (GTT) by alcohol.Alcohol-induced asthma is related to the genotypes of ALDH2and is caused by rapid elevation of blood Ac-CHO. ALDH1 playsa very important role in the oxidation of Ac CHO in blood.