bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio-Cultural Perceptions and Representations of Dementia in Brazzaville, Republic of Congo: The EDAC Survey
Authors: Faure-Delage Angélique , Mouanga Alain Maxime , M’belesso Pascal , Tabo André , Bandzouzi Bébène , Dubreuil Catherine-Marie , Preux Pierre-Marie , Clément Jean-Pierre , Nubukpo Philippe
Published: April 2012

Background: Dementia will concern more and more people in the developing countries, but the perception people have of dementia in these areas has not yet been studied. Method: During a general population survey (EDAC) carried out in Brazzaville (Republic of Congo), 27 elderly persons suspected of having dementia and 31 of their relatives, 90 cognitively impaired elderly persons and 92 of their relatives, as well as 33 hospital workers were interviewed according to the Explanatory Model Interview Catalogue. Results: Item prominence ratings indicate that the attention was mainly on the emotional and socio-economic consequences (scores >1.0 out of 5 points). Ageing and mental stress are the main perceived causes. Hospital workers are more aware of public stigma. Conclusion: The socio-cultural components of the dementia phenomenon have to be taken into account to enforce public health and social measures.
Acute Simultaneous Multiple Lacunar Infarcts: A Severe Disease Entity in Small Artery Disease
Authors: Lee Joon Hwa , Kim Young Jin , Moon Yeonsil , Cho Hyun-Ji , Kim Hahn Young
Published: April 2012

Background: We hypothesized that acute simultaneous multiple lacunar infarcts (sMLI) may have different clinico-radiological characteristics compared to acute single lacunar infarcts (SLI). Methods: We retrospectively reviewed stroke patients with sMLI or SLI in a consecutively collected stroke registry with a predefined long-term clinical follow-up. Clinical characteristics, including vascular risk factors, rheological profiles, premorbid functional status, and clinical outcome were evaluated. In addition, radiological characteristics, including white matter ischemic changes, previous lacunes, microbleeds, and concomitant intra- or extracranial arterial stenosis were evaluated. Results: Of the 548 acute ischemic stroke patients, sMLI was found in 23 (13.5%) and SLI in 148 (86.5%). There was no difference in vascular risk factors and rheological profiles between the two groups, except for advanced age and more frequent previous history of stroke in the sMLI group. The sMLI group also showed more previous lacunes (p < 0.001) and microbleeds (p < 0.001). A cardioembolic or atherothrombotic stroke mechanism was rare in both groups. Recurrent strokes were more frequent in the sMLI group. Conclusions: The main pathophysiology of sMLI may be small artery disease. However, clinico-radiological characteristics suggest that sMLI may be a more severe entity of small artery disease compared to SLI.
Investigation of Genome Instability in Exfoliated Colonic Epithelial Cells and in Mitogen-Stimulated Lymphocytes of Patients with Ulcerative Colitis
Authors: Karaman Ahmet , Hamurcu Zuhal , Donmez Hamiyet , Bitken Nazmiye , Karaman Hatice , Baskol Mevlut , Gursoy Sebnem , Guven Kadri , Ozbakir Omer , Yucesoy Mehmet
Published: April 2012

Objective: The present study aimed to evaluate the micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN frequency in exfoliated colonic epithelial cells obtained from both the diseased and healthy colonic mucosa of patients. Design: The study was conducted in 22 newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD values scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. In addition, the MN values in exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa of patients were evaluated. Results: We found significantly higher MN, NPB and NBUD frequencies in the BN cells of patients with UC than in those of the control subjects (1.61 ± 0.75 vs. 0.89 ± 0.29, 3.93 ± 1.91 vs. 1.39 ± 1.10, and 1.55 ± 0.89 vs. 0.64 ± 0.48, p = 0.001). Also, a statistically significant difference was found between MN frequencies obtained from the diseased and healthy colonic mucosa of patients (1.07 ± 0.46 vs. 0.59 ± 0.21, p = 0.001). No significant relationship was found between age and MN frequency in patients with UC (r = 0.076, p = 0.735). Conclusion: Increased MN, NPB and NBUD frequencies observed in both the lymphocytes and exfoliated colonic epithelial cells obtained from patients with UC may reflect genomic instability.
Effects of Gum Arabic (Acacia senegal) on Renal Function in Diabetic Mice
Authors: Nasir Omaima , Umbach Anja T. , Rexhepaj Rexhep , Ackermann Teresa F. , Bhandaru Madhuri , Ebrahim Ammar , Artunc Ferruh , Kempe Daniela S. , Puchchakayala Goverdhan , Siraskar Balasaheb , Föller Michael , Saeed Amal , Lang Florian
Published: April 2012

Background/Aims: Gum arabic (GA) is a Ca2+-, Mg2+- and K+-rich dietary fiber used for the treatment of patients with chronic kidney disease in Middle Eastern countries. In healthy mice, GA treatment increases creatinine clearance, renal ADH excretion, as well as intestinal and renal excretion of Mg2+ and Ca2+. GA decreases plasma Pi concentration, urinary Pi and Na+ excretion. The present study explored the effects of GA on renal function in diabetic mice. Methods: Metabolic cage experiments were performed on Akita mice (akita+/–), which spontaneously develop insulin deficiency and thus hyperglycemia. Plasma and urinary concentrations of Na+, K+ and Ca2+ were measured by flame photometry (AFM 5051, Eppendorf, Germany), creatinine by the Jaffé method, phosphate photometrically, urea by an enzymatic method, glucose utilizing a glucometer and an enzymatic kit, aldosterone using an RIA, urinary albumin fluorometrically, and blood pressure by the tail-cuff method. Results: GA (10% in drinking water) significantly increased urinary excretion of Ca2+ and significantly decreased plasma phosphate and urea concentrations, urinary flow rate, urinary Na+, phosphate and glucose excretion, blood pressure and proteinuria. Conclusions: GA treatment decreases blood pressure and proteinuria in diabetic mice and may thus prove beneficial in diabetic nephropathy.
Validation of the Cannabis Abuse Screening Test in a Sample of Cannabis Inpatients
Authors: Legleye Stéphane , Kraus Ludwig , Piontek Daniela , Phan Olivier , Jouanne Céline
Published: April 2012

The present study aims at validating the Cannabis Abuse Screening Test (CAST) in a clinical sample of adolescent and young adult cannabis users seeking treatment. Applying a classical test theory approach using DSM-IV diagnoses as gold standard, two versions of the CAST questionnaire are compared. The sample consisted of 140 subjects aged 15–26 years (mean 18.9) recruited from two cannabis treatment centers. Gold standard diagnoses were assessed using the Adolescent Diagnostic Interview-Light. Internal structure and consistency of the CAST were assessed by principal component analysis and Cronbach’s α. Optimal thresholds were defined using receiver operating characteristic analysis. Both the binary and the full test version revealed unidimensional structures with moderate to satisfactory internal consistency (α = 0.66 and 0.73). Screening properties were unsatisfactory when the CAST was compared against cannabis dependence. With regard to cannabis use disorders, both test versions yielded comparable and good sensitivity and specificity at cut-off 3 (binary: 92.2%, 66.7%) and 6 (full: 93.0%, 66.7%). Overall, the full CAST may be used for screening cannabis use disorders in clinical settings. Further research may use validation methods that do without gold standard.
Influence of Maternal Factors on Health Outcomes in Gastroschisis: A Canadian Population-Based Study
Authors: Brindle Mary E. , Flageole Helene , Wales Paul W. ,   for The Canadian Pediatric Surgery Network (CAPSNet)
Published: April 2012

Background: Gastroschisis is increasing in incidence worldwide. There is a need for a disease-specific, population-based approach to determining factors linked with gastroschisis and its outcome. Objectives: To examine racial, socioeconomic, health and geographic predictors of gastroschisis and its outcome in Canada. Methods: 535 cases of gastroschisis from the Canadian Pediatric Surgery Network national database were included from May 2005 to May 2010. Baseline characteristics of mothers were compared with those reported by Statistics Canada. Factors associated with adverse neonatal outcomes were examined using regression analyses. Results: Mothers of infants with gastroschisis are young, often from small communities. Smoking (37%) and illicit drug use are common in this population. Single mothers receive less perinatal care (OR 0.06; 95% CI 0.02–0.28). Geographically isolated mothers are more likely to undergo caesarian section (OR 3.84; 95% CI 1.26–11.74). Cocaine use predicts a lower odds of delivering at a planned center (OR 0.25; 95% CI 0.08–0.79), and is also associated with an increased likelihood of intestinal injury at birth (OR 6.26; 95% CI 1.52–25.72). Infants of mothers from isolated communities will spend a mean of 31.9 days longer in hospital. Aboriginal status is not independently predictive of perinatal or neonatal outcome. Conclusion: Gastroschisis in Canada occurs frequently in young mothers, aboriginals and smokers. Features associated with worse outcomes include single parent status, cocaine use and maternal hometown geographic isolation.
Effects of Enterally Administered Surfactant in a Rat Model of Necrotizing Enterocolitis
Authors: Canpolat Fuat Emre , Yurdakök Murat , Ersin Süleyman Cem
Published: April 2012

Background: Despite technical and scientific improvements in neonatal medicine, there is still no efficient treatment for or prevention of neonatal necrotizing enterocolitis (NEC). Objective: The aim of this study was to determine the protective effect of surfactant on intestinal cells in hypoxia-induced experimental NEC in rats. Methods: The study was performed on Sprague Dawley rat pups divided into three groups. Group 1 served as nonhypoxic controls (n = 15). Group 2 rats (untreated; n = 15) were subjected to hypoxia and reoxygenation (H/O). Group 3 rats (surfactant treated; n = 15) were treated with surfactant (Curosurf; 400 mg/kg enterally) for 5 days and then subjected to H/O. All animals were killed on day 5, and histological and biochemical examinations were performed on intestinal samples. Results: There were no histopathological changes in the control group. The histological findings in untreated rats were similar to those seen in neonatal NEC, with destruction of villi and crypts and extension to the muscularis layer. The mean histological grade of group 1 was 0.2 (range 0–1), and in group 2, it was 2.1 (range 1–3). There was no statistical difference between the histological grades of groups 2 and 3 (p > 0.05). However, there was a difference between the groups that did and did not receive surfactant with regard to superoxide dismutase (SOD), glutathione peroxidase (GSH) and malondialdehyde (MDA). Conclusion: Although surfactant did not have a protective effect on histological changes in hypoxic neonatal rat intestine, it improves biochemical markers such as SOD and GSH and reduces MDA levels.
Pretherapeutic Expression of the hOCT1 Gene Predicts a Complete Molecular Response to Imatinib Mesylate in Chronic-Phase Chronic Myeloid Leukemia
Authors: Nardinelli Luciana , Sanabani Sabri Saeed , Didone Alline , Ferreira Patricia de Barros , Serpa Mariana , Novaes Mafalda Megumi Yoshinaga , Marchiani Mariana , Ruiz Antonio Lancha , Lima Ismael Severino , Chamone Dalton de Alencar Fischer , Bendit Israel
Published: April 2012

In this retrospective study we evaluated the pretherapeutic mRNA expression of the hOCT1 (human organic cation transporter 1) gene in patients with chronic-phase (CP) chronic myeloid leukemia (CML) who varied in terms of their response to imatinib (IM). hOCT1 mRNA was quantiﬁed by real-time PCR. Patients were classified as expressing either high (n = 44) or low hOCT1 mRNA (n = 44). The complete cytogenetic response rates observed at 6, 12 and 18 months were 47.7, 84.1 and 91%, respectively, in patients with high hOCT1 mRNA and 47.5, 81.8 and 86.3%, respectively, in patients with low hOCT1 transcripts. The major molecular response rates were not significantly different between patients with high and low hOCT1 mRNA after 6 months of therapy (22.7 vs. 9.1%; p = 0.07), but they were significantly different after 12 months (54.5 vs. 31.8%; p = 0.026) and 18 months (77.2 vs. 56.8%; p = 0.034). Complete molecular responses were observed in 5 patients with low and 17 patients with high hOCT1 mRNA (p = 0.003). The 5-year event-free and overall survival analyses revealed no significant differences between the groups. These data imply that knowledge of the pretherapeutic level of hOCT1 could be a useful marker to predict IM therapy outcome in treatment-naïve CP CML patients.
An Update on the Use of C-Reactive Protein in Early-Onset Neonatal Sepsis: Current Insights and New Tasks
Authors: Hofer Nora , Zacharias Eva , Müller Wilhelm , Resch Bernhard
Published: April 2012

C-reactive protein (CRP) is one of the most studied and most used laboratory tests for neonatal sepsis. As part of the acute-phase reaction to infection, it plays a central role in the humoral response to bacterial invasion. The delayed synthesis during the inflammatory response accounts for its low sensitivity during the early phases of the disease. Diagnostic accuracy clearly improves by the performance of serial determinations and by the combination with earlier markers such as interleukins or procalcitonin. CRP is as well particularly useful for monitoring the response to treatment and guiding antibiotic therapy, though nothing replaces the clinical impression and the gold standard (i.e. culture results). In spite of the large amount of research done on CRP in neonates, some topics are still not fully understood, such as the influence of noninfectious factors on CRP levels in healthy as well as in symptomatic neonates and the role of gestational age and birthweight on CRP kinetics. In this review, we aim to give an update on the current evidence on the use of CRP in neonates.
Diagnostic Value of an Interleukin-6 Bedside Test in Term and Preterm Neonates at the Time of Clinical Suspicion of Early- and Late-Onset Bacterial Infection
Authors: Batfalsky A. , Lohr A. , Heussen N. , Neunhoeffer F. , Orlikowsky T.W.
Published: April 2012

Background: For quick detection or exclusion of neonatal early-onset bacterial infection (EOBI) or late-onset bacterial infection (LOBI), interleukin (IL)-6 is used. Its clinical use is sometimes limited due to prolonged recall times. Therefore, an IL-6 bedside test was established. Objective: To compare the diagnostic value of plasma IL-6 and an IL-6 bedside test at the time of clinical suspicion in the course of EOBI and LOBI. Methods: Eighteen term (mean gestational age 40.2 weeks, SD 1.3) and 88 preterm (mean gestational age 30.1 weeks, SD 4.2) neonates with clinical and serological signs of bacterial infection were analysed. Eight had an EOBI, and 24 had a LOBI, of whom 13 were blood culture positive. Twelve term and 62 preterm neonates with risk factors but without proven EOBI/LOBI served as a non-infected group. Results: At the time of clinical suspicion, the sensitivity of the IL-6 bedside test in comparison to plasma IL-6 was 69 versus 75% (p = 0.7744, McNemar’s test), and specificity was 77 versus 81% (p = 0.6476, McNemar’s test; cutoff level 50 ng/l). For LOBI, both the sensitivity (75%) and specificity (82%) of the bedside test exceeded values calculated for EOBI (sensitivity 50%, specificity 75%). Conclusion: No significant difference between the bedside and established plasma IL-6 test was detected for LOBI. For detection of EOBI, the bedside test was not sensitive enough. Larger studies are needed to verify our findings before IL-6 bedside tests can be recommended routinely.
Curcumin and Inflammatory Bowel Disease: Biological Mechanisms and Clinical Implication
Authors: Ali Tauseef , Shakir Faiz , Morton Jordan
Published: April 2012

Increased recognition of the limits of conventional medicine has helped drive the growing interest in complementary and alternative medicine which is now being commonly used in patients with chronic diseases, including individuals with Crohn’s disease and ulcerative colitis. Recently, scientific interest has unraveled the beneficial pharmacological effects of curcumin. We present an updated concise review of currently available in vitro, animal and clinical studies demonstrating the therapeutic effect of herbal medication in inflammatory bowel disease.
Capability of Identifying Red Nuclei in Different Pulse Sequences of Regular 1.5-Tesla Magnetic Resonance Images
Authors: Chiou Shang-Ming , Lo Yu-Chien , Lin Hung-Lin
Published: April 2012

Objective: To investigate the optimal pulse sequences of commonly used 1.5-tesla MRI for identifying the red nucleus (RN) to aid targeting of the subthalamic nucleus (STN). Methods: Forty-six healthy adults were enrolled for this prospective study. All subjects underwent MR studies of 5 sequences: diffusion-weighted imaging (DWI), T1-weighted fluid-attenuated inversion recovery (T1IR), fast spin echo T2-weighted imaging (FSE-T2WI), T2-weighted fluid-attenuated inversion recovery (T2FLAIR) and T2*-weighted gradient-echo (T2*-GRE) sequences. The clearness of the RN contour was analyzed. Results: Overall, the RN was identified in 98% subjects without gender and age differences. The RN was demarcated on a 5-mm slice relatively better in T2FLAIR (93.5%), followed by FSE-T2WI (78.3%), T2*-GRE (65.2%) and DWI (43.5%) sequences, but was completely invisible on the T1IR image. Generally, the signal intensity in all MR sequences decreased mildly on 2-mm slices with a similar identifying power. The detecting power on 5-mm slices was in favor of T2FLAIR with 94% sensitivity, 10% specificity, and 1.89 odds ratio compared to FSE-T2WI. In addition, the scanning time of T2FLAIR was longer in comparison to the FSE-T2WI study. Conclusion: T2FLAIR is an alternative to FSE-T2WI that can readily demarcate the RN to help target the STN.
Persistence of Hyperdense Middle Cerebral Artery Sign on Follow-Up CT Scan after Intravenous Thrombolysis Is Associated with Poor Outcome
Authors: Paliwal Prakash R. , Ahmad Aftab , Shen Liang , Yeo Leonard L.L. , Loh Pei Kee , Ng Kay W.P. , Chong Vincent F. , Ong Benjamin K.C. , Venketasubramanian N. , Sinha Arvind K. , Teoh Hock L. , Bathla Girish , Chan Bernard P.L. , Sharma Vijay K.
Published: April 2012

Background: The rates and extent of recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA) remain highly variable. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment unenhanced computerized tomography (CT) of the brain represents the presence of thrombus, often associated with severe neurological deficits and poor clinical outcome at 3 months. However, HMCAS is reliable only in AIS patients managed conservatively. In patients treated with systemic thrombolysis, HMCAS may disappear (representing clot dissolution) or persist (persisting clot) on the follow-up CT scan of the brain. We aimed at evaluating whether disappearance or the persistence of HMCAS on follow-up CT scan of the brain can predict the final outcome at 3 months. Methods: Data from consecutive AIS patients treated with IV-tPA, in a standardized protocol, from January 2007 to March 2010 were included in the prospective thrombolysis registry at our tertiary care center. For this evaluation, posterior circulation stroke was excluded. HMCAS was assessed on admission as well as follow-up CT by 2 independent stroke neurologists, blinded to the patient data or outcomes. Functional outcomes assessed by the modified Rankin Scale (mRS) at 3 months were dichotomized as good (mRS score 0–1) and poor (mRS score 2–6). The data were analyzed for the early predictors of poor functional outcome with SPSS version 19 for Windows. Results: Of the total of 2,238 patients admitted during the study period, 226 (11%) with anterior circulation AIS treated with intravenous thrombolysis were included. Median age of the patients was 65 years (range 19–92), 63% were males and they had a median National Institutes of Health Stroke Scale (NIHSS) score of 16 points (range 4–32). HMCAS was observed on admission CT scan in 109 (48.2%) patients and persisted on follow-up CT in 52 (47.7%) of them. Overall, 108 (47.8%) patients achieved poor functional outcome at 3 months. Admission NIHSS score (OR per 1-point increase = 1.241; 95% CI = 1.151–1.337, p < 0.0005), lesser change in NIHSS score at 24 h (OR per 1-point reduction = 0.730; 95% CI = 0.666–0.800, p < 0.0005) and persistence of HMCAS on follow-up CT scan (OR = 3.352; 95% CI = 1.991–11.333, p = 0.039) were associated with poor outcome at 3 months. Conclusion: Persistence of HMCAS on the follow-up CT scan of the brain in acute ischemic stroke patients treated with IV-tPA can be used as an early predictor of poor functional outcome.
Vascularization in Tissue Engineering: Angiogenesis versus Inosculation
Authors: Laschke M.W. , Menger M.D.
Published: April 2012

Background/Purpose: The key challenge in tissue engineering is the establishment of an efficient vascularization for tissue constructs guaranteeing long-term survival and function. Vascularization may be achieved by the stimulation of angiogenesis or the inosculation of preformed microvascular networks within the implants to the host microvasculature. The present review provides an overview of these two concepts applied in tissue engineering. Methods: A literature search was performed in PubMed for publications focusing on vascularization, angiogenesis and inosculation in tissue engineering. Results: Several strategies have been proposed to stimulate the ingrowth of new blood vessels into tissue constructs. These include the modification of the chemical composition and architecture of scaffolds, their bioactivation by incorporation of growth factor delivery systems or by cell seeding as well as the stimulation of stem cell recruitment. However, because angiogenesis is a time-consuming process, all of these approaches cannot prevent ischemic cell death within larger 3-dimensional tissue constructs during the initial phase after implantation. To overcome this problem, in vitro or in situ prevascularization has emerged as a novel concept in tissue engineering. This bears the advantage that preformed microvascular networks within tissue constructs simply have to inosculate with the host microvasculature at the implantation site to get completely blood-perfused within a short period of time. Conclusions: During the last years, considerable progress has been made in the development of promising vascularization strategies in tissue engineering. Particularly the inosculation of preformed microvascular networks has the great potential to markedly improve the survival of tissue constructs after implantation. The optimization of this vascularization strategy may pave the way for a broad clinical use of tissue engineering applications in the future.
Diet and Dietary-Niche Breadth of Diurnal Rain Forest Primates in the Central Western Ghats, India
Authors: Roy Kuladeep , Singh Mewa , Singh Mridula
Published: April 2012

We studied the feeding ecology of 3 sympatric primate species, the lion-tailed macaque (Macaca silenus), bonnet macaque (Macaca radiata) and Hanuman langur (Semnopithecus entellus), in a tropical rain forest of the Central Western Ghats, India. Since the availability of leaves is much higher than that of fruits, we expected that the primarily folivorous langurs would use a larger number of resources than the primarily frugivorous macaques. Since fruits are a relatively total resource, unlike leaves, of which only selected parts are consumed, we expected that the primarily frugivorous macaques would use resources more proportionately than the folivorous langurs, resulting in a wider food niche breadth in macaques. We collected data on these primate species over a period of 2 years using scan sampling in a contiguous rain forest. We calculated Levin’s standardised food niche breadth for each species. Langurs used a larger number of tree species than macaques, but their niche breadth was narrower than that of macaques. The majority of their diet (over 50%) came from only a few trees in the case of all three primate species. Long-term data are provided herein for the first time on the feeding ecology of bonnet macaques and Hanuman langurs in a tropical rain forest.
Simultaneous Determination of a Novel Diphenylpiperazine Calcium Channel Blocker and Its Four Metabolites in Rat Liver Microsomes by Liquid Chromatography Tandem Mass Spectrometry
Authors: Guo Wei , Kong Dezhi , Du Yingfeng , Shi Xiaowei , Wang Wei , Wang Yongli
Published: April 2012

Dipfluzine hydrochloride (Dip), a novel diphenylpiperazine calcium channel blocker, has revealed the characteristics of a promising candidate for the treatment of cerebral vascular diseases in preclinical studies. Our research identified and quantified Dip and its 4 metabolites (M1, M2, M4 and M5) in rat liver microsomes by liquid chromatography tandem mass spectrometry. The results showed that Dip was firstly metabolized to M1 and M5 by 1- and 4-dealkylation from a piperazine nitrogen, and then the latter was subsequently metabolized to M2 and M4. The concentrations of Dip, M1, M2 and M5 were 557.3 ± 26.3, 854.3 ± 46.0, 2796.7± 126.9, 2473.3 ± 82.6 and 4.0 ± 0.4, 2.4 ± 0.1, 318.2 ± 8.7 and 27.4 ± 1.5 ng/ml in male and female rats, respectively. M4 (404.2 ± 22.2 ng/ml) was detected only in males not in females, suggesting that there is gender difference in the metabolism of Dip.
Galangin Induces Autophagy through Upregulation of p53 in HepG2 Cells
Authors: Wen Min , Wu Jun , Luo Hui , Zhang Haitao
Published: April 2012

Aim: To investigate the mechanism by which galangin, a polyphenolic compound derived from medicinal herbs, induces autophagy of HepG2 cells. Methods: The MTT [3-(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide] assay was used to measure cell viability. Apoptosis was evaluated by TUNEL assay with flow cytometry, and PARP cleavage was detected by Western blotting. Autophagy was measured by fluorescence microscopy and transmission electron microscopy. Protein expressions were detected by Western blotting. Pifithrin-α was used for pretreatment and siRNA was used to knock down p53 expression to explore the pathway mediated by galangin in HepG2 cells. Furthermore, Hep3B cells were used to express the exogenous wild-type p53. Results: Galangin treatment inhibited cell proliferation and induced autophagy (130 µmol/l) and apoptosis (370 µmol/l). In particular, galangin treatment in HepG2 cells caused (1) an accumulation of autophagosomes, (2) elevated levels of microtubule-associated protein light chain 3, and (3) an increased percentage of cells with vacuoles. p53 expression was also increased. The galangin-induced autophagy was attenuated by the inhibition of p53 in HepG2 cells, and overexpression of p53 in Hep3B cells restored the galangin-induced higher percentage of cells with vacuoles to normal level. Conclusion: Our results indicate that galangin not only induced apoptosis but also prompted cell autophagy in different concentrations. Galangin mediates autophagy through a p53-dependent pathway in HepG2 cells. Our findings may help in the discovery of a chemotherapeutic drug with the novel pattern of inhibiting cell proliferation for the treatment of hepatocellular carcinoma cells.
Unchanged Antibiotic Susceptibility in Escherichia coli and Pseudomonas aeruginosa after Long-Term in vitro Exposure to Antineoplastic Drugs
Authors: Kvakkestad Kristin M. , Gammelsrud Karianne W. , Brandtzaeg Petter , Høiby E. Arne
Published: April 2012

Background: Certain antineoplastic drugs inhibit bacterial growth. Whether these drugs also cause genetic changes in bacteria that lead to increased antibiotic resistance is not yet documented. Given the massive and repeated antibiotic treatment most cancer patients undergo, this question is important. We have examined the possible effects of in vitro long-term antineoplastic exposure on antibiotic resistance. Methods: Using the disc diffusion method, two bacterial strains (Escherichia coli, ATCC 25922, and Pseudomonas aeruginosa, ATCC 27583) were exposed to methotrexate, fluorouracil, vincristine, doxorubicin and cytarabine during 50 overnight cycles. The bacterial strains were susceptibility-tested to several antibiotics before and after repeated exposure to antineoplastics. Results: No changes in antibiotic susceptibility were seen in the two bacterial strains after long-term exposure to any of the antineoplastic drugs tested. Conclusion: Long-term in vitro antineoplastic exposure did not change the antibiotic susceptibility in the E. coli or P. aeruginosa strains.
Novel Intrapleural Therapies for Malignant Diseases
Authors: Haas Andrew R. , Sterman Daniel H.
Published: April 2012

Pleural malignancies, either primary or metastatic, are common and problematic clinical issues in thoracic oncology and pulmonary medicine. Malignant pleural mesothelioma and metastatic pleural effusions often present late in the course of a disease and have a dramatic impact on the patient’s quality of life and survival. Novel approaches to manage mesothelioma and malignant pleural effusions are desperately needed and the pleural space provides a unique platform as an easily accessible body cavity for developing and assessing these treatments and their responses. In this review, we discuss the unique intrapleural chemotherapeutic, immunotherapeutic and genetic treatments that have been investigated, as well as those under current clinical development. While responses have been demonstrated to variable degrees with all these approaches, an integrated multimodality approach incorporating these methods with other anti-neoplastic interventions ultimately will ensure the best responses and patient outcomes.
Pericardial Involvement in Diseases of the Heart and Other Contiguous Structures: Part I – Pericardial Involvement in Infarct Pericarditis and Pericardial Involvement following Myocardial Infarction
Authors: Mehrzad Raman , Spodick David H.
Published: April 2012

Active contiguous abnormalities can frequently involve the pericardium. Prominent among these are cardiac conditions which encroach on the pericardium, particularly transmural myocardial infarction (newly always with Q-waves). Complications of infarctions, notably myocardial pseudoaneurysm, have one wall which is pericardium. Furthermore, dissecting aneurysm of the aorta and the intramural aortic hemorrhage may rupture into the pericardium with tamponade, or, if limited, mimic acute pericarditis. Diseases of the lungs and pleura, including the diaphragmatic pleura, also result in pulmonary embolism which can produce several syndromes. Many mediastinal diseases, notably inflammation and malignancy, especially involving the lymph nodes, induce mediastinal inflammation and fibrosis. Many esophageal disorders can penetrate or produce a fistula usually with pneumopericardium. Rarely, primarily pericardial disorders like purulent pericarditis, malignancies, and rough pericardial calcifications affect the contiguous tissues. We discuss the many syndromes and disorders under each of these topics.
Pericardial Involvement in Diseases of the Heart and Other Contiguous Structures: Part II – Pericardial Involvement in Noncardiac Contiguous Disorders
Authors: Mehrzad Raman , Spodick David H.
Published: April 2012

Active contiguous abnormalities can frequently involve the pericardium. Prominent among these are cardiac conditions which encroach on the pericardium, particularly transmural myocardial infarction (newly always with Q-waves). Complications of infarctions, notably myocardial pseudoaneurysm, have one wall which is pericardium. Furthermore, dissecting aneurysm of the aorta and the intramural aortic hemorrhage may rupture into the pericardium with tamponade, or, if limited, mimic acute pericarditis. Diseases of the lungs and pleura, including the diaphragmatic pleura, also result in pulmonary embolism which can produce several syndromes. Mediastinal diseases, notably inflammation and malignancy, especially involving the lymph nodes, induce mediastinal inflammation and fibrosis. Many esophageal disorders can penetrate or produce a fistula usually with pneumopericardium. Rarely, primarily pericardial disorders like purulent pericarditis, malignancies, and rough pericardial calcifications affect the contiguous tissues. We discuss the many syndromes and disorders under each of these topics.
Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events
Authors: Greif Martin , Leber Alexander Wolfgang , Saam Tobias , Uebleis Christopher , von Ziegler Franz , Rümmler Janine , D’Anastasi Melvin , Arias-Herrera Vivian , Becker Christoph , Steinbeck Gerhard , Hacker Marcus , Becker Alexander
Published: April 2012

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 ± 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 ± 2,269 vs. 538 ± 1,150, p < 0.01), and the CAC score was highly correlated with the relative risk of a future cardiac event: 2.4 (1.8–3.7; p = 0.01) for scores >400, 3.5 (1.9–5.4; p = 0.007) for scores >800 and 5.9 (3.7–7.8; p = 0.005) for scores >1,600. When additionally a PAT volume >200 cm3 was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9–4.2; p = 0.01) for scores >400, 4.0 (2.1–5.0; p = 0.006) for scores >800 and 7.1 (4.1–10.2; p = 0.005) for scores >1,600. Conclusions: The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification.
Transoral Robotic Surgery with Laser for Head and Neck Cancers: A Feasibility Study
Authors: Benazzo Marco , Canzi Pietro , Occhini Antonio
Published: April 2012

Aims: To assess the feasibility of a flexible thulium laser coupled with a novel robotic introducer for head and neck cancers. Methods: In a prospective nonrandomized clinical trial, 58 patients were evaluated. When indicated, transoral robotic surgery (TORS) with laser was performed using an Intuitive da Vinci S System with the Intuitive Surgical® Endo Wrist Introducer, 5Fr to hold and position thulium surgical laser fibers. Results: Six patients underwent TORS with laser for early supraglottic and oropharyngeal squamous cell carcinomas. All approaches were successfully completed without the need for microscopic/open conversion or positive margins to the final pathological study. No intraoperative adverse events occurred and recovery was relatively quick, with no evidence of disease recurrence at the time of reporting, the short observation time notwithstanding. Conclusions: In our preliminary experience, TORS with laser showed feasible and promising results. Further studies are mandatory to demonstrate thulium laser benefits in surgical and oncological practice.
Methicillin-Resistant Staphylococcus aureus Laryngitis: A Report of Two Cases with Different Clinical Presentations
Authors: Antunes Marcelo B. , Ransom Evan R. , Leahy Kevin P.
Published: April 2012

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infection has been described in multiple areas of the head and neck. Recently, otolaryngologists have recognized MRSA infection in the glottis. We describe 2 cases of MRSA laryngitis with divergent clinical presentations: acute airway obstruction and recalcitrant hoarseness. Methods: Report of 2 cases and review of the literature. Results: In the first case, a 44-year-old woman presented with near aphonia despite maximal medical therapy. Examination showed diffuse erythema and edema of the endolarynx with yellowish plaques lining the glottis and supraglottis. Complete resolution was achieved with long-term trimethoprim-sulfamethoxazole. In the second case, a 54-year-old woman presented with recent-onset hoarseness with rapid progression to respiratory distress and biphasic stridor. Endoscopy revealed exuberant granulation tissue in the glottis with a narrowed airway. Treatment required prolonged courses of antibiotics and steroids. Diagnosis in both cases was confirmed with biopsies taken during direct laryngoscopy. Conclusions: MRSA treatment is a growing part of otolaryngologic practice and should be included in the differential diagnosis of hoarseness and stridor.
Anti-Inflammatory Gallic Acid and Wedelolactone Are G Protein-Coupled Receptor-35 Agonists
Authors: Deng Huayun , Fang Ye
Published: April 2012

G protein-coupled receptor-35 (GPR35) has been shown to be a target of the asthma drugs cromolyn disodium and nedocromil sodium. Gallic acid and caffeic acids are reported to modulate allergic reactions via unknown mode(s) of action. Here we attempt to elucidate whether both phenolic acids share a common mode of action with the two asthma drugs. Label-free dynamic mass redistribution (DMR) assays showed that both phenolic acids triggered robust DMR signals in HT-29 cells, whose characteristics were similar to that of cromolyn disodium. Both phenolic acids resulted in detectable β-arrestin translocation signals in an engineered U2OS cell line stably expressing a C-terminal-modified GPR35, but with lower efficacy than cromolyn disodium. Antiallergic wedelolactone was found to be a potent β-arrestin-biased GPR35 agonist. These results suggest that certain anti-inflammatory phytochemicals including gallic acid and wedelolactone may modulate inflammatory allergic action via their agonism at GPR35. GPR35 may represent a target for the treatment of allergic disorders including asthma.
Absence of Clinically Relevant Growth Acceleration in Untreated Children with Non-Classical Congenital Adrenal Hyperplasia
Authors: Pijnenburg-Kleizen Karijn J. , Borm George F. , Otten Barto J. , Schott Dina A. , van den Akker Erica L. , Stokvis-Brantsma Wilhelmina H. , Voorhoeve Paul G. , Bakker Boudewijn , Claahsen-van der Grinten Hedi L.
Published: April 2012

Background/Aims: In classical congenital adrenal hyperplasia (CAH), elevation of adrenal androgens leads to accelerated growth and bone maturation with compromised adult height. In untreated children with non-classical CAH (NC-CAH), in which adrenal androgens are generally only slightly increased, growth velocity may not be significantly elevated. Methods: Twenty-four patients were included and divided into a symptomatic and an asymptomatic group. Height was expressed as height standard deviation scores (HSDS) and corrected for target height (HSDS-THSDS). Bone maturation was expressed as bone age acceleration (BAc = bone age – calendar age). Linear mixed models with random factor patient were used for the analysis of growth and bone age. Results: In symptomatic patients (n = 17), HSDS-THSDS only slightly increased by 0.06 SDS per year (95% CI 0.02–0.10). Mean BAc was 2.21 years (SDS 0.66, p < 0.0001). In asymptomatic patients (n = 7), no significant growth acceleration or BAc was found. Conclusions: In untreated NC-CAH children, growth acceleration is small and generally not visible on their growth charts. BAc is more pronounced. Therefore, the absence of an increase in growth velocity does not exclude the diagnosis of NC-CAH. When considering this diagnosis, bone age acceleration should also be taken into account.
Rise to Power: A Case Study of Male Fecal Androgen and Cortisol Levels before and after a Non-Aggressive Rank Change in a Group of Wild White-Faced Capuchins (Cebus capucinus)
Authors: Schoof Valérie A.M. , Jack Katharine M. , Carnegie Sarah D.
Published: April 2012

We examined fecal androgen and cortisol levels in three adult male white-faced capuchin monkeys (Cebus capucinus) before and after a non-aggressive rank increase in one habituated group residing in the Santa Rosa Sector of the Área de Conservación Guanacaste, Costa Rica. Fecal samples (n = 116) were collected opportunistically between July 2006 and July 2007. Alpha males had higher mean androgen levels than subordinates, and acquisition of the alpha position was linked to an immediate increase in mean androgens. Cortisol levels also increased in the alpha male after acquisition of his new rank, though this increase was delayed relative to the change in rank. These results indicate that, during a non-aggressive rank change, androgen and cortisol levels in male white-faced capuchins are physiological responses to dominance rank, rather than precursors that facilitate rank acquisition.
Development of Nanoaptamers Using a Mesoporous Silica Model Labeled with 99mTc for Cancer Targeting
Authors: Sá Lucas Torres Miranda , Pessoa Claudia , Meira Assuero Silva , da Silva Maria Isabel Pais , Missailidis Sotiris , Santos-Oliveira Ralph
Published: April 2012

The use of mesoporous silica in targeted cancer therapy is increasing daily. The combination of a rigid model of nanoparticles like mesoporous silica and biological compounds with an affinity for oncological diseases is the most promising drug-targeting system nowadays. In this study, we used the mesoporous silica SBA-15 combined with aptamer (functionalized for tumor with MUC1). The results obtained were of interest and showed the formation of the silica mesoporous structure. The impregnation methodology of mesoporous silica with the aptamer was also confirmed. Cytotoxicity results demonstrated that the particle associated with the aptamer has no cytotoxicity. We conclude that although further studies are required, the mesoporous silica nanoparticle model loaded with aptamer is very functional and can be used for other applications, especially in nuclear medicine.
Osseointegration Technique in Patients with Acquired Auricular Deformities and Failed Previous Reconstruction: A Retrospective Study of Long-Term Follow-Up and Chinese Experience
Authors: Si Yu , Fan Shao Chong , Sun Wei , Chen Yu Bin , Zhang Zhi Gang
Published: April 2012

Objectives: To evaluate the complication rate and patient satisfaction of reconstruction of acquired auricular deformities and failed previous reconstruction by the osseointegration technique. Methods: The study enrolled 24 patients from January 2002 to December 2005. Data collected included demographic information, success rate of auricular prostheses, site of implants, survival rate of implants, occurrence of skin reaction and condition of the prosthetic ear. Results: Twenty-five ears (24 patients) were implanted. All ears were healing well with a lifelike appearance, stable fixation and natural color; except for 2 instances of implants dislocated by trauma, the rest survived well by first intention; skin reaction was the most troublesome complication, no patient was able to maintain a consistent level of soft-tissue health for the whole follow-up period, but the ratio and degree of skin reaction decreased gradually. The time of wearing prosthetic ears was more than 8 h/day. The average time length until prosthetic ear replacement was 3.5 years. There were no intracranial or systemic complications. Conclusion: The osseointegration technique can be the method of choice for acquired auricular defects and failed reconstructions. Follow-up management is important to the health of the implants and the surrounding soft tissue and to preserve the prosthesis and its retention mechanism.
Relationship among Salivary Carbonic Anhydrase VI Activity and Flow Rate, Biofilm pH and Caries in Primary Dentition
Authors: Frasseto F. , Parisotto T.M. , Peres R.C.R. , Marques M.R. , Line S.R.P. , Nobre dos Santos M.
Published: April 2012

This study aimed to determine the activity of carbonic anhydrase isoenzyme VI (CAVI) in the saliva of preschool children with caries and to investigate the relationship between caries and salivary CAVI activity, salivary flow rate and biofilm pH before and after a 20% sucrose rinse. Thirty preschool children aged 45.3–80.3 months were divided into two groups: a caries-free group and a caries group. Clinical examinations were conducted by one examiner (ĸ = 0.95) according to WHO criteria (dmfs) and early caries lesions. From each subject, CAVI activity, salivary flow rate and plaque pH were determined before and after a sucrose rinse. The results were submitted to Wilcoxon, Mann-Whitney and Spearman correlation tests (α = 0.05). The results showed that prerinse CAVI activity and its variation were higher in the saliva from caries children than from caries-free children. No difference was found between the two groups in postrinse salivary CAVI activity. After rinsing, biofilm pH differences were lower in both groups (p = 0.0012 and p = 0.0037 for the caries and caries-free groups, respectively). Also, after the sucrose rinse, salivary flow rate significantly increased in caries and caries-free groups (p = 0.0003, p = 0.0037). The variation of salivary CAVI activity was negatively correlated with caries (r = –0.501, p = 0.005). Child’s age showed a positive correlation with caries (r = 0.456, p = 0.011). These results suggest that variation of salivary CAVI activity and child’s age are associated with dental caries in preschool children.
A Methyl-Deficient Diet Modifies Early B Cell Development
Authors: Kurogi Toshiaki , Inoue Hiroko , Guo Yun , Nobukiyo Asako , Nohara Keiko , Kanno Masamoto
Published: April 2012

A functional methyl group donor is essential for the epigenetic regulation of all biological events due to the importance of DNA methylation and histone methylation as an epigenetic marker. However, the epigenetic alterations in the immune system due to methyl donor deficiency are not well known. In this study, we tried to address this question by studying the lymphocyte development and DNA methylation changes caused by a methyl-deficient diet (MDD). We fed one group of C57BL/6J mice with a methyl-sufficient diet (MSD) and the other group with an MDD for 5 months. Flow cytometry analyses of their immune systems showed a decrease in B220+ IgM+ (immature B) cells and an increase in B220+ IgM– (pro/pre-B) cells in the bone marrow of mice fed an MDD. By means of an in vitro OP9 coculture system, we recognized that this B220+ IgM– cell fraction from the MDD has an intrinsic developmental defect. When we quantitatively measured the mRNA expression levels of transcription factors and recombination machinery related to B cell development in the B220+ IgM– cell fraction of their bone marrow, we found that ADA, EBF1, DNTT and Pax5 mRNA expression levels were significantly downregulated in mice fed with an MDD. In addition, there was a drastic decrease in histone methylation profile H3K4me3 in the Pax5 and EBF1 promoters in these B220+ IgM– B cells. However, CpG-DNA methylation profiles had not changed and this revealed that these two promoters are demethylated even under an MSD condition. We also found changed expression levels of the Polycomb group genes (mel18, bmi1, Pc1, Pc2, Ring1A, Ring1B, Ph1) on semi-quantitative RT-PCR. These results indicate that under an MDD condition, early B cell development in bone marrow is easily affected by epigenetic alterations.