bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA interference–mediated cyclooxygenase-2 inhibition prevents prostate cancer cell growth and induces differentiation: modulation of neuronal protein synaptophysin, cyclin D1, and androgen receptor
Authors: Narayanan Bhagavathi A. , Narayanan Narayanan K. , Davis Leland , Nargi Dominick
Published: May 2006

Cyclooxygenase-2 (COX-2) plays an important role in tumor development and progression. Inconsistent reports on the expression of COX-2 in early versus advanced prostate cancer raised the question on whether COX-2 inhibition affects prostate carcinogenesis. Evidence from recent studies indicates that prostate carcinogenesis depends on the altered expression of several factors including androgen receptor signaling, proinflammatory, and cell cycle regulatory genes. Very often, the outcome of androgen ablation treatment is not effective and, eventually, the cancer becomes androgen independent followed by activation of several survival genes and transcription factors. Most importantly, the extent of the influence of COX-2 on the regulation of the androgen receptor, cyclin D1, and other factors involved in cancer growth is not known. Using RNA interference–mediated COX-2 inhibition in metastatic prostate cancer cells, this study has shown that the silencing of COX-2 at the mRNA level can induce cell growth arrest and down-regulate androgen receptor and cyclin D1. We have further shown for the first time that COX-2 knockdown prostate cancer cells depict morphologic changes associated with enhanced expression of differentiation markers, particularly the neuronal protein synaptophysin along with activation of p21(Waf1/Cip1) and p27(Kip1). In summary, our findings determined the role of COX-2 in prostate carcinogenesis and its control on COX-2-independent targets. Second, abrogation of COX-2 and activation of synaptophysin provide evidence for the control of COX-2 on the expression of a neuronal protein. Finally, our findings provide evidence of COX-2-independent targets promoting cell growth arrest and differentiation in cells lacking COX-2 expression at the mRNA level. [Mol Cancer Ther 2006;5(5):1117–25]
Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins
Authors: Aziz Moammir H. , Nihal Minakshi , Fu Vivian X. , Jarrard David F. , Ahmad Nihal
Published: May 2006

Prostate cancer is a major health problem in the U.S. and the available treatment and surgical options have proven to be inadequate in controlling the mortality and morbidity associated with this disease. It is therefore necessary to intensify our efforts to better understand this disease and develop novel approaches for its prevention and treatment. This study was conducted to evaluate the chemopreventive/antiproliferative potential of resveratrol (trans-3,4′,5,-trihydroxystilbene) against prostate cancer and its mechanism of action. Treatment with resveratrol (0–50 μmol/L for 24 hours) resulted in a significant (a) decrease in cell viability, (b) decrease of clonogenic cell survival, (c) inhibition of androgen (R1881)-stimulated growth, and (d) induction of apoptosis in androgen-responsive human prostate carcinoma (LNCaP) cells. Interestingly, at similar concentrations, resveratrol treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cells. Furthermore, our data showed that resveratrol-treatment resulted in significant dose-dependent inhibition in the constitutive expression of phosphatidylinositol 3′-kinase and phosphorylated (active) Akt in LNCaP cells. Resveratrol treatment for LNCaP cells was also found to result in a significant (a) loss of mitochondrial membrane potential, (b) inhibition in the protein level of antiapoptotic Bcl-2, and (c) increase in proapoptotic members of the Bcl-2 family, i.e., Bax, Bak, Bid, and Bad. Taken together, our data suggested that resveratrol causes an inhibition of phosphatidylinositol 3′-kinase/Akt activation that, in turn, results in modulations in Bcl-2 family proteins in such a way that the apoptosis of LNCaP cells is promoted. Based on these studies, we suggest that resveratrol could be developed as an agent for the management of prostate cancer. [Mol Cancer Ther 2006;5(5):1335–41]
Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells
Authors: Kampa Marilena , Kogia Christina , Theodoropoulos Panayiotis A. , Anezinis Ploutarchos , Charalampopoulos Ioannis , Papakonstanti Evangelia A. , Stathopoulos Efstathios N. , Hatzoglou Anastassia , Stournaras Christos , Gravanis Achille , Castanas Elias
Published: May 2006

Genomic signaling mechanisms require a relatively long time to get into action and represent the main way through which steroid hormones affect target cells. In addition, steroids may rapidly activate cellular functions by non-genomic signaling mechanisms involving membrane sites. Understanding in depth the molecular mechanisms of the non-genomic action represents an important frontier for developing new and more selective pharmacologic tools for endocrine therapies. In the present study, we report that membrane-impermeable testosterone-bovine serum albumin (BSA) acts synergistically with paclitaxel in modifying actin and tubulin cytoskeleton dynamics in LNCaP (androgen sensitive) and DU-145 (androgen insensitive) human prostate cancer cell lines. In addition, coincubation of either cell line with testosterone-BSA and paclitaxel induced inhibition of cell proliferation and apoptosis. Finally, in vivo experiments in LNCaP and DU-145 tumor xenografts in nude mice showed that both agents decrease tumor mass, whereas testosterone-BSA enhances the effect of paclitaxel. Our findings suggest that chronic activation of membrane androgen receptors in vitro and in vivo facilitates and sustains for a longer time the antitumoral action of cytoskeletal acting agents. [Mol Cancer Ther 2006;5(5):1342–51]
1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes inhibit colon cancer cell and tumor growth through PPARγ-dependent and PPARγ-independent pathways
Authors: Chintharlapalli Sudhakar , Papineni Sabitha , Safe Stephen
Published: May 2006

1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes containing p-trifluoromethyl, t-butyl, and phenyl [1,1-bis(3′-indolyl)-1-(p-phenyl)methane (DIM-C-pPhC6H5)] substituents induce peroxisome proliferator-activated receptor γ (PPARγ)–mediated transactivation in SW480 colon cancer cells. These PPARγ-active compounds also inhibit cell proliferation and modulate some cell cycle proteins. At concentrations from 2.5 to 7.5 μmol/L, the PPARγ agonists induce caveolin-1 and phosphorylation of Akt and cotreatment with the PPARγ antagonist GW9662 inhibited the induction response. In contrast, higher concentrations (10 μmol/L) of 1,1-bis(3′-indolyl)-1-(p-substituted phenyl)methanes containing 1,1-bis(3′-indolyl)-1-(p-trifluoromethyl)methane and DIM-C-pPhC6H5 induce apoptosis, which is PPARγ independent. This was accompanied by loss of caveolin-1 induction but induction of proapoptotic nonsteroidal anti-inflammatory drug activated gene-1. In athymic nude mice bearing SW480 cell xenografts, DIM-C-pPhC6H5 inhibits tumor growth at doses of 20 and 40 mg/kg/d and immunohistochemical staining of the tumors showed induction of apoptosis and nonsteroidal anti-inflammatory drug activated gene-1 expression. Thus, the indole-derived PPARγ-active compounds induce both receptor-dependent and receptor-independent responses in SW480 cells, which are separable over a narrow range of concentrations. This dual mechanism of action enhances their antiproliferative and anticancer activities. [Mol Cancer Ther 2006;5(5):1362–70]
Peripheral Opioids for Functional GI Disease: A Reappraisal
Authors: Lembo Anthony
Published: May 2006

Opioids have been used medicinally and recreationally for thousands of years. The clinical use of opioids for gastrointestinal conditions has been limited by central nervous system side effects. A new generation of peripheral opioid receptor ligands free of central nervous system side effects is being developed. Clinical trials with the peripherally acting mu opioid receptor antagonists’ alvimopan and N-methylnaltrexone show promise for improving postoperative ileus- and opioid-induced constipation. Likewise, preliminary studies with the peripherally acting kappa opioid agonist fedotozine showed promise in the treatment of irritable bowel syndrome (IBS) and functional dyspepsia. Further studies are on hold presumably due to lack of efficacy in subsequent studies. However, clinical studies are underway for newer kappa opioid agonists such as asimadoline and ADL 10-0101.
Emerging Biological Treatments in Inflammatory Bowel Diseases
Authors: van Assche Gert , Vermeire Séverine , Rutgeerts Paul
Published: May 2006

Although the advent of infliximab has changed the treatment paradigm and goals in inflammatory bowel disease, it does not provide a cure for it and recent evidence has demonstrated that the immunogenicity of this chimeric anti-tumor necrosis factor antibody is associated with secondary loss of response and intolerance. In ulcerative colitis the efficacy of infliximab was demonstrated in two large clinical trials, but long-term maintenance efficacy data are lacking. Novel biological agents have entered clinical development and pioneering trials have been reported in the last 2 years. For Crohn’s disease the fully human IgG1 anti-tumor necrosis factor monoclonal adalimumab, and the humanized anti-α4-integrin IgG4 antibody, natalizumab have yielded the most promising results in controlled trials, but also agents inhibiting the crucial interleukin-12/interferon-γ feedback loop suggest therapeutic potential. For severe ulcerative colitis infliximab has been shown to be an effective rescue treatment and the anti-T-cell CD3 antibody has shown promising open-label results. Crucial in the development of novel biological agents, however, is the benefit:risk ratio. As illustrated by unexpected but devastating brain infections with anti-adhesion molecules, clinicians should be aware that the powerful immunomodulatory capacity of biologicals necessitates a rigorous safety follow-up.
Pharmacological Prevention and Treatment of Acute Pancreatitis: Where Are We Now?
Authors: Lankisch Paul Georg , Lerch Markus M.
Published: May 2006

Acute pancreatitis is a disease of increasing prevalence, unchanged mortality over many decades, and limited treatment strategies. Progress has been made in developing therapies that reduce the rate of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatitis and in preventing infected pancreatic necrosis with intravenous carbapenems. Attempts at reducing pancreatic enzyme output or inhibiting the activity of digestive enzyme proteases have not yielded encouraging results – nor have anti-inflammatory strategies for the treatment of acute pancreatitis been found to be effective so far. Future therapeutic options that are presently being developed or under investigation attempt to restore pancreatic secretory function, interfere with inflammatory pathways in a more effective manner, or inhibit digestive enzyme proteases more selectively.
NSAID-Associated Dyspepsia and Ulcers: A Prospective Cohort Study in Primary Care
Authors: Hollenz Margrit , Stolte Manfred , Leodolter Andreas , Labenz Joachim
Published: May 2006

Background and Aim: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause dyspeptic complaints and lesions in the upper gastrointestinal tract. The true incidence of these side effects in the everyday situation remains uncertain. We therefore investigated as to how often patients on NSAIDs in the primary care setting must be expected to develop troublesome dyspepsia and/or ulcers in the upper gastrointestinal tract. Patients and Methods: Admitted to the study were consecutive patients requiring NSAID treatment for at least 2 weeks, who were free of treatment-requiring dyspeptic symptoms, and who were not receiving any prophylactic co-medication. After a minimum of 2 weeks of treatment with a NSAID, a standardized questionnaire and endoscopy of the upper gastrointestinal tract were obtained. Results: 104 patients (median age 53 years, 91 women) were recruited to the study. Four patients had to be excluded for protocol violations. NSAID treatment was applied mainly with diclofenac (n = 67), followed by ibuprofen (n = 22) and rofecoxib (n = 9). The main indication was degenerative complaints affecting the vertebral column and joints. Under treatment, 35% of the patients developed troublesome dyspepsia that required treatment. The frequency of dyspepsia was independent of the duration of NSAID use. Ulcer prevalence was 16% (duodenal ulcer: n = 5; gastric ulcer: n = 11; cardiac ulcer: n = 1). Relevant epigastric pain was experienced more frequently by ulcer patients than those with no ulcer (35 vs. 18%, p = n.s.), but their overall symptom frequency was no higher than in the latter. Predictors for the development of ulcer were smoking (odds ratio 5.11 [1.59–16.48]), regular use of alcohol (odds ratio 4.49 [1.34–15.07]) and duration of treatment less than 1 month (odds ratio 4.95 [1.06–23.09]). No ulcer complications occurred during the period under observation. Overall, 44% of the patients developed troublesome dyspepsia and/or ulcer. Conclusion: Primary care patients with an average risk profile frequently develop dyspeptic symptoms requiring treatment, and ulcers while on NSAIDs. Patients who developed an ulcer were not identifiable on the basis of symptoms or risk factors.
Enteropatías inmunes y autoinmunes
Authors: Sherman Philip M. , Cutz Ernest , Goulet Olivier
Published: May 2006

La enteropatía autoinmune se presenta normalmente en la lactancia en forma de diarrea prolongada. Deben excluirse los trastornos subyacentes de la función inmunitaria, incluyendo las células T reguladoras. Entre las opciones terapéuticas destacan las siguientes: rehabilitación nutricional, inmunosupresión y, en casos seleccionados, trasplante de médula ósea.
Enteropatía congénita y trasplante intestinal
Authors: Goulet Olivier
Published: May 2006

La insuficiencia intestinal (II) exige el uso de nutrición parenteral (NP). Entre las causas de II prolongada grave destacan el síndrome del intestino corto, trastornos de la motilidad grave (aganglionosis total o subtotal o síndrome de seudoobstrucción intestinal crónica) y enfermedades congénitas del desarrollo de los enterocitos. Puede aparecer insuficiencia hepática grave en pacientes con II como consecuencia de una enfermedad digestiva subyacente y una NP no adaptada. La sepsis relacionada con el catéter y/o la trombosis vascular extensa pueden impedir el mantenimiento de una NP segura y eficiente. Por tanto, el tratamiento de pacientes con II exige la identificación precoz del proceso y el análisis de su riego de irreversibilidad. La cronología de la derivación para trasplante intestinal continúa siendo una cuestión crucial. En consecuencia, la asistencia debe incluir tratamientos adaptados a cada una de las etapas de la II, basándose en la puesta en práctica de un enfoque multidisciplinario en centros que cuenten con gastroenterología pediátrica, experiencia en NP, programa de NP domiciliaria, cirugía pediátrica y programa de trasplantes de hígado e intestino.
Sodium Ion Pumps and Hydrogen Production in Glutamate Fermenting Anaerobic Bacteria
Authors: Boiangiu Clara D. , Jayamani Elamparithi , Brügel Daniela , Herrmann Gloria , Kim Jihoe , Forzi Lucia , Hedderich Reiner , Vgenopoulou Irini , Pierik Antonio J. , Steuber Julia , Buckel Wolfgang
Published: May 2006

Anaerobic bacteria ferment glutamate via two different pathways to ammonia, carbon dioxide, acetate, butyrate and molecular hydrogen. The coenzyme B12-dependent pathway in Clostridium tetanomorphum via 3-methylaspartate involves pyruvate:ferredoxin oxidoreductase and a novel enzyme, a membrane-bound NADH:ferredoxin oxidoreductase. The flavin- and iron-sulfur-containing enzyme probably uses the energy difference between reduced ferredoxin and NADH to generate an electrochemical Na+ gradient, which drives transport processes. The other pathway via 2-hydroxyglutarate in Acidaminococcus fermentans and Fusobacterium nucleatum involves glutaconyl-CoA decarboxylase, which uses the free energy of decarboxylation to generate also an electrochemical Na+ gradient. In the latter two organisms, similar membrane-bound NADH:ferredoxin oxidoreductases have been characterized. We propose that in the hydroxyglutarate pathway these oxidoreductases work in the reverse direction, whereby the reduction of ferredoxin by NADH is driven by the Na+ gradient. The reduced ferredoxin is required for hydrogen production and the activation of radical enzymes. Further examples show that reduced ferredoxin is an agent, whose reducing energy is about 1 ATP ‘richer’ than that of NADH.
Ischemic Preconditioning: A Novel Target for Neuroprotective Therapy
Authors: Blanco Miguel , Lizasoain Ignacio , Sobrino Tomás , Vivancos José , Castillo José
Published: May 2006

Ischemic preconditioning involves a brief exposure to ischemia in order to develop a tolerance to injurious effects of prolonged ischemia. The molecular mechanisms of neuroprotection that lead to ischemic tolerance are not yet completely understood. However, it seems that two distinct phases are involved. Firstly, a cellular defense function against ischemia may be developed by the mechanisms inherent to neurons such as posttranslational modification of proteins or expression of new proteins via a signal transduction system to the nucleus. Secondly, a stress response and synthesis of stress proteins (heat shock proteins) may be activated. These mechanisms are mediated by chaperones. The objective of ischemic preconditioning research is to identify the underlying endogenous protective cellular receptors and signaling cascades, with the long-term goal of allowing therapeutic augmentation of the endogenous protective mechanisms in cerebral ischemia and possibly development of new neuroprotective strategies for ischemic stroke treatment.
Neurorepair versus Neuroprotection in Stroke
Authors: Hurtado Olivia , Pradillo Jesus M. , Alonso-Escolano David , Lorenzo Pedro , Sobrino Tomás , Castillo José , Lizasoain Ignacio , Moro María Angeles
Published: May 2006

Stroke is the second to third leading cause of death and the main cause of severe, long-term disability in adults. However, treatment is almost reduced to fibrinolysis, a therapy useful in a low percentage of patients. Given that the immediate treatment for stroke is often unfeasible in the clinical setting, the need for new therapy strategies is imperative. After stroke, the remaining impairment in functions essential for routine activities, such as movement programming and execution, sensorimotor integration, language and other cognitive functions have a deep and life-long impact on the quality of life. An interesting point is that a slow but consistent recovery can be observed in the clinical practice over a period of weeks and months. Whereas the recovery in the first few days likely results from edema resolution and/or from reperfusion of the ischemic penumbra, a large part of the recovery afterwards is due mainly to brain plasticity, by which some regions of the brain assume the functions previously performed by the damaged areas. Neurogenesis and angiogenesis are other possible mechanisms of recovery after stroke. An understanding of the mechanisms underlying functional recovery may shed light on strategies for neurorepair, an alternative with a wide therapeutic window when compared with neuroprotective strategies.
Evolving Paradigms for Neuroprotection: Molecular Identification of Ischemic Penumbra
Authors: Castellanos Mar , Sobrino Tomás , Castillo José
Published: May 2006

Ischemic penumbra defines the existence of tissue at risk of infarction and which is, hence, potentially salvageable and the target for current stroke reperfusion and neuroprotective therapies. Penumbral tissue evolves toward irreversibly damaged tissue at different rates in individual stroke patients yielding different therapeutic windows depending on the individual duration of risk of infarction of this tissue. An accurate identification of the penumbra is then necessary in order to individualize the window of opportunity for therapeutic interventions. Imaging techniques, although helpful, may not give the most accurate information as to the existence of penumbra given that the threshold for identification of penumbra varies depending on the technique used. A better identification of the true penumbral tissue might be based on the cascade of molecular events that are responsible for the evolution of the penumbra toward infarcted tissue. Multiple penumbras can be defined in molecular terms taking into account which vessel is occluded, the time of evolution of the ischemia, the degree of the ischemia, and the sensitivity to ischemia of the different cells. Future studies are necessary to clarify whether the enhancement of cytoprotective mechanisms, and/or the block of cytotoxic mechanisms confirming the existence of penumbra at different times of ischemic evolution, are effective neuroprotective strategies.
Non-Pharmacological Neuroprotection: Role of Emergency Stroke Management
Authors: Leira Rogelio , Blanco Miguel , Rodríguez-Yáñez Manuel , Flores José , García-García Jorge
Published: May 2006

Acute stroke should be considered a medical emergency, where actions taken in the first hours are fundamental for achieving recovery of the damaged cerebral tissue and a better prognosis for the patient. Recanalization and neuroprotective treatment has been used with mixed results. The effectiveness observed in the first hours with thrombolytic drug treatment is only applicable to a small percentage of patients, and attempts to widen this treatment window have not yet proved fruitful. Pharmacological neuroprotective treatment has not yet demonstrated the clinical effectiveness observed in experimental models. The concept of neuroprotection in cerebral ischemia also involves a series of mechanisms that take place at the cerebral level following vascular occlusion. In this context, it should be borne in mind that a series of physiological functions usually involved in the cerebral metabolism (control of blood pressure, of temperature, of glycemia and of arterial oxygen saturation) play a key role in modulation of the ischemic process. Changes in the control of these mechanisms may aggravate the process of cerebral damage in the first hours of ischemic stroke. In this work we review the prognostic importance of the main mechanisms that may influence the acute phase of cerebral ischemic stroke, as well as their therapeutic management and control in the clinical situation.
Age-Related Changes of the Cutaneous Microcirculation in vivo
Authors: Li Li , Mac-Mary Sophie , Sainthillier Jean-Marie , Nouveau Stephanie , de Lacharriere Olivier , Humbert Philippe
Published: May 2006

Background: The architectural frameworks of the skin microcirculation are rather complex and change continuously with aging. But these changes are yet poorly documented in vivo. Objectives: Using non-invasive methods belonging to the field of biometrology, the study aimed to investigate quantitatively the changes of the cutaneous microvasculature in different anatomic sites with age. Methods: Measurements were performed on crow’s feet, forehead, volar forearm and dorsum of hand in 50 women (aged 20–74 years who consisted of 10 probands in each live decades). The superficial vascular plexus was scanned by videocapillaroscopy and assessed with the software Capilab Toolbox®. The subpapillary vascular plexus was explored with laser Doppler flowmetry. The skin color a* was analyzed by chromametry. Results: A marked site and age effect on the skin microcirculation has been demonstrated. The density of capillary loops in the eldest group decreased by about 40–70% compared with the youngest group whereas the vascular length increased by 35–156%. The capillary density in the back of the hand was 4 times higher than in the crow’s feet. The vascular length in the crow’s feet was 3 times longer than in the back of the hand. Both blood flow and skin redness (a*) increased also with age. Conclusion: Both morphology and quantification of the cutaneous microvasculature showed changes with site and age. Videocapillaroscopy associated to an image processing and laser Doppler flowmetry revealed different vascular layers. So the combination of both instruments offers an easy way to observe the architectural frameworks in vivo.
Is Hand-Held Dynamometry Useful for the Measurement of Quadriceps Strength in Older People? A Comparison with the Gold Standard Biodex Dynamometry
Authors: Martin H.J. , Yule V. , Syddall H.E. , Dennison E.M. , Cooper C. , Aihie Sayer A.
Published: May 2006

Background: The lower limb muscle strength is an important determinant of physical function in older people. However, measurement in clinical and epidemiological settings has been limited because of the requirement for large-scale equipment. A protocol using a novel, versatile hand-held dynamometer (HHD) has been developed to measure the quadriceps strength in a supine position. Objective: The objective of this study was to assess the validity of this new methodology for measuring the lower limb muscle strength compared to the gold standard Biodex dynamometer. Methods: The supine quadriceps strength was measured twice with each of the Biodex and the HHD in 20 men and women, aged 61–81 years, on their non-dominant leg. The agreement between the peak torques obtained by Biodex and HHD was analyzed. Results: The mean peak Biodex and HHD results were 83.4 ± (SD) 28.0 Nm and 68.9 ± 19.6 Nm, respectively. The HHD undermeasured the quadriceps strength by an average of 14.5 Nm (95% CI 8.5, 20.6) compared to the Biodex, and this effect was most marked in the strongest participants. Nevertheless, there was a good correlation between the measures (r = 0.91, p < 0.0001). Classification of individuals into tertiles of muscle strength showed good agreement between the two methods (Kappa = 0.69, p < 0.0001). Conclusions: Our findings suggest that the HHD using a supine positioning offers a feasible, inexpensive, and portable test of quadriceps muscle strength for use in healthy older people. It underestimates the absolute quadriceps strength compared to the Biodex particularly in stronger people, but is a useful tool for ranking muscle strength of older people in epidemiological studies. It may also be of value for quick and objective assessment of physical function in the clinical setting.
A New Approach for the Surgery of Large Renal Masses: Abdominal Wall Flap Incision
Authors: Türkeri Levent N. , Temiz Yusuf , Özgur Abdurrahman , Önol Fikret Fatih
Published: May 2006

Introduction: The type of skin incision affects the course of surgery during radical nephrectomy. We investigated the efficacy of a new type of incision for the surgical approach to large renal masses. Patients and Methods: Fourty patients (23 males and 17 females, mean age 63 years) who underwent radical nephrectomy in our department between 2002 and 2004 were evaluated. The outcomes in the groups with chevron incision and abdominal wall flap incision (AFI) were compared in terms of greatest tumor diameter, operation duration, perioperative blood loss, postoperative complications, and duration of hospitalization. Statistical analysis was made by independent-samples t test. Results: Chevron incision was used in the first 15 patients, while subsequent 25 patients were operated via AFI. The operation duration was slightly longer in the AFI group (3.78 vs. 3 h); however, the mean largest tumor diameter was significantly greater in patients operated via AFI (11.3 vs. 7.4 cm, p < 0.05). The mean blood losses were 1,100 and 590 ml in the chevron incision and AFI groups, respectively (p < 0.05). There was no significant difference in terms of duration of hospitalization and postoperative morbidity. Conclusion: In our experience, AFI provides the best exposure and improved control of renal vessels and vena cava during radical nephrectomy and enables a safe dissection even in very large tumors with minimal blood loss.
When Does It Hurt? Pain during Flexible Cystoscopy in Men
Authors: Taghizadeh A.K. , El Madani A. , Gard P.R. , Li C.-Y. , Thomas P.J. , Denyer S.P.
Published: May 2006

Introduction: In this observational study, pain was measured continuously in men undergoing flexible cystoscopy, in order to help to identify which parts of the procedure were the most painful. Patients and Methods: Men who were to undergo flexible cystoscopy were recruited. Pain was measured continuously throughout flexible cystoscopy by asking the subject to squeeze a pressure-sensing rubber bulb in proportion to the amount of discomfort experienced giving a score of 0–10. Results: The most painful part of the procedure was as the cystoscope passed through the membranous urethra with a median pain score of 2.82. The initial lidocaine administration gives a median pain score of 0.84. The other parts of the cystoscopy produced median scores of between 0.14 and 0.33. The difference in the pain scores was significant (p = 0.03). There was no statistically significant difference in the pain scores between those who were having their first cystoscopy and those who were having repeat cystoscopy. The subjects’ age did not influence the degree of pain experienced. Conclusion: This study gives further understanding of how pain is experienced during flexible cystoscopy. It may help explain why previous studies have not reached a clear consensus on the value of lidocaine during flexible cystoscopy.
Questionnaire Survey of Urologists’ Initial Treatment Practices for Acute Urinary Retention Secondary to Benign Prostatic Hyperplasia in Korea
Authors: Ku Ja Hyeon , Kim Soo Woong , Paick Jae-Seung
Published: May 2006

Background: We undertook a survey of Korean urologists to establish initial treatment practices for acute urinary retention secondary to benign prostatic hyperplasia. Methods: Probability samples were drawn from the Korean Urological Association Registry of Physicians, and a random sample of 850 Korean urologists were asked to complete a questionnaire that explored practice characteristics and treatment strategies in the management of acute urinary retention. The returned questionnaires were statistically analyzed. Results: Of the 850 questionnaires sent, 302 were returned, and 277 of those were included in the final analysis (response rate 32.6%). Korean urologists preferred urethral catheterization as the initial management. Of respondents, 154 (55.6%) and 109 (39.4%) started their patients on α-blockers and α-blockers with finasteride, respectively. Nearly half (50.2%) used a trial without catheter 7 days after catheterization. One failed trial without catheter was an indication for surgery for only 69 (24.9%) of the respondents. A second trial without catheter was advocated by 108 (39.0%). Most urologists (82.3%) expected to be successful with the above management in 50% or greater. Physician’s demographics or types of initial management did not influence physician’s perception of expected success rate when the expected success rate was divided as ≤50% and >50. Conclusions: These data provide a picture of current practice regarding the management of acute urinary retention secondary to benign prostatic hyperplasia in Korea. There is no uniformity in the management of acute urinary retention in Korea.
How Do Patients with Familial Benign Prostatic Hyperplasia Differ Clinically from Those with Sporadic Benign Prostatic Hyperplasia?
Authors: Öztekin Ç. Volkan , Öztürk Bülent , Tas Metin , Ugurlu Özgür , Çetinkaya Mesut
Published: May 2006

Introduction: The aim of this study was to compare age, prostatic volume, International Prostate Symptom Score (IPSS), maximal flow rate, serum total prostate-specific antigen (PSA), serum free PSA, free/total PSA ratio and PSA density values of familial and sporadic benign prostatic hyperplasia (BPH) patients suffering moderate or severe lower urinary tract symptoms. Materials and Methods: Between September 1999 and August 2004, 511 patients with moderate or severe lower urinary tract symptoms (IPSS ≧8) due to BPH were included in the study. Patients with at least 2 first-degree relatives who had undergone surgery or received medication for BPH were classified as having the familial form of the disease, while the remaining patients were taken as sporadic cases. Mean age, prostatic volume, symptom score, maximal flow rate, PSA, free PSA, free/total PSA ratio and PSA density values of the familial and sporadic groups were compared using student’s t test. Results: Thirty-eight patients had a positive family history and formed the familial group, while the remaining 473 made up the sporadic group. No significant difference was observed in the parameters studied, except that mean prostate volume of the familial group was found to be greater and the mean age to be lower than those of sporadic patients in accordance with the literature. Conclusions: Patients with familial BPH need treatment significantly earlier and have larger prostates than those with sporadic BPH.
Laparoscopic Peritoneal Drainage of Symptomatic Lymphoceles after Pelvic Lymph Node Dissection Using Methylene Blue Instillation
Authors: Varga Zoltan , Hegele Axel , Olbert Peter , Hofmann Rainer , Schrader Andres Jan
Published: May 2006

Background: Lymphoceles are frequent complications of pelvic lymph node dissection. While small lymphoceles often remain undetected, larger ones can cause complications and require further treatment, e.g. percutaneous tube drainage alone or in combination with sclerotherapy. However, recurrence rates are considerable, and long-lasting drainage may lead to infection, prolonged hospitalization, and as a consequence, increased overall costs. We report the results of a simplified laparoscopic approach to drain lymphoceles after radical prostatectomy plus pelvic lymphadenectomy using methylene blue instillation. Methods: 13 patients with large symptomatic pelvic/retroperitoneal lymphoceles refractory to percutaneous tube drainage and doxycycline sclerotherapy received a laparoscopic transperitoneal marsupialization following instillation of a sterile diluted methylene blue solution into the drained cavity to refill and mark the lymphocele. Results: All lymphoceles were sterile and ranged in size from 7 × 6 × 4 to 15 × 12 × 6 cm. Clinical symptoms included lower abdominal swelling, tenderness in the iliac fossa, ipsilateral lymphedema, deep venous thrombosis, wound fistula, and hydronephrosis due to ureteral obstruction. After methylene blue instillation, the lymphoceles were easily identified and opened. Median total operative time was 50 (range 25–70) min; blood loss was negligible. There was one complication in the form of a metachronous infection in the operating field and no relapses. Patients were discharged 1–5 (median 3) days after the surgical procedure. Conclusions: Laparoscopic peritoneal drainage requires greater operative skill than percutaneous approaches. However, the instillation of a methylene blue solution simplifies this procedure as the extent and location of the lymphoceles can be precisely identified during laparoscopy. We recommend early application of laparoscopic peritoneal drainage following methylene blue instillation for patients with sterile lymphoceles after pelvic lymph node dissection in whom temporary percutaneous drainage and sclerotherapy failed to resolve the lymph fluid collection.
Antibiotics-Induced Acute Interstitial Nephritis in 6 Children
Authors: Papachristou Fotis , Printza Nikoleta , Farmaki Evagelia , Leontsini Maria , Kavaki Despina , Kollios Konstantinos
Published: May 2006

Introduction: Antibiotics-induced acute interstitial nephritis (AIN) is a rare disorder in children, and the diagnosis is often delayed. However, many commonly prescribed antibiotics seem to be implicated. Patients and Methods: We reviewed the medical records of 6 children, age range from 10 months to 14 years, with biopsy-confirmed antibiotics-induced AIN. Clinical presentation, morphological findings, and outcomes are reported. Results: Symptoms of AIN started 2–4 weeks after antimicrobial therapy with β-lactam antibiotics in 5 children and with gentamicin in 1 child. All patients presented with acute renal failure and fever. The glomerular filtration rate was dramatically reduced in 2 cases and mildly reduced in 4 patients. Two of our patients had supportive treatment, 2 received corticosteroid therapy, and 2 children remained under peritoneal dialysis for 12 and 22 days, respectively. Five patients had a full recovery of their renal function, and 1 child, 2 years later, still presented impairment of the renal function. Conclusion: AIN should be considered in case of acute renal failure in children, mostly when other common causes have been excluded, and there is a history of drug exposure.
A Case of Primary Extragonadal Seminoma Arising in the Perineum
Authors: Hosono T.Y. , Kuratsukuri K. , Nitta Y. , Sugimura K. , Harada T. , Nakatani T.
Published: May 2006

We report the first case of primary extragonadal seminoma arising in the perineum. A 34-year-old-man presented with a 2-cm painless mass in the perineum. He underwent surgical resection, and histology showed poorly differentiated adenocarcinoma. Three months later, local recurrence occurred. Whole evaluation including ultrasound and MRI of the testes were normal, so he underwent surgical wide excision, and pathology showed the tumor was pure seminoma. He received two courses of bleomycin, etoposide and cisplatin (BEP) therapy, and there has been no evidence of recurrence for 1 month.
Laparoscopic Repair of Vesicovaginal Fistula
Authors: Modi Pranjal , Goel Rajiv , Dodia Sharad
Published: May 2006

Vesicovaginal fistula (VVF) may be a complication of prolonged repair or urogynecologic surgery. Failing conservative management, it may be repaired using an abdominal or vaginal approach. We herein report laparoscopic repair of VVF following vaginal hysterectomy and detail the operative steps.
Mitogen-Activated Protein Kinase Signaling, Oxygen Sensors and Hypoxic Induction of Neurogenesis
Authors: Zhou Li , Miller Carol A.
Published: May 2006

In the adult nervous system, neuronal subpopulations sustain a hierarchical pattern of selective vulnerability to hypoxia. Hypoxia also activates quiescent neural progenitor cells (NPCs) resulting in their amplification and subsequent differentiation into neurons and glia. Use of rat organotypic hippocampal cultures facilitates examination of early signaling events in response to hypoxia and reoxygenation that result in neurogenesis. Cultures were exposed to hypoxia for up to 6 h followed by reoxygenation. CA1 neurons showed focal nuclear condensation by 2 h of hypoxia, but CA2 and CA3 neurons were spared. JNKs and c-Jun reached peak activation by 4 h, returning to basal levels by 6 h. Expression of oxygen sensors, hemoxygenase 2 and HIF1, were elevated by 30 min and 2 h, respectively. By 24 h of reoxygenation, there was proliferation of nestin-positive NPCs. With U0126, an upstream inhibitor of ERK activation, BrdU labeling was markedly reduced immunohistochemically as well as PCNA protein expression, suggesting a role for ERKs in the proliferation response. Immunohistochemically, antinestin detected NPCs and on Western blots reached peak levels by 24–48 h of reoxygenation. Proliferation and differentiation of endogenous NPCs in the area of neuronal loss further suggests that mechanisms potentially exist in vitro for replacement with functional neurons.
Induction of Signalling in Non-Erythroid Cells by Pharmacological Levels of Erythropoietin
Authors: Dunlop E.A. , Percy M.J. , Boland M.P. , Maxwell A.P. , Lappin T.R.
Published: May 2006

Erythropoiesis is maintained by the hormone erythropoietin (Epo) binding to its cognate receptor (EpoR) on erythroid progenitor cells. The Epo-EpoR interaction initiates a signal transduction process that regulates the survival, growth and differentiation of these cells. Originally perceived as highly lineage-restricted, Epo is now recognised to have pleiotropic effects extending beyond the maintenance of red cell mass. Functional interactions between Epo and EpoR have been demonstrated in numerous cells and tissues. EpoR expression on neoplastic cells leads to concern that recombinant human erythropoietin, used to treat anaemia in cancer patients, may augment tumour growth. Here we demonstrate that EPO, at pharmacological concentrations, can activate three major signalling cascades, viz. the Jak2/STAT5, Ras/ERK and PI3K/Akt pathways in non-small cell lung carcinoma (NSCLC) cell lines. EpoR synthesis is normally under the control of GATA-1, but NSCLC cells exhibit decreased GATA-1 levels compared to GATA-2, -3 and -6, suggesting that GATA-1 is not essential for EpoR production. The increased Epo-induced signalling was not associated with a growth advantage for the NSCLC cells.
Cell Transplantation for Ischemic Stroke
Authors: Vora Nirav , Jovin Tudor , Kondziolka Douglas
Published: May 2006

Cell replacement therapy has been evaluated as a regenerative strategy for patients with fixed neurologic deficits after ischemic stroke. Animal models have identified specific cell lines which lead to regeneration and improvement in behavior and motor function after implantation into areas of ischemic injury. This has led to the development of pilot studies in humans, which have mainly investigated the safety and pilot efficacy of such approaches with promising early results. As research in this area progresses, further prospective trials are necessary not only to demonstrate clinical efficacy but also to understand the mechanisms underlying the early positive experiences, to select appropriate patients for cell replacement therapy, and to elucidate the optimal timing and mode of cell delivery.
Large-Scale Analysis of Neural Stem Cells and Progenitor Cells
Authors: Shin Soojung , Rao Mahendra S.
Published: May 2006

The past few years have seen remarkable progress in our understanding of stem cell biology. The wealth of genomic data and the multiplicity of sources have enabled researchers to begin to profile stem cells in detail. In this paper we describe the biological and technical controls necessary to obtain reliable data and the relative merits of various large-scale analytical techniques including microarray, expressed sequence tag enumeration, serial analysis of gene expression and massively parallel signature sequencing. We suggest that while much has been learned, additional information remains to be gleaned by meta-analysis of existing data.
2-DE Proteomic Profiling of Neuronal Stem Cells
Authors: Hoffrogge Raimund , Beyer Susanne , Völker Uwe , Uhrmacher Adelinde M. , Rolfs Arndt
Published: May 2006

Proteomics has become a powerful tool in neuroscience studies. Although numerous human neural stem cells are available for research purposes since many years, there exists only limited information on proteomic data from stable neural stem cell lines. Profiling and functional proteome studies of neuronal stem cells will help to describe the protein inventory as well as protein activity and interactions, subcellular localization and posttranslational modifications. The proteomic analysis of neuronal differentiation processes will elucidate the complex events leading to the generation of different phenotypes via distinctive developmental programs that control self-renewal, differentiation, and plasticity. Using the ReNcell VM197 model, a cell line derived from human fetal ventral mesencephalon stem cells, we studied the protein inventory of the stem cells by 2-DE gel electrophoresis and mass spectrometric protein identification and constructed a 2-DE protein map consisting of more than 400 identified protein spots. This proteome reference database constitutes the basis for further investigations of differential protein expression during differentiation. A profiling of the neuronal differentiation-associated changes displayed the large rearrangement of the proteome during this process, and the proteomic techniques proved to be a valuable tool for the elucidation of neuronal differentiation process and for target protein screening.
Trends in Prosthodontics
Authors: Carlsson Gunnar E. , Omar Ridwaan
Published: May 2006

Prosthodontics is concerned with the impact of tooth or tissue damage and partial or complete loss of teeth onoral function in its broadest sense. It deals with this largely through prosthetic replacement. The discipline occupies a major portion of a dental school curriculum, and dental practitioners usually devote much of their practiceto prosthodontic services. With the rapid improvement in oral health and the reduction of edentulism in many countries, increasing numbers of people are retaining more teeth later in life.Gradually,the main focus in prosthodontics has shifted from removable dentures to fixed prostheses, while implant-supported restorations have attracted intenseinterest in the dental community. Another factor increasingly influencing prosthodontic practice is patients’ awareness of newer technologies in aesthetic dentistry. Because prosthodontic interventions as well as maintenance and repair are by nature costly, the global development in the field manifests fundamentalinequalities in the levels of service that patients can access. Diminishing resources for health care in general challenges educators and practitioners of prosthodontics alike. This review is an attempt to describe the recent developments in prosthodontics and its therapeutic areas, and the impact such developments may have on the theory and practice of the discipline.
The Prevalence of Neuropathy and Relationship with Risk Factors in Diabetic Patients: A Single-Center Experience
Authors: Tamer Ali , Yildiz Serpil , Yildiz Nebil , Kanat Mustafa , Gunduz Huseyin , Tahtaci Mustafa , Celebi Harika
Published: May 2006

Objective: To determine the rate of distal symmetrical polyneuropathy (DSP) in patients with type 2 diabetes mellitus, to evaluate the role of history, neurological examination and the electrodiagnostic methods in the diagnosis of DSP, and to determine the association between electromyography-supported neuropathy (ESN), neuropathic complaints (NCs) and risk factors. Subjects and Methods: A total of 191 type 2 DM patients (109 female, 82 male; mean age 58.7 ± 10 years) were recruited. The NCs were recorded. All patients had electromyographic (EMG) examinations. The relationship between ESN, NCs and risk factors were evaluated. Results: Of the 191 patients, 83 (43.5%) had DSP on EMG examinations and 92 (48.2%) patients suffered from NCs. Among the ESN patients, a significant relationship existed with HbA1c level, illness duration, smoking, male gender or insulin usage (p < 0.05) but not with age, hypertension, hypercholesterolemia or hypertriglyceridemia. The frequency of NCs was higher in patients with ESN. There was also a significant association between NCs and ESN (p < 0.05). The presence of NCs was not related to age, gender, smoking, hypertension, hypercholesterolemia and hypertriglyceridemia (p > 0.05) but NCs were correlated to HbA1c level, illness duration and insulin usage (p < 0.05). Conclusion: Our data show that a strong association exists between the presence of DSP and illness duration, HbA1c, smoking, thereby indicating that cessation of smoking and near normal glycemic control would be additional precautions to delay the beginning or progression of polyneuropathy.