bluuebunny/crossref_metadata_2025 huggingface dataset:
Silymarin inhibits UV radiation-induced immunosuppression through augmentation of interleukin-12 in mice
Authors: Meeran Syed M. , Katiyar Suchitra , Elmets Craig A. , Katiyar Santosh K.
Published: August 2006

We have shown previously that silymarin, a plant flavonoid, inhibits UVB-induced photocarcinogenesis in mice. As UVB-induced immunosuppression has been implicated in the development of skin cancer, we investigated whether silymarin can modulate the effects of UVB radiation on the immune system. Treatment of C3H/HeN mice with topically applied silymarin (0.5 or 1.0 mg/cm2) or silibinin, a major component of silymarin, markedly inhibited UVB (180 mJ/cm2)–induced suppression of contact hypersensitivity response in a local model of immunosuppression and had a moderate inhibitory effect in a systemic model of contact hypersensitivity. Silymarin reduced the UVB-induced enhancement of the levels of the immunosuppressive cytokine, interleukin (IL)-10, in the skin and draining lymph nodes and enhanced the levels of the immunostimulatory cytokine, IL-12. Intraperitoneal injection of mice treated with silymarin with an endotoxin-free neutralizing anti-IL-12 antibody abrogated the protective effects of the silymarin against UVB-induced suppression of the contact hypersensitivity response. Furthermore, the treatment of silymarin did not prevent UVB-induced suppression of the contact hypersensitivity response in IL-12 knockout mice but prevented it in their wild-type mice. Moreover, i.p. injection of IL-12 to silymarin-treated or non-silymarin-treated IL-12 knockout mice resulted in an enhanced response to contact hypersensitivity compared with the response in mice that were exposed to either UVB alone or silymarin plus UVB. These data indicate for the first time that silymarin has the ability to protect mice from UVB-induced immunosuppression and that this protective effect is mediated, at least in part, through IL-12. [Mol Cancer Ther 2006;5(7):1660–8]
5-Methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1, exhibits activity against human pancreatic cancer in vitro and in vivo
Authors: Dehn Donna L. , Siegel David , Zafar Khan Shoeb , Reigan Philip , Swann Elizabeth , Moody Christopher J. , Ross David
Published: August 2006

The enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) has been found to be up-regulated in pancreatic cancer as well as many other solid tumors. A recent study showed that inhibition of NQO1 in pancreatic cancer cells using the nonselective inhibitor dicumarol suppressed the malignant phenotype. The authors suggested that inhibition of cell growth might result from an increase in intracellular superoxide production due to inhibition of NQO1. We have recently shown that NQO1 can directly scavenge superoxide and this effect may become physiologically relevant in cells containing high NQO1 levels. We therefore tested the hypothesis that 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), a specific mechanism-based inhibitor of NQO1, would be an effective agent for the treatment of pancreatic tumors. The human pancreatic tumor cell lines BxPC-3 and MIA PaCa-2 contain high levels of NQO1 activity and protein as verified by immunoblot and immunocytochemical staining of human pancreatic tumor cells. ES936 treatment inhibited NQO1 activity by >98% in MIA PaCa-2 and BxPC-3 cells. In addition, ES936 treatment induced growth inhibition [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in MIA PaCa-2 and BxPC-3 cells with an IC50 of 108 and 365 nmol/L, respectively. Treatment of MIA PaCa-2 cells with ES936 also inhibited the ability of these cells to form colonies and grow in soft agar in a dose-dependent manner. Treatment of mice carrying MIA PaCa-2 xenograft tumors with ES936 resulted in a significant difference in growth rates in ES936-treated and DMSO-treated (control) tumors. Our data did not show an increase in either intracellular superoxide production or oxygen consumption after treatment of cells with ES936, contrary to the effects seen with dicumarol. In summary, mechanism-based inhibitors of NQO1, such as ES936, may be useful therapeutic agents for the treatment of pancreatic cancer, although the underlying mechanism seems to be independent of superoxide generation. [Mol Cancer Ther 2006;5(7):1702–9]
Blockade of transforming growth factor-β signaling in tumor-reactive CD8+ T cells activates the antitumor immune response cycle
Authors: Zhang Qiang , Yang Ximing J. , Kundu Shilajit D. , Pins Michael , Javonovic Borko , Meyer Robert , Kim Seong-Jin , Greenberg Norman M. , Kuzel Timothy , Meagher Richard , Guo Yinglu , Lee Chung
Published: August 2006

Transforming growth factor-β (TGF-β) is a potent immunosuppressant. Overproduction of TGF-β by tumor cells leads to evasion of host immune surveillance and tumor progression. Results of our early studies showed that adoptive transfer of tumor-reactive, TGF-β-insensitive CD8+ T cells into immunocompetent mice was able to eradicate lung metastasis of mouse prostate cancer. The present study was conducted with three objectives. (a) We tested if this technology could be applied to the treatment of solid xenograft tumors in allogeneic immunodeficient hosts. (b) We determined relevant variables in the tumor microenvironment with the treatment. (c) We tested if immune cells other than CD8+ T cells were required for the antitumor effect. Mouse prostate cancer cells, TRAMP-C2 of the C57BL/6 strain, grown in immunodeficient allogeneic hosts of BALB/c strain, were used as a xenograft model. Tumor-reactive CD8+ T cells from C57BL/6 mice were isolated, expanded ex vivo, and rendered insensitive to TGF-β by introducing a dominant-negative TGF-β type II receptor vector. Seven days following s.c. injection of TRAMP-C2 cells (5 × 105) into the flank of male BALB/c-Rag1−/− mice, tumor-reactive, TGF-β-insensitive CD8+ T cells (1.5 × 107) were transferred with and without the cotransfer of an equal number of CD8-depleted splenocytes from C57BL/6 donors. Naive CD8+ T cells or green fluorescent protein-empty vector–transfected tumor-reactive CD8+ T cells were transferred as controls. Forty days following the transfer, the average tumor weight in animals that received cotransfer of tumor-reactive, TGF-β-insensitive CD8+ T cells and CD8-depleted splenocytes was at least 50% less than that in animals of all other groups (P < 0.05). Tumors in animals of the former group showed a massive infiltration of CD8+ T cells. This was associated with secretion of relevant cytokines, decreased tumor proliferation, reduced angiogenesis, and increased tumor apoptosis. Based on these results, we postulated a concept of antitumor immune response cycle in tumor immunology. [Mol Cancer Ther 2006;5(7):1733-43]
Discovery and characterization of inhibitors of human palmitoyl acyltransferases
Authors: Ducker Charles E. , Griffel Lindsay K. , Smith Ryan A. , Keller Staci N. , Zhuang Yan , Xia Zuping , Diller John D. , Smith Charles D.
Published: August 2006

The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for high-throughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening. [Mol Cancer Ther 2006;5(7):1647–59]
Ratiometric dosing of anticancer drug combinations: Controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice
Authors: Mayer Lawrence D. , Harasym Troy O. , Tardi Paul G. , Harasym Natashia L. , Shew Clifford R. , Johnstone Sharon A. , Ramsay Euan C. , Bally Marcel B. , Janoff Andrew S.
Published: August 2006

Anticancer drug combinations can act synergistically or antagonistically against tumor cells in vitro depending on the ratios of the individual agents comprising the combination. The importance of drug ratios in vivo, however, has heretofore not been investigated, and combination chemotherapy treatment regimens continue to be developed based on the maximum tolerated dose of the individual agents. We systematically examined three different drug combinations representing a range of anticancer drug classes with distinct molecular mechanisms (irinotecan/floxuridine, cytarabine/daunorubicin, and cisplatin/daunorubicin) for drug ratio–dependent synergy. In each case, synergistic interactions were observed in vitro at certain drug/drug molar ratio ranges (1:1, 5:1, and 10:1, respectively), whereas other ratios were additive or antagonistic. We were able to maintain fixed drug ratios in plasma of mice for 24 hours after i.v. injection for all three combinations by controlling and overcoming the inherent dissimilar pharmacokinetics of individual drugs through encapsulation in liposomal carrier systems. The liposomes not only maintained drug ratios in the plasma after injection, but also delivered the formulated drug ratio directly to tumor tissue. In vivo maintenance of drug ratios shown to be synergistic in vitro provided increased efficacy in preclinical tumor models, whereas attenuated antitumor activity was observed when antagonistic drug ratios were maintained. Fixing synergistic drug ratios in pharmaceutical carriers provides an avenue by which anticancer drug combinations can be optimized prospectively for maximum therapeutic activity during preclinical development and differs from current practice in which dosing regimens are developed empirically in late-stage clinical trials based on tolerability. [Mol Cancer Ther 2006;5(7):1854–63]
A new generation of anticancer, drug-loaded, colloidal vectors reverses multidrug resistance in glioma and reduces tumor progression in rats
Authors: Garcion Emmanuel , Lamprecht Alf , Heurtault Béatrice , Paillard Archibald , Aubert-Pouessel Anne , Denizot Benoît , Menei Philippe , Benoît Jean-Pierre
Published: August 2006

By focusing on rat glioma, we elucidated whether new lipid nanocapsules (LNC) were able to improve anticancer hydrophobic drug bioavailability while also overcoming multidrug resistance. Blank LNCs and LNCs loaded with the antineoplastic agent paclitaxel were formulated by an emulsion inversion phase process. Expression of efflux pumps by rat glioma cells was assessed by reverse transcription-PCR, Western blot, and immunohistochemistry, and their activity was followed using the tracer 99Tcm-methoxyisobutylisonitrile. Modalities of LNC action were addressed by using confocal microscopy detection of fluorescently labeled LNCs, fluorescence-activated cell sorting, high-performance liquid chromatography measurement of paclitaxel release, and analysis of tumor cell growth. This revealed an interaction between LNCs and efflux pumps that resulted in an inhibition of multidrug resistance in glioma cells, both in culture and in cell implants in animals. LNCs were able to target the intracellular compartment of glioma cells, a mechanism that was abrogated by using intracellular cholesterol inhibitors but not by clathrin-coated pit or caveolae uptake inhibitors. This result can be correlated to the LNC inhibitory effects on efflux pump activity that is itself known to be stimulated by intracellular cholesterol. In parallel, we showed that paclitaxel-loaded LNCs were active reservoirs from which paclitaxel could be released. Finally, we established that paclitaxel-loaded LNCs were more efficient than the commercially available paclitaxel formulation (Taxol) for clinical use, thus reducing tumor expansion in vitro and in vivo. Considering the physiologically compatible nature of LNC excipients, these data may represent an important step towards the development of new clinical therapeutic strategies against cancers. [Mol Cancer Ther 2006;5(7):1710–22]
Renal Injury: 5-Year Experience and Literature Review
Authors: Gourgiotis S. , Germanos S. , Dimopoulos N. , Vougas V. , Anastasiou T. , Baratsis S.
Published: August 2006

Introduction: Appropriate management of renal trauma is controversial. The purpose of this study is to present our 5-year experience in renal trauma and review the literature. Materials and Methods: From 1999 to 2003, 28 patients were identified with renal injuries. 25 (89.3%) of the injuries were caused by blunt trauma, 2 (7.1%) by stab wounds, and 1 (3.6%) by gunshot wound. Methods for diagnosis included ultrasonography (US), computed tomography (CT), diagnostic peritoneal lavage (DPL), combinations of more than one technique or no one of them. The English-language literature about renal trauma was also identified using Medline, and additional cited works not detected in the initial search obtained. Results: 18 patients underwent immediate or during 24 h operation; while 5 nephrectomies were performed. 11 patients with grade I to III injuries were selected for nonoperative management of renal injuries. All complications were noted and studied according to the initial therapeutic management and grade. Follow-up was clinical and radiological. 3 postoperative deaths were observed. Conclusion: The goals of treatment of renal injuries include accurate staging and minimal complications. Surgery can be avoided in most cases of blunt renal injury but there is also a trend towards conservative management of penetrating trauma. Nephrectomy is associated with high-grade renal injuries, while minor renal injuries can safely be managed conservatively.
Operative Failure during Ureteroscopic Pneumatic Lithotripsy: Factors Affecting Successful Outcome
Authors: Miroglu Cengiz , Horasanli Kaya , Tanriverdi Orhan , Altay Bülent , Gumus Eyüp
Published: August 2006

Aim: We aimed to evaluate the predictive factors that would in turn indicate stone migration and the effects of these factors on the ultimate success of the intervention. Method: Patients were divided into two groups with respect to the migration of the stone treated. Group I: patients demonstrating stone migration during manipulation; group II: no migration of the stones noted. In the second phase of the study, the results of ureteroscopic management in 433 patients were evaluated with respect to the success rates obtained. Parameters such as stone size, stone burden, experience of the surgeon, length of the ureter proximal to the stone treated, and lastly transverse diameter of the ureter were noted in all patients as possible risk factors for stone migration. Results: Statistical analysis of ureteroscopic success in all patients revealed that there was a meaningful correlation with respect to the length of the proximal ureteral portion (p < 0.0001) and surgeon’s experience (p = 0.004). p value for the correlation between stone burden and operative success was 0.056. There was no significant correlation between stone size (p = 0.51), ureter diameter (p = 0.78), and operative success. Conclusion: Stones that are close to the renal pelvis and treated by inexperienced physicians are the ones most likely to migrate to the renal pelvis during manipulation with pneumatic lithotripsy.
Preliminary Report of a Multicentric Study on Environmental Risk Factors in Ta-T1 Transitional Cell Carcinoma of the Bladder
Authors: Serretta V. , Morgia G. , Altieri V. , Pavone-Macaluso M. , Scuto F. , Allegro R. , Di Lallo A. , Cindolo L. , Melloni D.
Published: August 2006

Objective: The distribution of potential environmental risk factors among patients affected by superficial transitional cell carcinoma of the bladder (TCCB) has been analyzed. Methods: Patients affected by superficial TCCB underwent TUR and early intravesical chemotherapy. Detailed data about age, sex, residence, employment, active and passive cigarette smoking, water resource and hair dye use were centralized. Analysis has been conducted on 474 patients affected by Ta-T1 G1-2 TCCB at medium risk for recurrence. Patients with primary single Ta G1-2, Tis or T1G3 tumors were excluded from the present analysis. Results: Over 80% of the patients lived in urban areas, 22% were employed in industries presumed at risk for bladder cancer, 8% used hair dye and 75% were smokers. Bottled water was the only water resource in 42% of the patients. Employment in industry at risk (p = 0.01) and cigarette smoking (p = 0.04) resulted in being statistically related to tumor multiplicity. Moreover, the period of cigarette smoking was significantly longer in patients with recurrent tumors (p = 0.026). The municipal water supply represented the main water source in never-smokers (p = 0.01) rather than in smokers and in patients harboring T1 rather than Ta tumors (p = 0.03). Conclusions: Employment in industry at risk and cigarette smoking resulted in being related to tumor multiplicity. The length of exposure to cigarette smoking was related to the natural history of the tumor. A drinkable water source emerged as a risk factor in absence of cigarette smoking.
Epidemiological Aspects of Recruitment of Male Volunteers for Non-Invasive Urodynamics
Authors: Avagyan V. , van Mastrigt R. , Huang Foen Chung J.W.N.C. , Bohnen A.M. , Bosch J.L.H.R. , Mulder P.G.H.
Published: August 2006

Introduction: We studied epidemiological aspects of recruitment of volunteers for a non-invasive urodynamic study. Materials and Methods: 9,236 volunteers were invited by 20 general practitioners (GPs), using two different recruitment methods, i.e. by mail only, or during a subsequent visit to the GP’s office. Factors influencing the response rates were analyzed. We also tested how much the recruited population of volunteers differed from the general population, by comparing it to another, proven representative study carried out earlier in 1,662 subjects. Results: In the recruited population the prostate volumes were not significantly different from the proven representative study, but the symptom score was statistically significantly higher, although the difference was so small it may be called clinically irrelevant. Recruitment of volunteers in two steps, i.e. asking them first to visit the GP’s office, and inviting them there to visit the outpatient clinic, rather than directly inviting them (in writing) to the clinic seemed to lead to a higher response, although this effect could not be statistically discriminated from the difference in response rates between GPs. Conclusion: The population recruited was not urologically different from the general population. The response depended on age, being highest around the age of 60, and increased with social economic status. It also depended on the GP who recruited the subjects, and/or on the recruitment method.
Spontaneous Priapism after Radical Retropubic Prostatectomy
Authors: Böhlen Dominik , Eberle Johannes , Schmid Hans-Peter
Published: August 2006

We present the first case of priapism following radical prostatectomy. A 66-year-old man with normal erections underwent radical retropubic prostatectomy with unilateral nerve sparing. Pathology showed a pT2c pN0 Gleason score 3 + 3 = 6 prostate cancer and the postoperative course was uneventful. Ten days after surgery he recognized a spontaneous painful penile erection without sexual stimulation which occurred in a standing position and disappeared in a supine position. These episodes recurred several times during the next 3 weeks and then completely vanished. Pathophysiologically, we postulate intermittent position-depending venous obstruction due to local hematoma or thrombosis.
Adenomatous Polyp of the Verumontanum Accompanied by Parabulbous Epidermoid Cyst and Cryptorchidism in an Adult Male
Authors: Kalafatis Panagiotis , Zougkas Konstantinos
Published: August 2006

The coexistence of polyp of the verumontanum, epidermoid paraurethral cyst and cryptorchidism presents a mosaic of congenital anomalies of the urogenital tract. We present a 30-year-old patient with a medical history of unilateral cryptorchidism, urinary tract infections, obstructive voiding symptoms and perineal discomfort. Clinical and laboratory evaluation revealed a pending filling defect in the prostatic urethra and a palpable elastic mass located on the right side of the bulbar urethra. Transurethral resection of the urethral polyp with a simultaneous excision of the cystic formation via a perineal approach followed by a left-sided funiculolysis and orchiopexy were performed. Discussion focuses on the etiology and differential diagnosis of this unusual complex entity.
Treatment of Radiation-Induced Hemorrhagic Cystitis with Laparoscopic Cystoprostatectomy
Authors: Alkan Ilter , Jeschke Stephan , Leeb Karl , Albquami Nasser , Janetschek Gunter
Published: August 2006

Hemorrhagic cystitis can occur 6 months to 10 years after pelvic irradiation. Various palliative treatment alternatives may be unsuccessful in the management of severe hemorrhagic cystitis, so that in rare cases radical surgery will be the last resort.A 77-year-old man with persistent bleeding due to hemorrhagic cystitis after radiotherapy for prostate cancer was initially treated with conservative measures. All of these treatment methods were unsuccessful. His condition deteriorated and became life-threatening. As a last resort, laparoscopic cystoprostatectomy and mini-laparotomy ileal conduit diversion were successfully performed with no intraoperative or postoperative complications. To our knowledge, this is the first report on laparoscopic cystoprostatectomy for a patient with previous radiotherapy to the pelvis.
Human Obesity: Its Hormonal Basis and the Role of Gastric Inhibitory Polypeptide
Authors: Marks Vincent
Published: August 2006

Obesity is an abnormal expansion of the adipose organ and is a pathophysiological response to an imbalance between energy intake and energy expenditure. It is the result of a large number of diverse factors involving heritable and environmental characteristics. A simple definition of obesity is difficult and unsatisfactory and its age dependency has largely been ignored. Differentiation between healthy, age-related plumpness and obesity is often blurred and responsible for overdiagnosis of obesity in the developed world. In the past, epidemiological studies have often ignored the different prognostic significance of the two major phenotypes of human obesity making their conclusions of limited value. The role of heritable factors in determining both the propensity to develop obesity under favourable environmental conditions, including inactivity and unlimited access to fat-rich foods, and the phenotype it assumes received an enormous fillip from experiments involving genetically modified animals. The most important of these have demonstrated the key role played by a number of newly discovered or recently resurrected polypeptide hormones that are released from the intestine in response to food. Molecular manipulation of these hormones, especially of glucose-dependent insulin-stimulatory polypeptide offers a new therapeutic approach.
Agenesis of the Gallbladder with Primary Choledochal Stones
Authors: Afifi El-Sayed M. , Atef Husseiny , Wael Baidas
Published: August 2006

Objective: To report a case of true agenesis of the gallbladder (GB) with obstructive jaundice due to primary choledochal stone. Clinical Presentation and Intervention: A 66-year-old woman presented with a full picture of obstructive jaundice, both clinically and biochemically. Ultrasound and endoscopic retrograde cholangiopancreatography failed to show the GB but showed dilatation of extrahepatic ducts with a stone in the common bile duct (CBD). Upon exploration, the GB was found to be absent and through a choledochotomy, the stone in the CBD was removed. Conclusion: This case shows that proper exploratory laparotomy and intraoperative cholangiography may be required to confirm absence of the GB.
Carotid Body Tumors and Adrenal Pheochromocytomas in Siblings of a Turkish Family
Authors: Erem Cihangir , Hacihasanoglu Arif , Cinel Akif , Isik A. Cemal Umit , Reis Abdülkadir , Sari Ahmet , Ersöz Halil Önder , Ukinç Kubilay
Published: August 2006

Objective: This is a report of 2 hypertensive siblings with a history of carotid body tumors and subsequent benign adrenal pheochromocytomas (pheos) in a family where the mother had died of possible adrenal carcinoma. Clinical Presentation and Intervention: The first case was a 35-year-old woman with paroxysmal hypertensive attacks and a right adrenal mass. She had earlier undergone surgery to remove bilateral carotid body tumors. Investigation revealed excessive excretion of catecholamines and their metabolites in the urine. Abdominal MRI and 131I-MIBG scintigraphy revealed a right adrenal tumor. Right adrenalectomy was performed. The second case, the 45-year-old brother of the first case, was found to have a left adrenal mass on abdominal MRI. Catecholamines and their metabolites in the urine were found to be increased. He had also had surgery to remove bilateral carotid body tumors of the neck. Left adrenalectomy was performed. Both siblings showed no evidence of other familial syndromes, such as multiple neoplasia type 2, von Hippel-Lindau disease or neurofibromatosis type 1. Conclusion: Although the combination of familial carotid body tumors and pheo is rare, a patient who remains hypertensive after removal of a carotid body tumor deserves a careful evaluation to exclude pheo. Such tumors may be extra-adrenal or multifocal.
Incidence and Prevention of Ischemic Stroke following Myocardial Infarction: Review of Current Literature
Authors: Dutta Monisha , Hanna Elias , Das Pranab , Steinhubl Steven R.
Published: August 2006

Myocardial infarction is the leading cause of death today. With the fast progress in pharmacotherapy and revascularization technology, outcomes following a myocardial infarction have become very favorable. While most of the complications from a myocardial infarction can be adequately managed, thus leading to reduced mortality, stroke following a myocardial infarction remains a challenge even today, and can lead to potentially devastating complications. We discuss the incidence, pathophysiology, and management options of non-hemorrhagic stroke following a myocardial infarction.
High Blood Pressure in Acute Ischemic Stroke and Underlying Disorders
Authors: Toyoda Kazunori , Okada Yasushi , Jinnouchi Juro , Gotoh Seiji , Yokoyama Yoko , Fujimoto Shigeru , Ibayashi Setsuro
Published: August 2006

Background: The Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) study indicated that early treatment with an angiotensin type 1 receptor blocker in acute stroke patients who had relatively high blood pressure improved cardiovascular morbidity and mortality in the chronic stage. To better interpret the findings of this study, we determined whether stroke patients with high acute blood pressure had specific underlying conditions. Methods: We divided 712 consecutive patients who were hospitalized within 48 h after the onset of brain infarction into two groups: 77 patients with high acute blood pressure that met the criteria of the ACCESS study and the 635 remaining patients. Underlying risk factors and comorbidities, stroke characteristics, as well as mortality, vascular events, and disability at 3 weeks were compared between the two groups. Results: Patients with high acute blood pressure more frequently had diabetes mellitus (p < 0.01), intracranial arterial stenosis (p < 0.02), higher levels of hemoglobin A1c (p < 0.005), higher creatinine levels (p < 0.005), and tended to more frequently have ischemic heart disease (p < 0.09) and infarcts <1.5 cm in diameter (p < 0.09) than the other patients. On multivariate analysis, high levels of hemoglobin A1c, high creatinine levels, and intracranial arterial stenosis were independently predictive of high acute blood pressure. At 3 weeks after the stroke onset, patients with high acute blood pressure were more dependent in their daily living activities (p < 0.02) and more frequently developed vascular events or death (p < 0.005) than the other patients. Conclusions: Poorly controlled diabetes mellitus and advanced renal damage appeared to correlate with acute hypertension after stroke. Since intracranial arterial stenosis also seemed to contribute to high acute blood pressure, one should be careful not to induce cerebral hypoperfusion by the early use of antihypertensives.
Could Platelet Aggregation Ratio Be an Indicator for Differential Diagnosis of Transient Ischemic Attack and Cerebral Ischemic Stroke?
Authors: Tatli Mehmet , Guzel Aslan , Akyuz Aytekin , Batun Sabri
Published: August 2006

Background: Platelet aggregation plays an important role in the pathogenesis of thromboembolic cerebrovascular disease. Platelet aggregation ratio (PAR) and its derivates have been used successfully to identify the effectiveness of antiplatelet agents and their optimum dosage in patients suffering from stroke. However, we failed to find any study using PAR as a predictive factor in differential diagnosis of ischemic cerebrovascular diseases. In this study, we aimed to investigate PAR in patients with acute ischemic stroke and transient ischemic attack (TIA), comparing their neuroradiological features, and whether PAR values could be an indicator for differential diagnosis of TIA and cerebral ischemic stroke. Methods: The study consisted of 75 adult patients who were admitted with suspected stroke and 25 control healthy individuals. All patients were diagnosed with acute ischemic stroke or TIA and the diagnoses were confirmed by clinical examination and computed tomography (CT). The stroke group consisted of 45, and the TIA group of 30 consecutive patients. The patients included in this study had noncardioembolic stroke. PAR values were measured on admission in all groups, according to the modified method of Wu and Hoak. The statistical significance of differences was evaluated using one-way ANOVA, the unpaired Student t test and the Bonferroni and Tamhane post hoc tests.Results:Differences in PARs between the control and TIA groups, control and stroke groups and stroke and TIA groups were significant (p < 0.001). Nevertheless, in each group, differences between genders were not statistically significant. Initial CT scan demonstrated early infarction sign in 26 stroke patients (57%); however, in 19 stroke patients, it was not detected. Differences in PARs between TIA and stroke patients, whose initial CT scan findings were negative, were found to be significant. However, differences in PARs between CT negative stroke patients and positive stroke patients were not significant. Conclusion: We believe that the use of PAR values in the assessment of acute ischemic stroke and TIA could open up a new perspective in the management of such patients. In differential diagnosis, PAR values have to combine with neurological examination and CT scan signs. The current test is not able to differentiate vascular occlusive diseases in other organs from vascular occlusive problems in the brain. Further study is needed to determine the sensitivity and specificity of this test in all patients and to confirm the prognostic value in stroke patients.
Long-Term in vitro Growth of Human Insulin-Secreting Insulinoma Cells
Authors: Gartner Wolfgang , Koc Filiz , Nabokikh Anastasya , Daneva Teodora , Niederle Bruno , Luger Anton , Wagner Ludwig
Published: August 2006

Objective: Long-term in vitro maintenance of human insulin-secreting insulinoma cells. Methods: (1) Cell culture of ex vivo-derived insulinoma cell suspensions from 8 individual human donors, using various cell culture medium supplementations; (2) determination of insulin synthesis and secretion using immunocytochemistry and insulin and pro-insulin radioimmunoassays; (3) nestin-immunostaining of long-term in vitro grown insulinoma cell suspensions, and (4) phase-contrast light microscopy for analyzing the in vitro growth characteristics of the insulinoma cells. Results: (1) Parallel persistence of in vitro insulinoma cell proliferation as well as insulin-synthesizing and -secreting capacity depended on both the co-culture of insulinoma cells with human fibroblasts and the supplementation of the cell culture medium with tissue culture supernatant derived from the rodent pituitary adenoma cell line GH-3; (2) immunostaining for insulin and secretagogin confirmed the neuroendocrine origin of the insulinoma cells grown in vitro; (3) insulin secretion capability persisted up to an observation period of 25 weeks; (4) insulin secretion rates after 6 weeks of in vitro growth ranged from 3.5 to 83.3 µU/ml/h/60,000 cells plated, and (5) after long-term in vitro growth of insulinoma-derived cell suspensions with persistent insulin-secreting capacity, nestin staining was observed predominantly in co-cultured fibroblasts. Conclusion: Our data describe for the first time the long-term in vitro culture of insulin-secreting human insulinomas and highlight the importance of β-cell trophic factors for insulinoma cell growth.
Readministration of IgE Is Required for Repeated Passive Cutaneous Anaphylaxis in Mice
Authors: Xiang Zou , Möller Christine , Nilsson Gunnar
Published: August 2006

Background: Homologous passive cutaneous anaphylaxis (PCA) is an established technique that provides a useful tool to study local inflammation due to mast cell activation. Since mast cells are responsive to repeated challenge by IgE receptor crosslinking in vitro, we investigated the responsiveness of mice to repeated PCA activation. Methods: Female BALB/c mice were sensitized with intradermal injection of IgE into the ear and provocated through intravenous injection of trinitrophenol-BSA. Repeated provocation was administered, and the outcome was determined by colorimetrical measurement of Evans blue dye leakage. Results: After local IgE injection, mice could be challenged to demonstrate a PCA reaction at least up to 13 days after IgE sensitization. In contrast, passively sensitized mice did not respond to repeated antigen challenge, i.e. a second provocation administered between 1 and 12 days after the first PCA reaction. However, if these mice were intradermally resensitized with IgE at the same site after the first challenge, they became responsive to the repeated challenge. Conclusions: Mast cells become desensitized upon PCA reaction, and resensitization with IgE is critical for mice repeatedly stimulated by PCA activation.
Repetitive Fluctuations in Blood Glucose Enhance Monocyte Adhesion to the Endothelium of Rat Thoracic Aorta
Authors: Azuma Kosuke , Kawamori Ryuzo , Toyofuku Yukiko , Kitahara Yoshiro , Sato Fumihiko , Shimizu Tomoaki , Miura Kyoko , Mine Tomoyuki , Tanaka Yasushi , Mitsumata Masako , Watada Hirotaka
Published: August 2006

Background—

The aim of this study was to elucidate the effect of repetitive fluctuations in blood glucose concentrations on monocyte adhesion to the aortic endothelium.

Methods and Results—

Nonobese type 2 diabetes, Goto–Kakizaki (GK) rats were fed twice daily to induce repetitive postprandial glucose spikes. Then, we compared the number of monocytes adherent to the endothelium of thoracic aorta in these rats with that in rats fed ad libitum. To suppress the glucose spikes, rats were injected with an inhibitor of sodium–glucose transporter, phloridzin, just before each meal for 12 weeks. GK rats fed twice daily showed significantly lower HbA
1c
than GK rats fed ad libitum. However, the former group showed markedly higher number of monocytes adherent to the endothelium than the latter, together with increased arterial intimal thickening. Phloridzin significantly reduced the number of adherent monocytes in GK rats fed twice daily.

Conclusion—

Our data demonstrated that repetitive postprandial fluctuation in glucose concentration evokes monocyte adhesion to endothelial cells that was worse than that induced by stable hyperglycemia in vivo. Suppression of such fluctuations efficiently suppressed monocyte adhesion to the aortic endothelium.
Course of Platelet Activation and Platelet-Leukocyte Interaction in Cerebrovascular Ischemia
Authors: Htun Patrik , Fateh-Moghadam Suzanne , Tomandl Bernd , Handschu René , Klinger Kathrin , Stellos Konstantinos , Garlichs Christoph , Daniel Werner , Gawaz Meinrad
Published: August 2006

Background and Purpose—

Platelet activation plays a crucial role in the pathophysiology of cerebral ischemia. The aim of this study was to investigate the contribution of platelet activation and leukocyte-platelet interactions to the disease.

Methods—

One hundred thirty-five patients with transient ischemic attack (TIA) or stroke were enrolled in this single-center study. They underwent cranial computer tomography within 24 hours of clinical onset and after 3 months, and systemic venous blood samples were drawn. Platelet activation (CD62P expression), leukocyte activation (L-selectin expression), and the appearance of platelet-specific antigens on leukocytes as an index of platelet-leukocyte aggregation were measured by flow cytometric techniques in the acute state and at 3-month follow-up.

Results—

Patients with a completed stroke or TIA had significantly increased circulating platelet-leukocyte aggregates, increased P-selectin expression on platelets, and decreased L-selectin expression in the acute state compared with the control group (healthy volunteers). No differences in regard to the tested activation markers could be detected between patients with stroke or TIA in the acute phase of the disease. However, platelet and leukocyte activations were normalized after 3 months in patients with TIA, whereas leukocyte activation (reduced L-selectin expression) remained in stroke patients.

Conclusions—

In patients with TIA and completed stroke, platelet and leukocyte activation is substantially enhanced in the acute phase of the disease. The sustained leukocyte activation observed in stroke but not in TIA patients at 3-month follow up might play a pathophysiological role in the course of the disease.
Cluster Randomized Pilot Controlled Trial of an Occupational Therapy Intervention for Residents With Stroke in UK Care Homes
Authors: Sackley Catherine , Wade Derick T. , Mant David , Atkinson Jo Copley , Yudkin Patricia , Cardoso Karina , Levin Sonya , Lee Vanessa Blanchard , Reel Kevin
Published: August 2006

Background and Purpose—

A pilot evaluation of an occupational therapy intervention to improve self-care independence for residents with stroke-related disability living in care homes was the basis of this study.

Methods—

A cluster randomized controlled trial with care home as the unit of randomization was undertaken in Oxfordshire, UK. Twelve homes (118 residents) were randomly allocated to either intervention (6 homes, 63 residents) or control (6 homes, 55 residents). Occupational therapy was provided to individuals but included carer education. The control group received usual care. Assessments were made at baseline, postintervention (3 months) and at 6-months to estimate change using the Barthel Activity of Daily Living Index (BI) scores, “poor global outcome”, (defined as deterioration in BI score, or death) and the Rivermead Mobility Index.

Results—

At 3 months BI score in survivors had increased by 0.6 (SD 3.9) in the intervention group and decreased by 0.9 (2.2) in the control group; a difference of 1.5 (95% CI allowing for cluster design, −0.5 to 3.5). At 6 months the difference was 1.9 (−0.7 to 4.4). Global poor outcome was less common in the intervention group. At 3 months, 20/63 (32%) were worse/dead in the intervention group compared with 31/55 (56%) in the control group, difference −25% (−51% to 1%). At 6 months the difference was similar, −26% (−48% to −3%). Between-group changes in Rivermead Mobility Index scores were not significantly different.

Conclusion—

Residents who received an occupational therapy intervention were less likely to deteriorate in their ability to perform activities of daily living.
Termites and mites – adaptive behavioural responses to infestation?
Authors: Fuchs Alexander , Korb Judith
Published: August 2006

Rapid adaptation to their hosts' defence systems usually allows parasites to keep the upper hand in the co-evolutionary arms race between hosts and parasites. However, although morphological and physiological adaptations are generally far slower in hosts than in their parasites, the former can rapidly respond to a parasite challenge by dispersal-related, adaptive changes in their behaviour. We investigated whether the drywood termite Cryptotermes secundus altered its behaviour in response to an infestation with parasitic, astigmatic mites. The frequency of the vital, dispersal-related behaviours allogrooming and proctodeal trophallaxis did not differ between colonies or between individuals with mites compared to without mites. However, activity levels were lower in mite-infested colonies and individuals spent more time resting and feeding when mites were present in the colony, irrespective of whether they were infested themselves or not. This behavioural pattern shown by individuals from infested mite-colonies is known to be associated with a development of C. secundus workers into winged dispersing sexuals. As dispersing individuals were less likely to have mites, this behavioural response to the mites' infestation might be an adaptive response to escape the deteriorating nest conditions.
Nest-mate recognition and the effect of distance from the nest on the aggressive behaviour of Camponotus chilensis (Hymenoptera: Formicidae)
Authors: Velásquez Nelson , Gómez María , González Jorge , Vásquez Rodrigo A.
Published: August 2006

Nest-mate recognition and territorial behaviour in ants are widely studied phenomena. However, few studies have analysed, under field conditions, how nest-mate recognition varies with distance from the resident's colony. In a natural population of Camponotus chilensis in central Chile, we studied nest-mate recognition and spatial variation in aggressive behaviour. C. chilensis individuals were able to discriminate nest-mates from intruders, showing no aggression toward nest companions, while aggressiveness toward allo-colonial con-specifics decreased significantly with distance. Further, the overall number of interactions and the aggressiveness of the resident ants were significantly greater at 25 cm from their colony than at further distances. Given that antennation behaviour is regularly present at all distances from the nest, it seems to entail information acquisition. Biting and intruder-dragging, the most conspicuous aggressive displays, were mainly observed at distances close to the resident colony. Other behaviours such as threatening with open mandibles, ventral bending of the gaster, and backward-movement, were observed at all distances, and they seem to represent the first signs of intruder rejection.
Innovation in wild Bornean orangutans (Pongo pygmaeus wurmbii)
Authors: van Noordwijk Maria A. , van Schaik Carel P. , Wich Serge A.
Published: August 2006

In most studies to date, innovations were studied if their origination was witnessed or if they arose in response to a pronounced environmental change, making it difficult to generalize. In this study, we use an operational definition developed by Ramsey et al. (MS) to design a procedure for recognizing the standing repertoire of innovations (in the sense of behaviors) in a natural population. The data were derived from an intensive field study of orangutans at Tuanan, Borneo. The main recognition criteria are (1) the incomplete geographic prevalence of the behavior, (2) identified causes of its absence in a population or an individual, and (3) comparison with the incidence of the behavior among captive orangutans. Using this procedure, we recognized 19 innovations at Tuanan and 43 for orangutans in general. Cumulative curves of number of innovations indicated that the total number of innovations observed at Tuanan remained stable after some 3,000 hours of observation, and is thus adequate for comparison with other studies. Additionally, an individual's repertoire size remained stable after ca 1,000 hours. The results showed that innovations are found in multiple domains (subsistence, comfort, and social communication), and that innovations that are performed more often are more likely to reach cultural status in a population. Across populations, innovations that increase comfort are less likely to become cultural than those that serve subsistence or are used in communication. Orangutan and chimpanzee innovation repertoires do not show significant differences across the three domains. Systematic comparisons across sites and with captivity will make it possible to validate the approach.
A likely ranking interpolation for resolving dominance orders in systems with unknown relationships
Authors: Wittemyer G. , Getz W.M.
Published: August 2006

In many animal systems agonistic interactions may be rare or not overt, particularly where such interactions are costly or of high risk as is common for large mammals. We present a technique developed specifically for resolving an optimized dominance order of individuals in systems with transitive (i.e. linear) dominance relationships, but where not all relationships are known. Our method augments the widely used I&SI method (de Vries, 1998) with an interpolation function for resolving the relative ranks of individuals with unknown relationships. Our method offers several advantages over other dominance methods by enabling the incorporation of any proportion of unknown relationships, resolving a unique solution to any dominance matrix, and calculating cardinal dominance strengths for each individual. As such, this method enables novel insight into difficult to study behavioural systems.
Love for sale and its fitness benefits: nuptial gifts in the scorpionfly Panorpa vulgaris represent paternal investment
Authors: Engels Sierk , Peter Sauer Klaus
Published: August 2006

Nuptial feeding is a very common strategy shown by males of various insect taxa in order to obtain copulations. In the majority of cases these gifts presented during or after courtship and/or copulation can be considered as mating effort. In this study we present data which indicate that nuptial feeding in Panorpa vulgaris (Mecoptera: Panorpidae) represents paternal investment. During copulations males produce salivary secretions which are consumed by the females. The more salivary masses a male produces the longer the copulation will last. Since sperm are transferred continuously during copulation and fertilization of eggs follows the fair raffle principle, females allocate paternity in accordance to copulation duration and therefore to the amount of nuptial gifts they receive from a certain male. In the present study we are able to show that the number of salivary masses consumed significantly affects the number of eggs a female produces. Thus, in P. vulgaris the nuptial gift increases the reproductive output of females and hence must not only be considered as mating effort but also as paternal investment. The mechanism by which salivary masses increase female fecundity is yet unknown. We hypothesize that the secretions may not only transfer nutrients but may possibly operate as carriers for an allohormone that manipulates the females' physiology in terms of increasing egg production.