Biomedical subjects

Seiji Naito

Publications and source records attributed to Seiji Naito.

At least 19 recordsLinked to original sources

PubMed2004

Alteration in copy numbers of genes as a mechanism for acquired drug resistance.

Chemoresistance is a major obstacle for successful treatment of cancer. To identify regions of the genome associated with acquired resistance to therapeutic drugs, we conducted molecular cytogenetic analyses of 23 cancer-cell lines, each resistant to either camptothecin, cisplatin, etoposide (VP-16), Adriamycin, or 1-beta-D-arabinofuranosylcytosine, although the parental tumor lines were not. Subtractive comparative genomic hybridization studies revealed regions of gain or loss in DNA-copy numbers that were characteristic of drug-resistant cell lines; i.e., differences from their drug-sensitive parental cell lines. Thirteen ATP-binding cassette (ABC) transporter genes [ABCA3, ABCB1 (MDR1), ABCB6, ABCB8, ABCB10, ABCB11, ABCC1 (MRP1), ABCC4, ABCC9, ABCD3, ABCD4, ABCE1, and ABCF2] were amplified among 19 of the resistant cell lines examined. Three genes encoding antiapoptotic BCL-2 proteins (BCL2L2, MCL1, and BCL2L10) were also amplified and consequently overexpressed in three of the derivative lines. Down-regulation of BCL2L2 with an antisense oligonucleotide sensitized a VP-16 resistant ovarian-cancer cell line (SKOV3/VP) to VP-16. A decrease in copy numbers of genes encoding deoxycytidine kinase, DNA topoisomerase I, and DNA topoisomerase II alpha reduced their expression levels in one cytosine arabinoside-resistant line, two of three camptothecin-resistant lines, and two of five VP-16-resistant cell lines, respectively. Our results indicated that changes in DNA-copy numbers of the genes mentioned can activate or down-regulate them in drug-resistant cell lines, and that such genomic alterations might be implicated in acquired chemoresistance.

ATP-Binding Cassette Transporters↗

PubMed2004

Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients.

OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level <or=4 ng/ml) rate, the 12 week overall tumor response rate (proportion with a partial response or better) and the proportion of withdrawals due to adverse drug reactions (ADRs) at follow-up. This interim analysis was undertaken after a minimum of 6 months' follow-up (median 15 months). RESULTS: The 12 week PSA normalization rate was 79.4% for MAB and 38.6% for LHRH agonist monotherapy (P < 0.001). The 12 week overall tumor response rate was 77.5 and 65.3%, respectively (P = 0.063). The withdrawal rate due to ADRs was 8.8% and 10.9%, respectively. There were differences in favor of MAB over monotherapy with respect to time to treatment failure (TTTF) (P = 0.038) and time to progression (TTP) (P = 0.016). There have been too few deaths (n = 10) to analyze survival. The profiles of adverse events and ADRs were broadly similar in the two treatment groups. CONCLUSION: In Japanese patients with advanced prostate cancer, first-line treatment with bicalutamide 80 mg in combination with an LHRH agonist is superior to LHRH agonist monotherapy in terms of the antitumor response at 12 weeks, and also time to treatment failure and progression, and does not compromise treatment safety. The study is ongoing.

Aged↗

PubMed2004

Comparisons of percent equol producers between prostate cancer patients and controls: case-controlled studies of isoflavones in Japanese, Korean and American residents.

BACKGROUND: Our previous case-control study revealed that the Japanese residents in Japan could be divided into those who are able to degrade daidzein, a soybean isoflavone, to equol and those without this ability, and that the incidence of prostate cancer is higher in the latter group. METHODS: We recently conducted a similar case-control study involving not only Japanese residents in Japan but also Korean residents in Korea. The incidence of prostate cancer in Korean residents is known to be close to that of Japanese residents in Japan. On the other hand, American residents in the United States have a markedly higher incidence of prostate cancer as compared to Japanese residents in Japan. RESULTS: The number of subjects was 295 in Japan (133 patients and 162 controls), 122 in Korea (61 patients and 61 controls) and 45 in the United States (24 patients and 21 controls). The percentage of equol producers among patients and controls was 29% and 46% in Japan (P = 0.004) and 30% and 59% in Korea (P = 0.001), respectively. The active isoflavone level was markedly lower and the percentage of equol producers was also lower (17% for patients and 14% for controls) for Americans as compared to the Japanese and Koreans. CONCLUSIONS: These results suggest that the ability of producing equol or equol itself is closely related to the lower incidence of prostate cancer. The results also suggest that a diet based on soybean isoflavones will be useful in preventing prostate cancer.

Adult↗

PubMed2004

A randomized controlled trial of short-term versus long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder.

PURPOSE: In a prospective randomized controlled study, we investigated the optimal schedule for intravesical instillation of epirubicin for maximizing its effect on prophylaxis and disease progression after transurethral resection of newly diagnosed Ta/T1 bladder cancer. MATERIALS AND METHODS: The patients were instilled with epirubicin (30 mg/30 ml in normal saline) within 24 hours after transurethral resection and then randomized into 2 groups after a definite histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients received 19 intravesical instillations of epirubicin in the year after transurethral resection (group 1). The second group of 73 patients received 9 intravesical instillations of epirubicin during the 3 months after transurethral resection (group 2). Nonrecurrence rates and toxicity were compared. RESULTS: In the followup period, 10 group 1 patients (13.0%) and 23 group 2 patients (31.5%) had recurrent disease. The 3-year nonrecurrence rate was 85.2% in group 1, whereas it was 63.9% in group 2. The nonrecurrence rate of group 1 was significantly higher than that of group 2 throughout the observation period (p = 0.005). The incidence and severity of toxicity were not significantly different between the 2 groups. CONCLUSIONS: Our study indicates that long-term instillation of epirubicin is more effective than short-term instillation in preventing recurrence after transurethral resection of Ta/T1 bladder cancer.

Administration, Intravesical↗

PubMed2004

Ca2+ sensitization in contraction of human bladder smooth muscle.

PURPOSE: The role of Ca2+ sensitization in the contraction of human bladder urinary smooth muscle (UBSM) was investigated. MATERIALS AND METHODS: Simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension in fura-2 loaded intact strips and receptor coupled strips permeabilized with alpha-toxin were applied. Protein expressions was confirmed by Western blot analysis. RESULTS: In intact fura-2 loaded strips 1 microM carbachol (CCh) induced a greater contraction and a lower [Ca2+]i elevation than that induced by 60 mM K depolarization. In alpha-toxin permeabilized strips 1 microM CCh induced contraction at constant [Ca2+]i and produced a leftward shift in the [Ca2+]i-tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCK II and CPI-17 proteins were expressed in human UBSM. In intact fura-2 loaded strips the application of 3 microM Y-27632, a ROCK inhibitor, or 3 microM bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, during the sustained phase of contraction induced by 1 microM CCh induced relaxation without changing [Ca2+]i. In alpha-toxin permeabilized strips the application of 3 microM Y-27632 or 3 microM GF109203X during the sustained contraction induced by 0.3 microM Ca plus 10 microM guanosine triphosphate and 1 microM CCh induced relaxation at constant [Ca2+]i. CONCLUSIONS: These results indicate that in human UBSM CCh induces contraction, not only by increasing [Ca2+]i, but also by increasing the Ca2+ sensitivity of the contractile apparatus in a ROCK and protein kinase C dependent manner. Antagonism of Ca2+ sensitization pathways may represent an alternative target in the treatment of overactive bladder.

Aged↗

PubMed2004

A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet.

The age-adjusted incidence of prostate cancer is low in Japan, and it has been suggested that the traditional Japanese diet, which includes many soy products, plays a preventive role against prostate cancer. We performed a case-control study on dietary factors and prostate cancer in order to assess the hypothesis that the traditional Japanese diet reduces the risk of prostate cancer. Four geographical areas (Ibaraki, Fukuoka, Nara, and Hokkaido) of Japan were selected for the survey. Average daily intake of food from 5 years before the diagnosis was measured by means of a semi-quantitative food frequency questionnaire. We studied 140 cases and 140 individually age ( +/- 5 years)-matched hospital controls for analysis. Estimates of age-adjusted odds ratios (ORs) and linear trends were calculated by conditional logistic regression models with adjustment for cigarette smoking and total energy intake as confounding factors. Consumption of fish, all soybean products, tofu (bean curds), and natto (fermented soybeans) was associated with decreased risk. ORs of the fourth vs. first quartile and 95% confidence intervals (95%CIs) were 0.45 (0.20-1.02) for fish, 0.53 (0.24-1.14) for all soybean products, 0.47 (0.20-1.08) for tofu, and 0.25 (0.05-1.24) for natto. Consumption of fish and natto showed significantly decreasing linear trends for risk (P < 0.05). Consumption of meat was significantly associated with increased risk (the OR of the second vs. first quartile was 2.19, 95%CI 1.00-4.81). Consumption of milk, fruits, all vegetables, green-yellow vegetables, and tomatoes showed no association. Our results provide support to the hypothesis that the traditional Japanese diet, which is rich in soybean products and fish, might be protective against prostate cancer.

Adenocarcinoma↗

PubMed2004

Direct inhibition of EGF receptor activation in vascular endothelial cells by gefitinib ('Iressa', ZD1839).

The development of gefitinib ('Iressa', ZD1839) by targeting the EGFR tyrosine kinase is a recent therapeutic highlight. We have reported that gefitinib is antiangiogenic in vitro, as well as in vivo. In this study, we asked if the anti-angiogenic action of gefitinib is due to a direct effect on activation of vascular endothelial cells by EGF. EGF, as well as VEGF, caused pronounced angiogenesis in an avascular area of the mouse cornea, and i.p. administration of gefitinib almost completely blocked the response to EGF, but not to VEGF. Immunohistochemical analysis demonstrated phosphorylation of EGFR by EGF in the neovasculature, and gefitinib markedly reduced this effect. Gefitinib also inhibited downstream activation of ERK 1/2 via EGFR in cultured microvascular endothelial (HMVE) cells. These findings suggest that the anti-angiogenic effect of gefitinib in the vascular endothelial cells of neo-vasculature is partly attributable to direct inhibition of EGFR activation, and that endothelial cells in malignant tumors play a critical role in the cancer therapeutic efficacy of gefitinib.

Antineoplastic Agents↗

PubMed2004

Multicentric papillary renal cell carcinoma associated with renal adenomatosis.

A case of multicentric papillary renal cell carcinoma (RCC) associated with renal adenomatosis in the bilateral kidneys is reported. Bilateral multiple renal cysts in a 46-year-old man were pointed out incidentally by ultrasonography. Some of the left renal lesions were considered to be RCC, and left radical nephrectomy was performed accordingly. The left kidney was occupied by numerous solid nodules, which ranged from yellow to tan in color, and some of the large ones had foci of hemorrhage and necrosis. Microscopically, most of the tumors showed papillary RCC associated with renal adenoma, while others consisted only of adenomas. Ten months later, multiple lesions of the right kidney, which were initially considered to be multiple cysts, were found to have become enlarged and some of them were diagnosed as RCC. Thus, right radical nephrectomy was also performed, and these tumors showed the same features as the left renal tumors. The patient's familial history was not remarkable. The kidneys revealed various histological features, ranging from dysplastic to adenoma or carcinoma, including transitional or overlapping features between them. The findings suggest an adenoma-carcinoma sequence in papillary RCC. It is worth considering such entities.

Adenoma↗

PubMed2004

[Location of extraprostatic extension and positive surgical margin in radical prostatectomy specimens].

BACKGROUND: Extraprostatic extension and positive surgical margin increase a risk of treatment failure after radical prostatectomy in patients with localized prostate cancer. We analyzed the location of extraprostatic extension and positive surgical margin in radical prostatectomy specimens. MATERIALS AND METHODS: In 104 radical prostatectomy cases the location of the extraprostatic extension (EPE) and/or positive surgical margin (PSM) were studied using step-sectioned specimens. RESULTS: In 54 cases EPE and/or PSM were recognized. In 34 of 38 cases (89.5%) with EPE, the EPE was identified at lateral, posterolateral and/or posterior portions in base and/or middle of the prostate. Particularly, in 31 cases (81.6%) the EPE was found posterolaterally. Only in 5 of these 34 cases (14.7%) PSM resulted from the EPE. When 35 cases with PSM were evaluated, the PSM occurred apically in 22 (62.9%) and anteriorly in 11 (31.4%). Only in 4 cases (14.3%) PSM was caused by EPE of apical and/or anterior portions. CONCLUSIONS: The majority of EPE were observed at the posterolateral portion of the prostatic base and/or middle. However, PSM were frequently identified apically and/or anteriorly. These findings suggest that modifications of surgical technique of apical dissection might reduce the frequency of PSM.

Humans↗

PubMed2004

The 3rd Conference on Asian Trends in Prostate Cancer Hormone Therapy.

From its inception in 2001, the Conference on Asian Trends in Prostate Cancer Hormone Therapy has served as an annual forum for Asian urologists to compare data on prostate cancer and to discuss issues regarding the use of hormone therapy. The 3rd conference, held in Tokyo in December 2003, began with participants from China, Indonesia, Japan, Korea, Singapore, and Taiwan presenting QOL data deriving from a survey of patients with prostate cancer. For this purpose, each country translated the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire into its own language. Although the surveys conducted in each country included a heterogeneous cohort of patients and gave very mixed results, the trial of FACT-P in Asian countries seemed propitious and in future may provide insights that could prove beneficial to patients. Day 2 of the conference included 2 discussions, focusing on the most appropriate number of biopsy cores and the implementation of prospective trials involving the collaboration of Asian countries, respectively. In the latter discussion, although a varied assortment of proposals were put forth, the participants generally agreed that any collaborative study must be a prospective outcome study conducted in a relatively short time not exceeding 2-3 years, and that patient registration should be done using the Internet.

Androgen Antagonists↗

PubMed2003

The effects of MCC-134 on the ATP-sensitive K+ channels in pig urethra.

We have investigated the effects of MCC-134 (1-[4-(1H-imidazol-1-yl)benzoyl]-N-methyl-cyclobutanecarbothioamide) on membrane currents and ATP-sensitive K(+) channel (K(ATP) channel) opener-induced currents in pig urethra by use of patch-clamp techniques (conventional whole-cell configuration and nystatin perforated patch recordings). Tension measurement was also performed to study the effects of MCC-134 on the resting tone of pig urethral strips. MCC-134 reduced the resting tone of pig urethra in a concentration-dependent manner (EC(50)=6 microM). The MCC-134 (30 microM)-induced relaxation was suppressed by glibenclamide. In voltage-clamp experiments, MCC-134 produced a concentration-dependent inward K(+) current which was suppressed by application of glibenclamide at a holding potential of -50 mV (symmetrical 140 mM K(+) conditions). Application of MCC-134 enhanced diazoxide-induced inward currents and inhibited pinacidil-induced inward currents in a concentration-dependent manner at -50 mV. These results suggest that MCC-134 induces glibenclamide-sensitive K(ATP) currents in pig urethra.

Adenosine Triphosphate↗

PubMed2003

Deregulated expression of KRAP, a novel gene encoding actin-interacting protein, in human colon cancer cells.

We have identified a novel gene, designated KRAP (Ki- ras-induced actin-interacting protein), encoding a protein of 1,259 amino acids with coiled-coil regions and transmembrane regions, from the cDNA library of human colon cancer HCT116 cells, as one of the genes upregulated by activated Ki- ras. While KRAP was rarely expressed in normal colon epithelium, deregulated constitutive KRAP expression was observed in some other colon cancer cells. In normal tissues, KRAP was strongly expressed in pancreas and testis. Anti-KRAP polyclonal antibodies detected endogenous KRAP as the molecular size of Mr 180,000, and immunofluorescence microscopy and cytochalasin E treatment revealed that KRAP was clearly associated with the actin filaments. Furthermore, KRAP was localized as a membrane-bound form with extracellular regions. These results together suggested KRAP might be involved in the regulation of filamentous actin and signals from the outside of the cells.

Amino Acid Sequence↗

PubMed2003

Downregulation of Cap43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells.

We previously identified 9 genes (i.e., thymosin beta4, secreted protein acidic and rich in cysteine, Cap43, ceruloplasmin, serum amyloid A, heat shock protein 90, LOT1, osteopontin and casein kinase Igamma) that are more highly expressed in cancerous regions than in noncancerous regions in human renal cancers. In our study, we considered the possibility that the von Hippel-Lindau (VHL) tumor suppressor gene might be able to affect the expression of these 9 genes in renal cancer cells. We first established 2 VHL-positive cell lines, 786/VHL-1 and 786/VHL-2, after the introduction of wild-type VHL into VHL-negative renal cancer 786-O cells. Of these 9 genes, expression of the Cap43 gene was specifically downregulated by VHL. Expression of Cap43 was also much lower in 4 other VHL-positive renal cancer cell lines than in VHL-negative 786-O cells. Cap43 promoter assays with several deletion or mutation constructs demonstrated that the Sp1 site in the element from -286 base pairs (bp) to -62 bp was partly responsible for VHL-induced suppression of the Cap43 gene. Immunostaining analysis with human specimens of renal cancers demonstrated that the Cap43 protein was expressed in most cancer cells and macrophages. We also observed a marked and specific increase of Cap43 mRNA levels in response to hypoxia or nickel in all VHL-positive cell lines. Cellular expression of Cap43 mRNA in response to hypoxia or nickel thus is closely associated with VHL gene expression in renal cancer cells. Although the function of the Cap43 protein remains unclear, the expression of Cap43 protein could be a molecular marker closely associated with VHL in renal cancer.

Carcinoma, Renal Cell↗

PubMed2003

Modulation of renal glomerular disease using remote delivery of adenoviral-encoded solubletype II TGF-beta receptor fusion molecule.

BACKGROUND: Systemic adenoviral (Ad) gene therapy for renal disorders is largely hampered by the unique architecture of the kidney. Consequently, currently available Ad vectors are of only limited therapeutic utility in the context of glomerular and fibroproliferative renal diseases. METHODS: The Ad vectors studied in the context of blocking renal fibrosis were AdTbeta-ExR and AdCATbeta-TR. AdTbeta-ExR encodes a chimeric soluble molecule comprising the entire ectodomain of the human type II TGF-beta receptor, genetically fused to the Fc fragment of the human IgG1 (sTbetaRII), while AdCATbeta-TR encodes only the dominant-negative truncated ectodomain of the human type II TGF-beta receptor. The biologic activity of the type II TGF-beta receptor was evaluated in vitro by its ability to inhibit cellular proliferation and in vivo in a unilateral ureter obstruction fibrosis model. Renal targeting with sTbetaRII was evaluated immunohistochemically after intramuscular (IM) delivery of AdTbeta-ExR. The renal antifibrotic effect of the Ad vectors was evaluated in a lupus murine model with both light and electron microscopy and urinalysis. RESULTS: sTbetaRII was detected in the glomeruli after remote IM injection of AdTbeta-ExR, but not the control AdCATbeta-TR, indicating renal deposition of the heterologous soluble fusion protein after its expression in the muscle and secretion into the circulation. AdTbeta-ExR, but not AdCATbeta-TR, could transiently inhibit mesangial expansion, glomerular hypercellularity, proteinuria and cortical interstitial fibrosis in a murine lupus model. However, the autoimmune renal disease eventually surpassed the antifibrotic effect. CONCLUSIONS: These results indicate the superiority of a soluble type II TGF-beta receptor over a dominant-negative, non-soluble type II TGF-beta receptor in the context of blocking renal fibrosis in murine models.

Adenoviridae↗

PubMed2003

Surgical outcome of laparoscopic radical prostatectomy: summary of early multiinstitutional experience in Japan.

BACKGROUND: Because laparoscopic radical prostatectomy requires significant laparoscopic expertise, it needs to be evaluated critically before being accepted as a standard therapeutic option for localized prostate cancer. METHODS: A total of 148 men diagnosed as having clinically resectable prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early biochemical and oncological outcomes were investigated. RESULTS: Policies underlying the selection of laparoscopic radical prostatectomy did not appear to be consistent among the participating institutions. Pathologically organ-confined disease was found in 64.0% of the patients who had undergone neoadjuvant therapy and in 77.2% of those who had not. Positive surgical margins were found in 36.0% and 34.1%, respectively, of the specimens. The most common site was the apex, which accounted for 77.8% of positive margins in patients who had undergone neoadjuvant therapy and 50.0% in those who had not. Seven patients have experienced biochemical failure at a median follow-up of 9.0 months. No clinical progression has been reported. CONCLUSIONS: Continuing improvements in each step of laparoscopic radical prostatectomy, especially apical dissection, should be sought as we pursue the goal of still better oncological outcomes. A systematic approach and therapeutic guidelines should help to reduce the learning curve for competent performance of this procedure.

Aged↗

PubMed2003

Tendency toward increase in the frequency of isolation of beta-lactamase-nonproducing Neisseria gonorrhoeae exhibiting penicillin resistance, and recent emergence of multidrug-resistant isolates in Japan.

Six hundred and ninety-nine strains of Neisseria gonorrhoeae were examined by the agar dilution method according to the M7-A5 guidelines established by the National Committee for Clinical Laboratory Standards (NCCLS) determine to their beta-lactamase production and susceptibility to penicillin G, cefixime, ceftriaxone, tetracycline, spectinomycin, ciprofloxacin, and azithromycin. The frequency of isolation of penicillinase-producing N. gonorrhoeae decreased gradually, from 7.3% of the test isolates (55 isolates) in 1995 to about 1% in 1998 and 1999. In contrast, while beta-lactamase-nonproducing N. gonorrhoeae exhibiting chromosomally mediated penicillin G resistance were not isolated from clinical specimens in 1995, the incidence of isolation of such resistant strains increased markedly, to 8.2% of 159 isolates, in 1997 and 14.9% of 242 isolates in 1999. The incidence of the isolation of tetracycline-resistant strains also increased between 1996 (none detected) and 1998-1999 (each 7%-8%), and a tendency towards an increase in the frequency of isolates of ciprofloxacin-resistant strains was also observed between 1995 (9.8%) and from 1997 to 1999 (more than 20%). There were no isolates resistant to any two antibiotics among penicillin G, tetracycline, and ciprofloxacin until 1997, but, in subsequent surveys in recent years, multidrug-resistant isolates (resistant to penicillin G, tetracycline, and ciprofloxacin) were detected in 1999.

Chromosomes, Bacterial↗

PubMed2003

Inhibition of gluconeogenesis and p-aminohipuric acid accumulation in rat renal cortical slices by ionic and nonionic contrast media.

BACKGROUND: Renal dysfunction is a well-recognized complication induced by contrast media (CM). Nonionic CM have been introduced into clinical use to replace conventional ionic CM in an effort to reduce toxicity. However, the nephrotoxic effects of nonionic CM have not been fully evaluated. We previously determined the activities of N-acetyl-beta- d-glucosaminidase and gamma-glutamyltransferase released from rat and human renal slices incubated with contrast media. Dose-dependent enzyme release from renal slices was observed, but there was no statistical difference in the increase of enzyme activities between ionic and nonionic CM. The present experiment was conducted to compare the effects of ionic and nonionic CM on the metabolic function of rat renal slices. METHODS: Rat renal cortical slices were incubated with ionic CM (diatrizoate, iothalamate) and nonionic CM (iopamidol, iohexol) at 37 degrees C for 90 min. To examine the dose-response effects of CM on gluconeogenesis and p-aminohipuric acid (PAH) accumulation in the rat renal slices, slices were incubated with 30, 60, and 90 mg I/ml of CM. The inhibitory effects of nonionic CM on gluconeogenesis and PAH accumulation were compared with those of ionic CM in an independent experiment, in which slices were incubated with CM at a concentration of 60 mg I/ml. In addition, rat renal slices were incubated with mannitol instead of CM to investigate the effects of osmotic pressure on gluconeogenesis and PAH accumulation. RESULTS: A dose-dependent reduction of gluconeogenesis in rat renal slices was demonstrated by both ionic CM and nonionic CM. The inhibition of PAH accumulation was dose-dependent with nonionic CM, but not with ionic CM. Gluconeogenesis and PAH accumulation within the renal slices were both inhibited according to the increase in osmotic pressure produced by mannitol. The reduction in gluconeogenesis and PAH accumulation within the rat renal slices incubated with 60 mg I/ml of nonionic CM were significantly less than those resulting from the same concentration of ionic CM. CONCLUSIONS: Nonionic CM is less nephrotoxic than ionic CM with regard to gluconeogenesis and PAH accumulation in rat renal slices. These differences in nephrotoxic effect between ionic and nonionic CM may in part be attributable to differences in osmotic pressure.

Animals↗

PubMed2003

Morbidity of laparoscopic radical prostatectomy: summary of early multi-institutional experience in Japan.

AIM: Laparoscopic radical prostatectomy is being evaluated throughout the world. The aim of the present study is to report early multi-institutional experience of the procedure in Japan. METHODS: A total of 148 men who were diagnosed with clinically localized prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early complications (within 30 days postoperatively) and postoperative convalescence were reviewed retrospectively. The median age of patients was 68.0 years (range, 51-80). RESULTS: The median operative time was 403 minutes (range, 167-925; average, 427). Blood loss ranged from 50 to 5000 mL (median, 540; average, 856). A total of 66 complications were reported in 55 patients (37.2%). Intraoperative complications were noted in 25 of 148 patients (16.9%): 10 rectal injuries (6.8%); five bladder injuries (3.4%); five cases of subcutaneous emphysema (3.4%); two intestinal injuries (1.4%); one major vessel injury (0.7%); one ureteral injury (0.7%); and one obturator nerve injury (0.7%). Overall, 16 of 148 patients (10.8%) required open conversion or postoperative open surgical repair. The most common postoperative complications were anastomotic leakage (6.8%), wound-related complications (4.7%) and perineal pain (4.7%). The bladder catheter was removed on day 7 or earlier in 73 cases (49.3%). The median time to ambulation was 1 day (mean 1.4, range 1-5). Oral intake was started on postoperative day 1 in 67 patients (45.2%) and on postoperative day 2 in 65 (43.9%). CONCLUSION: Although laparoscopic radical prostatectomy is technically demanding, reduced blood loss and shorter convalescence periods can be expected from the procedure. Surgeons should be aware of the disturbingly high morbidity rate related to early experience. By mastering laparoscopic skills and sharing knowledge, surgeons could reduce the impact of the learning curve required to complete this procedure competently.

Aged↗