Content variations of the tomato saponin esculeoside A in various processed tomatoes

A tomato saponin, esculeoside A, may be metabolized into various steroidal hormones such as pregnane derivatives that are expected to exhibit various bioactivities in the body, such as anti-osteoporosis, anti-menopausal disorder and anti-tumor actions. Therefore, we attempted to examine the esculeoside A contents of fresh tomatoes, tomatoes boiled in water, tomatoes heated using a microwave oven, freeze-dried tomatoes, and commercially available processed tomato products contained in plastic bottles and cans, in order to develop a health food.     

Inhibition of mTOR by temsirolimus contributes to prolonged survival of mice with pleural dissemination of non-small-cell lung cancer cells

Temsirolimus (CCI-779), a recently synthesized analogue of rapamycin, specifically inhibits mTOR and has been approved for clinical use in renal cell carcinoma. Recent reports have indicated the growth inhibitory effect of temsirolimus in some cancers including non-small-cell lung carcinoma (NSCLC). In this study, we aimed to explore the potential therapeutic use of temsirolimus as a treatment for NSCLC. Using cultured NSCLC cells (A549, H1299, and H358), we determined the effect of temsirolimus on cell proliferation and its antitumor effects on subcutaneous tumors, as well as its contribution to the survival of mice having pleural dissemination of cancer cells, mimicking advanced NSCLC. Temsirolimus suppressed proliferation of NSCLC cells in a dose-dependent manner, with an IC(50) of <1 nM. Western blot analysis revealed that temsirolimus treatment specifically inhibited the phosphorylation of mTOR and its downstream effectors in 1 h, accompanied by an increased cell population in the G(0) /G(1) phase, but according to flow cytometry, the cell population did not increase in the sub-G(0) phase. When NSCLC subcutaneous tumor-bearing mice were treated with temsirolimus, tumor volume was significantly reduced (tumor volume on day 35: vehicle vs temsirolimus = 1239 vs 698 cm(3) ; P < 0.05). Furthermore, prolonged survival was observed in pleural disseminated tumor-bearing mice with temsirolimus treatment (median survival: vehicle vs temsirolimus = 53.5 vs 72.5 days; P < 0.05). These results suggest that temsirolimus could be useful for NSCLC treatment, due to its antiproliferative effect, and could be a potential treatment for advanced NSCLC, giving prolonged survival.     

Prediction of outcome of patients with oral squamous cell carcinoma using vascular invasion and the strongly positive expression of vascular endothelial growth factors

Vascular invasion and lymph node metastasis have been used as histopathological prognosticators of cancers including oral squamous cell carcinoma (OSCC). In addition to metastatic potential via blood vessels, tumor-induced angiogenesis might also be associated with prognosis. However, the efficacy of combined evaluation of vascular invasion and angiogenesis-associated molecules for the prognosis of OSCC remains obscure. This is also the case in lymph node metastasis and lymphovasculogenesis-associated molecules. The aim of this study was to examine factors related to prognosis to improve the accuracy of prognostic prediction of OSCC using vasculogenesis-associated markers. Ninety specimens of patients from 1991 to 2002 with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed using antibodies for vascular endothelial growth factor (VEGF)-A, VEGF-C, cyclooxygenase (COX)-2 and Midkine. The ninety cases were composed of 72 well-differentiated, 12 moderately differentiated and 6 poorly differentiated OSCC. Efficient models of prognostic prediction were evaluated by extensive statistical analyses. The presence of vascular invasion or lymph node metastasis was confirmed to be significantly associated with poor prognosis in the univariate analysis. Multivariate logic regression analysis suggested that patients with the strongly positive expression of either VEGF-A or VEGF-C had a significant association with poor prognosis even in patients without vascular invasion and in early-stage patients. Neither COX-2 nor Midkine contributed to predict the prognosis of the patients. The strongly positive expression of VEGF-A or VEGF-C was suggested to reinforce the histopathological diagnosis of vascular invasion and improve the accuracy and efficacy of prognostic prediction of OSCC.     

Nutritional recovery after open and laparoscopic gastrectomies

Background  

The aim of this study was to evaluate longitudinal changes in body composition after laparoscopic and open gastrectomies for gastric cancer.     

Double vascular anastomosis in the neck for reliable free jejunal transfer

To reduce the possibility of necrosis in free jejunal transfer after total pharyngolaryngo-oesophagectomy, we made a second set of arterial and venous anastomoses in addition to the usual cervical arterial and venous anastomoses. To obtain two different arterial flows (carotid and subclavian systems), the recipient arteries were the superior thyroid and the transverse cervical. For venous flow, the internal and external jugular veins were used. All flaps survived. This procedure, which is limited to the already dissected neck with no procedures in other areas, is less invasive than others. Its advantages are that when one vessel has thrombosed the other vessel functions as a safety valve, and the greater pliability of the vascular pedicles makes it easier to reach the recipient vessels. Because this method is theoretically safe and results in less possibility of losing a flap when the anastomosis is unreliable, the double-pedicled transfer can be an option for safer free jejunal transfer.     

Comparative Effects of Benidipine and Amlodipine on Proteinuria,Urinary 8-OHdG,Urinary L-FABP,and Inflammatory and Atherosclerosis Markers in Early-Stage Chronic Kidney Disease

IntroductionWe examined the effects of 2 calcium channel blockers, benidipine (T-, L-, and N-type) and amlodipine (L- and N-type), on renal, inflammatory, oxidative, and atherosclerosis markers in hypertensive patients with mild chronic kidney disease (CKD).MethodsForty hypertensive patients with CKD were assigned randomly to either of the 2 treatments: 8 mg benidipine once daily (n = 20, group A) or 5 mg amlodipine once daily (n = 20, group B). Treatment was continued for 12 months. Blood pressure, serum creatinine, estimated glomerular filtration rate, urinary protein excretion, urinary liver-type fatty acid-binding protein, interleukin-6, high mobility group box-1 protein, urinary 8-hydroxy-2′- deoxyguanosine, pulse wave velocity, intima-media thickness, and blood asymmetric dimethylarginine were monitored.ResultsBlood pressure decreased equally in both groups (P < 0.001, at 6 and 12 months versus before treatment). Serum creatinine and estimated glomerular filtration rate changed little during the experimental period in each group. However, urinary protein excretion (P < 0.001), urinary liver-type fatty acid-binding protein (P < 0.001), urinary 8-hydroxy-2'-deoxyguanosine (P < 0.001), blood interleukin-6 (P < 0.001), blood high mobility group box-1 (P < 0.5), and pulse wave velocity (P < 0.01) decreased more in group A than in group B with 12 months of treatment. The percent reductions in intima-media thickness and blood asymmetric dimethylarginine were significantly greater in group A than in group B (P < 0.001).ConclusionsBenidipine is more effective than amlodipine for protecting renal function and potentially for ameliorating atherosclerosis in hypertensive patients with mild CKD. T-type calcium channel blockers may be effective in patients with CKD.     

Adaptor protein is essential for insect cytokine signaling in hemocytes

Growth-blocking peptide (GBP) is an insect cytokine that stimulates a class of immune cells called plasmatocytes to adhere to one another and to foreign surfaces. Although extensive structure-activity studies have been performed on the GBP and its mutants in Lepidoptera Pseudaletia separata, the signaling pathway of GBP-dependent activation of plasmatocytes remains unknown. We identified an adaptor protein (P77) with a molecular mass of 77 kDa containing SH2/SH3 domain binding motifs and an immunoreceptor tyrosine-based activation motif (ITAM)–like domain in the cytoplasmic region of the C terminus. Although P77 showed no capacity for direct binding with GBP, its cytoplasmic tyrosine residues were specifically phosphorylated within seconds after GBP was added to a plasmatocyte suspension. Tyrosine phosphorylation of P77 also was observed when hemocytes were incubated with Enterobactor cloacae or Micrococcus luteus, but this phosphorylation was found to be induced by GBP released from hemocytes stimulated by the pathogens. Tyrosine phosphorylation of the integrin β subunit also was detected in plasmatocytes stimulated by GBP. Double-stranded RNAs targeting P77 not only decreased GBP-dependent tyrosine phosphorylation of the integrin β subunit, but also abolished GBP-induced spreading of plasmatocytes on foreign surfaces. P77 RNAi larvae also showed significantly higher mortality than control larvae after infection with Serratia marcescens, indicating that P77 is essential for GBP to mediate a normal innate cellular immunity in insects. These results demonstrate that GBP signaling in plasmatocytes requires the adaptor protein P77, and that active P77-assisted tyrosine phosphorylation of integrins is critical for the activation of plasmatocytes.     

Left ventricular-free wall rupture after successful coronary intervention: Report of a case

We experienced the case of a left ventricular-free wall rupture (LVFWR) following successful coronary intervention for acute myocardial infarction (AMI). A 73-year-old woman was hospitalized because of chest oppression that had been continuing for 8 days. She was diagnosed to have AMI, and percutaneous coronary intervention (PCI) was performed. PCI was successful. However, immediately following PCI, she developed electromechanical dissociation secondary to tamponade because of blow-out-type LVFWR. The perforation tear was initially closed by a direct suture, followed by reinforcement using bovine pericardium patches sealed with GRF glue. The patient died of irreversible brain damage on postoperative day 3, but no re-bleeding or aneurysmal dilatation was detected at autopsy.     

Effect on outcome of an increase of serum cardiac troponin T in patients with healing or healed ST-elevation myocardial infarction

Recently, an association between minimally elevated cardiac troponin levels and cardiovascular risk in the general population has been reported. However, the prevalence and clinical importance of elevated cardiac troponin T (cTnT) levels remain unclear in patients with histories of myocardial infarction (MI). In this study, 1,807 consecutive patients with ST-segment elevation MIs were prospectively studied (77.1% men; mean age 64.4 years). Venous blood samples were obtained in the chronic stage of MI (28 +/- 7 days after onset), and serum cTnT levels were determined. During the average follow-up of 1,042 days, 84 patients died and 83 had nonfatal reinfarctions. Patients with cTnT levels in the highest quartile (> or = 0.040 ng/ml [n = 353]) had a higher incidence of all-cause death (8.2% vs 5.2%, p = 0.049) and nonfatal reinfarction (8.3% vs 5.1%, p = 0.048) than patients with cTnT levels from the lower 3 quartiles (<0.040 ng/ml [n = 1,064]). Multivariate Cox regression analysis revealed that a minimally elevated cTnT level (> or =0.040 ng/ml) was a significant predictor of all-cause mortality (hazard ratio 1.79, 95% confidence interval 1.10 to 2.90, p <0.02) and nonfatal reinfarction (hazard ratio 1.50, 95% confidence interval 1.13 to 2.20, p <0.03). Subgroup analysis showed that an elevated cTnT level was also a predictor of all-cause mortality and nonfatal reinfarction in patients without heart failure. In conclusion, minimally elevated cTnT levels in the chronic stage of MI predicted long-term adverse clinical outcomes.