Adhesion of the subacromial bursa may cause subacromial impingement in patients with rotator cuff tears: pressure measurements in 18 patients

In order to determine whether adhesion of the subacromial bursa leads to impingement, we measured the subacromial contact pressures before and after release of adhesion of this bursa. 18 shoulders with cuff tears and adhesion of the subacromial bursa were evaluated in 8 male and 10 female patients, of mean age 62 (53-71) years and who had no particular limitation of shoulder motion. We recorded subacromial pressures using a very sensitive film inserted under the acromion during surgery. In passive scapular plane elevation (scaption) at 100 degrees, the mean subacromial contact pressure and area declined from 1.43 (SD 0.23) MPa before release to 1.14 (SD 0.35) MPa after release (p < 0.001), and from 163 (SD 81) mm2 before release to 80 (SD 46) mm2 after release (p < 0.001), respectively. We suggest that adhesion of the subacromial bursa increases impingement between the acromion and the insertion of rotator cuff tendons.     

Alveolar rhabdomyosarcoma originating in spermatic cord: a case report

A 19-year-old man visited our hospital complaining of swelling of the left inguinal region. A thumb head-sized tumor was palpated through the skin on the left spermatic cord. Tumor resection was performed because it was dissected easily apart from the left spermatic cord. Pathological examination revealed alveolar rhabdomyosarcoma with positive surgical margin. Computed tomographic scanning revealed no retroperitoneal lymph node swelling, and there were no clinical findings of distant metastasis (clinical stage I). Radical inguinal orchiectomy with combined chemotherapy using vincristine, dactinomycin, and ifosfamide (VAI) was performed. He has been alive without any recurrence for 8 years and 8 months after the surgery.     

The AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 genes, which encode functionally redundant kinesins, are essential for cytokinesis in Arabidopsis

Cytokinesis is the critical step during which daughter cells are separated. We showed previously that a protein complex that consists of NACK1 (and NACK2) kinesin-like protein and NPK1 MAPKKK and its substrate NQK1 MAPKK are required for progression of cytokinesis in Nicotiana tabacum. The genome of Arabidopsis thaliana encodes homologues of NACK1 and NACK2, namely, AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2, respectively. Loss-of-function mutations in AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 result in the occasional failure of somatic and male-meiotic cytokinesis, respectively. However, it is likely that these genes function redundantly to some extent in somatic tissues and female gametogenesis. We describe the phenotypes of Arabidopsis plants that have mutations in both the AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 genes. These phenotypes suggest that the two genes are essential during both male and female gametogenesis. Female gametes with atnack1 atnack2 double mutations failed to cellularize and to generate a central cell, synergids and the egg cells. Male gametes with atnack1 atnack2 mutations were also not transmitted to the next generation. The AtNACK1/HINKEL and STUD/TETRASPORE/AtNACK2 genes for kinesin-like proteins have overlapping functions that are essential for gametogenetic cytokinesis. They appear to be essential components of a MAP kinase cascade that promotes cytokinesis of plant cells in both gametophytic (haploid) and sporophytic (diploid) proliferation.     

Carcinogenic susceptibility to N-bis(2-hydroxypropyl)nitrosamine (DHPN) in rasH2 mice

To evaluate the susceptibility of rasH2 mice to N-bis(2-hydroxypropyl)nitrosamine (DHPN), a potent carcinogen targeting the lung, liver, thyroid, and kidney, male, 6-week old, rasH2 mice and wild-type littermates (non-Tg mice) were given DHPN in drinking water at 0, 20 or 200 ppm, and 0 or 200 ppm, respectively, for 26 weeks. The experiment using rasH2 mice given 200 ppm DHPN and non-Tg mice given 200 and 0 ppm DHPN was completed at 20 weeks, since mortality in these groups was remarkably increased due to hemangiosarcomas of the liver. Histologically, tumors developed in the lung and liver in both rasH2 and non-Tg mice treated with DHPN. In addition, proliferative lesions were observed in the forestomach, urethra, and excretory duct of salivary glands in rasH2 mice given 200 ppm DHPN. RT-PCR analysis showed no marked difference in expression of mRNAs for the transgene and the endogenous mouse ras gene between the whole lung tissue containing a neoplasm and normal lung tissue. Our results suggest that rasH2 mice are highly susceptible to DHPN, the target organs including the forestomach, salivary gland and urethra, which have not been found to develop tumors in previous long-term carcinogenicity studies of DHPN in rats and mice.     

Comparison of intraperitoneal continuous infusion of floxuridine and bolus administration in a peritoneal gastric cancer xenograft model

Purpose To identify the optimal schedule for intraperitoneal (i.p.) infusion of floxuridine (FUDR) against peritoneal micrometastases from gastric cancer.Methods The efficacy of continuous i.p. infusion of FUDR was compared with that of bolus i.p. administration in peritoneal gastric cancer (MKN45) xenografts. The FUDR continuous delivery system in this study was in the form of injectable poly(lactic-coglycolic) acid (PLGA) microspheres intended for i.p. injection. Animals were treated by continuous i.p. infusion using FUDR-loaded microspheres or bolus i.p. administration of FUDR.Results In vitro testing demonstrated that FUDR was released slowly from the microspheres at a rate of approximately 5% of the total encapsulated drug per day. In in vivo studies, the peritoneal level was found to persist and was approximately 5- to 50-fold higher than that of plasma for more than 2 weeks following a single injection of the microspheres. An in vitro MTT assay showed that exposure time clearly influenced the cytotoxic potency of FUDR. In vivo, continuous infusion was more effective against peritoneal tumor than bolus administration at equivalent doses. However, compared with bolus administration, toxicity was increased, resulting in a reduced maximum tolerated dose (MTD) with continuous infusion. When the treatment was carried out at each MTD (continuous 1 mg/kg, bolus 600 mg/kg), continuous infusion had no advantage in inhibiting tumor growth.Conclusions Owing to the higher toxicity and the equal efficacy of continuous infusion compared with bolus administration, continuous infusion is not recommended in i.p. FUDR treatment.This study was supported in part by a grant from the Japan Society for the Promotion of Science and by a grant from the Setsuro Fujii Memorial Osaka Foundation for Promotion of Fundamental Medical Research.     

Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and selegiline on bradykinesia and dopamine levels in a rat model of Parkinson's disease induced by the Japanese encephalitis virus

We previously reported that exogenously administered isatin, an endogenous monoamine oxidase (MAO) inhibitor, significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. Selegiline [(-)-deprenil] was developed as a MAO-B inhibitor more than 30 years ago and widely used in the treatment of Parkinson's disease. Effects of isatin or selegiline were investigated in Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test for detecting motor activity and by the determination of biogenic amine levels. Motor activity of JEV-induced rats receiving isatin (100 mg/kg per day for 1 week, i.p.) or selegiline (0.2 mg/kg per day for 1 week, i.p.) was significantly improved compared with that of untreated JEV-infected rats. Both isatin and selegiline prevented the decrease in striatal DA levels in JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not by selegiline. These results suggested that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.     

Permeation characteristics of a hydrophilic basic compound across a bio-mimetic artificial membrane

In the present study, the permeation characteristics of a hydrophilic basic compound (HBC) in a bio-mimetic parallel artificial membrane permeability assay (bio-mimetic PAMPA) were investigated in detail. The bio-mimetic PAMPA membrane was constructed on a hydrophobic filter by impregnating a lipid solution consisting of phosphatidylcholine (0.8%, w/w), phosphatidylethanolamine (0.8%, w/w), phosphatidylserine (0.2%, w/w), phosphatidylinositol (0.2%, w/w), cholesterol (1.0%, w/w), and 1,7-octadiene (97.0%, w/w). The pH-permeability curve (pH 3-10), the effect of lipid composition, concentration dependency (0.02-2.00 mM), and inhibition by other cationic compounds, were investigated for several HBCs. Ketoprofen and methylchlorpromazine were also employed as an acidic and a quaternary ammonium compound, respectively. At pH 3-6, the permeability of timolol, a HBC, was higher than expected from the pH-partition hypothesis, especially in the PI-containing membrane, whereas the pH-permeability curve of ketoprofen followed the pH-partition hypothesis. Permeation of HBC was saturable and inhibited by basic and quaternary ammonium compounds. Similar results were also found for methylchlorpromazine. The permeation characteristics of HBC observed in the present study are not usually expected in a passive permeation process across an artificial membrane. The participation of facilitated permeation of cationic species was suggested, in addition to a simple passive diffusion of un-dissociated species. Ion pair transport was suggested as a possible permeation mechanism of cationic species. However, further investigation is necessary to clarify the reason for the permeation characteristics of HBC.