bluuebunny/crossref_metadata_2025 huggingface dataset:
45Calcium Uptake During the Transition from Reversible to Irreversible Liver Injury Induced by D-Galactosamine In Vivo
Authors: Schiessel Clemens , Forsthove Claudia , Keppler Dietrich
Published: August 2008

The hepatic uptake of45calcium (45Ca) was studied in rats after administration of D-galactosamine (3 mmoles per kg, i.v.). In contrast to measurements of the hepatic calcium content,45Ca uptake served as a dynamic rather than a static indicator of calcium homeostasis during the transition from reversible to irreversible liver injury which occurs between 3 and 4 hr after injection of the hepatotoxin.45Ca uptake during a 1 hr-labeling period increased from 25 to 100% above control between 3 and 4 hr and subsequently remained at this level.

The rise in45Ca uptake and in hepatic calcium content occurred 2 to 3 hr after the D-galactosa-mine-induced depletion of UTP, UDP-galactose, UDP-glucose and UDP-glucuronate. The level of UDP-glucuronate was the earliest to recover. The enhanced45Ca uptake was associated with hepatic glycogen breakdown and with an increased SGPT activity in plasma. Inhibition of RNA polymerase II by α-amanitin (0.5 mg per kg, i.p.) and of dolichol-dependent protein glycosylation as well as ganglioside synthesis by tunicamycin (2 mg per kg, i.p.) were used to imitate two of the early actions of D-galactosamine and indicated that an interference with either process can lead to an enhanced uptake of45Ca into the liverin vivo.

Uridine, at a dose replenishing uracil nucleotide pools after their depletion by D-galactosamine, prevented or reversed the rise in45Ca uptake. The antiinflammatory steroid dexamethasone, injected prior to or simultaneously with D-galactosamine also protected against the loss of calcium homeostasis and the development of liver injury. This action of the steroid may be related to its indirect phospholipase inhibition. The results emphasize the disturbance in calcium homeostasis and provide further insight into the pathogenetic sequence provoked by D-galactosamine in which uridine protects at an early stage and dexamethasone at a later stage and with less specificity for this hepatotoxin.
The Effect of Chronic Ethanol Ingestion on Ethanol Metabolizing Enzymes in Isolated Periportal and Perivenous Rat Hepatocytes†
Authors: Väänänen Hannu , Salaspuro Mikko , Lindros Kai
Published: August 2008

Periportal (pp) and perivenous (pv) hepatocyte populations were separated using a two-diree-tional closed perfusion technique with selective addition of collagenase either to direct or retrograde perfusions (Vaananen, H. et al.,Liver1983; 3:131). The activity of GPT in hepatocytes from the pp-area was 1.9 times higher than in cells from the pv-area (p < 0.01). The distribution of glutamate dehydrogenase and pyruvate kinase activities was reversed; pp/pv ratios of 0.7 and 0.5, respectively, were observed (p < 0.001, p < 0.05). Chronic ethanol consumption for 12 weeks (mean daily ethanol intake 11.4 gm per body weight corresponding to 29% of total energy intake) did not cause histological changes but decreased GPT activity, increased glutamate dehydrogenase and pyruvate kinase activities and did not alter their pp/pv distribution. Alcohol dehydrogenase and aldehyde dehydrogenase activities were evenly distributed in pp- and pv-hepatocytes. Chronic ethanol treatment slightly decreased alcohol dehydrogenase activity (p < 0.05) and increased the activity of low Kmaldehyde dehydrogenase (p < 0.001, p < 0.05). The specific activity of NADPH-dependent microsomal ethanol oxidation was 50% higher in pv-hepatocytes (p < 0.05). Chronic ethanol treatment did not increase the specific activity of microsomal ethanol oxidation but reduced the pp-pv activity difference.

The results indicate that the enzymatic capacity to oxidize ethanol is evenly distributed in the acinus and that, after long-term moderate ethanol treatment, despite lack of parenchymal lesions, changes in the activity of enzymes involved in ethanol metabolism are observed. These changes occur to the same extent in different acinar sites.
Origins of Biliary Copper†
Authors: Kressner Michael S. , Stockert Richard J. , Morell Anatol G. , Sternlieb Irmin
Published: August 2008

We tested the hypothesis that the copper present in bile-the major route of elimination of the metal from the body-is derived exclusively from hepatocytes by administering radiocopper (84Cu or 67Cu)-labeled ionic Cu, desialylated (AsCPN) or intact human ceruloplasmin (CPN), intravenously, to rats with cannulated bile ducts. The rates of appearance and the total amounts of radiolabeled isotope recovered in bile were measured. The three vehicles chosen for the delivery of radiocopper interact differently with hepatocytes: ionic Cu is taken up by a passive process (Schmitt, R. C. et al., Am. J. Physiol. 1983; 244:G183-G191); AsCPN is promptly cleared from the circulation by specific receptor-mediated endocytosis, and CPN largely remains in the circulation for the duration of the experiment. Similar amounts of radiocopper were recovered following injections of ionic Cu (3.1%) or CPN (2%), but substantially larger amounts (8.1%) were excreted after administration of AsCPN. Using an antibody to CPN which reacts also with AsCPN, we found about 70% of the bile radioactivity to be immunoprecipitable following injections of either glycoprotein, indicating that a fraction of these copper proteins had entered the bile essentially unmodified. Our observations indicate that in addition to the lysosomal compartment which catabolizes a portion of the AsCPN in hepatocytes, there appears to be a direct route for AsCPN from hepatocellular sinusoids to the bile canaliculi. Since CPN does not interact significantly with hepatocytes, its presence in bile suggests transcytosis via the biliary epithelium.
Controlled Trial of Vasopressin and Balloon Tamponade in Bleeding Esophageal Varices
Authors: Correia Pinto J. , Alves Martins M. , Alexandrino P. , Silveira J.
Published: August 2008

In a randomized controlled trial, the effect of continuous intravenous administration of vasopressin was compared with Sengstaken-Blakemore balloon tamponade in 37 episodes of bleeding esophageal varices in patients with cirrhosis. The majority were Group A and B of Child’s classification. Bleeding was controlled in 11 of 17 (65%) patients on vasopressin and in 14 of 20 (70%) patients on tamponade. The patients who failed to respond initially (6 episodes on vasopressin and 5 on tamponade) were treated successfully with the alternative method. Overall mortality was similar in both groups: 3 patients in the vasopressin group and 4 in the tamponade group died. Only one patient died of uncontrolled bleeding; 4 patients probably died of complications of treatment, 2 of cardiac ischemia after vasopressin and 2 of pulmonary infection after tamponade.

The vasopressin group required significantly fewer blood transfusions than did the tamponade group.
Centrilobular Liver Necrosis Induced by Hypoxia in Chronic Ethanol-Fed Rats
Authors: French Samuel W. , Benson Nancy C. , Sun Piera S.
Published: August 2008

Rats fed ethanol from 21 to 130 days were subjected to one or more episodes of hypoxia (6% O2) in order to determine if ethanol predisposed to centrilobular liver necrosis induced by hypoxia. Pair-fed control rats were fed the diet regimen in parallel with the ethanol-fed rats through an indwelling gastric cannula. The diet and ethanol were fed continuously 24 hr per day so as to maintain high blood alcohol levels in the ethanol-fed rats. Serum enzyme levels, SGOT and SGPT were measured before and after the hypoxic episodes as an indicator of centrilobular necrosis. Animal livers were studied for centrilobular necrosis by light and electron microscopy. Necrosis was documented to be present when flocculent densities were found in hepatocytic mitochondria or the plasma membrane permitted lanthanum entrance into the cell. The results showed that ethanol feeding to maintain high blood alcohol levels did increase the propensity of the liver to undergo centrilobular necrosis when the rats were subjected to hypoxia (1 hr 45 min to 5 hr 30 min). Centrilobular necrosis was observed in the ethanol-fed rats only. Serum enzyme levels (SGPT and SGOT) rose to very high levels in these rats when they were permitted to die of hypoxia. Serum sediment from the ethanol-fed rats contained numerous cell fragments and free organelles. Since the plasma membranes were missing along the sinusoidal face of centrilobular hepatocytes and microbodies were present, it was concluded that the cell fragments in the blood had originated from necrotic hepatocytes.
Early Structural and Functional Changes in Liver of Rats Treated with a Single Dose of Valproic Acid
Authors: Jezequel Anne Marie , Bonazzi Patrizia , Novelli Giuseppe , Venturini Cinzia , Orlandi Francesco
Published: August 2008

Valproic acid (VPA) is a simple fatty acid largely used as anticonvulsivant agent. Side effects are uncommon, but cases of fatal hepatic failure have been reported. To elucidate the mechanism of VPA-induced hepatotoxicity, the functional and structural changes associated with administration of sodium valproate (NaVPA) to rats (200 or 600 mg per kg, i.p.) were analyzed. NaVPA produced an immediate, dose-dependent and prolonged increase in bile salt-independent bile flow with a decrease in biliary cholesterol and phospholipid output. At 3 and 5 hr, marked ultrastruc-tural changes were evident in hepatocytes, including formation of autophagic vacuoles engulfing altered mitochondria and occasionally peroxisomes. A modest accumulation of lipoprotein particles was evident at 5 hr in the Golgi cisternae. Twelve-hour samples appeared normal. Bile canaliculi and junctional complexes remained unaltered throughout. The changes observed differ from those previously reported with other hydrocholeretics, such as diethylmaleate; they are likely related to hepatic biotransformation of VPA, which undergoes β and ω-oxidation, and glucuronidation. While VPA-induced choleresis reflects the physiological osmotic effect of the glucuronide excreted in bile, the ultrastructural changes likely reflect interference by VPA with β-oxidation of endogenous fatty acids and temporary accumulation of transformation products in the mitochondrial matrix.
Culture-Negative Neutrocytic Ascites: A Variant of Spontaneous Bacterial Peritonitis
Authors: Runyon Bruce A. , Hoefs John C.
Published: August 2008

A review of the medical records of patients diagnosed as having “spontaneous bacterial peritonitis” (SBP) revealed 18 episodes of culture-negative neutrocytic ascites (CNNA) in 17 patients. The following criteria were all required in order to qualify for this diagnosis: (i) an ascitic fluid neutrophil count greater than 500 cells per mm3; (ii) negative ascitic fluid culture (5); (iii) absence of an intraabdominal source of infection; (iv) no antibiotic treatment within 30 days, and (v) no evidence of pancreatitis. Five patients had positive blood cultures. Two patients with CNNA had SBP in the past, and two other patients, who survived the episode of CNNA, subsequently developed SBP. Clinical signs and symptoms of patients with CNNA were not different from those of 32 patients with 33 episodes of culture-positive SBP. The mortality of CNNA (50%) was not different from that of SBP (70%). Because of the high mortality and because of the similarity of CNNA to SBP, it is presumed that many patients with CNNA have bacterial infection of their ascitic fluid, and it is recommended that they be treated with antibiotics.
Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model
Authors: Miao Jiangyong , Mu David , Ergel Burce , Singavarapu Rajasekhar , Duan Zhenfeng , Powers Scott , Oliva Esther , Orsulic Sandra
Published: August 2008

Hepsin is a serine protease that is widely expressed in different tissues and cell types, most prominently in the normal liver and kidney. Overexpression of hepsin has been associated with prostate cancers, ovarian cancers and renal cell carcinomas. The physiological functions of hepsin in normal tissues and tumors are poorly understood. To gain insight into its function in ovarian cancer, we analyzed the expression and subcellular localization of hepsin protein in ovarian cancer cell lines and tumors. We showed that the membrane‐associated hepsin protein is present at desmosomal junctions, where it colocalizes with its putative proteolytic substrate hepatocyte growth factor. Consistent with the growing evidence that desmosomal junctions and their constituents play a role in cancer progression, we demonstrated that overexpression of hepsin promotes ovarian tumor growth in a mouse model. The ability of ectopic hepsin to induce tumor growth in mice is abrogated by the mutation of 3 critical residues in the catalytic domain, thus implicating the enzymatic activity of hepsin in promoting tumor progression. © 2008 Wiley‐Liss, Inc.
Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome 11q23, is downregulated in unfavorable neuroblastoma without promoter hypermethylation
Authors: Ando Kiyohiro , Ohira Miki , Ozaki Toshinori , Nakagawa Atsuko , Akazawa Kohei , Suenaga Yusuke , Nakamura Yohko , Koda Tadayuki , Kamijo Takehiko , Murakami Yoshinori , Nakagawara Akira
Published: August 2008

Although it has been well documented that loss of human chromosome 11q is frequently observed in primary neuroblastomas, the smallest region of overlap (SRO) has not yet been precisely identified. Previously, we performed array‐comparative genomic hybridization (array‐CGH) analysis for 236 primary neuroblastomas to search for genomic aberrations with high‐resolution. In our study, we have identified the SRO of deletion (10‐Mb or less) at 11q23. Within this region, there exists a TSLC1/IGSF4/CADM1 gene (Tumor suppressor in lung cancer 1/Immunoglobulin superfamily 4/Cell adhesion molecule 1), which has been identified as a putative tumor suppressor gene for lung and some other cancers. Consistent with previous observations, we have found that 35% of primary neuroblastomas harbor loss of heterozygosity (LOH) on TSLC1 locus. In contrast to other cancers, we could not detect the hypermethylation in its promoter region in primary neuroblastomas as well as neuroblastoma‐derived cell lines. The clinicopathological analysis demonstrated that TSLC1 expression levels significantly correlate with stage, Shimada's pathological classification, MYCN amplification status, TrkA expression levels and DNA index in primary neuroblastomas. The immunohistochemical analysis showed that TSLC1 is remarkably reduced in unfavorable neuroblastomas. Furthermore, decreased expression levels of TSLC1 were significantly associated with a poor prognosis in 108 patients with neuroblastoma. Additionally, TSLC1 reduced cell proliferation in human neuroblastoma SH‐SY5Y cells. Collectively, our present findings suggest that TSLC1 acts as a candidate tumor suppressor gene for neuroblastoma. © 2008 Wiley‐Liss, Inc.
Rcl is a novel ETV1/ER81 target gene upregulated in breast tumors
Authors: Shin Sook , Bosc Denis G. , Ingle James N. , Spelsberg Thomas C. , Janknecht Ralf
Published: August 2008

ETV1 (ER81) is a transcription factor that can be activated by HER2/Neu, a proto‐oncoprotein often overexpressed in metastatic breast tumors. Here, we demonstrate that ETV1 downregulation suppresses proliferation of HER2/Neu‐positive MDA‐MB‐231 breast cancer cells in vitro and tumor formation in vivo, proving for the first time the existence of a critical role of ETV1 in breast cancer cell physiology. A screen for novel ETV1 target genes hinted at Rcl, an enzyme involved in nucleotide metabolism. To characterize the human Rcl gene, we cloned its promoter and found that ETV1 and HER2/Neu cooperated in activating the Rcl promoter, whereas a dominant‐negative ETV1 molecule suppressed the Rcl promoter. Moreover, ETV1 and HER2/Neu synergized to upregulate the endogenous Rcl gene. ETV1 also bound to the Rcl promoter in vivo, indicating that Rcl is a bona fide target gene of ETV1. Hybridization of Rcl cDNA to a breast cancer array revealed that Rcl is overexpressed in ∼40% of all breast tumors. Importantly, its expression significantly escalates with increasing tumor grade, strongly implicating that Rcl contributes to breast tumorigenesis. Since joint overexpression of Rcl with vascular endothelial growth factor, another target gene of ETV1, has been shown to induce tumor formation, Rcl may be one crucial effector of ETV1 and HER2/Neu in breast tumors. Furthermore, given its expression pattern and enzymatic function in nucleotide metabolism, Rcl presents itself as a novel target in breast cancer therapy via modulation of its activity by small molecule drugs. J. Cell. Biochem. 105: 866–874, 2008. © 2008 Wiley‐Liss, Inc.
ERK activation and nuclear signaling induced by the loss of cell/matrix adhesion stimulates anchorage‐independent growth of ovarian cancer cells
Authors: Al‐Ayoubi Adnan , Tarcsafalvi Adel , Zheng Hui , Sakati Wayne , Eblen Scott T.
Published: August 2008

Ovarian cancer metastasis involves the sloughing of epithelial cells from the ovary into the peritoneal cavity, where the cells can survive and proliferate in peritoneal ascites under anchorage‐independent conditions. For normal epithelial cells and fibroblasts, cell adhesion to the extracellular matrix is required to prevent apoptosis and for proper activation and nuclear signaling of the ERK MAP kinase. The mechanisms of ERK regulation by adhesion have been determined by our lab and others. In this report, we elucidate a novel means of ERK regulation by cellular adhesion in ovarian cancer cells. We demonstrate that ERK and its activator MEK are robustly stimulated after cell detachment from a substratum in several ovarian cancer cell lines, but not a benign ovarian cell line, independent of serum and FAK or PAK activity. MEK and ERK activation was sustained for 48 h after detachment, while activation by serum or growth factors in adherent cells was transient. Re‐attachment of suspended ovarian cells to fibronectin restored basal levels of MEK and ERK activity. ERK activity in suspended cells was dynamically controlled through an autocrine stimulatory pathway and prevalent phosphatase activity. Suspended cells demonstrated higher levels of ERK nuclear signaling to Elk1 compared to adherent cells. Inhibition of ERK activation with the MEK inhibitor U0126 had minor effects on adherent cell growth, but greatly decreased growth in soft agar. These data demonstrate a unique regulation of ERK by cellular adhesion and suggest a mechanism by which ERK may regulate anchorage‐independent growth of metastatic ovarian cancer cells. J. Cell. Biochem. 105: 875–884, 2008. © 2008 Wiley‐Liss, Inc.
Distinct roles of the three Akt isoforms in lactogenic differentiation and involution
Authors: Maroulakou Ioanna G. , Oemler William , Naber Stephen P. , Klebba Ina , Kuperwasser Charlotte , Tsichlis Philip N.
Published: August 2008

The three Akt isoforms differ in their ability to transduce oncogenic signals initiated by the Neu and PyMT oncogenes in mammary epithelia. As a result, ablation of Akt1 inhibits and ablation of Akt2 accelerates mammary tumor development by both oncogenes, while ablation of Akt3 is phenotypically almost neutral. Since the risk of breast cancer development in humans correlates with multiple late pregnancies, we embarked on a study to determine whether individual Akt isoforms also differ in their ability to transduce hormonal and growth factor signals during pregnancy, lactation and post‐lactation involution. The results showed that the ablation of Akt1 delays the differentiation of the mammary epithelia during pregnancy and lactation, and that the ablation of Akt2 has the opposite effect. Finally, ablation of Akt3 results in minor defects, but its phenotype is closer to that of the wild type mice. Whereas the phenotype of the Akt1 ablation is cell autonomous, that of Akt2 is not. The ablation of Akt1 promotes apoptosis and accelerates involution, whereas the ablation of Akt2 inhibits apoptosis and delays involution. Mammary gland differentiation during pregnancy depends on the phosphorylation of Stat5a, which is induced by prolactin, a hormone that generates signals transduced via Akt. Here we show that the ablation of Akt1, but not the ablation of Akt2 or Akt3 interferes with the phosphorylation of Stat5a during late pregnancy and lactation. We conclude that the three Akt isoforms have different roles in mammary gland differentiation during pregnancy and this may reflect differences in hormonal signaling. J. Cell. Physiol. 217: 468–477, 2008. © 2008 Wiley‐Liss, Inc.
Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy
Authors: Kusamura Shigeki , Dominique Elias , Baratti Dario , Younan Rami , Deraco Marcello
Published: August 2008

At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. Conflicting points concerning drugs, carrier solution and optimal temperature for hyperthermic intraperitoneal chemotherapy (HIPEC) were discussed. J. Surg. Oncol. 2008;98:247–252. © 2008 Wiley‐Liss, Inc.
Locoregional treatment of peritoneal carcinomatosis from gastric cancer
Authors: Bozzetti F. , Yu W. , Baratti Dario , Kusamura Shigeki , Deraco Marcello
Published: August 2008

The authors reviewed the natural history and the main features of the peritoneal carcinomatosis from gastric cancer briefly and analyzed the pertinent literature concerning the locoregional modalities for prevention and for treatment. Results of the web based voting by experts were also summarized. As regards the peritoneal perfusion with cytotoxic drugs with or without hyperthermia for preventing peritoneal carcinomatosis in high risk patients, there are some randomized clinical trials and one meta‐analysis supporting a benefit of the procedure. However, disparity in methodology (drugs, dosage, duration of the treatment, addition of hyperthermia, etc.) precludes the adoption of a shared protocol to be used in the clinical practice in high risk patients. Once the peritoneal carcinomatosis is established, the approach reported in literature is the peritonectomy associated with hyperthermic perfusion. However, data supporting benefits are scanty, and limited to few centers with a specific experience in this field. With regard to the main questions addressed to the experts' panel and concerning the indications for treatment and methodology, there was a general consistency among the experts and agreement with the findings of the literature. The need for a large multicenter trial to confirm the benefit and risk of intraperitoneal chemotherapy was recognized by both the experts and the authors. J. Surg. Oncol. 2008;98:273–276. © 2008 Wiley‐Liss, Inc.
Consensus statement on peritoneal mesothelioma
Authors: Deraco Marcello , Bartlett David , Kusamura Shigeki , Baratti Dario
Published: August 2008

Diffuse malignant peritoneal mesothelioma (DMPM) has been traditionally regarded as a rapidly lethal disease. Recently, several independent prospective trials have reported improved survival with an intensive loco‐regional treatment strategy including cytoreductive surgery (CRS) along with peri‐operative intra‐peritoneal chemotherapy (PIC). However, most of the surgical data comes from mono‐institutional phase I or II studies and there is a broad range of variability regarding inclusion criteria, cytoreductive surgical procedures, drugs, temperatures and methods of delivering the heated chemotherapy (open vs. closed abdomen). This manuscript critically analyze and discuss the results of a group of health care providers trying to achieve a consensus statement in the management of this group of patients. The main conflicting points regarding preoperative evaluation, patient eligibility, combined treatment methodology, postoperative follow‐up and future investigational perspectives were summarized as a list of multiple‐choice questions. A questionnaire was placed on the website of the “5th International Workshop on Peritoneal Surface Malignancies” and the group members voted via internet. The results were presented for further debate during a dedicated session of the Workshop. The general treatment guidelines and future investigational perspectives were defined. J. Surg. Oncol. 2008;98:268–272. © 2008 Wiley‐Liss, Inc.
The Fifth International Workshop on Peritoneal Surface Malignancy (Milan, Italy, December 4–6, 2006): methodology of disease‐specific consensus
Authors: Baratti Dario , Kusamura Shigeki , Deraco Marcello
Published: August 2008

Peritoneal surface malignancies (PSM) have been traditionally regarded as uniformly terminal conditions. The combination of cyto‐reductive surgery and perioperative intraperitoneal chemotherapy has changed PSM management from palliation to possible cure. Due to the inherent differences in biological and clinical behavior, the optimal adaptation of comprehensive treatment to each PSM is still a matter of debate. A session of “The Fifth International Workshop on Peritoneal Surface Malignancy” (Milan, Italy, December 4–6, 2006) was committed to reach a consensus pertaining to conceptual and technical aspects of the loco‐regional treatment of each PSM. The consensus developing process was based on principles of the Delphi method. A total of 103 international experts from 17 countries were included in six Working Groups (WG) for each of the following PSM: peritoneal mesothelioma, abdominal sarcomatosis, carcinomatosis of gastric, colo‐rectal, appendiceal, and ovarian origin. Evidence reports were written by the respective WG. The main conflicting points (CP) regarding preoperative evaluation, patient eligibility, combined treatment methodology, postoperative follow‐up and future investigational perspectives were summarized as a list of multiple‐choice questions. Overall, 160 CP were identified. A consensus ≥51% of voters favoring one option was reached in 143/160 CP (89.4%). The general treatment guidelines and future investigational perspectives were defined. J. Surg. Oncol. 2008;98:258–262. © 2008 Wiley‐Liss, Inc.
Technical aspects of cytoreductive surgery
Authors: Kusamura Shigeki , O'Dwyer Sarah T. , Baratti Dario , Younan Rami , Deraco Marcello
Published: August 2008

At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. Five conflicting points were discussed: radicality of the peritonectomy procedure, cytoreduction of neoplastic nodules <2.5 mm, the timing of bowel anastomoses in relation to hyperthermic intraperitoneal chemotherapy (HIPEC) and indications of protective ostomies. According to the panel of experts a partial parietal peritonectomy restricted to the macroscopically involved regions could be indicated in all listed clinical conditions with the exception of peritoneal mesothelioma. No expert was of the opinion that a radical parietal peritonectomy is advisable irrespective of the disease being treated. All the experts agreed that electrovaporization of small (<2.5 mm) non‐infiltrating metastatic nodules in the mesentery would be appropriate, even if theoretically the HIPEC affords microscopic cytoreduction. The panel also agreed that in the closed technique for HIPEC administration the intestinal anastomoses should be fashioned after completion of the perfusion. Finally when considering the place for protective ostomies the experts voted for a flexible approach allowing the surgeon to exercise discretion for individual patients. J. Surg. Oncol. 2008;98:232–236. © 2008 Wiley‐Liss, Inc.
Corroborating evidence of posttraumatic growth
Authors: Shakespeare‐Finch Jane , Enders Tracey
Published: August 2008

Over the last decade, a healthy shift in the trauma literature has meant that published theory and research in the posttraumatic growth (PTG) domain has burgeoned, but the validity of the self‐report questionnaires used to measure PTG has recently been criticized. Corroboration of these subjective reports by an observer would provide convergent validity. Therefore, this study's aim was to validate the Posttraumatic Growth Inventory (PTGI; Tedeschi & Calhoun, 1996). Sixty‐one trauma survivors and 61 paired significant others completed the PTGI. A significant correlation was reported between the total PTGI scores of the trauma survivors and the corroborating significant others, supporting the use of the PTGI as an appropriate measure of positive posttrauma changes.
Spanish and English versions of the PTSD Checklist–Civilian version (PCL‐C): Testing for differential item functioning
Authors: Miles Jeremy N. V. , Marshall Grant N. , Schell Terry L.
Published: August 2008

Interpretation of ethnic differences in PTSD is predicated on demonstration that differences are not due to measurement bias. This is difficult when multiple languages are used in the assessment. This study used confirmatory factor analysis to examine possible differential item functioning (DIF) across English and Spanish versions of the PTSD Checklist‐Civilian Version (PCL‐C). Data were derived from two assessments of Hispanics (Ns = 304, 213), who were hospitalized with physical injuries. After correction for multiple testing, univariate tests revealed no statistically significant DIF effects; multivariate tests revealed some indication of DIF at the initial assessment only. This bias was inconsistent across waves and unlikely to be substantively consequential, indicating that the two versions of the PCL‐C were generally equivalent.
Association of objective measures of trauma exposure from motor vehicle accidents and posttraumatic stress symptoms
Authors: Fujita Goro , Nishida Yasushi
Published: August 2008

Associations of objective measures of trauma exposure with psychological sequelae following motor vehicle accidents (MVA) were examined in a Japanese population. Impact and injury severity of 93 MVA victims was assessed using on‐the‐scene in‐depth investigations measured by the Injury Severity Score (ISS), barrier equivalent speed (BES), and change in velocity during the impact (Delta‐v). Results showed that ISS, BES, and Delta‐v were not related to posttraumatic stress symptoms (PTSS) or psychiatric symptoms at 5 and 14 months after the MVA. Subjective measures (e.g., perceived life risk, persistent medical problems) were significantly related to psychological sequelae. These findings suggest that the objective measures of trauma exposure are not associated directly with PTSS or psychiatric symptoms after an MVA.
Analysis of major proteins and fat fractions associated with mare's milk fat globules
Authors: Barello Cristina , Garoffo Lorenza Perono , Montorfano Gigliola , Zava Stefania , Berra Bruno , Conti Amedeo , Giuffrida Maria Gabriella
Published: August 2008

Although several studies have aimed to identify mare's milk proteins, only the major whey proteins and some caseins have yet been characterized. Incomplete sequencing of the equine genome and the difficulty of recovering highly hydrophobic proteins mean that little is known to date about the proteins associated with milk fat globules, which have been shown to play an important role in newborns' defense mechanisms. The fat fraction, in particular the distribution of unsaturated fatty acids, has been more extensively studied, but complex lipids are only partially elucidated. This study reports a 2‐DE approach combined with a powerful method for de novo protein sequencing, and quali‐quantitative data on complex lipid composition determined by high performance TLC (HPTLC) and GC. The presence in mare's milk of long‐chain highly unsaturated fatty acids, and the evidence of close similarity between equine and human milk fat globule membrane proteins, support the use of mare's milk for human nutrition.
Knockouts of Se‐glutathione peroxidase‐1 and Cu,Zn superoxide dismutase exert different impacts on femoral mechanical performance of growing mice
Authors: Wang Xiaodan , Gillen Elizabeth A. , van der Meulen Marjolein C. H. , Lei Xin Gen
Published: August 2008

The objective of this study was to determine the impact of knockout of Cu,Zn‐superoxide dismutase (SOD1) and Se‐glutathione peroxidase‐1 (GPX1) on murine bone biomechanical properties. Femora samples were collected from wild‐type (WT), SOD1‐knockout [SOD1(–/–)] and GPX1‐knockout [GPX1(–/–)] female mice (9‐wk old, n = 7–8 per genotype) to assay for bone enzyme activities and mechanical properties in three point bending. Prior to testing, all mice were fed a torula yeast diet supplemented with 0.4 mg Se/kg as sodium selenite. Compared with the WT mice, SOD1(–/–) mice displayed a series of reductions (p < 0.05): 24% in body mass, 8% in femoral length, 43% in femoral structural strength, and 32% in bending stiffness. When differences in body size were accounted for, femoral failure moment in SOD1(–/–) mice remained lower (p < 0.05) than that of WT. Femoral tartrate resistant acid phosphatase activity in SOD1(–/–) was 47% greater (p < 0.05) than the WT. In contrast, GPX1(–/–) mice showed no significant differences in femoral mechanical properties from those of WT mice. In conclusion, knockout of SOD1 exerted a greater impact on femoral mechanical characteristics than that of GPX1 in growing mice.
Mechanisms of selenium chemoprevention and therapy in prostate cancer
Authors: Nadiminty Nagalakshmi , Gao Allen C.
Published: August 2008

Prostate cancer (PC) chemoprevention has generated considerable interest in the last decade and selenium and combinations of selenium have been recognized as one of the most efficacious chemopreventive agents against PC. This review focuses on a discussion of the knowledge hitherto gained about the mechanisms of action of the various in vitro and in vivo used selenium compounds and their effects on cellular processes and signaling pathways. We also describe the clinical and preclinical studies that have contributed enormously to the knowledge about dose, duration of exposure, and the chemical form of selenium effective in different scenarios. Even though the jury is still out about whether selenium can be used as a chemopreventive agent in the clinic and whether studies with cell lines and populations at low, medium, or high risk can adequately represent the physiological behavior of this micronutrient, it can safely be said to offer the most diverse spectrum of protective effects against this particular type of cancer which may augur well for its future as a chemopreventive agent.
Anthocyanins and their metabolites are weak inhibitors of cytochrome P450 3A4
Authors: Dreiseitel Andrea , Schreier Peter , Oehme Anett , Locher Sanja , Hajak Goeran , Sand Philipp G.
Published: August 2008

The cytochrome P450 enzyme cytochrome P450 3A4 (CYP3A4) controls the metabolism of about 60% of all drugs, and its inhibition may dramatically affect drug safety. Modulation of cytochrome P450 activity has been observed by constituents of fruit extracts including several flavonoids. The present investigation addresses CYP3A4 inhibition by anthocyanins, their aglycons, proanthocyanidins, and phenolic metabolites using a chemiluminescent assay. Test compounds inhibited CYP3A4 activity in a concentration‐dependent manner featuring IC50values from 12.2 up to 7,842 μM. In the order of decreasing effect size, anthocyanidins were followed by anthocyanins, proanthocyanidins, and phenolic acids. When compared to earlier data on furanocoumarins from grapefruit extract, the inhibitory activity of tested anthocyanins, and anthocyanidins was shown to be about 10 000‐fold weaker, and was negligible for phenolic acids (>100 000‐fold weaker). Future studies are invited to address effects of the above flavonoids on other CYP isoforms for more detailed toxicity profiles.
Wave propagation in nonlinear one‐dimensional soil model
Authors: Ahn J. , Biscontin G. , Roesset J. M.
Published: August 2008

The objective of the research conducted by the authors is to explore the feasibility of determining reliable in situ values of shear modulus as a function of strain. In this paper the meaning of the material stiffness obtained from impact and harmonic excitation tests on a surface slab is discussed. A one‐dimensional discrete model with the nonlinear material stiffness is used for this purpose. When a static load is applied followed by an impact excitation, if the amplitude of the impact is very small, the measured wave velocity using the cross‐correlation indicates the wave velocity calculated from the tangent modulus corresponding to the state of stress caused by the applied static load. The duration of the impact affects the magnitude of the displacement and the particle velocity but has very little effect on the estimation of the wave velocity for the magnitudes considered herein. When a harmonic excitation is applied, the cross‐correlation of the time histories at different depths estimates a wave velocity close to the one calculated from the secant modulus in the stress–strain loop under steady‐state condition. Copyright © 2008 John Wiley & Sons, Ltd.
Three‐dimensional steady‐state response of a railway system on layered half‐space soil medium subjected to a moving train
Authors: Sun Honglei , Cai Yuanqiang , Xu Changjie
Published: August 2008

The paper presents a three‐dimensional study on the steady‐state response of a track system and layered half‐space soil medium subjected to the load induced by the passages of a moving train with the substructure method. Practically, due to the ground water table being several meters beneath the ground surface, the soil profile can be divided into two layers: the upper layer modeled by an elastic medium and the lower layer by a fully saturated poroelastic medium governed by Biot's theory. In the meanwhile, the rails are regarded as an infinitely long Euler beam, and the sleepers are represented by a continuous mass. The effect of the ballast is accounted for by introducing the Cosserat model for granular medium, and the train is described by a series of moving axle point loads, depending on the geometry of the train. The influences of the thickness, the mass and the rigidity of the elastic layer and the mass of the ballast on rail's displacement responses are carefully investigated. Numerical results show that the influences of these parameters are significant for high train velocity, while vanishes for low velocity. Copyright © 2008 John Wiley & Sons, Ltd.
Coupled HM analysis using zero‐thickness interface elements with double nodes. Part I: Theoretical model
Authors: Segura J. M. , Carol I.
Published: August 2008

In recent years, the authors have proposed a new double‐node zero‐thickness interface element for diffusion analysis via the finite element method (FEM) (Int. J. Numer. Anal. Meth. Geomech. 2004; 28(9): 947–962). In the present paper, that formulation is combined with an existing mechanical formulation in order to obtain a fully coupled hydro‐mechanical (or HM) model applicable to fractured/fracturing geomaterials. Each element (continuum or interface) is formulated in terms of the displacements (u) and the fluid pressure (p) at the nodes. After assembly, a particular expression of the traditional ‘u–p’ system of coupled equations is obtained, which is highly non‐linear due to the strong dependence between the permeability and the aperture of discontinuities. The formulation is valid for both pre‐existing and developing discontinuities by using the appropriate constitutive model that relates effective stresses to relative displacements in the interface. The system of coupled equations is solved following two different numerical approaches: staggered and fully coupled. In the latter, the Newton–Raphson method is used, and it is shown that the Jacobian matrix becomes non‐symmetric due to the dependence of the discontinuity permeability on the aperture. In the part II companion paper (Int. J. Numer. Anal. Meth. Geomech. 2008; DOI: 10.1002/nag.730), the formulation proposed is verified and illustrated with some application examples. Copyright © 2008 John Wiley & Sons, Ltd.
Response of saturated and nearly saturated porous media: Different formulations and their applicability
Authors: Ulker M. B. C. , Rahman M. S.
Published: August 2008

The response of saturated porous medium is of significant interest in many fields ranging from geomechanics to biomechanics. Biot was the first to formulate the basic equations governing the process of coupled flow and deformation in porous media. Depending on the nature of loading vis‐à‐vis the characteristics of the media, different formulations (fully dynamic, partly dynamic, quasi‐static) are possible. In this study, analytical solutions are developed for the response of saturated and nearly saturated porous media under plane strain condition. The solutions for different formulations are developed in terms of non‐dimensional parameters. The response is studied for various conditions and the regions of validity for various formulations are identified in a parametric space. An assessment of the needed formulation for few important problems is also presented. Copyright © 2008 John Wiley & Sons, Ltd.
Desmopressin, as a “designer‐drug,” in the treatment of overactive bladder syndrome
Authors: Hashim Hashim , Malmberg Lars , Graugaard‐Jensen Charlotte , Abrams Paul
Published: August 2008

Aims

This study looked at whether oral desmopressin, by decreasing kidney urine production, would prolong bladder filling‐time thereby increasing the time to reach maximum capacity, thus reducing overactive bladder (OAB) symptoms, and providing an alternative method of treatment to OAB sufferers.

Methods

An investigator‐initiated, 2‐week, multi‐national, multi‐centre, “proof‐of‐concept,” phase IIb, double‐blind, placebo‐controlled, prospective, randomized, cross‐over study was conducted using 0.2 mg of oral desmopressin in adults suffering with OAB. Patients were included in the trial period if they had ≥4 voids in the first 8‐hr of the day after rising, excluding the first morning void. The primary endpoint was evaluation of effectiveness of desmopressin in increasing the time to the first OAB symptom episodes during the first 8‐hr following treatment.

Results

Time to first void was 8‐min later on the drug than on placebo (P = 0.27). However, the drug led to one less void (3.2 vs. 4.2) in the same period (P < 0.001). There was an increase in the time to first urgency episode with a decrease in the number of urgency episodes in the drug days compared to placebo (P < 0.003). There was a subjective improvement in frequency and urgency and overall quality‐of‐life as measured by the ICIQ‐OAB. Twenty‐seven people reported adverse events which were all mild, headache being the commonest and no hyponatremia was recorded.

Conclusions

Antidiuresis, using oral desmopressin tablets, is a novel, feasible and safe (short‐term basis) method of treatment for adults with OAB, and could be considered in the armamentarium of drugs available for the treatment of OAB. Neurourol. Urodynam. 28:40–46, 2009. © 2008 Wiley‐Liss, Inc.
Numerical methods for palindromic eigenvalue problems: Computing the anti‐triangular Schur form
Authors: Mackey D. Steven , Mackey Niloufer , Mehl Christian , Mehrmann Volker
Published: August 2008

We present structure‐preserving numerical methods for the eigenvalue problem of complex palindromic pencils. Such problems arise in control theory, as well as from palindromic linearizations of higher degree palindromic matrix polynomials. A key ingredient of these methods is the development of an appropriate condensed form—the anti‐triangular Schur form. Ill‐conditioned problems with eigenvalues near the unit circle, in particular near ±1, are discussed. We show how a combination of unstructured methods followed by a structured refinement can be used to solve such problems accurately. Copyright © 2008 John Wiley & Sons, Ltd.
Life course theory as a framework to examine becoming a mother of a medically fragile preterm infant
Authors: Black Beth Perry , Holditch‐Davis Diane , Miles Margaret S.
Published: August 2008

Life course theory, a sociological framework, was used to analyze the phenomenon of becoming a mother, with longitudinal narrative data from 34 women who gave birth prematurely after a high‐risk pregnancy, and whose infant became medically fragile. Women faced challenges of mistimed birth and mothering a technologically dependent infant. Before social ties were established, legal and biological ties required mothers to make critical decisions about their infants. Liminality characterized mothers' early involvement with their infants. The mothers worked to know, love, and establish deeper attachments to this baby. The infant's homecoming was a key turning point; it decreased liminality of early mothering, increased mothers' control of infants' care, and gave them time and place to know their infants more intimately. © 2008 Wiley Periodicals, Inc. Res Nurs Health 32:38–49, 2009
Examining criteria for identifying and differentiating fossil faunal assemblages accumulated by hyenas and hominins using extant hyenid accumulations
Authors: Kuhn B. F. , Berger L. R. , Skinner J. D.
Published: August 2008

Numerous authors have put forth criteria for distinguishing between assemblages collected by hyenas and hominins. Of the seven most recognised criteria used to distinguish hyenid from hominin assemblages, it has recently been suggested that four be rejected and three retained. The four rejected criteria are: an excessive proportion of horns and horn cores in hyena accumulated assemblages; the absence of small, hard, compact bones; mortality profiles; and the ratio of cranial bones to postcranial bones. The three criteria previous researchers suggested be retained are: a carnivore MNI ratio of ≥20%; an abundance of cylinder fragments; and hyena‐inflicted damage upon the bones. In this examination of over 27,000 faunal remains associated with all three species of extant bone‐collecting hyenids from four countries and two continents, six of the seven previously established criteria and reconsiderations of criteria have been evaluated. The results of the present study indicate that of the six criteria examined, none, as written, are indicative of hyenid activity on bone assemblages of unknown origin. Copyright © 2008 John Wiley & Sons, Ltd.
Optimal multi‐interval control of a cantilever beam by a recursive control algorithm
Authors: Lin Chun‐Hung , Bruch John C. , Sloss James M. , Adali Sarp , Sadek Ibrahim S.
Published: August 2008

The optimal‐distributed control of a transversely vibrating cantilever beam is studied with the objective of minimizing the deflection and velocity in a given period of time with the minimum possible expenditure of force. The beam undergoes transient vibrations and is subject to given displacement and velocity initial conditions. The control is exercised by means of a transversely distributed force referred to as the control force. In the present study, a multi‐interval optimal control method is developed with the application of a maximum principle. The method consists of dividing the control duration into several intervals and using the maximum principle to obtain the optimality conditions at each interval. The explicit solutions for a cantilever beam are obtained by a recursive algorithm that takes the final conditions of the last interval as the initial conditions of the next interval. The formulation and the method of solution are suitable and convenient for digital computation. Numerical results are given, which compare the deflections, velocities and the control force under the optimal multi‐interval control with those under the optimal single‐interval control. Copyright © 2008 John Wiley & Sons, Ltd.