Dose and Load Studies for Subcutaneous and Oral Delivery of Poly(lactide-co-glycolide) Microspheres Containing Ovalbumin

Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 µm were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 µg of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fishers paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 µg OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freunds adjuvant.     

Bone Metastases from Soft Tissue Sarcomas

The incidence, distribution, time of appearance, and radiologic findings of bone metastases from soft tissue sarcomas, exclusive of lymphomas, were evaluated in 320 patients with soft tissue sarcomas. Thirty patients (9.4%) had evidence of 58 bone metastases. Five of 30 patients presented with metastases, and 25 of 30 patients developed metastases up to 66 months after presentation with a mean time interval of 21.3 months. The incidence of skeletal metastases differed among histologic subtypes of sarcomas; alveolar soft part sarcoma (5 of 8), dedifferentiated liposarcoma (2 of 4), angiosarcoma (2 of 4), and rhabdomyosarcoma (5 of 16) tended to show a higher incidence of bone metastases. The sarcomas metastasized to the regional bones close to the primary tumor in 16 (53%) of 30 patients and to the axial bones in 18 (60%). On conventional radiographs, the osseous metastases demonstrated predominantly osteolytic changes, and evidence of pathological fracture was observed in 31% of 58 metastases.     

Zelkovamycin, a new cyclic peptide antibiotic from Streptomyces sp. K96-0670. II. Structure elucidation

The structure of antibiotic zelkovamycin was elucidated as a cyclic peptide comprising glycyl, 2-aminobutanoyl, 2-amino-2-butenoyl, N-methyl glycyl, alanyl, 1,3-thiazoyl, 7-methoxytryptophanyl and 2-methyldehydrothreonyl residues. The sequence of the amino acids was established by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC, 13C-1H HMBC, 15N-1H HMQC and 15N-1H HMBC NMR experiments.     

Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979

Beauveria sp. FO-6979, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. A new compound beauveriolide III was isolated along with a known compound beauveriolide I from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Beauveriolides I and III caused a reduction in the number and size of cytosolic lipid droplets in macrophages at 10 microM without any cytotoxic effect on macrophages.     

Ferroverdins, inhibitors of cholesteryl ester transfer protein produced by Streptomyces sp. WK-5344. I. Production, isolation and biological properties

Streptomyces sp. WK-5344, a soil isolate, was found to produce structurally related inhibitors of cholesteryl ester transfer protein (CETP). New active compounds, designated ferroverdins B and C, were isolated along with known ferroverdin A from the fermentation broth by solvent extraction, ODS column chromatography and silica gel column chromatography. All ferroverdins showed a dose-dependent inhibitory activity against human CETP. The IC50 values were 21, 0.62 and 2.2 microM for ferroverdins A, B and C, respectively, indicating that ferroverdin B is one of the most potent CETP inhibitors of microbial origin.     

Proliferation of intrahepatic bile-duct epithelium in biliary atresia

Proliferating cell nuclear antigen (PCNA) and transforming growth factor (TGF) are considered as markers of cell proliferation. The expression of PCNA and TGF was evaluated immunohistochemically using anti-PCNA antibody and TGF in 31 patients with biliary atresia (BA) (15 jaundice-free and 16 with persistent jaundice) and 6 control infants. The labeling indices (LI) for PCNA- and TGF-positive bile-duct epithelium in BA were 14.1±14.0% and 51.4±33.7%, respectively, which was significantly higher than in the controls (P <0.01). In BA, the number of PCNA-immunoreactive cells was higher in the peripheral bile ductules than in the central bile ducts of the portal tract (P <0.01). LI was not related to patient age at the time of hepatic portoenterostomy in two groups divided at the age of 60 days. Patients in the persistent jaundice group had greater expression of PCNA and TGF (21.7±16.0% and 76.9±20.7%, respectively) compared to those in the jaundice-free group (6.0±2.7% and 24.3±20.9%, P <0.001). PCNA and TGF expression in the bile-duct epithelium of the portal tract was closely related to prognosis in BA patients, and thus could be useful as a prognostic marker.     

Clinical backgrounds in two kinds (absolute and relative) of mild pregnancy induced hypertension]

The criteria for pregnancy induced hypertension (PIH) have been determined by the Japanese Obstetrics and Gynecology Society. Mild PIH is classified into two types. One is "Absolute-PIH (A-PIH)" diagnosed by 1) systolic blood pressure (SBP) greater than = 140mmHg and less than 160mmHg or 2) diastolic blood pressure (DBP) greater than = 90mmHg and less than 110mmg. Another one is "Relative-PIH (R-PIH)" diagnosed by 3) an increase in SBP greater than = 30mmHg compared to normal SBP or 4) an increase in DBP greater than = 15mmHg compared to normal DBP. However, there has been no report in which two types of PIH are assessed. Our hypothesis is that the pathophysiology of two types of PIH is different. The purpose of this study is to clarify the pathophysiological difference by evaluating the clinical backgrounds. We evaluated 963 nullipara and 747 multipara whose pregnancies were recorded from the 1st trimester (multiple pregnancy and pre-term delivery before 32 gestational weeks were excluded). Among 765 nullipara women, 79.4% were diagnosed as having normal blood pressure (N-group), 7.1% as A-PIH, and 13.0% as R-PIH. In the multipara N-group, the figures were 632 women (84.6%), A-PIH, 4.6% and R-PIH, 10.3%. Clinical backgrounds showed that the incidence of hypertensive family history, high hematocrit (greater than = 39.0) before the 12th gestational week or obesity (Kaup index greater than = 24 before pregnancy) was significantly higher in A-PIH than in the N-group of nullipara and higher in the A-PIH than in the R-PIH and N-groups of multipara.(ABSTRACT TRUNCATED AT 250 WORDS)     

One-year prevalence and incidence of depression among first-year university students in Japan: a preliminary study

A structured interview was used to examine the 1-year incidence and prevalence of depression among 116 first-year university students. While 24 of the subjects (20.7%) met the Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV) criteria for Major Depressive Episode (MDE), 62 (53.4%) met the Diagnostic and Statistical Manual of Mental Disorders 3rd ed. Revised (DSM-III-R) criteria for MDE, and 27 (23.3%) also met the Research Diagnostic Criteria (RDC) for Major Depressive Disorder (MDD) for the 12 months prior to the interview. Moreover, 23 of the subjects (19.8%) had onset of the DSM-IV criteria for MDE, 54 (46.6%) had onset of the DSM-III-R criteria for MDE, 24 (20.7%) had onset of the RDC for MDD, during the same time period. These high rates of depression may be explained by the students' difficulties in and by their readjustment after entering university.     

Management of Hyperthyroidism Due to Graves' and Nodular Diseases

Endocrine surgeons have had an important role in the management of hyperthyroidism due to either Graves' disease or toxic nodule(s). Since alternative treatments such as antithyroid drugs or radioiodine are also available, the decision-making for management should be based on clear assessment of advantages and limitations of each of the treatment options. Surgery provides rapid resolution of these conditions, and cure rates are high, although it may be associated with perioperative complications and postoperative thyroid dysfunction. The authors' experience in the surgical treatment of hyperthyroidism and a review of the recent literature are outlined in this report.