bluuebunny/crossref_metadata_2025 huggingface dataset:
Ouabain-Induced Vacuolar Formation in Marginal Cells in the Stria Vascularis Is Dependent on Perilymphatic Na+
Authors: Higashiyama Kasumi , Takeuchi Shunji , Azuma Hiroshi , Sawada Shoichi , Kakigi Akinobu , Takeda Taizo
Published: March 2010

In the stria vascularis (SV), it is known that the Na+-K+-ATPase is expressed abundantly and its activity in the basolateral membrane of marginal cells is high. Ouabain, an inhibitor of the Na+-K+-ATPase, causes not only a decline in the endocochlear DC potential but also acute vacuolar formation in marginal cells. We studied the ionic mechanisms underlying the ouabain-induced vacuolar formation in marginal cells using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with 1 mM ouabain dissolved in the artificial perilymph for 50 min caused many vacuoles of a wide range of sizes in the apical cytoplasm of marginal cells, the bulging of marginal cells into the scala media and strial volume increase. Removal of K+ from the perilymph reduced the proportion of vacuoles and strial thickening, but the bulging of marginal cells remained. In contrast, the sizes of vacuoles were drastically reduced and extrusion of marginal cells into the scala media could not be observed in the absence of perilymphatic Na+. Furthermore, the total volume of SV was obviously reduced in comparison with the control. These results indicate that perilymphatic Na+ and K+ are responsible for these morphological changes caused by ouabain, and that perilymphatic Na+ plays an important role in the cellular volume regulation in SV in the presence of ouabain. It is supposed that the transport system of perilymphatic Na+ and K+ into marginal cells may contribute to vacuolar formation when ouabain is administered. Regarding Na+, we hypothesize two possibilities for the perilymphatic Na+ transporting pathway as follows. Na+ in the perilymph could enter the endolymph via Reissner’s membrane or the basilar membrane; Na+ in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na+-K+-ATPase in the basolateral membrane. Another, less likely, possibility is that Na+ in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na+-K+-ATPase of intermediate cells. Regarding K+, it is expected that the K+ recycling pathway plays a role in ouabain-induced vacuolar formation in marginal cells.
Time Course of Vestibular Function Changes of Experimental Endolymphatic Hydrops in Guinea Pigs
Authors: Kakigi Akinobu , Taguchi Daizo , Takeda Taizo , Takeda Setsuko , Nakatani Hiroaki
Published: March 2010

Objective: To investigate the relationship between endolymphatic hydrops and vestibular dysfunction. Methods: 20 pigmented guinea pigs were used: 15 for a hydrops group and 5 for a sham group. Endolymphatic hydrops was produced by electrocauterization of the endolymphatic sac on the left ears. In the horizontal vestibuloocular reflex (HVOR) study, HVOR responses were recorded before and 1, 2, and 4 weeks after surgery in 9 animals of the hydrops group and 5 animals of the sham group. HVOR gain under sinusoidal rotation with a maximal head velocity of 45°/s and frequencies of 0.05, 0.1, 0.2, 0.4 and 0.8 Hz was analyzed. In the nystagmus study, spontaneous nystagmus was recorded in all animals of the hydrops and the sham groups for 1 h in the dark and the maximum slow-phase velocity was measured before and 1, 2, 4 weeks after surgery. Morphological changes in the inner ear were measured light microscopically. Results: In the hydrops group, the HVOR gains at all stimulation frequencies seemed to decrease 1 week after surgery and recover 2 or 4 weeks after surgery; however, there were no statistical differences among HVOR gains in any periods after surgery. The incidence of spontaneous nystagmus gradually increased after surgery and the direction and onset showed large variation. The duration of nystagmus was approximately 10 min. The degree of endolymphatic hydrops showed large variation. In the sham group, HVOR gains at all stimulation frequencies showed no statistically different change in any period after surgery. In the sham group, no animal showed spontaneous nystagmus. Conclusion: Experimentally induced endolymphatic hydrops seems to contribute to vestibular dysfunction to some extent. We speculated that when endolymphatic hydrops is progressing, vestibular dysfunction might occur.
Low Dosage of Rasagiline and Epigallocatechin Gallate Synergistically Restored the Nigrostriatal Axis in MPTP-Induced Parkinsonism
Authors: Reznichenko Lydia , Kalfon Limor , Amit Tamar , Youdim Moussa B.H. , Mandel Silvia A.
Published: March 2010

Background: The anti-Parkinson monoamine oxidase B inhibitor rasagiline appears to be the first neuroprotective disease-modifying therapy in early-stage Parkinson’s disease (PD). Objective: Using a polypharmacy paradigm, we tested whether the distinct neuroprotective pharmacological profile of rasagiline would complement that of (–)-epigallocatechin-3-gallate (EGCG), the main antioxidant/iron chelator polyphenol constituent of green tea, and restore the neuronal loss and molecular targets damaged in animal parkinsonism. Methods/Results: We show by high-performance liquid chromatography, immunohistochemistry and Western blot analyses that the combination of rasagiline and EGCG, at subliminal doses which have no profound protective effect, acts synergistically to restore the nigrostriatal axis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. A detailed analysis revealed a complementary action of these drugs, differentially acting at MPTP-injured molecules/targets in the substantia nigra (SN): induction of brain-derived neurotrophic factor by rasagiline, increased membranal levels of the protein kinase C α-isoform by EGCG and a synergistic replenishment of their downstream effector, the serine/threonine kinase Akt/protein kinase B, suggesting that this kinase might represent one point of convergence of the distinct mechanisms of action of the drug cocktail. Conclusion: These results provide molecular evidence that activation of multiple brain targets by the combination of rasagiline and EGCG may synergistically contribute to the rescue of the dopamine neurons in the SN and replenishment of striatal dopamine. This may have important implications for rasagiline-treated PD patients who could further benefit from an adjunct administration of EGCG.
Improved Synthesis of ADAM10 Inhibitor GI254023X
Authors: Hoettecke Nicole , Ludwig Andreas , Foro Sabine , Schmidt Boris
Published: March 2010

Background: The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation. Objective: The inhibition of these proteases is a promising target in the treatment of inflammation and cancer. Methods and Results: In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling. Conclusion: This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations.
Evaluation of Transforming Growth Factor-β Signaling Pathway in the Wall of Normal and Varicose Veins
Authors: Kowalewski Radoslaw , Malkowski Andrzej , Sobolewski Krzysztof , Gacko Marek
Published: March 2010

Objective(s): Extracellular matrix remodeling in the vein wall is involved in varicose vein pathogenesis, with transforming growth factor β1 (TGF-β1) playing a potential role. The aim of the study was to assess the TGF-β signaling pathway including its receptor (TGF-β RII) and phosphorylated receptor-regulated Smads (p-Smad2/3) in varicose veins. Methods: Varicose veins from patients undergoing varicose vein surgery were the studied material, whereas normal greater saphenous veins from patients undergoing infrainguinal arterial bypass surgery were the control material. Expression of TGF-β RII mRNA was assessed with RT-PCR, whereas expression of TGF-β RII and p-Smad2/3 proteins was assessed with Western blot. Results: A significantly increased TGF-β RII mRNA level was found in varicose veins (287 ± 24%), when compared with normal veins (100 ± 26%). The receptor protein expression reflected a changed mRNA level with significantly increased TGF-β RII protein in varicose veins (290 ± 21%), when compared with controls (100 ± 16%). Enhanced TGF-β RII expression was accompanied by increased p-Smad2/3 protein expression in varicose veins (257 ± 19%) in comparison with normal veins (100 ± 9%). Conclusion(s): Increased TGF-β RII expression and activation in the wall of varicose veins may be involved in extracellular matrix remodeling related to TGF-β1 and supports its role in the disease pathogenesis.
HMGB1 Attenuates Anti-Metastatic Defense of the Lymph Nodes in Colorectal Cancer
Authors: Moriwaka Yukiko , Luo Yi , Ohmori Hitoshi , Fujii Kiyomu , Tatsumoto Naokuni , Sasahira Tomonori , Kuniyasu Hiroki
Published: March 2010

Background: Cancer-secreted high mobility group 1 (HMGB1) induces apoptosis of macrophages and suppresses the host anti-cancer immune system. Objective: We here examined the effect of HMGB1 on macrophages in the lymph nodes of colorectal cancer (CRC) patients. Methods: Regional lymph nodes of 50 Dukes C CRCs were compared with 50 Dukes B CRCs. Results: Dukes C tumors exhibited higher HMGB1 labeling indices and higher HMGB1 concentrations in primary tumors than Dukes B CRCs. Macrophages in the regional lymph nodes were decreased in non-metastasized nodes as well as metastasized nodes in Dukes C cases, whereas macrophage numbers in Dukes B nodes were higher than in Dukes C nodes. Nodal HMGB1 concentration was higher in Dukes C nodes than in Dukes B nodes, being inversely correlated with macrophage numbers. Nodal HMGB1 concentration was correlated with HMGB1 concentration and lymph vessel density in the primary tumors. Conclusion: These data suggest that HMGB1 secreted from primary tumors spread to the regional lymph nodes decreases the number of macrophages to attenuate the anti-metastatic defense of the lymph nodes in patients with CRCs.
TDP43-Positive Intraneuronal Inclusions in a Patient with Motor Neuron Disease and Parkinson’s Disease
Authors: Chanson Jean-Baptiste , Echaniz-Laguna Andoni , Vogel Thomas , Mohr Michel , Benoilid Aurélien , Kaltenbach Georges , Kiesmann Michèle
Published: March 2010

Background: The role of the 43-kDa transactivation-responsive DNA-binding protein (TDP43) in neurodegenerative diseases is not yet clearly established. Objective: To assess for the first time the presence of TDP43 in a patient with motor neuron disease (MND) and Parkinson’s disease (PD). Methods: A 78-year-old woman developed poorly dopa-responsive parkinsonism without cognitive alteration. Three years later, MND appeared and led to death in less than a year. Neuropathologic examination was performed. Results: We observed the presence of PD and MND lesions with TDP43-positive cytoplasmic inclusions in the spinal cord and bulbar nuclei but not in the dentate gyrus and neocortex. The MND was characterized by a severe degeneration of bulbar and cervical lower motor neurons. Numerous senile plaques and topographically limited neurofibrillary tangles were also observed. Conclusion: The mechanisms underlying the rare co-occurrence of PD and MND are still unclear. The assessment of an abnormal reactivity for TDP43 in our case might gain more insight into the pathophysiology of this association of two diseases. Further studies are needed to confirm these findings and to understand the role of TDP43 in neurodegenerative diseases.
Anatomical Detection of Inflammatory Changes Associated with Plantar Warts by Ultrasound
Authors: Wortsman Ximena , Jemec Gregor B.E. , Sazunic Ivo
Published: March 2010

Background: Plantar warts are common and pain is one of the main symptoms. The anatomical alterations associated with the primary lesion are unclear. Moreover, an adequate separation between the lesion and the surrounding tissue abnormalities could help to better manage this pathology and enable the provision of comprehensive information to physicians and patients. Methods: A color Doppler ultrasound examination was performed on 29 recurrent plantar warts and 10 healthy controls. The morphology and extension of the warts and surrounding soft tissue abnormalities are described. The diagnosis of a plantar wart was correlated with a standard histology in all cases. Statistical analysis was performed by the Student t test. Results: On ultrasound, all warts were recognizable, and sonographic signs of soft tissue inflammation were detected that were associated with the warts: in 79% (23/29) of the cases there was an increase in sublesional arterial blood flow in the dermis, 54% (16/29) had a plantar bursitis, and 52% (15/29) had a focal decrease in subcutaneous echogenicity. No signs of inflammation were seen in the unaffected controls. Conclusion: Ultrasound can provide detailed anatomical data on warts and their inflammatory changes in the surrounding tissues. This noninvasive imaging technique may help to manage difficult cases.
Cutaneous Sarcoidosis Occurring during Anti-TNF-Alpha Treatment: Report of Two Cases
Authors: Dhaille F. , Viseux V. , Caudron A. , Dadban A. , Tribout C. , Boumier P. , Clabaut A. , Lok C.
Published: March 2010

We report two cases of cutaneous granuloma induced by anti-TNF-α therapy: a 47-year-old man suffering from psoriatic arthritis treated with infliximab and a 56-year-old woman treated with adalimumab for polyarticular juvenile rheumatoid arthritis. The biospies confirmed the diagnosis of a ‘sarcoidosis-like’ reaction. No systemic involvement was observed. Such cases of noninfectious granulomatous diseases occurring during anti-TNF-α therapy are becoming increasingly frequent.
Regional Body Composition of Indian Women from a Low-Income Group and Its Association with Anthropometric Indices and Reproductive Events
Authors: Kulkarni Bharati , Shatrugna Veena , Nagalla Balakrishna , Rani K. Usha
Published: March 2010

Background and Aims: The study examined the body composition of women from an urban slum who have a low prevalence of obesity. Since the quantification of regional fat distribution is important for evaluating health risks, the regional body composition was assessed in relation to anthropometric indices and reproductive events. Methods: The body composition of 278 women was assessed using dual energy X-ray absorptiometry. Results: Their mean age, height, body mass index, percentage of whole body fat and trunk fat mass to leg fat mass ratio (an indicator of android obesity) were 40.8 years, 149 cm, 22, 33 and 1.22, respectively. Receiver-operating characteristic analyses indicated that a body mass index of 20 and 22 corresponded to a percentage of whole body fat of 30 and 35, respectively. Higher weight was associated with increased android fat distribution and taller height was associated with higher lean body mass and gynoid fat distribution. Multiple linear regression analyses indicated that menopausal status was associated with lower lean mass and higher android obesity whereas breast-feeding was related to lower leg fat mass. Heavy occupational work was associated with higher lean mass. Conclusion: The study women had a ‘high fat muscle poor’ phenotype. The association of regional body composition with anthropometric indices and reproductive events provided important insights.
Hydrogen Breath Test – Diet and Basal H2 Excretion: A Technical Note
Authors: Avallone E.V. , De Carolis A. , Loizos P. , Corrado C. , Vernia P.
Published: March 2010

Background: Hydrogen breath tests are widely used in clinical practice. For a correct evaluation of data, low basal H2 excretion is required, thus, 12-hour fasting is usually prescribed. An additional reduction in the intake of complex carbohydrates in the preceding 24 h is suggested in some centers. The issue, however, has never been directly investigated. Aim: The aim of the present study was to analyze the effect of the pretest diet on the basal H2 excretion and the number of subjects excluded from the test due to high basal H2 excretion. Methods: Two cohorts of 500 consecutive patients undergoing a lactose tolerance test in the years 1997–1998 (when 12-hour fasting was required) and in 2007–2008 (when a low-carbohydrate diet in the preceding 24 h was also prescribed) were retrospectively reviewed. Results: The mean basal H2 excretion was significantly lower (p < 0.0001) in the low-carbohydrate diet group (2.46 ± 6.8 vs. 4.73 ± 3.3 ppm). In 1997–1998, 46/500 patients (9.2%) were excluded from the test due to basal H2 values as compared to 7/500 (1.4%) in the period 2007–2008. Discussion: To the best of our knowledge, ours is the first study to provide objective data on the advantage offered by reducing the intake of complex carbohydrates before H2 breath tests.
Effects of TGF-β on Podocyte Growth and Disease Progression in Proliferative Podocytopathies
Authors: Lee Hyun Soon , Song Chi Young
Published: March 2010

Injured podocytes proliferate in cellular focal segmental glomerulosclerosis (FSGS), collapsing FSGS and crescentic glomerulonephritis, where TGF-β1 is overexpressed in hyperplastic podocytes. Yet effects of podocyte TGF-β on podocyte growth and development of glomerulosclerosis have not been clearly defined. TGF-β activates Smads, Ras/extracellular signal-regulated kinase (ERK) and phosphatidyl inositol-3-kinase (PI3K) pathways in podocytes, of which the major TGF-β/Smad signaling pathway appears to override the minor TGF-β-induced Ras/ERK/PI3K pathways. We provide evidence that increasedTGF-β/Smad signaling activity by hyperplastic podocytes may lead to mesangial cell matrix overproduction and eventually to podocyte apoptosis and/or detachment, culminating in the development of glomerulosclerosis. In this regard, TGF-β, which is overexpressed by hyperplastic podocytes, may play an important role for the cellular and collapsing variants of FSGS to evolve into the classic FSGS pattern. In contrast, podocyte proliferation that is induced by Ras/ERK signaling activity in proliferative podocyte diseases seems to be mostly independent of TGF-β1 activity. Collectively, these data bring new insights into our understanding of the overexpression of TGF-β in hyperplastic podocytes in progressive glomerular diseases.
Biomechanics of Resistance Artery Wall Remodeling in Angiotensin-II Hypertension and Subsequent Recovery
Authors: Nádasy György L. , Várbíró Szabolcs , Szekeres Mária , Kocsis Adrienn , Székács Béla , Monos Emil , Kollai Márk
Published: March 2010

Background/Aims: To identify the relationship between systemic and local hemodynamics, as well as segmental biomechanical properties in a musculocutaneous resistance artery during angiotensin-II hypertension and its recovery. Methods: Rats were infused with angiotensin-II using implanted osmotic minipumps (ALZET 2ML4, 150 ng/kg/min) for 4 weeks. Measurements were made either immediately following infusion or after an additional 4-week recovery period. Parallel controls were created. Segmental geometry and blood flow were determined in vivo on microsurgically exposed segments of the saphenous arterial branch (350 µm). Pressure-radius plots of excised cylindrical segments were recorded by pressure arteriography. Results: Eutrophic hypertensive wall remodeling developed, with reduced passive radius, increased wall thickness, elevated low-stress elastic modulus, reduced norepinephrine contraction, and reduced endothelium-mediated dilation. Relaxed wall geometry fully healed in 4 weeks of recovery, but an increased contractility and a reduced in vivo lumen persisted. Regional hemodynamic resistance correlated positively with systemic arterial pressure and wall thickness in vivo, and negatively with in vivo lumen size throughout these studies. Conclusion: A partial recovery of the biomechanical parameters was found. Healing of eutrophic hypertensive remodeling of the resistance artery wall is a complex biomechanical process, not a simple reversal of the original pathological sequel.
Psoriasis Associated with Hepatitis C but Not with Hepatitis B
Authors: Cohen Arnon D. , Weitzman Dahlia , Birkenfeld Shlomo , Dreiher Jacob
Published: March 2010

Purpose: To investigate the association between psoriasis and viral hepatitis. Methods: Psoriasis patients were compared to controls regarding the prevalence of viral hepatitis in a case-control study using logistic multivariate models. The study was performed utilizing the medical database of Clalit Health Services. Results: The study included 12,502 psoriasis patients >20 years old and 24,287 age- and sex-matched controls. The prevalence of hepatitis C in patients with psoriasis was increased compared to the prevalence in controls (1.03 vs. 0.56%; p < 0.001). In a multivariate analysis, psoriasis was associated with hepatitis C. An interaction with smoking was noted (smokers: odds ratio, OR = 1.93, 95% confidence interval, CI = 1.30–2.67; nonsmokers: OR = 2.22, 95% CI = 1.63–3.04). The prevalence of hepatitis B in patients with psoriasis was higher than in the controls (0.74 vs. 0.56%; p = 0.043). However, in a multivariate analysis psoriasis was not associated with hepatitis B (OR = 1.22, 95% CI = 0.93–1.60, p = 0.15). Conclusion: Our observation supports previous reports of an association between psoriasis and hepatitis C but not with hepatitis B. Physicians who care for patients with psoriasis should be aware of this possible association and consider screening patients with psoriasis for hepatitis C.
Transcriptome Analysis of the Response of Cultured Murine Podocytes to Puromycin Aminonucleoside
Authors: Kang H.G. , Paik K.H. , Cho H.Y. , Lee B.H. , Ha I.S. , Choi Y. , Cheong H.I.
Published: March 2010

Aims: Idiopathic nephrotic syndrome is known as a disease of the renal glomerular epithelial cells (podocytes). Recent advances in podocyte biology showed that podocytopathy is the culprit of nephrotic syndrome. To obtain comprehensive information about the response of podocytes to injury, we investigated the gene expression profile of podocytes in response to puromycin aminonucleoside (PAN)-induced injury. Methods: Differentiated mouse podocyte cell line (MPC5) cells were treated with 25 µg/ml PAN for 24, 48, or 72 h. Gene expression profiles of these cells were analyzed. Real time PCR analysis was used to confirm the findings of microarray. Results: Expression levels of 23 genes (differentially expressed genes, DEGs), including laminin α1 and MMP3, were significantly different between PAN-treated podocytes and untreated cells. Gene ontology of DEGs indicated that their functional categories were cell adhesion, extracellular matrix (ECM) formation, and ECM degradation. Real-time PCR and indirect immunohistochemistry of PAN-treated and untreated podocytes confirmed the differential expression of DEGs. Conclusion: Using unbiased global gene expression profiling, we found that podocytes respond to PAN-induced injury by down-regulating the expression of genes involved in cell adhesion and extracellular matrix.
Alexithymia and Cancer Pain: The Effect of Psychological Intervention
Authors: Tulipani Cinzia , Morelli Francesco , Spedicato Maria Rosaria , Maiello Evaristo , Todarello Orlando , Porcelli Piero
Published: March 2010

Background: Alexithymia is likely to be involved in the pain experience of cancer patients, but the extent to which psychological interventions may modify both pain and alexithymia is unclear. Methods: A group of 52 consecutive cancer patients were enrolled in a 6-month multicomponent psychological intervention trial, and compared to 52 control patients who received standard medical care. Validated scales for pain, alexithymia, coping with disease, illness behavior, psychological distress, and psychosocial functioning were administered at baseline and 6 months later. Results: Pain was strongly associated with alexithymia and several psychological dimensions. Although at baseline patients in the intervention group had worse psychological and somatic health, at follow-up their level of pain intensity, alexithymia, and somatic concerns had significantly improved compared to control patients. Patients in the intervention group showed dramatic improvements in pain perception, alexithymia, and other psychological variables, while control patients showed an unexpected significant worsening of alexithymia, depression, and adjustment to disease. Multiple regression showed that psychological intervention and alexithymia were both independently associated with the reduction in pain perception. Conclusions: These findings confirm the close association between alexithymia and pain, and show that multicomponent psychological intervention may significantly reduce both alexithymia and cancer pain. Although the present findings need replication, they should strongly encourage clinicians to provide patients with psychological interventions targeting alexithymic difficulties and helping patients to cope better with both feelings and somatic perception.
Neutrophil Adsorption by Polymyxin B-Immobilized Fiber Column for Acute Exacerbation in Patients with Interstitial Pneumonia: A Pilot Study
Authors: Abe Shinji , Seo Yoshitsugu , Hayashi Hiroki , Matsuda Kuniko , Usuki Jiro , Azuma Arata , Kudoh Shoji , Gemma Akihiko
Published: March 2010

Background/Aims: Polymyxin B-immobilized fiber (PMX) treatment has beneficial effects in patients with acute lung injury/acute respiratory distress syndrome or acute exacerbation of idiopathic pulmonary fibrosis. This study was aimed to clarify the mechanism of PMX treatment for acute exacerbation of interstitial pneumonia (IP). Materials and Methods: Sixteen consecutive IP patients with acute exacerbation were included. The patients were treated with PMX once daily for 2 successive days at a flow rate of 80–100 ml/min for 6 h. Cells adsorbed by PMX were analyzed morphologically by electron microscopy. Surface markers of these cells were determined by flow cytometry. Serum matrix metalloproteinase (MMP)-9 was measured before and after PMX treatment. Results: Cells adsorbed by PMX were neutrophils and highly expressed HLA-DR, CD14, CD62L and CD114. Serum MMP-9 levels were significantly decreased after PMX treatment. Conclusion: This pilot study demonstrated neutrophil adsorption by PMX and its possible clinical application for acute exacerbation of IP.
Renal Dysfunction in Patients with Beta-Thalassemia Major Receiving Iron Chelation Therapy either with Deferoxamine and Deferiprone or with Deferasirox
Authors: Economou Marina , Printza Nikoletta , Teli Aikaterini , Tzimouli Vassiliki , Tsatra Ioanna , Papachristou Fotis , Athanassiou-Metaxa Miranda
Published: March 2010

There are limited studies on renal involvement in β-thalassemia, mainly involving patients on deferoxamine, reporting both glomerular and tubular dysfunction. The aim of the present study was to investigate renal involvement in young thalassemia patients, using both conventional and early markers of renal dysfunction, and to correlate findings to iron chelation therapy. Forty-two patients aged 4–23 years were studied and, for analysis purposes, were divided into two groups based on chelation therapy (group A receiving deferasirox and group B receiving deferoxamine and deferiprone combination therapy). In addition to conventional renal biochemistries, creatinine clearance, estimated glomerular filtration rate, serum cystatin C (Cys C), fractional excretion of sodium, tubular phosphorus reabsorption and urine calcium, protein, β2-microglobulin (β2-MG) and glucose levels were measured. A considerable number of patients demonstrated impaired renal function with elevated Cys C levels (36%), glomerular dysfunction with proteinuria (24%) and tubulopathy with hypercalciuria (35.5%) and elevated excretion of β2-MG (33.5%). Renal involvement seems to be present even in young patients with β-thalassemia, therefore, routine use of early markers of renal dysfunction is recommended. Further studies are needed in order to investigate the role of new chelators in tubular function parameters.
Is the Incidence of Urinary Bladder Endometriosis Increasing? Figures from Finland
Authors: Vaarala Markku H. , Hellstrom Pekka , Santala Markku
Published: March 2010

Objective: Urinary bladder endometriosis is a severe form of endometriosis often requiring surgery. The several cases treated at our hospital in recent years has led us to evaluate the incidence of urinary bladder endometriosis in Finland. Methods: We performed a register-based analysis of incidence of urinary bladder endometriosis. The patients were identified according to registered diagnosis and operation codes. Results: Six urinary bladder endometriosis cases were diagnosed at Oulu University Hospital during 1991–2007. These cases have been presented. The annual incidence, as evaluated from The Finnish Care Register HILMO, increased from 3.6 to 9.4 cases/1,000,000 females aged 15–49 years per year during 1996–1999 and 2004–2007, respectively, in Finland. Conclusion: There is an apparent increase in incidence of urinary bladder endometriosis in Finland. The low number of cases detected at Oulu University Hospital, and the limitations of the incidence evaluation based on the HILMO register, exclude the presentation of an accurate incidence. The results presented warrant further and careful evaluation of potential increases in urinary bladder endometriosis elsewhere.
Enhanced Absorption through Damaged Skin: An Overview of the in vitro Human Model
Authors: Gattu S. , Maibach H.I.
Published: March 2010

Background/Aim: Quantifying percutaneous absorption of topical drugs as well as those compounds relevant to occupational exposure is important for assessing delivery, efficacy and toxicology. Methods for assessing absorption are established for intact skin; however, what may be equally relevant is how much absorption occurs through damaged skin. Methods: The Embase database was accessed online in March 2009 in search of human in vitro studies measuring absorption through damaged or diseased skin. Results: Few studies have measured absorption through damaged human skin in vitro but those that have demonstrate a modest but clear enhancement in absorption with enhancement favoring hydrophilic molecules. Conclusions: Damaged or diseased skin may display a modest increase in absorption compared to intact skin; however, more studies with consistent methods and correlations to in vivo data are needed to fully elucidate how much absorption occurs through damaged skin.
Epidermal Permeability Barrier Recovery Is Delayed in Vitiligo-Involved Sites
Authors: Liu J. , Man W.Y. , Lv C.Z. , Song S.P. , Shi Y.J. , Elias P.M. , Man M.Q.
Published: March 2010

Background/Objectives: Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. Methods: A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13–51 years (mean age: 27.91 ± 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. Results: In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 ± 5.39% vs. 58.30 ± 4.71%; t = 2.441; p < 0.02). Conclusion: Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo.
Penicillin Allergy: Value of Including Amoxicillin as a Determinant in Penicillin Skin Testing
Authors: Lin Erina , Saxon Andrew , Riedl Marc
Published: March 2010

Background: Allergy to penicillins remains an important issue. Penicillin skin testing (PST) with major and minor determinants has been shown to be a highly valuable tool for identifying IgE-mediated penicillin allergy. The value of additional testing with side-chain-specific moieties from semisynthetic penicillins such as amoxicillin is not well-established in spite of the widespread use of these medications. Methods: A retrospective review of all consecutive inpatient PST results from 1995 to 2007 comprising 1,068 patients was performed in our institution on individuals with a self-reported history of beta-lactam allergy to assess the importance of including the amoxicillin determinant in a previously validated PST panel. Descriptive statistics were performed. The PST panel included penicilloyl-polylysine, penicillin G, penicilloate, penilloate and amoxicillin. Results: Of 1,068 patients, 243 (23%) had a positive skin test reaction on the PST panel. Testing with amoxicillin was positive in 30.9% of patients, the majority of whom (81%) were also positive to 1 or more standard penicillin reagents. Fourteen of the 243 positive patients (5.8%) had a positive skin test reaction only to amoxicillin. Additionally, the use of penicilloate and penilloate minor determinants in combination with penicillin G identified a greater percentage of penicillin-allergic individuals compared to using only penicillin G (22.6 vs. 6.6%), demonstrating their importance in the PST panel. Conclusions: These data indicate that the inclusion of the amoxicillin determinant appears to identify a small but important group of allergic individuals who may otherwise test negative on a PST panel.
The Russian Thistle (Salsola kali) Pollen Major Allergen, Sal k 1, Can Be Quantified in Allergenic Extracts and Airborne Pollen
Authors: Arilla M.C. , Ibarrola I. , Brena S. , Martínez A. , Colás C. , Asturias J.A.
Published: March 2010

Background: Russian thistle (Salsola kali) pollen is an important cause of pollinosis in areas where rainfall is not abundant. Our aim was to develop an ELISA for quantification of the major allergen of S. kali extracts, Sal k 1, and to assess the correlation of this allergen content with the allergenic activity of extracts. Methods: Sal k 1 was purified by ion exchange and gel permeation chromatography and identified by mass spectrometry. Monoclonal antibody 4C11 was used for capture at 5 µg/ml and biotin-labeled specific antiserum at 0.25 µg/ml served for detection. The allergenic activity of the pollen extracts was measured by enzyme allergosorbent test inhibition. Results: Sal k 1 reacted to 85% of sera from 40 S. kali-allergic patients and was able to inhibit 92% of the IgE-binding capacity of patients’ serum pool to the whole extract. The ELISA had a lineal range between 1.25 and 20 ng/ml of purified Sal k 1. The intra- and interassay coefficients of variation were lower than 5 and 10%, respectively. The assay was very sensitive since it had a detection limit of 0.08 ng/ml. No reactivity was found outside the Amaranthaceae family where only Kochia and Salicornia sp. gave significant reactivity. A good correlation (Spearman’s ρ = 0.92) was obtained between Sal k 1 content of different S. kali extracts and their IgE-binding activity. Conclusions: The results proved the usefulness of the two-site sandwich ELISA for aeroallergen control and for the standardization of S. kali pollen extracts intended for clinical use.
Combined Stimulation with Poly(I:C), TNF-α and Th2 Cytokines Induces TARC Production by Human Fibroblasts from the Nose, Bronchioles and Lungs
Authors: Nonaka Manabu , Ogihara Nozomu , Fukumoto Akira , Sakanushi Atsuko , Kusama Kaoru , Pawankar Ruby , Yagi Toshiaki
Published: March 2010

Background: Th2 cells trigger allergic diseases in the respiratory tract. However, the mechanisms that cause Th2 cell infiltration remain unclear. Viral infections exacerbate allergic diseases in the respiratory tract. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. Resident fibroblasts are thought to contribute to inflammatory cell infiltration through chemokine production. We compared the abilities of nasal, bronchiolar and lung fibroblasts to produce TARC. Methods: Expression of TARC mRNA was evaluated by real-time RT-PCR, while the amount of TARC in supernatants was measured by ELISA. Results: Costimulation with TNF-α and Th2 cytokines (IL-4, IL-13) or with poly(I:C) and Th2 cytokines (IL-4, IL-13) induced TARC production by nasal (polyp and normal) fibroblasts. Costimulation with TNF-α and Th2 cytokines (IL-4, IL-13) also induced TARC production by both bronchiolar and lung fibroblasts, but costimulation with poly(I:C) and Th2 cytokines (IL-4, IL-13) caused no induction. Combined exposure of cells to poly(I:C), TNF-α and Th2 cytokines (IL-4, IL-13) resulted in substantial production of TARC by nasal and lung fibroblasts, but much less by bronchiolar fibroblasts. Conclusions:TARC is directly inducible in diverse fibroblast populations from the respiratory tract (nose, bronchioles and lungs), but the mechanisms and levels of TARC production differ. Fibroblasts in the respiratory tract may contribute to Th2 cell infiltration and viral-induced exacerbation of allergic diseases, such as allergic sinusitis, asthma and allergic lung inflammation.
The Involvement of µ-Opioid Receptors in the Central Nervous System in the Worsening of Allergic Airway Inflammation by Psychological Stress in Mice
Authors: Okuyama Kaori , Wada Kana , Sakurada Shinobu , Mizoguchi Hirokazu , Komatsu Hiroshi , Sora Ichiro , Tamura Gen , Ohkawara Yuichi , Takayanagi Motoaki , Ohno Isao
Published: March 2010

Background: Psychological stress has a recognized association with asthma symptoms. However, the mechanisms linking stress to the exacerbation of asthma are not well defined. µ-Opioid receptors (MOR) have been shown to be involved in the shift of the immune system toward a Th2-predominant response caused by psychological stress. Objective: To test the hypothesis that MOR play a role in the worsening of allergic airway inflammation evoked by psychological stress. Methods: Sensitized mice were exposed to restraint stress followed by antigen challenge. The levels of corticosterone and ovalbumin (OVA)-specific IgE in the blood and the levels of inflammatory cells and cytokine contents in bronchoalveolar lavage fluid were compared between stressed and nonstressed mice. The effects of MOR gene deletion and MOR antagonists/agonists were also investigated. Results: Stress exposure was confirmed by an increase in corticosterone levels. Although OVA-specific IgE levels were not significantly different, the numbers of inflammatory cells and Th2 cytokine levels after antigen challenge in stressed mice were significantly higher than in nonstressed mice. MOR gene deletion ameliorated the stress-induced worsening of antigen-induced airway inflammation, and the administration of morphine, a MOR agonist, reproduced the stress-induced antigen-induced airway inflammation. Selective blocking of MOR in the central nervous system (CNS) significantly reduced stress-induced inflammatory exacerbation, but the blocking of peripheral MOR did not. Conclusions: MOR in the CNS are involved in psychological stress-induced aggravation of allergic airway inflammation.
Targeted HER2 Treatment in Advanced Gastric Cancer
Authors: Jørgensen Jan Trøst
Published: March 2010

Amplification of the HER2 gene and over-expression of the HER2 protein in gastric cancer have been shown in a large number of studies. HER2 positivity can be detected in approximately 20% of patients, which is a characteristic associated with poor prognosis. Preclinical in vitro and in vivo studies have demonstrated that both trastuzumab and lapatinib are effective in different gastric cancer models and have thus lead to the initiation of clinical studies. In the first phase III study, the ToGA trial, HER2-positive patients with advanced gastroesophageal and gastric adenocarcinoma were randomized to receive 5-fluorouracil/capecitabine and cisplatin either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in the patients who received the combined treatment of trastuzumab and chemotherapy. It is expected that the encouraging results from the ToGA trial will have an immediate impact on the management of patients and that routine HER2 testing of patients with advanced gastric cancer will be initiated within a relatively short period of time.
Depersonalization in Patients with Schizophrenia Spectrum Disorders, First-Degree Relatives and Normal Controls
Authors: Gonzalez-Torres Miguel Angel , Inchausti Lucía , Aristegui Maialen , Ibañez Berta , Diez Luis , Fernandez-Rivas Aranzazu , Bustamante Sonia , Haidar Karim , Rodríguez-Zabaleta Maier , Mingo Argiñe
Published: March 2010

Background: Depersonalization occurs in healthy individuals and across a broad range of psychiatric patients. Data on depersonalization in persons linked to patients through genetics, environment or education are scarce. Due to their higher risk of developing psychosis, first-degree healthy relatives might show differences with the general population. This study examines depersonalization in patients with schizophrenia or schizophrenia spectrum disorders, their first-degree healthy relatives and normal controls. Methods: The Cambridge Depersonalization Scale was used to measure depersonalization in a sample of 147 clinically stable patients with schizophrenia or schizophrenia spectrum disorders, 73 first-degree relatives with no psychiatric history and 172 healthy controls. Mixed effect models were used to account for both the familial structure of the data and the effect of sociodemographic characteristics. Results: Patients obtained higher scores than relatives and controls for frequency and duration of depersonalization experiences, number of items responded positively and total depersonalization, while first-degree relatives obtained lower scores than patients and controls for all these characteristics. Conclusions: First-degree relatives of patients reported fewer episodes of depersonalization, which were less intense and of shorter duration, than healthy controls. This finding might be related to a protection mechanism that keeps first-degree relatives away from near-psychotic experiences. The nature of such a mechanism remains to be discovered.
Influence of Suboptimal Treatment in Patients with Mediastinal Primary Nonseminomatous Germ Cell Tumors
Authors: Yonemori Kan , Kouno Tsutomu , Ando Masashi , Hirakawa Akihiro , Yamamoto Harukaze , Ono Makiko , Hirata Taizo , Shimizu Chikako , Tamura Kenji , Katsumata Noriyuki , Fujiwara Yasuhiro
Published: March 2010

Objectives: The aim of this study was to analyze the prognostic impact of suboptimal treatment in patients with mediastinal primary nonseminomatous germ cell tumor (MNSGCT). Methods: We retrospectively reviewed the clinical data of 23 consecutive MNSGCT patients who were referred to the National Cancer Center Hospital between 1999 and 2007. Optimal treatment was defined as a primary chemotherapy regimen comprising a standard dosage of bleomycin + etoposide + cisplatin or etoposide + ifosfamide + cisplatin with sufficient dose intensity according to the guidelines of the European Germ Cell Cancer Consensus Group. Results: Ten and 13 patients received optimal and suboptimal treatment, respectively. The progression-free survival was statistically different between the patients who received optimal and suboptimal treatment (p = 0.01), and the hazard ratio of the optimal treatment group relative to the suboptimal treatment group was 0.19 (95% CI, 0.04–0.89). Although the overall survival was not statistically different between the 2 patient groups (p = 0.12), the hazard ratio in this regard was 0.36 (95% CI, 0.10–1.38). Conclusions: Patients who receive suboptimal treatment have poor clinical outcomes. Providing treatment after considering evidence-based guidelines may be important for improving the clinical outcomes of MNSGCT patients.
Suicide Attempts after Subthalamic Nucleus Stimulation for Parkinson’s Disease
Authors: Rodrigues Ana M. , Rosas Maria J. , Gago Miguel F. , Sousa Cláudia , Fonseca Rosália , Linhares Paulo , Basto Margarida A. , Sousa Graça , Garrett Carolina , Vaz Rui
Published: March 2010

A higher risk of suicidal attempt after subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) has been consistently reported. We retrospectively analyzed 3 PD patients with suicide attempts after STN-DBS. All patients had normal pre- and immediate postoperative psychopathological and cognitive evaluations, with STN-DBS yielding a good motor benefit. Levodopa medication was markedly reduced. Albeit there was a significant reduction in dopaminergic medication, there was also a considerable time lag to suicide attempt. Impulsive behavior could have played a higher role, going unnoticed in punctual psychopathological examinations. STN-DBS patients need a closer postoperative psychiatric and behavioral follow-up.
The Ankle Retinacula: Morphological Evidence of the Proprioceptive Role of the Fascial System
Authors: Stecco Carla , Macchi Veronica , Porzionato Andrea , Morra Aldo , Parenti Anna , Stecco Antonio , Delmas Vincent , De Caro Raffaele
Published: March 2010

Study Design: Research report. Objectives: To evaluate the anatomical characteristics of the ankle retinacula and their relationship with the fasciae and muscles in healthy subjects and in patients with ankle sprain outcomes. Background: The role of the retinacula in proprioception has begun to emerge, but without clear anatomical bases or descriptions of their possible damage in patients with ankle sprain outcomes. Methods: Dissection, histological and immunohistochemical analysis of 27 legs. An in vivo radiological study by MRI was also performed on 7 healthy volunteers, 17 patients with outcomes of ankle sprain, and 3 amputated legs. Results: The retinacula are thickenings of the deep fascia presenting bone or muscular connections. They are formed of 2–3 layers of parallel collagen fibre bundles, densely packaged with a little loose connective tissue, without elastic fibres but many nervous fibres and corpuscles. By MRI, the retinacula appeared as low-signal-intensity bands with a mean thickness of 1 mm. In patients with outcomes of ankle sprain, MR findings were abnormal retinacula thickness, signal intensity, and full-thickness gap. Discussion: The retinacula are not static structures for joint stabilisation, like the ligaments, but a specialisation of the fascia for local spatial proprioception of the movements of foot and ankle. Their anatomical variations and accessory bundles may be viewed as morphological evidence of the integrative role of the fascial system in peripheral control of articular motility.