bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Insulin Load, Dietary Insulin Index, and Colorectal Cancer
Authors: Bao Ying , Nimptsch Katharina , Meyerhardt Jeffrey A. , Chan Andrew T. , Ng Kimmie , Michaud Dominique S. , Brand-Miller Jennie C. , Willett Walter C. , Giovannucci Edward , Fuchs Charles S.
Published: December 2010

Background: Circulating insulin levels have been positively associated with risk of colorectal cancer; however, it remains unclear whether a diet inducing an elevated insulin response influences colorectal cancer risk. On the basis of a novel insulin index for individual foods, we estimated insulin demand for overall diets and assessed its association with colorectal cancer in the Nurses' Health Study and Health Professionals Follow-up Study.

Methods: We followed 86,740 women and 46,146 men who were free of cancer and diabetes at baseline and identified a total of 2,481 colorectal cancer cases during up to 26 years of follow-up. Dietary insulin load was calculated as a function of food insulin index and the energy content of individual foods was reported on food frequency questionnaires. Average dietary insulin index was calculated by dividing the dietary insulin load by the total energy intake.

Results: Dietary insulin load and dietary insulin index were not associated with risk of colorectal cancer. Comparing the highest with the lowest quintiles, the pooled multivariate relative risks of colorectal cancer were 0.91 (95% CI = 0.79–1.05) for dietary insulin load and 0.93 (95% CI = 0.81–1.08) for dietary insulin index. Body mass index and physical activity did not modify the association of dietary insulin load or index with colorectal cancer.

Conclusion: A diet high in foods that increase postprandial insulin levels did not increase the risk of colorectal cancer in this large prospective study.

Impact: This study is the first to investigate insulin index and load in relation to colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(12); 3020–6. ©2010 AACR.
Disparities in Liver Cancer Incidence by Nativity, Acculturation, and Socioeconomic Status in California Hispanics and Asians
Authors: Chang Ellen T. , Yang Juan , Alfaro-Velcamp Theresa , So Samuel K. S. , Glaser Sally L. , Gomez Scarlett Lin
Published: December 2010

Background: Asians and Hispanics have the highest incidence rates of liver cancer in the United States, but little is known about how incidence patterns in these largely immigrant populations vary by nativity, acculturation, and socioeconomic status (SES). Such variations can identify high-priority subgroups for prevention and monitoring.

Methods: Incidence rates and rate ratios (IRR) by nativity among 5,400 Hispanics and 5,809 Asians diagnosed with liver cancer in 1988–2004 were calculated in the California Cancer Registry. Neighborhood ethnic enclave status and SES were classified using 2000 U.S. Census data for cases diagnosed in 1998–2002.

Results: Foreign-born Hispanic males had significantly lower liver cancer incidence rates than U.S.-born Hispanic males in 1988–2004 (e.g., IRR = 0.54, 95% confidence interval [CI] = 0.50–0.59 in 1997–2004), whereas foreign-born Hispanic females had significantly higher rates in 1988–1996 (IRR = 1.42, 95% CI = 1.18–1.71), but not 1997–2004. Foreign-born Asian males and females had up to 5-fold higher rates than the U.S.-born. Among Hispanic females, incidence rates were elevated by 21% in higher-enclave versus lower-enclave neighborhoods, and by 24% in lower- versus higher-SES neighborhoods. Among Asian males, incidence rates were elevated by 23% in higher-enclave neighborhoods and by 21% in lower-SES neighborhoods. In both racial/ethnic populations, males and females in higher-enclave, lower-SES neighborhoods had higher incidence rates.

Conclusions: Nativity, residential enclave status, and neighborhood SES characterize Hispanics and Asians with significantly unequal incidence rates of liver cancer, implicating behavioral or environmental risk factors and revealing opportunities for prevention.

Impact: Liver cancer control efforts should especially target foreign-born Asians, U.S.-born Hispanic men, and residents of lower-SES ethnic enclaves. Cancer Epidemiol Biomarkers Prev; 19(12); 3106–18. ©2010 AACR.
Characterization of 9p24 Risk Locus and Colorectal Adenoma and Cancer: Gene–Environment Interaction and Meta-Analysis
Authors: Kocarnik Jonathan D. , Hutter Carolyn M. , Slattery Martha L. , Berndt Sonja I. , Hsu Li , Duggan David J. , Muehling Jill , Caan Bette J. , Beresford Shirley A.A. , Rajkovic Aleksandar , Sarto Gloria E. , Marshall James R. , Hammad Nazik , Wallace Robert B. , Makar Karen W. , Prentice Ross L. , Potter John D. , Hayes Richard B. , Peters Ulrike
Published: December 2010

Background: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive.

Methods: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women's Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case–control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene–environment interactions.

Results: SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI, 1.01–1.40; Ptrend = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI, 0.99–1.25; Ptrend = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene–environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03–1.12; Ptrend = 0.001).

Conclusions: Our results suggest the Aallele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies.

Impact: If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia. Cancer Epidemiol Biomarkers Prev; 19(12); 3131–9. ©2010 AACR.
Targeting the Urokinase Plasminogen Activator Receptor Inhibits Ovarian Cancer Metastasis
Authors: Kenny Hilary A. , Leonhardt Payton , Ladanyi Andras , Yamada S. Diane , Montag Anthony , Im Hae Kyung , Jagadeeswaran Sujatha , Shaw David E. , Mazar Andrew P. , Lengyel Ernst
Published: December 2010

Purpose: To understand the functional and preclinical efficacy of targeting the urokinase plasminogen activator receptor (u-PAR) in ovarian cancer.

Experimental Design: Expression of u-PAR was studied in 162 epithelial ovarian cancers, including 77 pairs of corresponding primary and metastatic tumors. The effect of an antibody against u-PAR (ATN-658) on proliferation, adhesion, invasion, apoptosis, and migration was assessed in 3 (SKOV3ip1, HeyA8, and CaOV3) ovarian cancer cell lines. The impact of the u-PAR antibody on tumor weight, number, and survival was examined in corresponding ovarian cancer xenograft models and the mechanism by which ATN-658 blocks metastasis was explored.

Results: Only 8% of all ovarian tumors were negative for u-PAR expression. Treatment of SKOV3ip1, HeyA8, and CaOV3 ovarian cancer cell lines with the u-PAR antibody inhibited cell invasion, migration, and adhesion. In vivo, anti-u-PAR treatment reduced the number of tumors and tumor weight in CaOV3 and SKOV3ip1 xenografts and reduced tumor weight and increased survival in HeyA8 xenografts. Immunostaining of CaOV3 xenograft tumors and ovarian cancer cell lines showed an increase in active-caspase 3 and TUNEL staining. Treatment with u-PAR antibody inhibited α5-integrin and u-PAR colocalization on primary human omental extracellular matrix. Anti-u-PAR treatment also decreased the expression of urokinase, u-PAR, β3-integrin, and fibroblast growth factor receptor-1 both in vitro and in vivo.

Conclusions: This study shows that an antibody against u-PAR reduces metastasis, induces apoptosis, and reduces the interaction between u-PAR and α5-integrin. This provides a rationale for targeting the u-PAR pathway in patients with ovarian cancer and for further testing of ATN-658 in this indication. Clin Cancer Res; 17(3); 459–71. ©2010 AACR.
Meta-Analyses of Early-Stage Hodgkin Lymphoma
Authors: Herbst Christine , Engert Andreas
Published: December 2010

Meta-analyses have followed some of the most important advances in the treatment of early-stage Hodgkin lymphoma (HL). In this review, details on all meta-analyses of patients with early-stage HL are discussed. In 1990, the first meta-analysis addressing patients with early-stage HL compared radiotherapy alone to combined-modality treatment (CMT). It was followed in 1998 by an individual-patient meta-analysis examining the role of radiotherapy with and without chemotherapy. In 2006, a comprehensive meta-analysis focusing on the risk of secondary malignancies, including most of the treatment regimens analyzed in clinical trials, was issued. The final analysis was published 2010 and provides important information for the ongoing discussion concerning the role of CMT compared to chemotherapy alone and is therefore discussed in more detail. In addition, the methodology and reporting of meta-analyses have improved over time.
Allogeneic Hematopoietic Cell Transplantation for Adult Patients with Acute Leukemia: The Role of Meta-Analyses
Authors: Ram Ron , Gafter-Gvili Anat , Shpilberg Ofer , Raanani Pia
Published: December 2010

In spite of decades of research in the field of allogeneic hematopoietic cell transplantation for the treatment of acute leukemia, controversies regarding the role of transplant still exist. These stem not only from contradictory results of different studies, but also from differences in the design and the strength of evidence of the various trials. Meta-analysis is considered the highest level of evidence and as such has the power to resolve clinical issues comparing between different treatment modalities. The aim of this review is to examine the contribution of meta-analyses to the establishment of the role of hematopoietic transplantation for acute leukemia and at the same time to highlight limitations and future directions.
Twist and Shout: One Decade of Meta-Analyses of Erythropoiesis-Stimulating Agents in Cancer Patients
Authors: Bohlius Julia , Tonia Thomy , Schwarzer Guido
Published: December 2010

Anemia associated with cancer and cancer therapy is a common and important issue in the treatment of patients with malignant disease. Conventionally, blood transfusions are used to treat severe cancer-related anemia. Short- and long-acting preparations of recombinant human erythropoiesis-stimulating agents (ESAs) offer an alternative treatment option. Multiple studies and subsequent meta-analyses have demonstrated that ESA treatment increases hemoglobin levels and reduces the likelihood of transfusion for a proportion of treated patients. However, studies that attempted to evaluate whether ESAs improve tumor response and survival have generated conflicting evidence. Results of smaller trials reporting improved survival outcomes were contradicted by large randomized controlled trials that reported more deaths in patients receiving ESAs. In addition, there is strong evidence that cancer patients receiving ESAs have an increased risk of thromboembolic and cardiovascular events. We herein review the main meta-analyses published in the field, their strengths and weaknesses, their contribution to patient management and future perspectives for systematic reviews.
Tuberculous Lymphadenitis at Penang General Hospital, Malaysia
Authors: Khan Amer Hayat , Sulaiman Syed Azhar Syed , Muttalif Abdul Razak , Hassali Mohamed Azmi , Khan Tahir Mehmood
Published: December 2010

Objective: To evaluate the incidence, treatment and clinical outcomes of tuberculous (TB) lymphadenitis at Penang General Hospital, Malaysia. Materials and Methods: Penang General Hospital is the referral center for all tuberculosis patients in the state of Penang. Patient records were reviewed to identify patients with confirmed diagnosis of TB lymphadenitis between January 2006 and December 2008. Data were analyzed using SPSS version 15. Results: Of 1,548 tuberculosis cases, 109 (7.0%) patients had TB lymphadenitis. The mean age was 36.4 ± 12.87 years and of the 109 patients with TB lymphadenitis, 35 (33.0%), 37 (34.0%) and 36 (33.0%) were observed for 2006, 2007 and 2008, respectively. Ethnically, 45 (41.3%) were Malay followed by 37 Chinese (33.9%). Among risk factors for TB lymphadenitis, HIV and diabetes mellitus were seen in 17 (15.6%) and 11 (10.0%) patients, respectively. Cough and fever were the most frequently reported symptoms. In a majority of cases (n = 90, 82.5%) positive results were obtained for fine-needle aspiration (FNA). Directly observed therapy was given to all patients. Sixty-two (56.9%) patients were successfully treated, and 5 (4.6%) patients died during the treatment. Conclusion: There was no increase in the incidence of TB lymphadenitis over the 3-year study period. The incidence was slightly higher in male than female gender and in Malay (ethnic group). Diabetes mellitus and HIV were the most commonly reported risk factors. FNA is the most reliable diagnostic test.
Can Calcium, Phosphate, Calcium Phosphate Product and Intact Parathyroid Hormone Levels Be Appropriately Controlled in Dialysis Patients?
Authors: Deger S.M. , Mutluay R. , Derici U. , Mandiralioglu F. , Arinsoy T. , Sindel S.
Published: December 2010

Objective: To review the target levels of calcium (Ca), phosphate (P), calcium phosphate products (Ca × P) and intact parathyroid hormone (iPTH) levels in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) and compare them with the Kidney Disease Outcome Quality Initiative (K/DOQI) recommendations. Subjects and Methods: Three hundred and fifty-seven patients who had been undergoing dialysis for more than 3 months were included. Patients who had undergone a parathyroidectomy were excluded. The levels of Ca, P, iPTH and Ca × P were monitored for the last 3 months. The Ca and P levels were measured by standard techniques, and iPTH was assessed by the intact molecule assay. Results: Between HD and PD patients, there was no statistically significant difference for age, duration of dialysis or primary disease causing end-stage renal disease. The percentage of patients whose serum Ca, P, Ca × P product and iPTH were within K/DOQI recommended target ranges were 61.2, 66.4, 82.2 and 28.3% in HD patients, and 56.3, 60.6, 85.9 and 22.5% in PD patients, respectively. When all results for each group – HD and PD – were analyzed, 12.8% of patients had all 4 markers within the target range. Conclusion: Achieving target ranges of mineral markers is important in dialysis patients, but reaching K/DOQI target levels is difficult. Hence, physicians should be careful in using P binders and vitamin D analogs to achieve the normal ranges.
Anti-Oxidative Effect of Lipoic Acid in Spinal Cord Ischemia/Reperfusion
Authors: Shaafi Sheyda , Afrooz Mohammad Razm , Hajipour Babak , Dadashi Alireza , Hosseinian Mohammad Mehdi , Khodadadi Ali
Published: December 2010

Objective: Lipoic acid (LA) is an effective anti-oxidant agent that can scavenge free radicals in biological systems. The aim of this research was to study the probable protective effect of LA in spinal ischemic/reperfusion (I/R) injury. Materials and Methods: Thirty male Wistar rats, weighing 230–285 g, were assigned randomly into 3 groups (10 animals in each group): sham spinal I/R, and spinal I/R + LA. The spinal I/R + LA rats received LA 100 mg/kg subcutaneously 3 days prior to ischemia induction and 3 days after. The induction of ischemia lasted for 30 min. Results: At 72 h postoperatively, the neurological status was worse in the I/R group than the sham group (p < 0.05). The neurological status of animals in the LA-treated group appeared better than the I/R group (p < 0.05). In the I/R group, tissue glutathione peroxidase (GPx) and super oxide dismutase (SOD) activity were significantly less compared to the control group (p < 0.05). In the LA-treated group, tissue GPx and SOD levels were higher compared to the I/R group (p < 0.05). Conclusions: LA pretreatment reduced neurologic injury in the rats, most probably by maintaining the oxidant/anti-oxidant ion balance during spinal cord ischemia. Reperfusion may have contributed to the protective effects seen in the LA pretreatment.
Estimates of Kidney Function in Obese African Americans with Chronic Kidney Disease
Authors: Hudson Joanna Q. , Mason Darius L. , Huch Kim M.
Published: December 2010

Background/Aims: Methods for assessing glomerular filtration rate (GFR) are controversial in obese individuals. This study compared clinical estimates of GFR in African Americans (AA) with chronic kidney disease (CKD) overall and by body mass index (BMI). Methods: The estimated GFR was determined in AA with CKD using (1) the 4-variable Modification of Diet in Renal Disease equation (MDRD4), (2) the Cockcroft-Gault equation with ideal, adjusted and total body weight (TBW, with and without normalization for body surface area), and (3) urine collection methods. Differences in mean values and CKD staging were compared for all patients and for subgroups with a BMI above and below 30. Results: The mean GFR by MDRD4 for individuals with a BMI of >30 was 35 ± 14 ml/min/1.73 m2 and ranged from 32 to 53 ml/min by other methods. Estimates using TBW differed significantly from the MDRD4, a finding not observed for the lower BMI subgroup or when using adjusted weights. The obese patients were more often categorized into a less severe CKD stage, whereas the lower BMI subgroup was commonly grouped into a more severe CKD stage compared to MDRD4 staging. Conclusion: Significant variations in estimated GFR between methods exist in the obese. Until other assessment methods are adequately evaluated, clinicians must be critical in applying clinical estimates of kidney function to patient care.
Primary Yolk Sac (Endodermal Sinus) Tumour of the Vulva: A Case Report
Authors: Subrahmanya Nagesh Babu , Kapadi Surendra Nayak , Junaid T.A.
Published: December 2010

Objective: To report a case of primary yolk sac (endodermal sinus) tumour (YST) of the vulva which is very rare and to highlight some unusual features of this tumour in the vulva. Clinical Presentation and Intervention: A 23-year-old woman presented with a 1-month swelling in the right labium majus that was non-tender and rapidly increasing in size. The mass was excised; it grossly measured 6 × 5 × 3 cm and was firm with a grey white cut surface. Microscopically it showed features of YST. The patient returned to the clinic only after 2 months with a recurrent mass of almost the same size with ipsilateral lymphadenopathy. At that time serum α-fetoprotein showed only a mild increase (13.4 µg/l, normal: 0–10 µg/l). Further management was not possible as she decided to return to her native country for treatment. A literature review shows that local excision with lymphadenectomy followed by cisplatin-based chemotherapy is the best mode of treatment for primary YST of the vulva. Conclusion: This case is presented for its rarity and to highlight the fact that serum α-fetoprotein estimation may not aid in the primary diagnosis or detection of recurrence in patients on follow-up for YST arising in the vulva unlike those seen in the gonads.
Hepar Lobatum Carcinomatosum Associated with Metastatic Rectal Carcinoma: An Unusual Cause of Liver Dysmorphy
Authors: Teke Zafer , Nessar Gurel , Kiremitci Saba , Aksoy Erol , Elbir Orhan Hayri
Published: December 2010

Objective: The aim of this study was to present a case of hepar lobatum resulting from metastatic rectal carcinoma. Clinical Presentation and Intervention: A 50-year-old man presented with a 2-year history of bleeding per anum, tenesmus, malaise and weakness. Initially, the patient received neoadjuvant chemoradiotherapy followed by abdominoperineal resection of the rectum. Abdominal computed tomography showed lobar enlargement and lobulated contour, mainly in the left lobe of the liver, but no primary or metastatic lesions were detected. Laparotomy revealed an irregularly lobulated hepatic deformity. Liver biopsy showed a necrotic tumor growth from adenocarcinoma of the rectum in subcapsular localizationof the liver. Conclusion: This case showed a patient with hepar lobatum carcinomatosum caused by metastatic rectal carcinoma. The report further highlights the need for clinicians and surgeons to keep in mind the possibility of hepar lobatum carcinomatosum while caring for rectal carcinoma patients, especially when the lobulated contour of the liver is detected at preoperative imaging studies or when the coarsely lobated liver is encountered during surgery for carcinoma of the rectum.
Detection of an Oseltamivir-Resistant Pandemic Influenza A/H1N1 Virus in the United Arab Emirates
Authors: Alfaresi Mubarak , Albedwawi Saif , Hag-Ali Mohammed
Published: December 2010

We report the identification of an influenza A(H1N1) viral isolate found to be resistant to oseltamivir. This is the first report of resistance of H1N1 to this medication in the United Arab Emirates. Sequencing of the isolate showed that it has the H275Y mutation.
An Epidemiological Study of Hemodialysis Patients Based on the European Fresenius Medical Care Hemodialysis Network: Results of the ARO Study
Authors: de Francisco Angel L.M. , Kim Joseph , Anker Stefan D. , Belozeroff Vasily , Canaud Bernard , Chazot Charles , Drüeke Tilman B. , Eckardt Kai-Uwe , Floege Jürgen , Kronenberg Florian , Macdougall Iain C. , Marcelli Daniele , Molemans Bart , Passlick-Deetjen Jutta , Schernthaner Guntram , Stenvinkel Peter , Wheeler David C. , Fouqueray Bruno , Aljama Pedro
Published: December 2010

Background/Aims: ARO, an observational study of hemodialysis (HD) patients in Europe, aims to enhance our understanding of patient characteristics and practice patterns to improve patient outcome. Methods: HD patients (n = 8,963) from 134 Fresenius Medical Care facilities treated between 2005 and 2006 were randomly selected from 9 European countries (Czech Republic, France, Hungary, Italy, Poland, Portugal, Spain, Slovak Republic and Slovenia) and Turkey. Information was captured on demographics, comorbidities, medications, laboratory and dialysis parameters, and outcome. Results: Patients were followed for 1.4 ± 0.7 years. Wide variation by country was observed for age, sex and diabetes as a cause of chronic kidney disease. Cardiovascular disease was present in 73% of patients. Dialysis parameters were homogeneous across countries. Arteriovenous fistulas were frequently used (73%). More incident patients had hemoglobin <11 g/dl than prevalent patients (50 vs. 33%, respectively). Phosphatemia and intact parathyroid hormone were similar between incident and prevalent patients (4.7 ± 1.2 mg/dl and 190 vs. 213 ng/l, respectively). Medication use varied widely by country. In total, 5% of patients underwent renal transplantation. Overall death rate was 124/1,000 patient-years. Conclusion: ARO revealed differences in HD practice patterns and patient characteristics in the 10 participating countries. Future ARO studies will fill gaps in the knowledge about the care of European HD patients.
High Plasma TIMP-1 and Serum CEA Levels during Combination Chemotherapy for Metastatic Colorectal Cancer Are Significantly Associated with Poor Outcome
Authors: Aldulaymi Bahir , Byström Per , Berglund Åke , Christensen Ib J. , Brünner Nils , Nielsen Hans J. , Glimelius Bengt
Published: December 2010

Objective: To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and overall survival. Materials and Methods: Eighty-eight patients with mCRC were included. Blood samples were collected before initiation and after 2, 4 and 6 weeks of treatment with an irinotecan-5-fluorouracil combination. Plasma TIMP-1 and serum CEA levels were determined by validated ELISA platforms. The first response evaluation was performed after 8 weeks of chemotherapy. Results: Median plasma TIMP-1 and serum CEA levels did not change significantly during 6 weeks of treatment. High plasma TIMP-1 and high serum CEA levels before treatment and at weeks 2, 4 and 6 were related to poor objective response. Moreover, high levels of plasma TIMP-1 before treatment and at weeks 2 and 4 were significantly associated with short TTP, while high levels of serum CEA at week 4 were significantly associated with short TTP. Finally, high levels of plasma TIMP-1 before and during treatment were significantly associated with poor overall survival; p < 0.0001 in all 4 determinations. A similar association between serum CEA and overall survival could only be demonstrated before treatment. Conclusion: Median plasma TIMP-1 or serum CEA levels do not change significantly during the first 6 weeks of chemotherapy for mCRC. The results indicate that plasma TIMP-1 in particular and serum CEA may be valuable biomarkers even in samples collected during treatment with chemotherapy.
The 6-Phosphogluconate Dehydrogenase of Leishmania (Leishmania) mexicana: Gene Characterization and Protein Structure Prediction
Authors: González Deyanira , Pérez José Luis , Serrano María Luisa , Igoillo-Esteve Mariana , Cazzulo Juan José , Barrett Michael P. , Bubis José , Mendoza-León Alexis
Published: December 2010

6-Phosphogluconate dehydrogenase (6PGDH) is a key enzyme of the oxidative branch involved in the generation of NADPH and ribulose 5-phosphate. In the present work, we describe the cloning, sequencing and characterization of a 6PGDH gene from Leishmania (Leishmania) mexicana. The gene encodes a polypeptide chain of 479 amino acid residues with a predicted molecular mass of 52 kDa and a pI of 5.77. The recombinant protein possesses a dimeric quaternary structure and displays kinetic parameter values intermediate between those reported for Trypanosoma brucei and T. cruzi with apparent Km values of 6.93 and 5.2 µM for 6PG and NADP+, respectively. The three-dimensional structure of the enzymes of Leishmania and T. cruzi were modelled from their amino acid sequence using the crystal structure of the enzyme of T. brucei as template. The amino acid residues located in the 6PGDH C-terminal region, which are known to participate in the salt bridges maintaining the protein dimeric structure, differed significantly among the enzymes of Leishmania, T. cruzi, and T. brucei. Our results strongly suggest that 6PGDH can be selected as a potential target for the development of new therapeutic drugs in order to improve existing chemotherapeutic treatments against these parasites.
Effect of Probiotic-Fermented Milk Administration onGastrointestinal Survival of Lactobacillus casei ATCC 393 and Modulation of Intestinal Microbial Flora
Authors: Sidira Marianthi , Galanis Alex , Ypsilantis Petros , Karapetsas Athanasios , Progaki Zoi , Simopoulos Constantinos , Kourkoutas Yiannis
Published: December 2010

The aim of the present study was to assess the survival of free and immobilized Lactobacillus casei ATCC 393 on apple pieces, contained in probiotic-fermented milk, after gastrointestinal (GI) transit and to investigate the potential regulation of intestinal microbial flora in a rat model. In in vitro GI stress tolerance tests, immobilized L. casei ATCC 393 exhibited significantly higher survival rates compared to free cells. At a second stage, probiotic-fermented milk produced by either free or immobilized cells was administered orally at a single dose or daily for 9 days in Wistar rats. By 12 h after single-dose administration, both free and immobilized cells were detected by microbiological and molecular analysis at levels ≧6 logCFU/g of feces. Moreover, daily administration led to significant reduction of staphylococci, enterobacteria, coliforms and streptococci counts. In conclusion, L. casei ATCC 393 contained in fermented milk survived GI transit and modulated intestinal microbiota.
Laboratory Paradigms of Impulsivity and Alcohol Dependence: A Review
Authors: Aragues M. , Jurado R. , Quinto R. , Rubio G.
Published: December 2010

Impulsivity can be defined as choosing a smaller, immediate reward over a larger, delayed reward. From this perspective, addictive behaviors such as substance abuse and pathological gambling reflect a series of impulsive choices. However, impulsivity is not a homogeneous construct. Laboratory measures of impulsivity reflect two types of processes. The first is related to behavioral inhibition and refers to an individual’s ability to appropriately inhibit thoughts or actions. The second is the delay of reward dimension, namely the degree to which immediate (rewarding) consequences have more control over an individual’s behavior than consequences that are delayed. In this review, we describe how alcohol is associated with significant impairments in these paradigms. We also suggest that they may have a role in the development of alcohol dependence. These results are in agreement with a model in which delay of gratification might be a marker for early use and/or abuse of alcohol, whereas impairment in behavioral inhibition might be a marker for maintained use in time and, therefore, for progression towards alcohol dependence.
Preventive Effect of Ginger (Zingiber officinale) Pretreatment on Renal Ischemia-Reperfusion in Rats
Authors: Maghsoudi S. , Gol A. , Dabiri S. , Javadi A.
Published: December 2010

Background/Aims: The present study examined the preventive effect of ginger against renal ischemia-reperfusion (I-R) injury. Methods: 30 adultmale rats were used. The animals were allocated to five groups of 6 rats: (1) normal (N), (2) normal + ginger (N+G), (3) right nephrectomy (Sham), (4) I-R, and (5) I-R + ginger (I-R+G). To induce renal ischemia, animals were unilaterally nephrectomized and subjected to 45 min of left renal pedicle occlusion with 24 h reperfusion. Ginger was administered orally 24 h and just before ischemia. At the end of the experiment, blood samples and urine were collected. The following renal functional parameters were studied: serum and urinary levels of creatinine and urea, fractional excretion of sodium, and creatinine clearance. Histopathological examination of the kidney was also performed. Results: Rats with renal I-R showed a significant increase in creatinine and urea concentration in serum and also a significant decrease in creatinine clearance compared with the other groups. In addition, renal histopathology in the I-R group showed severe alterations such as tubular dilatation and tubular epithelial necrosis. However, these changes were significantly reduced in the I-R+G group. Conclusion: This study suggests that ginger is a useful agent for the prevention of renal ischemia reperfusion-induced injury.
Hepatitis B Virus Reactivation in a Primary Central Nervous System Lymphoma Patient following Intrathecal Rituximab Treatment
Authors: Kim Min-Gang , Park So Young , Kim Eun Ji , Kim Yong-Min , Kim Ho Young , Lee Young Kyung , Zang Dae Young , Kim Hyo Jung
Published: December 2010

A 69-year-old woman with relapsed primary central nervous system (CNS) lymphoma was treated with intrathecal rituximab without a concomitant systemic steroid or other chemotherapeutic drugs. Her initial viral status was HBs Ag negative and anti-HBs Ab positive. After 12 weeks of the last intrathecal rituximab application, the levels of AST and ALT were 1,005 and 1,134 IU/l, respectively. The viral status was changed as follows: HBs Ag positive, anti-HBs Ab negative, anti-HBe Ag positive, and anti-HBe Ab negative. The titer of hepatitis B virus (HBV) DNA was 106,000 IU/ml. She was diagnosed with acute hepatitis due to HBV reactivation. To our knowledge, this is the first reported case of HBV reactivation occurring after intrathecal rituximab monotherapy, suggesting that monitoring of HBV markers should be considered during intrathecal rituximab treatment in primary CNS lymphoma patients who are HBs Ag positive or anti-HBs Ab positive.
Cardiomyocyte Apoptosis after Cardioplegic Ischemia: Comparison to Unprotected Regional Ischemia-Reperfusion
Authors: Malmberg M. , Parkka J. , Vahasilta T. , Saraste A. , Laitio T. , Kiss J. , Latva-Hirvela J. , Saukko P. , Savunen T.
Published: December 2010

Background: Cardiomyocyte apoptosis might contribute to left ventricular (LV) dysfunction following cardiac surgery. Magnetic resonance imaging is considered the most accurate method of determining LV function. We compared apoptosis (by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, TUNEL, staining and detection of caspase 3 activation) and LV function after regional ischemia-reperfusion (I-R) and global cardioplegic ischemia. Methods: Pigs were randomized to undergo regional myocardial I-R for 20 + 20 min, global myocardial ischemia with cardiopulmonary bypass (CPB) for 40 min or CPB without ischemia (control), followed by 274 min of reperfusion. Results: Compared with the control group, the number of TUNEL-positive cardiomyocytes was higher in the global ischemia group with CPB (0.024 ± 0.014%; p = 0.02) and further increased in areas of unprotected regional I-R (0.444 ± 0.562%; p = 0.003, vs. control). Myocytes with active caspase 3 were detected after global and regional ischemia. The global ejection fraction did not differ between CPB and regional I-R groups. Conclusions: The use of cardioplegia and CPB efficiently protects the heart from global I-R-induced cardiomyocyte apoptosis during open heart surgery.
In vitro Experiments with the Triangular Flap Cutter Applied to Functional Tracheoesophageal Shunt for Voice Rehabilitation after Total Laryngectomy
Authors: Wang P. , Guo J. , Shen P. , Liu B.
Published: December 2010

Backgrounds: Since the introduction and practice of functional tracheoesophageal shunt (FTES) for voice rehabilitation after total laryngectomy, patients have often suffered from fistula-related complications such as aspiration, tract stenosis and infection partly as a result of nonstandardized or incorrectly made flap operation. In striving to solve these problems as far as possible, a triangular flap cutter (TFC) was developed to perform the flap operation. Methods: Flap operations were performed using a TFC on 10 tracheoesophageal models (pigs) and 10 fresh esophageal models (esophageal cancer patients, with their informed consent) and incision parameters and incision effects were detected. Results: Perfect triangular flaps were achieved in 18 out of 20 cases using the TFC with minimal peripheral tissue injury (average time, 2–3 min). Of the 2 unsuccessful cases, 1 case exhibited insertion failure and the other experienced flap creation failure due to clinical contraindication for TFC use and insufficient operational skills, respectively. Conclusions: The TFC is a new device, which offers the unique advantage of precise incision for the creation of a flap, with the potential to resolve fistula-related problems and improve operation efficiency.
Techniques in Pediatric Surgery: Congenital Hyperinsulinism
Authors: Barthlen Winfried , Mohnike Wolfgang , Mohnike Klaus
Published: December 2010

For surgery in congenital hyperinsulinism (CHI), a distinct strategy and technique is required for focal, diffuse and atypical types. In focal CHI, a confined, localized and parenchyma-sparing resection which is guided by the PET-CT is always indicated in order to cure the patient. In diffuse CHI, however, the results of surgical therapy are unpredictable and cure is an exception. Therefore, a strong tendency exists nowadays that medical therapy should be preferred in diffuse CHI. In atypical CHI the situation is more complex: if the focal lesion or the segmental mosaic are not too extensive, cure by resection should be possible. But care must be taken in atypical cases not to resect too much of the gland in order not to induce diabetes.
Effect of Levothyroxine Suppression Therapy on Plasma Thrombin Activatable Fibrinolysis Inhibitor Antigen Levels in Benign Thyroid Nodules
Authors: Akinci Baris , Demir Tevfik , Comlekci Abdurrahman , Yener Serkan , Ozcan Mehmet Ali , Karaoglu Oguzhan , Yuksel Faize , Secil Mustafa , Yesil Sena
Published: December 2010

Objective: The aim of this prospective study was to investigate the effect of LT4 suppression therapy on plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen and plasminogen activator inhibitor-1 (PAI-1) levels in benign thyroid nodules. We also compared hyperthyroid patients and healthy controls. Subjects and Methods: Twenty premenopausal women with benign thyroid nodules were given LT4 suppression therapy for 1 year. Plasma TAFI and PAI-1 antigen levels were measured at baseline and after LT4 suppression treatment. The endogenous hyperthyroid group was composed of 19 premenopausal females with newly diagnosed endogenous hyperthyroidism. Eighteen age-matched euthyroid healthy premenopausal women were enrolled as the control group. Results: TAFI antigen levels decreased after LT4 suppression treatment; however, the difference was not statistically significant (p = 0.057). LT4 treatment resulted in a nonsignificant increase in PAI-1 levels. Patients with endogenous hyperthyroidism had decreased levels of TAFI antigen and increased levels of PAI-1 antigen (p < 0.05). There was a negative correlation between the FT4 and TAFI antigen levels. Serum TSH was positively correlated with the plasma levels of TAFI antigen. Conclusion: LT4 suppression therapy for benign thyroid nodules did not result in a significant decrease in TAFI antigen levels in premenopausal women, but endogenous hyperthyroidism was associated with significantly decreased levels of TAFI antigen.
Relationship between Thyroid Volume and Iodine, Leptin, and Adiponectin in Obese Women before and after Weight Loss
Authors: Eray Esin , Sari Funda , Ozdem Sabahat , Sari Ramazan
Published: December 2010

Objective: To investigate whether or not reduction of thyroid volume during weight loss is related to adipocytokines and urinary iodine excretion in obese women. Subjects and Methods: 98 obese and 31 non-obese women consecutively admitted to the endocrinology and metabolism outpatient clinic of the School of Medicine, Akdeniz University were included in the study. Thyroid volume, thyroid function tests, leptin and adiponectin levels, and urinary iodine excretion were measured at baseline and six months after treatment for obesity. Results: Thyroid volume increased in obese women (p = 0.048). After adjustment for body mass index, there were no significant differences in plasma leptin and serum adiponectin levels between obese and non-obese women (p > 0.05). Thyroid volume correlated positively with body mass index (r = 0.48, p = 0.04), leptin (r = 0.1, p = 0.03), and thyroid-stimulating hormone (r = 0.43, p = 0.001) levels, while there was a negative correlation between thyroid volume and urinary iodine (r = –0.38, p = 0.04) and urinary iodine/creatinine ratio (r = –0.25, p = 0.045) in obese women. Changes in body mass index (p = 0.022) and leptin levels (p = 0.039) were the only factors that significantly affected the change of thyroid volume during weight loss. Conclusion: Iodine status may play an important role in increased thyroid volume in obese women; however, iodine status did not seem to exert a significant influence on the changes in thyroid volume. On the other hand, changes in both body mass index and plasma leptin levels seemed to be important for changes in thyroid volume.
Age-Related Changes in the Oligodendrocyte Progenitor Pool Influence Brain Remodeling after Injury
Authors: Wright Jamie , Zhang Gui , Yu Tzong-Shiue , Kernie Steven G.
Published: December 2010

Brain remodeling occurs after all forms of brain injury, though the mechanisms underlying this phenomenon are mostly unknown. Neural stem and progenitor cells are one source of endogenous cells that may contribute to brain remodeling and subsequent recovery. In addition, certain populations of progenitors are particularly susceptible to injury, and their depletion may lead to the impairment of developmental processes that vary with age. We particularly focus on glial progenitors, which are more abundant postnatally and particularly susceptible to acquired brain injuries such as traumatic brain injury. We have recently characterized a novel transgenic mouse that expresses herpes thymidine kinase under the control of the neural-progenitor-specific nestin promoter and allows for temporally induced ablation of dividing progenitors. By genetically depleting dividing cortical progenitors at various times, we identify postnatal day 7 (P7) to P14 as a critical period for oligodendrogenesis. Targeted ablation of dividing progenitors during this window leads to cell-specific depletion of oligodendrocyte precursors expressing platelet-derived growth factor receptor-α and corresponding myelination and motor deficits. This modeling provides insight into how the age at which white matter injury occurs influences both injury severity and subsequent recovery.
Microbiota of Dentinal Caries as Assessed by Reverse-Capture Checkerboard Analysis
Authors: Lima K.C. , Coelho L.T. , Pinheiro I.V.A. , Rôças I.N. , Siqueira Jr. J.F.
Published: December 2010

Background/Aims: This study aimed to identify the microbiota of different layers of dentinal caries by using a culture-independent molecular biology approach. Methods: DNA was extracted from samples taken from 3 distinct layers (superficial, middle and deep) of advanced occlusal caries and analyzed for the presence and relative levels of 28 oral bacterial species/phylotypes using a reverse-capture checkerboard hybridization assay. Results: The mean number of target taxa per layer was 7.7 (±3.96) in the superficial, 7 (±3.4) in the middle, and 6.3 (±3.04) in the deep layer. No statistical significance was observed for these differences (p = 0.36). Overall, the most prevalent taxa in the 3 layers were Atopobium genomospecies C1 (72.5%), Fusobacterium nucleatum (69%), Lactobacillus casei (68%), Veillonella species (55%) and Lactobacillus fermentum (52%). No differences were found in the prevalence rates of the most frequent target species in the 3 layers. The most prevalent taxa found at levels above 105 in the advanced front line of deep-dentin caries were Atopobium genomospecies C1, F. nucleatum, Streptococcus mutans, Streptococcus species and Veillonella species. Conclusion: The present results revealed that the prevalences of several established or candidate caries pathogens do not differ significantly in the different zones of dentinal caries lesions. The finding that some as-yet-uncharacterized species and novel species were found in high frequencies join other molecular studies to include them in the set of candidate caries pathogens.
Sodium Setpoint and Sodium Gradient: Influence on Plasma Sodium Change and Weight Gain
Authors: Hecking Manfred , Kainz Alexander , Hörl Walter H. , Herkner Harald , Sunder-Plassmann Gere
Published: December 2010

Background/Aims: In hemodialysis and hemodiafiltration patients, the plasma sodium (PNa) measured before dialysis can be regarded as the sodium setpoint. By the end of dialysis, the PNa typically approximates the prescribed dialysate sodium (DNa), the difference between DNa and PNa being considered the sodium gradient. We determined the relationship between setpoint, gradient and pre- to postdialysis PNa change (delta PNa), and studied associations with dialysis-related variables. Methods: Cohort study. Measurements from 132 patients during 12 consecutive treatments included PNa and DNa concentrations, pre- to postdialysis body weight and predialysis systolic blood pressure. Results: Sodium setpoints were normally distributed (137.9 ± 2.4 mmol/l), DNa prescriptions were non-normally distributed (138.9 ± 1.8 mmol/l). The sodium gradient correlated strongly with delta PNa (r = 0.76, p < 0.001). Both sodium gradient and delta PNa correlated with relative interdialytic weight gain (IDWG; r = 0.25, p = 0.004, and r = 0.44, p < 0.001, respectively), but not with predialysis systolic blood pressure. These correlations were consistent after exclusion of patients with urine volume >500 ml/day and patients undergoing sodium profiling, and increased after exclusion of patients with hemodiafiltration protocols. Predictors for having higher relative IDWG (≧2.8%) were delta PNa concentrations ≧0 mmol/l and younger age. Predictors for having a delta PNa concentration ≧0 mmol/l were lower sodium setpoints, higher DNa prescriptions, use of Nikkiso machines, sodium profiling and younger age. Patients with positive delta PNa despite negative gradients were significantly younger, used more Nikkiso machines and presented with higher IDWG. Conclusion: IDWG correlated with the sodium gradient and more strongly with delta PNa, suggesting the need for studying other outcomes, such as morbidity and mortality.
Effect of Genetic Variations in Syntaxin-Binding Protein-5 and Syntaxin-2 on von Willebrand Factor Concentration and Cardiovascular Risk
Authors: van Loon Janine E. , Leebeek Frank W.G. , Deckers Jaap W. , Dippel Diederik W.J. , Poldermans Don , Strachan David P. , Tang Weihong , O'Donnell Christopher J. , Smith Nicholas L. , de Maat Moniek P.M.
Published: December 2010

Background—

Elevated von Willebrand factor (VWF) plasma levels are associated with an increased risk of cardiovascular disease. A meta-analysis of genomewide association studies on VWF identified novel candidate genes, that is, syntaxin-binding protein 5 (
STXBP5
) and syntaxin 2 (
STX2
), which are possibly involved in the secretion of VWF. We investigated whether VWF antigen levels (VWF:Ag), VWF collagen-binding activity (VWF:CB) and the risk of arterial thrombosis are affected by common genetic variations in these genes.

Methods and Results—

In 463 young white subjects (men ≤45 years of age and women ≤55 years of age), who were included 1 to 3 months after a first event of arterial thrombosis, and 406 control subjects, we measured VWF:Ag and VWF:CB. Nine haplotype tagging single-nucleotide polymorphisms of
STXBP5
and
STX2
were selected and subsequently analyzed using linear regression with additive genetic models adjusted for age, sex, and ABO blood group. The minor alleles of
rs
9399599 and
rs
1039084 in
STXBP5
were associated with lower VWF plasma levels and activity, whereas the minor allele of
rs
7978987 in
STX2
was associated with higher VWF plasma levels and activity. The minor alleles of the single-nucleotide polymorphisms in
STX2
were associated with a reduced risk of arterial thrombosis (
rs
1236: odds ratio, 0.73 [95% confidence interval, 0.59, 0.89];
rs
7978987: odds ratio, 0.81 [95% confidence interval, 0.65, 1.00];
rs
11061158: odds ratio, 0.69 [95% confidence interval, 0.55, 0.88]).

Conclusions—

Genetic variability in
STXBP5
and
STX2
affects both VWF concentration and activity in young individuals with premature arterial thrombosis. Furthermore, in our study, genetic variability in
STX2
is associated with the risk of arterial thrombosis. However, at this point, the underlying mechanism remains unclear.