Trehalose solution protects mesothelium and reduces bowel adhesions.

BACKGROUND: Preventing interbowel adhesions still remains a challenge. Peritoneal mesothelial damage can induce postoperative adhesions. Our study evaluated the effects of 3% trehalose solution on mesothelial protection and adhesion prevention. Also, we compared this novel solution with Seprafilm regarding efficacy. METHODS: Mesothelial damage was induced on the cultured human mesothelial cell (Met-5A) and rabbit cecum-serosal surface by air-drying for 60 min, and trehalose solution was applied. Cell integrity was tested by measuring lactate dehydrogenase, and serosal-morphologic changes were analyzed using scanning electron microscopy. Intra-abdominal adhesions were induced in rabbits by the combination of abrasion and air-drying procedures. Animals were divided into four groups: control, 3% trehalose solution, Seprafilm, and 3% trehalose solution with Seprafilm. Adhesions were evaluated blindly 7 d later. RESULTS: Lactate dehydrogenase release from the Met-5A cells was reduced dose-dependently by trehalose (P < 0.05). Morphologic studies clearly showed that mesothelial cells on the serosal surface were kept intact by 3% trehalose solution. In a rabbit adhesion model, 3% trehalose solution reduced adhesions between bowel and bowel or bowel and surrounding structures (P < 0.01 versus control and Seprafilm). Seprafilm reduced adhesions between abdominal wall and underlying viscera (P < 0.01 versus control and 3% trehalose solution). Three-percent trehalose solution with Seprafilm showed additive effects of adhesion prevention, reducing adhesion formation at the previously mentioned sites. CONCLUSIONS: Three-percent trehalose solution protects mesothelial cells and leads to reduced adhesions between bowel and bowel or bowel and surrounding structures. This effect seems to be resulted from the characteristics of the solution covering most areas that potentially develop adhesions.

Investigation of unifying transcutaneous transformer for transmission of energy and information.

When patients are fitted with a totally implantable artificial heart (TAH), they need to be implanted with two additional devices: one for the transmission of energy and one for information. However, this is a cumbersome process that affects the quality of life of the recipient. Therefore, we investigated the use of electromagnetic coupling for the transmission of energy and information and the possibility of unifying two transcutaneous transformers for the simultaneous transmission of energy and information. While unifying the transformers, it is important to suppress the electromagnetic coupling between energy and information transmission. Therefore, we ensured that the electromagnetic fields generated from the transformer windings for the transmissions of information and energy intersected perpendicularly. If the fields are perpendicular, the electromagnetic coupling between the energy and information transmissions will be suppressed significantly. The characteristics of the simultaneous transmission of information and energy using the unified transcutaneous transformer, developed experimentally, were evaluated by changing the number of windings used for the transmission of information. The electromagnetic coupling between the energy and information transmissions was suppressed by determining the direction of the magnetic field. Moreover, the optimum number of transformer windings required for the simultaneous transmission of energy and information was determined. We concluded that the externally coupled transcutaneous transformer unified for the simultaneous transmission of energy and information performed with good transmission characteristics.

Analysis of type of cell death induced by topoisomerase inhibitor SN-38 in human oral squamous cell carcinoma cell lines.

Despite frequent use of topoisomerase inhibitors (TIs) as antitumor agents, their application to oral squamous cell carcinoma (OSCC) has not been reported. We investigated three inhibitors of topoisomerase I [camptothecin, irinotecan, SN-38 (active metabolite of irinotecan)] and two inhibitors of topoisomerase II (etoposide, teniposide) for their cytotoxicity towards a total of 15 human tumor cell lines and normal cultured cells. All TIs exhibited higher cytotoxicity towards tumor cell lines (OSCC, glioblastoma, myelogenous leukemia) as compared with normal mesenchymal (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and epithelial cells (skin keratinocytes). Among TIs, SN-38 had the highest cytotoxicity towards OSCC cell lines, with a tumor specificity index of 1321 compared to mesenchymal cells and 22 compared with epithelial cells. SN-38 induced different types of cell death in two OSCC cell lines: apoptosis (caspase-3 activation and internucleosomal DNA fragmentation) in HSC-2 cells and autophagy (formation of autophagosome and secondary lysosome) in HSC-4 cells. The cell death of HSC-2 and HSC-4 cells was significantly inhibited by pre-treatment with caspase inhibitor (Z-VAD-FMK) and autophagy inhibitors (3-methyladenine, bafilomycin A1), respectively. The present study demonstrated that SN-38 is highly cytotoxic to OSCC cell lines, regardless of the type of induced cell death, suggesting its future application for chemotherapy of OSCC.

Relationship between single nucleotide polymorphisms in CYP1A1 and CYP1B1 genes and the bone mineral density and serum lipid profiles in postmenopausal Japanese women taking hormone therapy.

OBJECTIVE: The genetic variations of the genes encoding cytochrome P-450 enzymes are considered to play an important role in the metabolism of estradiol. The objective of this study was to evaluate the relationships among single nucleotide polymorphisms (SNPs) of cytochrome P-450 genes, lumbar bone mineral density (BMD), and serum lipids and to determine the effects of hormone therapy (HT). DESIGN: The participants were 124 Japanese women who had been diagnosed with osteopenia or osteoporosis and were taking HT for 12 months. Seven single nucleotide polymorphisms in the CYP1A1 and CYP1B1 genes were characterized. Lumbar BMD and the levels of serum lipids were measured before and after HT. RESULTS: A single nucleotide polymorphism in exon 3 of CYP1B1 was found to be significantly associated with the effect of HT on BMD and low-density lipoprotein cholesterol both in univariate and multivariate analyses. In the women with the GG genotype of L432V, the responses to HT of BMD and low-density lipoprotein cholesterol markedly decreased. The serum follicle-stimulating hormone level after HT was significantly higher in the women with the GG genotype of L432V. CONCLUSIONS: These results suggest that the L432V polymorphism in the CYP1B1 gene could therefore be used to predict the effect of HT on lumbar BMD and low-density lipoprotein cholesterol in Japanese women.

Non-apoptotic cell death induced by nutritional starvation in J774.1 mouse macrophage-like cell line.

The growth and amino acid utilization of a mouse macrophage-like cell line J774.1 was investigated in two different culture media supplemented with 10% fetal bovine serum (FBS). The J774.1 cells grew faster, and consumed glutamine and serine at higher rates in DMEM than in RPMI1640 medium. The consumption of other amino acids was much less, while considerable quantities of alanine, glutamic acid and glycine were produced by the J774.1 cells. When the cells became confluent, serine, but not glutamine, was nearly depleted from the culture medium, followed by cell death characterized by smear DNA fragmentation, slight caspase-3 activation and structural damage of the mitochondria. Serine is required for the growth of mouse macrophage-like cell lines, and DMEM is superior to RPMI1640 for long-term cell culture.

Four cases of fetal hypoechoic hepatomegaly associated with Trisomy 21 and transient abnormal myelopoiesis.

OBJECTIVE: Our objective was to determine the clinical significance of fetal hypoechoic hepatomegaly and serial change of liver sizes. METHODS: The liver sizes of four fetuses with hypoechoic hepatomegaly were serially estimated by liver length, as measured from the dome of the right hemidiaphragm to the tip of the right lobe. RESULTS: All cases were associated with trisomy 21 or transient abnormal myelopoiesis (TAM). Two cases were trisomy 21 with TAM, one case was a phenotypically normal newborn, who had developed TAM during the fetal period, and the last case was trisomy 21 without TAM. In the last case, it is speculated that TAM had developed and regressed completely before birth. Two cases, whose hepatomegaly had improved before birth, showed good prognosis and the other two cases, in whom improvement had not been observed, resulted in death after birth by liver failure. CONCLUSION: These experiences show that one of the differential diagnoses of hypoechoic hepatosplenomegaly is TAM and that the change of live size is a predictor of prognosis.

Prophylactic therapy for patients with reproductive failure who were positive for anti-phospholipid antibodies.

PROBLEM: To elucidate the efficacy of the treatment using a Japanese-modified Chinese herbal medicine, Sairei-to, and low-dose aspirin with or without a corticosteroid hormone for the patients with adverse pregnancy histories positive for anti-phospholipid antibodies. METHOD OF STUDY: Fifteen cases positive for anti-phospholipid antibodies, who had experienced preterm delivery in which an extremely low birthweight infant (<1000 g) was born as a result of intrauterine growth restriction with or without severe preeclampsia, were treated with the medication according to the current protocol. Four cases with the same condition, who were treated with only low-dose aspirin, or without medication, were chosen as a control population. The pregnancy outcome was compared between the two groups. RESULTS: The rate of patients in whom the next pregnancy continued until the 36th week of gestation or later was significantly higher in treated patients (80.0%) compared with the control population (0%). CONCLUSIONS: In this series, we obtained case report data that Sairei-to may provide some benefit for patients with reproductive disorders positive for anti-phospholipid antibodies; however, randomized controlled trial evidence is needed before current treatment can be recommended.

Stage IVa squamous cell carcinoma of the vulva managed with primary chemoradiation.

We present the case of a 53-year-old woman with International Federation of Gynecology and Obstetrics stage IVa (T3N2M0) squamous cell carcinoma of the vulva. Because the urethra was surrounded by a vulvar tumor, she was managed with primary chemoradiation in an attempt to spare the morbidity associated with exenterative vulvar surgery. Treatment was given as a planned split course, consisting of two separate courses of 23.8 Gy each. During each split course of radiation, 5-fluorouracil, 1000 mg/m2 per day, was given over the first 4 days, and cisplatin 50 mg/m2 was administered as a single infusion on the first day. During the 4 days of chemotherapy infusion, the radiation was administered in two daily fractions of 1.7 Gy each, given at least 6 h apart. There was no treatment break due to adverse effect, and a pathological complete response was achieved in the primary tumor and the lymph nodes. The patient did not undergo surgical intervention, and has had no evidence of recurrence for 24 months. Chemoradiation therapy should be considered as an option in patients with locally advanced vulvar cancer to avert the need for exenterative surgery, and to preserve sexual, gastrointestinal, and urinary function.

Effects of testosterone on cancellous bone, marrow adipocytes, and ovarian phenotype in a young female rat model of polycystic ovary syndrome.

OBJECTIVE: To investigate the effects of testosterone on cancellous bone and marrow adipocytes in a young female rat model of polycystic ovary syndrome (PCOS). DESIGN: Comparative and controlled study. SETTING: University animal research laboratory. PATIENT(S): Fifty-one Sprague-Dawley rats. INTERVENTION(S): The rats were divided into four groups based on the day of testosterone propionate (0.1 mg/weight (g)) injection: no testosterone treatment (control group, C); injected on the ninth day after birth (9D); injected 4 weeks after birth (4W); and injected 8 weeks after birth (8W). About 16 weeks after birth, all animals were killed. MAIN OUTCOME MEASURE(S): Bone mineral density (BMD) and bone and fat histomorphometry for the proximal tibia and serum hormonal parameters were measured. RESULT(S): The ovaries of group 9D showed many cystic follicles without corpora lutea. The BMD of group 9D (0.309 +/- 0.023 g/cm2) was significantly higher than the other groups groups (CONT, 0.262 +/- 0.017; 4W, 0.256 +/- 0.017; 8W, 0.256 +/- 0.022 g/cm2; P < .0001). Based on bone histomorphometry, group 9D had a higher bone volume (BV/TV), lower bone formation (OV/BV, OS/BS, sLS/BS, MAR, BFR/BS), lower bone resorption (ES/BS, Oc.S/BS), and lower rate of longitudinal growth compared to the other groups. Based on fat histomorphometry, group 9D had a lower bone fat volume and number of fat cells in the bone marrow compared to the other groups. On the other hand, groups 4W and 8W showed similar values of bone and fat histomorphometric parameters to group C. CONCLUSION(S): Female rats receiving testosterone within nine days of birth develop polycystic ovaries, high bone volume, low bone turnover, and lower fat content in the bone marrow.