bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of two preoptic cell groups in tonic and febrile control of rat tail sympathetic fibers
Authors: Tanaka Mutsumi , McKinley Michael J. , McAllen Robin M.
Published: February 2009

In response to cold and in fever, heat dissipation from the skin is reduced by sympathetic vasoconstriction. The preoptic region has been implicated in regulating basal, thermal, and febrile vasoconstriction of cutaneous vessels such as the rat's tail, but the neurons responsible for these functions have not been well localized. We recorded activity from single sympathetic nerve fibers supplying tail vessels in urethane-anesthetized rats, while microinjections of GABA (300 mM, 15–30 nl) were used to inhibit neurons in different parts of the preoptic region. Tail fiber activity increased promptly after GABA injections in two distinct regions: a rostromedial preoptic region (RMPO) centered around the organum vasculosum of the lamina terminalis, and a second region centered ∼1 mm caudolaterally (CLPO). Responses to GABA within each region were similar. The febrile mediator, PGE2(0.2 or 1 ng in 15 nl) was then microinjected into GABA-sensitive preoptic sites. Injections of PGE2into the RMPO induced a rapid increase in tail fiber activity followed by a rise in core temperature; injections into the rostromedial part of CLPO gave delayed tail fiber responses; injections into the central and caudal parts of CLPO were without effect. These results indicate that neurons in two distinct preoptic regions provide tonic inhibitory drive to the tail vasoconstrictor supply, but febrile vasoconstriction is mediated by PGE2selectively inhibiting neurons in the rostromedial region.
The PPARγ agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake
Authors: Festuccia William T. , Blanchard Pierre-Gilles , Turcotte Véronique , Laplante Mathieu , Sariahmetoglu Meltem , Brindley David N. , Richard Denis , Deshaies Yves
Published: February 2009

We investigated the mechanisms whereby peroxisome proliferator-activated receptor-γ (PPARγ) agonism affects glucose and lipid metabolism in brown adipose tissue (BAT) by studying the impact of PPARγ activation on BAT glucose uptake and metabolism, lipogenesis, and mRNA levels plus activities of enzymes involved in triacylglycerol (TAG) synthesis. Interscapular BAT of rats treated or not with rosiglitazone (15 mg·kg−1·day−1, 7 days) was evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (PAP or lipin-1), and diacylglycerol acyltransferase (DGAT). Rosiglitazone increased BAT mass without affecting whole tissue glucose uptake. BAT glycogen content (−80%), its synthesis from glucose (−50%), and mRNA levels of UDP-glucose pyrophosphorylase (−40%), which generates UDP-linked glucose for glycogen synthesis, were all reduced by rosiglitazone. In contrast, BAT TAG-glycerol synthesis in vivo and glucose incorporation into TAG-glycerol in vitro were stimulated by the agonist along with the activities and mRNA levels of glycerol 3-phosphate-generating phosphoenolpyruvate carboxykinase and glycerokinase. Furthermore, rosiglitazone markedly increased the activities of GPAT and DGAT but not those of lipin-1-mediated PAP-1, enzymes involved in the sequential acylation of glycerol 3-phosphate and TAG synthesis. Because an adequate supply of fatty acids is essential for BAT nonshivering thermogenesis, the enhanced ability of BAT to synthesize TAG under PPARγ activation may constitute an important mechanism by which lipid substrates are stored in preparation for an eventual thermogenic activation.
Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats
Authors: Yanes Licy L. , Sartori-Valinotti Julio C. , Iliescu Radu , Romero Damian G. , Racusen Lorraine C. , Zhang Huimin , Reckelhoff Jane F.
Published: February 2009

Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.
Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats
Authors: Kumagai Takanori , Nangaku Masaomi , Kojima Ichiro , Nagai Ryoji , Ingelfinger Julie R. , Miyata Toshio , Fujita Toshiro , Inagi Reiko
Published: February 2009

Methylglyoxal (MG), a highly reactive carbonyl compound generated by carbohydrate oxidation and glycolysis, is the major precursor of protein glycation and induces cytotoxicity leading to apoptosis. Although recent studies have emphasized that MG accumulates in not only chronic oxidative stress-related diseases but also acute hypoxic conditions, the pathogenic contribution of MG in acute diseases is unclear. MG is efficiently metabolized by the glyoxalase system, namely, glyoxalase I. We investigated the pathophysiological role of glyoxalase I as an MG detoxifier in rat renal ischemia-reperfusion (I/R) injury. I/R-induced tubulointerstitial injury was associated with a deterioration in renal glyoxalase I activity independent of its cofactor, GSH, as well as an increase in renal MG level. In in vitro studies, knockdown of glyoxalase I by small interference RNA transfection in rat tubular cells exacerbated cell death by hypoxia-reoxygenation compared with control cells. We also examined whether glyoxalase I overexpression prevented renal I/R damage in rats overexpressing human glyoxalase I with enzyme activity in the kidney 17-fold higher than in wild-type. The histological and functional manifestations of I/R in these rats were significantly ameliorated in association with a decrease in intracellular MG adduct accumulation, oxidative stress, and tubular cell apoptosis. In conclusion, glyoxalase I exerts renoprotective effects in renal I/R injury via a reduction in MG accumulation in tubular cells.
Inhibition of angiotensin type 1 receptor impairs renal ability of K conservation in response to K restriction
Authors: Jin Yan , Wang Yan , Wang Zhi-Jian , Lin Dao-Hong , Wang Wen-Hui
Published: February 2009

We have previously demonstrated that ANG II inhibits ROMK-like small-conductance K channels (SK) in the cortical collecting duct from rats on a K-deficient diet (KD) ( 35 ). In the present study, we examined the role of angiotensin type 1 receptor (AT1R) in mediating the effect of K restriction on K secretion. We confirmed the previous finding that K restriction increased the superoxide anion level, c-Src expression, and the phosphorylation of both p38 and extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) in renal cortex and outer medulla. However, the effect of K restriction on superoxide anion generation, c-Src expression, and MAPK phosphorylation was significantly attenuated in rats receiving losartan, an inhibitor of AT1R. In contrast, losartan treatment had no effect on superoxide anion level, c-Src expression, and MAPK phosphorylation in animals on a normal K diet (NK). K restriction decreased SK channel activity and increased the tyrosine phosphorylation of ROMK. However, inhibiting AT1R abolished the effect of K restriction on SK channels and tyrosine phosphorylation of ROMK channels. The notion that AT1R is involved in regulating renal K excretion was also supported by the experiments with metabolic cages showing that losartan treatment significantly enhanced urinary K loss in rats on a KD diet while it had no effect in animals on a NK diet. Consequently, losartan-treated animals had severe hypokalemia in response to K restriction compared with rats without losartan intake. We conclude that AT1R is involved in mediating the effect of K restriction on superoxide generation, c-Src, and MAPK and that inhibiting AT1R impairs renal ability of K conservation in response to K depletion.
Reaching to Multiple Targets When Standing: The Spatial Organization of Feedforward Postural Adjustments
Authors: Leonard Julia A. , Brown Ryan H. , Stapley Paul J.
Published: February 2009

We examined the spatial organization of feedforward postural adjustments produced prior to and during voluntary arm reaching movements executed while standing. We sought to investigate whether the activity of postural muscles before and during reaching was directionally tuned and whether a strategy of horizontal force constraint could be observed. To this end, eight human subjects executed self-paced reach-to-point movements on the random illumination of one of 13 light targets placed within a 180° array centered along the midline of the body. Analysis was divided into two periods: a first corresponding to the 250 ms preceding the onset of the reaching movements (termed pPA period) and a second 250-ms period immediately preceding target attainment (the aPA period). For both periods, electromyographic activity of the lower limb muscles revealed a clear directional tuning, with groups of muscles being activated for similar directions of reach. Analysis of horizontal ground reaction forces supported the existence of a force constraint strategy only for the pPA period, however, with those in the aPA period being more widely dispersed. We suggest that the strategy adopted for feedforward pPAs is one where the tuned muscle synergies constrain the forces diagonally away from the center of mass (CoM) to move it within the support base. However, the need to control for final finger and body position for each target during the aPA phase resulted in a distribution of vectors across reaching directions. Overall, our results would support the idea that endpoint limb force during postural tasks depends on the use of functional muscle synergies, which are used to displace the CoM or decelerate the body at the end of the reach.
Identification of MCAM/CD146 as the Target Antigen of a Human Monoclonal Antibody that Recognizes Both Epithelioid and Sarcomatoid Types of Mesothelioma
Authors: Bidlingmaier Scott , He Jiang , Wang Yong , An Feng , Feng Jinjin , Barbone Dario , Gao Dongwei , Franc Ben , Broaddus V. Courtney , Liu Bin
Published: February 2009

The prognosis for patients diagnosed with mesothelioma is generally poor, and currently available treatments are usually ineffective. Therapies that specifically target tumor cells hold much promise for the treatment of cancers that are resistant to current approaches. We have previously selected phage antibody display libraries on mesothelioma cell lines to identify a panel of internalizing human single chain (scFv) antibodies that target mesothelioma-associated, clinically represented cell surface antigens and further exploited the internalizing function of these scFvs to specifically deliver lethal doses of liposome-encapsulated small molecule drugs to both epithelioid and sarcomatous subtypes of mesothelioma cells. Here, we report the identification of MCAM/MUC18/CD146 as the surface antigen bound by one of the mesothelioma-targeting scFvs using a novel cloning strategy based on yeast surface human proteome display. Immunohistochemical analysis of mesothelioma tissue microarrays confirmed that MCAM is widely expressed by both epithelioid and sarcomatous types of mesothelioma tumor cells in situ but not by normal mesothelial cells. In addition, quantum dot-labeled anti-MCAM scFv targets primary meosthelioma cells in tumor fragment spheroids cultured ex vivo. As the first step in evaluating the therapeutic potential of MCAM-targeting antibodies, we performed single-photon emission computed tomography studies using the anti-MCAM scFv and found that it recognizes mesothelioma organotypic xenografts in vivo. The combination of phage antibody library selection on tumor cells and rapid target antigen identification by screening the yeast surface-displayed human proteome could be a powerful method for mapping the targetable tumor cell surface epitope space. [Cancer Res 2009;69(4):1570–7]
Protein Kinase Cβ Is an Effective Target for Chemoprevention of Colon Cancer
Authors: Fields Alan P. , Calcagno Shelly R. , Krishna Murli , Rak Sofija , Leitges Michael , Murray Nicole R.
Published: February 2009

Colon cancer develops over a period of 10 to 15 years, providing a window of opportunity for chemoprevention and early intervention. However, few molecular targets for effective colon cancer chemoprevention have been characterized and validated. Protein kinase CβII (PKCβII) plays a requisite role in the initiation of colon carcinogenesis in a preclinical mouse model by promoting proliferation and increased β-catenin accumulation. In this study, we test the hypothesis that PKCβII is an effective target for colon cancer chemoprevention using enzastaurin (LY317615), a PKCβ-selective inhibitor, in a mouse model of colon carcinogenesis. We find that enzastaurin potently reduces azoxymethane-induced colon tumor initiation and progression by inhibiting PKCβII-mediated tumor cell proliferation and β-catenin accumulation. Biochemically, enzastaurin reduces expression of the PKCβII- and β-catenin/T-cell factor–regulated genes PKCβII, cyclooxygenase II, and vascular endothelial growth factor, three genes implicated in colon carcinogenesis. Our results show that enzastaurin is an effective chemopreventive agent in a mouse model of sporadic colon cancer that significantly reduces both tumor initiation and progression by inhibiting expression of proproliferative genes. Thus, PKCβII is an important target for colon cancer chemoprevention and the PKCβ-selective inhibitor enzastaurin may represent an effective chemopreventive agent in patients at high risk for colon cancer. [Cancer Res 2009;69(4):1643–50]
Controversies in the Use of Portal Vein Embolization
Authors: van Gulik Thomas M. , van den Esschert Jacomina W. , de Graaf Wilmar , van Lienden Krijn P. , Busch Olivier R.C. , Heger Michal , van Delden Otto M. , Laméris Johan S. , Gouma Dirk J.
Published: February 2009

Background/Aims: Portal vein embolization (PVE) has reached worldwide acceptance to increase future remnant liver (FRL) volume before undertaking major liver resection. The aim of this overview is to point out and discuss current controversies in the application of PVE. Methods: Review of literature pertaining to techniques of PVE, complications, tumor proliferation, timing of resection, and hypertrophy response after PVE. Results: Procedure-related complications after PVE include hematoma, hemobilia, overflow of embolization material, and thrombosis of portal vein branch(es) of the non-embolized lobe. Persistence of the embolized, atrophic lobe is usually not harmful. Embolization of the portal branches to segment 4 in addition to embolization of the right portal trunk is controversial and is advised only in selected cases. It remains undecided whether embolization of the portal venous system is more effective in inducing hypertrophy of the FRL than ligation of the portal vein. Accelerated tumor growth after PVE is a major concern and requires consideration of post-PVE chemotherapy. A waiting time of 3 weeks between PVE and liver resection is advised. Post-hepatectomy regeneration is not hampered after preoperative PVE. Conclusion: PVE is a useful preoperative intervention to increase volume and function of the FRL. Further progress awaits clarification of the mechanisms of the hypertrophy response induced by PVE in conjunction with new embolization materials and protective chemotherapy.
Radiofrequency Ablation versus Resection for Resectable Colorectal Liver Metastases: Time for a Randomized Trial?
Authors: Mulier Stefaan , Ruers Theo , Jamart Jacques , Michel Luc , Marchal Guy , Ni Yicheng
Published: February 2009

Background: A recent proposal of a randomized trial comparing resection and radiofrequency ablation (RFA) in a selected subgroup of patients with small resectable colorectal liver metastases (CRLM) has initiated a debate on this issue. Meanwhile, new data have been published. The aim of the study was to update and critically review the oncological evidence in favor of and against the use of RFA for resectable CRLM in general and in favor of and against conducting a randomized trial in a selected subgroup of patients. Methods: An exhaustive review was carried out of papers and abstracts on RFA of colorectal metastases published before July 15, 2008. Results: Local recurrence rate after resection of CRLM is 1.2–10.4%. Local recurrence rate after RFA of CRLM is between 1.7 and 66.7%. For tumors <3 cm, local control after open RFA is equivalent to resection. Local recurrence rates, however, are higher for larger tumors and for the percutaneous and laparoscopic route. Accumulating evidence suggests that RFA and resection induce profoundly different biological effects, which may influence survival. Conclusions: Local recurrence rate after open RFA for CRLM <3 cm seems to be equivalent to resection. A randomized trial under strict conditions would be justified in this subgroup of patients. A randomized trial is currently not justified for larger tumors or for percutaneous or laparoscopic RFA, since local recurrence rates in these groups are too high to be acceptable for resectable tumors.
Treatment of Melanoma Metastases Confined to the Liver and Future Perspectives
Authors: Vahrmeijer Alexander L. , van de Velde Cornelis J.H. , Hartgrink Henk H. , Tollenaar Rob A.E.M.
Published: February 2009

The prognosis for patients with liver metastases derived from melanoma is very poor. Although being the gold standard for colorectal metastases, hepatic resection for melanoma lesions is rarely possible. For patients with liver metastases from cutaneous melanoma, the liver is not the only site of disseminated disease in the majority of the cases. Most experience has been obtained in patients with liver metastases from uveal melanoma because in 40% of these patients, the liver is the only site of disease. However, in these patients, resection is frequently not possible due to the number and localization of the metastases. Results from systemic chemotherapy are poor and therefore, in order to increase response rate, regional treatment modalities like hepatic artery infusion, isolated hepatic perfusion and hepatic arterial chemoembolization can be considered. In this review, we will describe the various treatment modalities as well as new developments.
Elevated Serum Lipase Levels in Patients with Dyspepsia of Unknown Cause in General Practice
Authors: Okada Rieko , Okada Akira , Okada Takashi , Okada Tohru , Hamajima Nobuyuki
Published: February 2009

Objective: To study the cause(s) of chronic dyspepsia among patients with no findings on general practice screening tests. Materials and Methods: A total of 272 consecutive patients at a general practice in Japan (125 males and 147 females, aged 14–89 years) who underwent abdominal ultrasound (US) and who had serum pancreatic enzyme (lipase or p-amylase) levels measured, were included in a 1-year study. Serum pancreatic enzyme levels were compared according to the duration of the symptoms and causes of dyspepsia, and then compared between two groups: a ‘known-cause group’ of 38 patients in whom the cause of the chronic (over 1 month) dyspepsia was determined by US or other diagnostic procedures; and an ‘unknown-cause group’ of 112 patients in whom no cause was found. Results: The mean lipase level in the unknown-cause group was significantly higher than that in the known-cause group (40.6 vs. 35.3 U/l, p = 0.008 after adjustment for age, sex, and serum creatinine). No difference between these groups was found for p-amylase. The proportion of patients with high lipase levels (above reference range) was higher in the unknown-cause group compared to the known-cause group, although this was not significant (21.4 vs. 10.5%). Conclusion: Our data showed that serum lipase levels were higher in patients with chronic dyspepsia of unknown than in those with a known cause. We therefore speculate that mild functional pancreatic disorder may underlie some cases with unexplainable chronic dyspepsia.
Bilateral Extensive Emphysematous Pyelonephritis
Authors: Lee Ing-Kit , Hsieh Ching-Jung , Liu Jien-Wei
Published: February 2009

Objective: We report a case involving a patient with bi- lateral emphysematous pyelonephritis (EPN) who was successfully treated with antibiotics and nephrostomy sparing nephrectomy. Case Presentation and Intervention: A 54-year-old diabetic man presented with the chief complaint of progressive abdominal pain for 10 days. Blood tests indicated acute renal failure and hyperglycemic hyperosmolar state. An abdominal radiograph disclosed gas distributed over regions where the bilateral kidneys are located and the right para-lumbosacral area. Computed tomography revealed bilateral enlarged kidneys with the presence of gas in the renal parenchyma and renal pelvis, left peri-renal space, bilateral ureter, bladder, prostate gland and right scrotum. Cultures of urine and blood grew Escherichia coli. The patient was successfully treated with antibiotics coupled with nephrostomy. Conclusion: Timely recognition and initiation of effective antibiotic therapy and nephrostomy may cure the patient with bilateral EPN, while sparing nephrectomy. Regarding clinical manifestations, EPN is nonspecific; hence, radiographs should be taken for diabetic patients with abdominal pain (especially those with poorly controlled blood sugar) to enable early diagnosis of potential EPN.
Evaluation of FITC-Induced Atopic Dermatitis-Like Disease in NC/Nga Mice and BALB/c Mice Using Computer-Assisted Stereological Toolbox, a Computer-Aided Morphometric System
Authors: Hvid Malene , Jensen Helene Kofoed , Deleuran Bent , Kemp Kaare , Andersson Christina , Deleuran Mette , Vestergaard Christian
Published: February 2009

Background: The NC/Nga mouse spontaneously develops eczematous atopic dermatitis (AD)-like skin lesions when maintained under conventional conditions, but not when kept under specific pathogen-free (SPF) conditions. Hence, there is a need for an AD model in mice housed under SPF conditions, as this is mandatory for research animals in many countries. Methods: We evaluated the use of the hapten FITC as an inducer of AD-like disease in NC/Nga and BALB/c mice maintained under SPF conditions. Mice were either untreated or treated with tacrolimus or betamethasone. Using the software Computer Assisted Stereological Toolbox as a stereological method, the mice were sensitized to FITC and the histological efficiency of disease induction with regard to inflammation and CD4+ and CD8+ lymphocytes, in addition to mast cells, was evaluated. The method was validated by comparison to a conventional semiquantitative observer-dependent method. Results: Our findings prove that FITC does indeed induce AD-like lesions in NC/Nga mice with regard to the histological appearance of the mice. However, when evaluating the immunological response in the affected areas of the mice with regard to the CD4/CD8 ratio and the effect of treatment, we found that the immune response in the NC/Nga mice differed from AD skin lesions in humans in certain aspects. Conclusions: These results emphasize the importance of an assessment of not only the histological but also the immunological appearance of the skin when evaluating AD-like disease in mice as a model for AD in humans.
Comparison of Acute Inflammatory and Chronic Structural Asthma-Like Responses between C57BL/6 and BALB/c Mice
Authors: Van Hove Chris L. , Maes Tania , Cataldo Didier D. , Guéders Maud M. , Palmans Els , Joos Guy F. , Tournoy Kurt G.
Published: February 2009

Background: The interactions between airway responsiveness, structural remodelling and inflammation in allergic asthma remain poorly understood. Prolonged challenge with inhaled allergen is necessary to replicate many of the features of airway wall remodelling in mice. In both mice and humans, genetic differences can have a profound influence on allergy, inflammation, airway responsiveness and structural changes. Methods: The aim of this study was to provide a comparative analysis of allergen-induced airway changes in sensitized BALB/c and C57BL/6 mice that were exposed to inhaled allergen for 2 (‘acute’), 6 or 9 weeks (‘chronic’). Inflammation, remodelling and responsiveness were analyzed. Results: Both strains developed a Th-2-driven airway inflammation with allergen-specific IgE, airway eosinophilia and goblet cell hyperplasia upon 2 weeks of allergen inhalation. This was accompanied by a significant increase in airway smooth muscle mass and hyperresponsiveness in BALB/c but not in C57BL/6 mice. However, airway eosinophilia was more pronounced in the C57BL/6 strain. Chronic allergen exposure (6 or 9 weeks) resulted in an increase in airway smooth muscle mass as well as subepithelial collagen and fibronectin deposition in both strains. The emergence of these structural changes paralleled the disappearance of inflammation in both C57BL/6 and BALB/c mice and loss of hyperresponsiveness in the BALB/c strain. TGF-β1 was accordingly elevated in both strains. Conclusion: Airway inflammation, remodelling and hyperresponsiveness are closely intertwined processes. Genetic background influences several aspects of the acute allergic phenotype. Chronic allergen exposure induces a marked airway remodelling that parallels a decreased inflammation, which was largely comparable between the two strains.
Association of Apolipoproteins with Symptoms of Asthma and Atopy among Schoolchildren
Authors: Nagel Gabriele , Weiland Stephan K. , Rapp Kilian , Link Bernhard , Zoellner Iris , Koenig Wolfgang
Published: February 2009

Background: There is evidence for an association between serum cholesterol concentrations and asthma, but little is known about the underlying mechanisms. We explored the associations between serum apolipoprotein concentrations and symptoms of asthma and atopy. Methods: In a population-based cross-sectional study among 10-year-old schoolchildren (n = 462), plasma concentrations of apolipoprotein AI (apoAI) and apolipoprotein B (apoB) were measured. Information on disease symptoms and diagnoses was collected by parental questionnaire. Multivariate logistic regression models were used to analyse the data. Results: High plasma apoAI concentrations (≥1.74 g/l) were associated with high prevalence of wheeze (OR 3.65; 95% CI 1.43–9.33), and a trend was seen with asthma (OR 3.35; 95% CI 0.94–11.93). In linear analyses, plasma apoAI concentrations were positively related to wheeze (β-coefficient = 3.20; p = 0.045) and non-atopic wheeze (β-coefficient = 4.47; p = 0.036), and a trend was found for asthma (β-coefficient = 3.29; p = 0.099). Overall, plasma apoB concentrations were not associated with either symptoms of asthma or allergy. Conclusion: Our results support the hypothesis that high apoAI is associated with the manifestation of asthma and atopy. The underlying pathomechanism still remains to be fully elucidated, but suggests that immune mechanisms may play a central role. However, our results are based on a small study sample and larger studies are warranted to confirm these observations.
Item Reduction of the Voice Handicap Index Based on the Original Version and on European Translations
Authors: Nawka T. , Verdonck-de Leeuw I.M. , De Bodt M. , Guimaraes I. , Holmberg E.B. , Rosen C.A. , Schindler A. , Woisard V. , Whurr R. , Konerding U.
Published: February 2009

Objective: Constructing an internationally applicable short-scale of the Voice Handicap Index (VHI). Methods: Subjects were 1,052 patients with 5 different types of voice disorder groups from Belgium, France, Sweden, Germany, Italy, The Netherlands, Portugal, and the USA. Different 9- and 12-item subsets were selected from the 30 VHI items using (1) the first factor of an unrotated factor analysis (narrow range subsets) and (2) the first three factors after promax rotation (broad range subsets). Country-specific subsets were selected to test deviations from the international subsets. For all subsets, reliability was investigated using Cronbach’s alphas and correlations with the total VHI. Validity was investigated using regression on voice disorder groups. All analyses were performed for the total and for all country-specific subject samples. Results: Reliability was high for all item subsets. It was lower for the international compared to the country-specific subsets and for the broad range compared to the narrow range subsets. Validity was best for the broad range subsets. Validity was better for the international than for the country-specific subsets. For all statistics the 12-item subsets were not essentially better than the 9-item subsets. Conclusion: The international broad range 9-item subset forms a scale which approximates well the total VHI.
Home Range Estimates Vary with Sample Size and Methods
Authors: Boyle Sarah A. , Lourenço Waldete C. , da Silva Lívia R. , Smith Andrew T.
Published: February 2009

Accurate estimates of a primate’s home range are important, yet methods vary greatly. This paper examines the accuracy of minimum convex polygon (MCP), adaptive kernel (AK) and fixed kernel (FK) estimators by comparing home range estimates of northern bearded saki monkeys (Chiropotes satanas chiropotes) living in forest fragments and continuous forest in the Brazilian Amazon area. MCP was more accurate than AK and FK in calculating home and day range when sample size was small, and AK overestimated range most frequently. It is important to consider the various home range methods, as the appropriate method may depend on sample size and the species’ behavioral ecology.
Effects of Oral Epigallocatechin Gallate Supplementation on the Minimal Erythema Dose and UV-Induced Skin Damage
Authors: Jeon H.Y. , Kim J.K. , Kim W.G. , Lee S.J.
Published: February 2009

Background/Aims: Excessive exposure to UV radiation causes acute adverse effects like sunburn and photosensitivity reactions and is involved in the induction and development of skin cancer. It has been reported that antioxidants have photoprotective effects against solar UV radiation. We investigated the effect of oral epigallocatechin gallate (EGCG), a powerful antioxidant in green tea, on the minimal erythema dose (MED) and UV-induced skin damage. Method: Female HWY/Slc hairless rats were fed the normal diet supplemented with 1,500 ppm EGCG for 8 weeks; then, the MED was determined and visual scores and transepidermal water loss were assessed to evaluate the severity of UV-induced skin damage. Results: At week 8 of the study, the use of dietary EGCG significantly increased MED. UV-radiation-induced sunburn severity and alterations in epidermal barrier function were also attenuated by the supplementation of EGCG. Conclusion: Regular intake of EGCG strengthens the skin’s tolerance by increasing MED and thus prevents UV-induced perturbation of epidermal barrier function and skin damage. These results suggest that EGCG is a potent candidate for systemic photoprotection.
Association of Infectious Mononucleosis with Multiple Sclerosis
Authors: Ramagopalan Sreeram V. , Valdar William , Dyment David A. , DeLuca Gabriele C. , Yee Irene M. , Giovannoni Gavin , Ebers George C. , Sadovnick A. Dessa
Published: February 2009

Background: Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, we investigate the relationship between prior clinical infection or vaccination and the risk of MS. Methods: Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls. Results: Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p < 0.001, corrected odds ratio 2.06, 95% confidence interval 1.71–2.48). Females were more aware of disease history than males (p < 0.001). Conclusions: The data further confirms a reporting distortion between males and females. Historically reported measles, mumps, rubella, varicella and vaccination for hepatitis B, influenza, measles, mumps and rubella are not associated with increased risk of MS later in life. A clinical history of infectious mononucleosis is conspicuously associated with increased MS susceptibility. These findings support studies implicating Epstein-Barr virus in MS disease susceptibility, but a co-association between MS susceptibility and clinically apparent infectious mononucleosis cannot be excluded.
Novel Cell Lines Derived by Long-Term Culture of Primary Uveal Melanomas
Authors: Nareyeck Gordon , Zeschnigk Michael , Bornfeld Norbert , Anastassiou Gerasimos
Published: February 2009

Aims: Uveal melanomas with or without monosomy 3 have different metastatic potentials. Therefore, it would be of great experimental importance to obtain cell lines of both groups – established and characterized under the same conditions. Methods: Long-term culture of biopsies derived from untreated primary uveal melanomas was performed, and the status of chromosome 3 in the tumour was determined. Characterization by immunocytochemistry and in vitro assays for cell migration, vasculogenic cord formation and proliferation were performed. Results: Establishment of cell lines succeeded in 6 out of 128 uveal melanomas. No histopathological feature was predictive for cultivation success. Two out of 4 cell lines derived from tumours with monosomy 3 were invasive in vitro. Both cell lines with disomy 3 showed higher proliferation levels (p = 0.002). Conclusions: The in vitro tendency for invasion did not correlate with the proliferative behaviour of uveal melanoma cell lines, but was partly associated with monosomy of chromosome 3.
The p53 Codon 72 Exon 4 BstUI Polymorphism and Endometrial Cancer in Caucasian Women
Authors: Zubor Pavol , Stanclova Andrea , Kajo Karol , Hatok Jozef , Klobusiakova Dasa , Visnovsky Jozef , Danko Jan
Published: February 2009

Objectives: Studies on the association between the p53 Arg72Pro polymorphism and endometrial cancer have reported contrasting conclusions. With the exception of Asian subjects, data demonstrating the influence of this polymorphism on endometrial carcinogenesis in other races/ethnic groups, including Caucasians, are scarce. Thus, we aimed to investigate its role in the development of endometrial cancer and its association with prognostic markers. Methods: A case-control study examining the p53 codon 72 polymorphism in a total of 451 samples (121 cancer patients, 330 healthy controls) using polymerase chain reaction and sequencing techniques was conducted. Genotypes were correlated with clinico-pathological factors and age. Logistic regression analyses were used to adjust for possible confounding variables, and data were evaluated using the Pearson χ2 test. Results: We found the Pro allele and genotype frequency to be insignificantly higher in cases than controls (Pro allele: 24.8 and 22.3%, respectively; genotypes: Arg/Pro 36.36 and 34.24%, Pro/Pro 6.61 and 5.15%, respectively). Logistic regression analysis revealed an increased risk for disease in carriers of the Pro allele, with an odds ratio (OR) of 1.13 [95% confidence interval (CI) 0.73–1.76] for heterozygotes and an OR of 1.36 (95% CI 0.56–3.30) for homozygotes. Furthermore, we noted a trend for Arg/Pro + Pro/Pro towards poor tumour differentiation, angioinvasion, pelvic lymph node spread and type II carcinomas, with ORs of 1.27 (95% CI 0.60–2.66), 1.24 (95% CI 0.67–2.30), 1.21 (95% CI 0.53–2.75) and 1.69 (95% CI 0.70–4.10), respectively. Additionally, the Pro genotype was associated with a lower risk for cancer in women with early menarche (OR 1.17, 95% CI 0.60–2.28) and late menopause (OR 0.70, 95% CI 0.30–1.63). Despite the increased or decreased risk observed for some variables, none of these trends were significant. Conclusions: Our data did not demonstrate any significant difference in the prevalence of the p53 Arg72Pro genotype between patients and controls, providing evidence that this polymorphism is only weakly associated with the risk of endometrial cancer and prognostic factors in Caucasian women.
Fluoride Retention in Proximal Plaque and Saliva Using Two NaF Dentifrices Containing 5,000 and 1,450 ppm F with and without Water Rinsing
Authors: Nordström A. , Birkhed D.
Published: February 2009

A total of 26 healthy volunteers participated in this randomized 4-leg crossover study designed to measure fluoride (F) retention in interdental plaque and saliva. Two NaF dentifrices (5,000 and 1,450 ppm F) were used, with and without postbrushing water rinsing. The 4 tooth brushing methods were carried out twice a day during 2 weeks. Interdental plaque was collected from all proximal sites after each method, using dental floss. Immediately after the plaque sampling, the subjects were asked to brush their teeth with the same toothpaste and use the postbrushing water rinsing procedure as previously. Proximal saliva was collected from 4 interdental sites, using small paper points, before and up to 60 min after the brushing. The present study showed that the 5,000 ppm F toothpaste without postbrushing water rinsing resulted in the highest F concentration in both plaque and saliva and the 1,450 ppm F toothpaste with water rinsing in the lowest. The difference in the area under the curve of saliva F concentration versus time between the 2 methods was 4.2 times (p < 0.001). The corresponding difference in F concentration per unit weight of plaque (n = 16) was 2.75 times (p < 0.05). Water rinsing immediately after tooth brushing with 5,000 ppm reduced the F concentration in saliva by 2.4 times (p < 0.001). The difference in F values in saliva between 5,000/rinsing and 1,450/no rinsing was minor and not significant. The increase of F in both proximal saliva and plaque, using a dentifrice with 5,000 ppm F without postbrushing water rinsing, may be of clinical importance.
Craving-Induced EEG Reactivity in Smokers: Effects of Mood Induction, Nicotine Dependence and Gender
Authors: Knott Verner J. , Naccache Luma , Cyr Emmanuelle , Fisher Derek J. , McIntosh Judy F. , Millar Anne M. , Villeneuve Crystal M.
Published: February 2009

Background/Aims: Cigarette craving is a core symptom of smoking withdrawal, which is more intense and more frequently observed in smokers with depressed mood. Using self-reports and electroencephalographic (EEG) indices of frontal hemispheric asymmetry, which has been shown to be sensitive to mood states, the purpose of this study was to investigate the neural basis of cue-elicited cigarette craving, its variation with experimentally induced depressed mood, and with differences in gender and smoker type. Methods: Cigarette-cue reactivity was examined in 11 (5 male) regular and 11 (6 male) light smokers in two sessions involving the induction of neutral or depressed mood. Results: Frontal EEG alpha asymmetry changes reflecting left frontal hypoactivation were evident with cigarette-cue exposure, particularly in female smokers. During cigarette-cue exposure, EEG evidenced both decreases and increases in brain state activation, with the latter activational increments also being influenced by depressed mood. Exposure to the cigarette cue, in addition to increasing withdrawal symptoms, increased cravings and negative affect, these latter effects being more evident in female and regular smokers. Conclusion: These findings, which appear to provide a physiological basis for ‘withdrawal-like’ negative affective experiences during craving, are discussed in relation to theories of drug reinforcement and smoking motivation.
Hyperreninemia Characterizing Women with Polycystic Ovary Syndrome Improves after Metformin Therapy
Authors: Diamanti-Kandarakis Evanthia , Economou Frangiskos N. , Livadas Sarantis , Tantalaki Evangelia , Piperi Christina , Papavassiliou Athanasios G. , Panidis Dimitrios
Published: February 2009

Background: Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation, hyperandrogenemia and insulin resistance. Hyperreninemia is observed in insulin resistance and hyperandrogenemic states. Aims: To investigate the levels of total plasma renin and their possible relationship with insulin resistance and hyperandrogenemia and to explore the effect of metformin on these parameters in PCOS women. Methods: 48 PCOS women who were age- and body mass index (BMI)-matched with 21 healthy women were studied. Total renin, aldosterone levels, glucose and insulin levels were measured at basal state and during an oral glucose tolerance test in all subjects. A subgroup of women with PCOS was evaluated 6 months after metformin administration. Results: Total renin levels were significantly higher in PCOS women compared to controls. PCOS women compared to controls displayed higher areas under the curve for glucose, insulin and total renin (AUCREN). Mean AUCREN was correlated significantly with insulin resistance indices and positively with free testosterone levels. Total renin, aldosterone, androgen levels and insulin sensitivity indices were significantly improved after 6 months on metformin treatment. Conclusions: PCOS women demonstrated an insulin resistance and hyperandogenemia-related increase in serum total renin levels. Metformin treatment was shown to significantly reduce total renin levels.
Spontaneous Tendon Ruptures in Patients with End-Stage Renal Disease
Authors: Basic-Jukic Nikolina , Juric Ivana , Racki Sanjin , Kes Petar
Published: February 2009

Spontaneous tendon ruptures in patients with end-stage renal disease (ESRD) have been occasionally reported. We describe the largest group of patients with spontaneous rupture of major tendons so far reported. Rupture of 16 tendons occurred in 9 patients. The mean patient age was 52.78 years; 77.7% were male. Four patients were treated with hemodialysis, 4 received a renal transplant and 1 was treated with automated peritoneal dialysis. Bilateral rupture was found in 5 patients (3 quadriceps, 1 Achilles and 1 supraspinatus and subscapularis tendon rupture). Distal brachial biceps tendon rupture, Achilles tendon rupture, unilateral quadriceps and rupture of the oblique internal abdominal muscle tendon were developed by 1 patient each. Patients were treated with renal replacement therapy for 3–21 years (mean 12.89). Five patients were treated with steroids and 6 patients received quinolone antibiotic before the tendon rupture. All patients had laboratory and clinical signs of hyperparathyroidism. A patient who was treated with automated peritoneal dialysis for 3 years had primary hyperparathyroidism with nephrolithiasis as the cause of ESRD. Our results demonstrated that patients with hyperparathyroidism are at increased risk for development of spontaneous tendon ruptures, and the risk is further amplified when they receive quinolone antibiotics and/or steroids.
Combination of Bisphosphonates and Antiangiogenic Factors Induces Osteonecrosis of the Jaw More Frequently than Bisphosphonates Alone
Authors: Christodoulou C. , Pervena A. , Klouvas G. , Galani E. , Falagas M.E. , Tsakalos G. , Visvikis A. , Nikolakopoulou A. , Acholos V. , Karapanagiotidis G. , Batziou E. , Skarlos D.V.
Published: February 2009

Background: The use of bisphosphonates is associated with osteonecrosis of the jaw (ONJ). Antiangiogenic agents are used with increasing frequency and may induce the risk of ONJ, especially when administered concurrently with bisphosphonates. Patients and Methods: We retrospectively reviewed data of 116 patients receiving bisphosphonates, 78 zoledronic acid and 38 ibandronic acid, with or without antiangiogenic agents for osseous metastases from various tumors in our department from June 2007 to June 2008. Results: ONJ developed in: 2 patients with breast cancer and 1 with colon cancer receiving concurrently bisphosphonates and bevacizumab, 1 patient with renal cell carcinoma receiving sunitinib and zoledronic acid concurrently, and 1 patient with prostate cancer receiving zoledronic acid without antiangiogenic agents. The incidences of ONJ among patients receiving bisphosphonates with or without antiangiogenic agents were 16 and 1.1%, respectively. The difference was statistically significant (p = 0.008). The treatment duration of bisphosphonates did not differ significantly between the 2 groups. Conclusions: The combination of bisphosphonates and antiangiogenic factors induces ONJ more frequently than bisphosphonates alone. These preliminary observations should be evaluated in large cohorts of patients and in prospective studies.
Reliability and Validity of the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire
Authors: Fava Maurizio , Iosifescu Dan V. , Pedrelli Paola , Baer Lee
Published: February 2009

Background: We have recently developed the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), a brief scale to measure cognitive and executive dysfunction in mood and anxiety disorders, and we here report on its reliability and validity. Methods: The internal consistency of the CPFQ was assessed by computing Cronbach’s coefficient α based upon the average intercorrelation of the 7 items of the CPFQ in a sample of depressed outpatients and by factor analyzing data from the same sample to confirm that the scale is unifactorial and measuring a single construct. Test-retest reliability of the CPFQ was assessed in a different sample of depressed outpatients by computing Pearson’s correlation coefficient between pretreatment screening scores and pretreatment baseline scores. Sensitivity to change of the CPFQ was assessed by computing the dependent t test for the subjects in the active treatment condition in the second sample of depressed outpatients. Finally, convergent validity for the CPFQ was assessed in two different ways. Results: We found that the CPFQ is a unifactorial scale, with strong internal consistency. It has good temporal stability as indicated by high test-retest reliability. The CPFQ was also found to be sensitive to change with treatment and displayed convergent validity by significant correlations with other measures of sleepiness, fatigue, apathy and neuropsychological functioning. Although, as expected, the CPFQ was significantly correlated with a measure of depression, the moderate correlation (r ∼ 0.30) indicates that the CPFQ is measuring a different construct. Conclusion: In summary, the CPFQ is a unifactorial scale, with strong internal consistency, good temporal stability and sensitivity to change with treatment. Further studies will be needed to assess the validity and reliability of this instrument in other psychiatric and neuropsychiatric conditions associated with cognitive dysfunction.