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2.
J Physiol Pharmacol ; 68(2): 181-189, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28614767

ABSTRACT

Progressive muscle wasting, frequently associated with inflammation, muscle fibre degeneration and fibrosis, is a characteristic of DMD (Duchenne muscular dystrophy). Its most common used animal model, the mdx mouse, however can overcome muscle degeneration by regeneration processes and is for this reason not suitable to answer all scientific questions. The aim of this study was to evaluate the ability of botulinum toxin A (BTX-A) in breaking down muscle regeneration in mdx mice. For this purpose, the right masseter muscle of 100 days old mdx and healthy mice was paralyzed by a single specific intramuscular injection of BTX-A. After 21 days, right and left masseter and temporal muscles as well as tongue muscle were carefully dissected, and gene and protein expression of caveolin-1, caveolin-3 and vascular endothelial growth factor (VEGF) were determined using quantitative RT-PCR and Western blot technique. Statistics were performed using Student's t-test and Mann Whitney U-test (significance level: P ≤ 0.05). After BTX-A injection, in both mice strains and for all three studied genes, no significant differences in mRNA amount could be detected between treated and untreated masseter muscles. A significant increase in caveolin-1, caveolin-3 and VEGF mRNA expression could only be found in the right temporal muscle of control mice compared to the left side. All three investigated proteins were more frequent to be found in dystrophic masseter muscle samples compared to the corresponding control samples, whereas significant decreased caveolin-3 protein levels could only be detected in the treated masseter versus untreated masseter muscle of controls. In contrast to previous conclusions, with this study it was not possible to prove a BTX-A-induced dystrophic phenotype in control animals, in which only the known decreases of caveolin-3 protein expression could be verified due to denervation. At the same time, however, gene and protein expression in dystrophic mice was not changed after BTX-A injection.


Subject(s)
Botulinum Toxins, Type A/pharmacology , Caveolin 1/metabolism , Caveolin 3/metabolism , Masseter Muscle/drug effects , Vascular Endothelial Growth Factor A/metabolism , Animals , Caveolin 1/genetics , Caveolin 3/genetics , Dystrophin/deficiency , Female , Male , Masseter Muscle/metabolism , Mice, Inbred C57BL , Mice, Inbred mdx , RNA, Messenger/metabolism , Vascular Endothelial Growth Factor A/genetics
3.
Eur J Intern Med ; 31: 20-4, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27053291

ABSTRACT

BACKGROUND: Patients with nonspecific complaints (NSC) such as generalized weakness present frequently to acute care settings. These patients are at risk of adverse health outcomes. The aim of our study was to test the hypothesis whether D-dimers are predictive for 30-day mortality in patients with NSCs. METHODS: Delayed type cross-sectional diagnostic study with a 30-day follow-up period, registered with ClinicalTrials.gov (NCT00920491). This study took place in 2 EDs in Northwestern Switzerland. Patients were enrolled in the study if they were over 18years of age, gave informed consent, and if they presented with NSCs such as generalized weakness. D-dimer levels were determined at ED presentation. RESULTS: The final study population consisted of 524 patients. Median age was 82years (IQR=75 to 87years); 40.5% were men. There were 489 survivors and 35 non-survivors at 30-day follow-up. Twenty-one (60%) of the non-survivors were males. D-dimer levels were significantly higher in non-survivors than in survivors (p<0.001). Univariate Cox regression models for D-dimer resulted in a C-index of 0.77 for prediction of mortality. A model including sex, age, Katz ADL and D-dimer in a multivariate Cox regression lead to a C-Index of 0.80. CONCLUSION: D-dimer testing might be an effective risk stratification tool in patients with NSC by helping to identify patients at low risk of short-term mortality with a sensitivity of 0.97 and a negative likelihood ratio of 0.121. The use of D-dimers for risk stratification in patients with NSC should be confirmed with prospective studies.


Subject(s)
Fibrin Fibrinogen Degradation Products/analysis , Mortality , Muscle Weakness/diagnosis , Risk Assessment/methods , Triage/methods , Aged , Aged, 80 and over , Biomarkers/analysis , Cohort Studies , Cross-Sectional Studies , Emergency Service, Hospital , Female , Humans , Kaplan-Meier Estimate , Male , Multivariate Analysis , Muscle Weakness/etiology , Predictive Value of Tests , Proportional Hazards Models , Severity of Illness Index , Switzerland/epidemiology
4.
J Occup Environ Hyg ; 12(10): 692-8, 2015.
Article in English | MEDLINE | ID: mdl-25897559

ABSTRACT

Air concentrations near pollutant sources can be modeled using two-zone and turbulent diffusion models. Each type of model requires a specific pollutant transport parameter: the interzonal air flow (ß) is used in the two-zone model and the turbulent diffusion coefficient (DT) in the diffusion model. In this study ß and DT were determined experimentally by using concentrations measured around the release of a tracer vapor. A robot arm provided motion in the space near the source to simulate worker actions. Eighty-two experiments were conducted at two room locations and with different robot arm motion programs. ß and DT for were calculated using room geometry, ventilation parameters and the measured concentrations during the experiments. The near zone geometry was a 0.4 m hemisphere. The presence of motion in the vicinity of the source was important for the appropriate application of both models. The values of ß were log-normally distributed with a mean of 2.03 m3/min, a geometric mean (GM) of 1.65 m3/min (1.42-1.93 95% C.I.) and a geometric standard deviation of 1.82. DT was also log-normally distributed with a mean of 0.586 m2/min, a GM of 0.545 m2/min (0.493-0.600 95% C.I.) and GSD of 1.45. The location within the room had an influence on the value of both ß and DT. The use of random airspeed and the free surface area around the source was confirmed as an appropriate method for determining ß. A recently developed algorithm was supported as useful for determination of DT. The results strengthen the application of both the two-zone and turbulent diffusion models for worker exposure modeling.


Subject(s)
Air Pollutants, Occupational/analysis , Environmental Monitoring/methods , Models, Theoretical , Occupational Exposure/analysis , Acetone/analysis , Air Movements , Diffusion , Ventilation
5.
Eur J Clin Nutr ; 69(3): 329-36, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25335442

ABSTRACT

BACKGROUND/OBJECTIVES: New methods to measure visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) may help discern sex, race and phenotype differences in the role of VAT in cardiometabolic risk. This study was designed (1) to compare relationships of DXA-VAT, anthropometric and body composition variables with cardiometabolic risk factors in obese women; (2) to determine which variables most robustly predict impaired glucose tolerance (IGT) and metabolic syndrome (MetSx); and (3) to determine thresholds for DXA-VAT by race. SUBJECTS/METHODS: VAT mass (g) and volume (cm(3)) were measured in 229 obese (body mass index (BMI), 30-49.9) women aged 21-69 years of European-American (EA=123) and African-American (AA=106) descent using the CoreScan algorithm on a Lunar iDXA scanner. Linear regression modeling and areas under the curve (AUC of ROC (receiver operating characteristic) curves) compared relationships with cardiometabolic risk. Bootstrapping with LASSO (least absolute shrinkage and selection operator) regression modeling determined thresholds and predictors of IGT and MetSx. RESULTS: DXA-VAT explained more of the variance in triglycerides, blood pressure, glucose and homeostatic model assessment-insulin resistance (HOMA-IR) compared with anthropometric and other body composition variables. DXA-VAT also had the highest AUC for IGT (0.767) and MetSx (0.749). Including race as a variable and the interaction between VAT and race in modeling did not significantly change the results. Thresholds at which the probability of developing IGT or MetSx was⩾50% were determined separately for AA women (IGT: 2120 cm(3); MetSx: 1320 cm(3)) and EA women (IGT: 2550 cm(3); MetSx: 1713 cm(3)). The odds for IGT or MetSx were fourfold greater with each standard deviation increase in DXA-VAT. CONCLUSIONS: DXA-VAT provides robust clinical information regarding cardiometabolic risk in AA and EA obese women and offers potential utility in the risk reduction interventions.


Subject(s)
Black or African American , Body Composition , Glucose Intolerance/etiology , Intra-Abdominal Fat/metabolism , Metabolic Syndrome/etiology , Obesity/complications , White People , Absorptiometry, Photon/methods , Adult , Anthropometry/methods , Cardiovascular Diseases/ethnology , Cardiovascular Diseases/etiology , Female , Glucose Intolerance/ethnology , Glucose Intolerance/metabolism , Humans , Metabolic Syndrome/ethnology , Obesity/ethnology , Obesity/metabolism , Risk Factors
6.
Urologe A ; 54(6): 811-8, 2015 Jun.
Article in German | MEDLINE | ID: mdl-25503897

ABSTRACT

BACKGROUND: Several tyrosine kinase inhibitors (TKI) are used in the treatment of metastasized renal cell carcinoma (mRCC). This article presents a feasibility study for the measurement of plasma levels of sunitinib, sorafenib and pazopanib using liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: A total of 23 patients suffering from mRCC under treatment with sunitinib (n=16), sorafenib (n=3) and pazopanib (n=4) were included. Plasma samples (100 µl) were separated by liquid chromatographic analysis and the plasma levels of the TKIs determined by tandem mass spectrometry. RESULTS: The plasma levels of sunitinib, sorafenib and pazopanib were measurable and the results reproducible. During storage of the plasma samples for 1 week at 4°C no significant decrease of the initial concentration was found. The highest plasma levels detected were 99 ng/ml for sunitinib, 9.8 µg/ml for sorafenib and 63 µg/ml for pazopanib. We could show variability in plasma levels according to changes in dosage of TKIs or during treatment-free intervals. CONCLUSION: Measurement of TKI plasma levels using LC-MS/MS is feasible. Further clinical studies have to be conducted to examine if there are any threshold levels for the incidence of adverse events or response to treatment.


Subject(s)
Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/secondary , Indoles/blood , Kidney Neoplasms/blood , Niacinamide/analogs & derivatives , Phenylurea Compounds/blood , Pyrimidines/blood , Pyrroles/blood , Sulfonamides/blood , Aged , Aged, 80 and over , Antineoplastic Agents/blood , Carcinoma, Renal Cell/drug therapy , Drug Monitoring/methods , Feasibility Studies , Female , Humans , Indazoles , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Male , Middle Aged , Niacinamide/blood , Niacinamide/therapeutic use , Phenylurea Compounds/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Reproducibility of Results , Sensitivity and Specificity , Sorafenib , Sulfonamides/therapeutic use , Sunitinib
7.
Z Orthop Unfall ; 152(5): 498-503, 2014 Oct.
Article in German | MEDLINE | ID: mdl-25313704

ABSTRACT

BACKGROUND: Minimally invasive treatment of diaphyseal femur fractures (DFF) with closed reduction and intramedullary nailing is a well established procedure. However, a femoral malrotation after intramedullary nailing is considered to be a substantial problem. Studies have described femoral malrotation (FMR) in 17-35 % after this procedure. Computed tomography (CT) of both femora is accepted as an objective, reproducible measurement method to determine a postoperative femoral malrotation. An anatomic reposition of the centreline of the femur remains of high importance since a malrotation > 15° can lead to a significant limitation of the range of motion (ROM) and to clinical symptomatic constraints. PATIENTS/MATERIAL AND METHODS: Between July 2007 and December 2011 patients with unilateral DFF were treated with closed reduction and intramedullary nailing. Exclusion criteria were defined as bilateral or prior treatment for femoral fractures, open epihyseal plate or pregnancy. In all cases a postoperative CT scan of the femora was conducted to analyse a femoral malrotation. The indication for a correction was posed in cases of a malrotation > 15°. The data were not randomised and evaluated retrospectively. RESULTS AND CONCLUSION: In total 94 patients with unilateral DFF were included. 21 female and 73 male with an average age of 33.15 ± 14.04 years (range 14-94). In the postoperative CT scan an average FMR of 11.58 ± 9.41° (range 0-44°) was determined. In 15 cases (15.95 %), 10 male (13.7 %) and 5 female (23.81 %) a FMR > 15° (average: 23.66 ± 5.74°) was noticed. A subsequent surgery with a correction in average of 17.53 ± 6.83° was performed. After the correction the malrotation averaged 6.07 ± 5.61°. The results support the existing data that the treatment of DFF with closed reduction and intramedullary nailing may lead to a significant femoral malrotation despite a precise intraoperative monitoring. The data demonstrate that nearly 15 % of all patients appear after closed reduction and intramedullary nailing with a femoral malrotation greater than 15°. A routinely utilised postoperative CT scan provides additional information to discover an occult malrotation. CONCLUSION: In spite of diligent attendance to the femoral torsion intraoperatively in DFF a significant femoral malrotation may result after closed reduction and intramedullary nailing. To prevent a limitation of ROM and clinical constraints a routinely performed postoperative CT scan with a adequate surgical correction is recommended.


Subject(s)
Bone Malalignment/etiology , Femoral Fractures/diagnosis , Femoral Fractures/surgery , Femur/abnormalities , Femur/surgery , Fracture Fixation, Intramedullary/adverse effects , Osteotomy/adverse effects , Adult , Bone Malalignment/diagnosis , Bone Malalignment/prevention & control , Combined Modality Therapy/adverse effects , Female , Femoral Fractures/complications , Humans , Longitudinal Studies , Male , Retrospective Studies , Treatment Outcome
8.
J Physiol Pharmacol ; 65(2): 317-24, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24781740

ABSTRACT

Duchenne Muscular Dystrophy (DMD) and its murine model, mdx, are characterized by Ca(2+) induced muscle damage and muscle weakness followed by distorted dentofacial morphology. In both, DMD patients and in mdx mice, could be proven so far that only the extraocular muscles (EOM) are not affected by muscular dystrophy. The EOMs are protected against calcium overload by enhanced expression of genes involved in the Ca(2+) homeostasis. We could recently demonstrate that masticatory muscles of mdx mice are differentially affected by muscle dystrophy. The dystrophic masseter and temporalis shows muscle histology comparable to all other skeletal muscles in this animal model, whereas dystrophic tongue muscles seem to develop a milder phenotype. Due to this fact it is to hypothesize that an altered Ca(2+) homeostasis seems to underlie the mdx masticatory muscle pathology. Aim of this study was to examine the mRNA and protein levels of the sarcoplasmic reticulum Ca(2+) ATPases SERCA1 and SERCA2, the plasma membrane Ca(2+) ATPases Atp2b1 and Atp2b4, the sodium/calcium exchanger NCX1, the ryanodine receptor 1, parvalbumin, sarcolipin, phospholamban and the L-type Ca(2+) channel alpha-1 subunit (Cacna1s) in Musculus masseter, temporalis, and tongue of 100 day old control and mdx mice. In mdx masseter muscle significant increased mRNA levels of NCX1 and Cacna1s were found compared to control mice. In contrast, the mRNA amount of RYR1 was significant reduced in mdx temporalis muscle, whereas ATP2b4 was significant increased. In mdx tongue a down-regulation of the ATP2b1, sarcolipin and parvalbumin mRNA expression was found, whereas the phospholamban mRNA level was significantly increased compared to controls. These data were verified by western blot analyses. Our findings revealed that mdx masticatory muscles showed an unequally altered expression of genes involved in the Ca(2+) homeostasis that can support the differences in masticatory muscles response to dystrophin deficiency.


Subject(s)
Calcium/metabolism , Gene Expression , Masticatory Muscles/metabolism , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/metabolism , Animals , Calcium Channels, L-Type/genetics , Female , Homeostasis , Male , Mice, Inbred C57BL , Mice, Inbred mdx , Muscle Proteins/genetics , Parvalbumins/genetics , Parvalbumins/metabolism , Plasma Membrane Calcium-Transporting ATPases/genetics , Proteolipids/genetics , RNA, Messenger/metabolism , Ryanodine Receptor Calcium Release Channel/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sodium-Calcium Exchanger/genetics , Sodium-Calcium Exchanger/metabolism
9.
Clin Oral Investig ; 17(3): 887-96, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22699659

ABSTRACT

OBJECTIVES: Botulinum toxin A (Botox) is increasingly used for treatment of muscle hyperfunction. For a better understanding of the possible morphologic and chewing changes in patients induced by a therapy with Botox, muscle fiber and myosin heavy chain (MyHC) mRNA alterations were examined in this animal study. MATERIALS AND METHODS: The investigation was carried out on 14-week-old pigs (seven treated animals, eight controls; calculated animal size with a power of 0.5). To initialise the total immobilisation of the right masseter, the Botox injection was distributed into ten areas. After a 56-day period, muscle tissue was taken from the left and right side of the masseter (three regions), temporal (two regions), medial pterygoid and geniohyoid muscles using a standardized method. The muscle fiber cross sections were examined immunohistochemically. Fiber staining was accomplished with antibodies to specific MyHC isoforms. The MyHC mRNA changes were analysed using real-time RT-PCR. RESULTS: Muscles adapt to such stress by changing fiber types and MyHC mRNA content. Paralysed masseters display atrophic changes while other masticatory muscles show hypertrophic changes. The results indicated that the typical distributions of type IIa und IIb fiber types in masticatory muscles were increased in the masseter muscles due to Botox application. On the other hand, the masseters without Botox in the treated group showed a significant increase of type I MyHC. CONCLUSIONS: Application of Botox may lead to uncontrolled structural changes in affected and unaffected muscles. CLINICAL RELEVANCE: Treatment of muscle hypertrophy with Botox may cause muscle imbalance.


Subject(s)
Botulinum Toxins, Type A/pharmacology , Facial Paralysis/drug therapy , Masseter Muscle/drug effects , Masticatory Muscles/pathology , Myosin Heavy Chains/genetics , Skeletal Muscle Myosins/genetics , Animals , Botulinum Toxins, Type A/therapeutic use , Hypertrophy , Masticatory Muscles/chemistry , Masticatory Muscles/drug effects , Muscle Denervation , Muscular Atrophy/drug therapy , Muscular Atrophy/pathology , Myosin Heavy Chains/drug effects , RNA, Messenger/analysis , Real-Time Polymerase Chain Reaction , Swine
10.
Adv Med Sci ; 57(1): 157-62, 2012 Jun 01.
Article in English | MEDLINE | ID: mdl-22472467

ABSTRACT

PURPOSE: Conventional radiography is a well-established method for imaging of the temporomandibular joint (TMJ) structures. However, the dental computer tomography becomes more important for the visualization of teeth in the jaw-bone. The applicability of dental computer tomography for the visualization of the TMJ it not yet been proven. The aim of the study was to identify TMJ structures using reference points with the magnetic resonance imaging (MRI) and the computed tomography (CT). METHODS: In order to compare the visualization and measurement of the TMJ a total of eight human cadaver heads was examined with CT and MRI and analysed using reference points. RESULTS: In both imaging techniques the selected reference points and distances are well definable and allow objective evaluation of anatomical structures. The CT images display a clearly better contrast to noise ratio than the MR images. The distance measurement of different width and length showed significant correlation of both images techniques. CONCLUSIONS: In TMJ diagnostics, maximum information could be obtained using both imaging techniques together due to synergistic effects.


Subject(s)
Temporomandibular Joint/diagnostic imaging , Humans , Magnetic Resonance Imaging , Tomography, X-Ray Computed
11.
Unfallchirurg ; 111(2): 126-31, 2008 Feb.
Article in German | MEDLINE | ID: mdl-18239902

ABSTRACT

According to the literature, differences in torsion of 15 degrees and more develop in 20-30% of cases after intramedullary nailing of femoral shaft fractures. A computer-assisted method makes it possible to determine the antetorsion angle during surgery. In this experimental study, the precision of the measurements obtained with the navigation system were checked with a femur model and compared with a CT reference method. The measurements are carried out on a femur model that is equipped with a rotation device in the middle of the shaft. Nine reproducible angles can be set. Two investigators each conduct the measurements of the antetorsion angle ten times. A comparison is drawn between the absolute values of the antetorsion angle measured and the difference values of the adjoining positions. When comparing the absolute values of the navigation and reference systems, the mean deviations of both methods are around 1 degrees (0.35; 1.75) and comparing the differences 0.5 degrees (-0.2; 1.17). The maximum deviation of the absolute values of the CT reference method amounts to 6.4 degrees . Under experimental conditions, measurement of the femoral antetorsion angle proved to be sufficiently precise for clinical specifications in comparison to a CT reference method.


Subject(s)
Bone Malalignment/surgery , Femoral Fractures/surgery , Fluoroscopy/instrumentation , Fracture Fixation, Intramedullary/instrumentation , Range of Motion, Articular/physiology , Surgery, Computer-Assisted/instrumentation , Humans , Sensitivity and Specificity , Tomography, X-Ray Computed
12.
Acta Physiol (Oxf) ; 192(3): 429-42, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17892519

ABSTRACT

AIMS: This study was performed to investigate the effects of NaCl intake on renal mRNA expression of pre-pro-endothelin-1 (ET-1), endothelin A (ET(A)) and endothelin B (ET(B)) receptors as well as on renal ET-1 content in rats. We further tested for NaCl intake-dependent differences in the contribution of the ET system to renal sodium handling. METHODS: Male Sprague-Dawley rats with telemetric devices were randomized to 0.15%, 0.60% and 1.80% NaCl diets with or without losartan. Renal sodium balance and arterial pressure were monitored. Renal blood flow and fractional sodium excretion (FENa) were measured in response to acute infusion of ET(A) and ET(B) blockers into the inner stripe of the outer renal medulla. RESULTS: Medullary pre-pro-ET-1, ET(A) and ET(B) receptor mRNA was 50%, 81% and 33% higher in rats on 0.15% vs. 1.80% NaCl. Losartan reduced medullary gene expression in rats on 0.15% NaCl. Medullary ET-1 content was 983 +/- 88 and 479 +/- 42 ng mg(-1) protein in rats on 0.15% and 1.80% NaCl (P < 0.001). Chronic ET(A) receptor blocker treatment reduced arterial pressure by 8-10 mmHg in rats on 0.15% vs. 1.80% NaCl without affecting renal sodium balances. Acute medullary ET(A) or ET(B) receptor blockade did not alter medullary blood flow and FENa in animals on either diet. CONCLUSION: In rats renal medullary ET-1 content and mRNA expression of three ET system components are inversely related to NaCl intake. Higher expression levels on low NaCl intake are AT(1) receptor dependent but are not associated with increased sensitivity of renal sodium handling to ET(A) receptor blockade.


Subject(s)
Endothelin-1/metabolism , Kidney Medulla/drug effects , Receptor, Endothelin A/metabolism , Sodium Chloride, Dietary/administration & dosage , Sodium/metabolism , Animals , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Drug Therapy, Combination , Endothelin A Receptor Antagonists , Endothelin B Receptor Antagonists , Gene Expression/drug effects , Kidney Medulla/metabolism , Losartan/pharmacology , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Endothelin A/genetics , Receptor, Endothelin B/genetics , Receptor, Endothelin B/metabolism , Renal Circulation/drug effects , Renal Circulation/physiology
13.
J Econ Entomol ; 98(2): 342-9, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15889722

ABSTRACT

Lycoriella mali Fitch (Diptera: Sciaridae) infests mushroom crops early in the crop cycle. Recent observations in mushroom houses indicated a difference in emergence time and size of adult L. mali developing on various strains of commercial mushrooms. Samples of adult flies from isolated mushroom houses growing Portabella mushrooms were significantly heavier then those from oyster mushroom houses, whereas flies from shiitake mushroom houses were lightest in weight. Flies collected from isolated Portabella mushroom houses were reared on four strains and species of Agaricus and Pleurotus mushrooms. After the adults emerged, females were weighed, mated, and allowed to oviposit. The number of eggs laid increased as the weight of the female increased. Flies collected from isolated Portabella mushroom houses were reared on eight strains and species of mushrooms. Flies were reared for four generations on each host mushroom mycelium then switched to different host mushrooms. Overall, the hybrid strain of Agaricus bisporus (Lange) Imbach (Agaricales: Agaricomycetideae) was the most favorable host for L. mali, whereas the wild strain of A. bisporus was the least favorable host. Mushroom hosts influence developmental time, survivorship, weight, and reproduction of L. mali.


Subject(s)
Agaricales , Diptera/growth & development , Life Cycle Stages , Agaricus , Animals , Female , Host-Parasite Interactions , Male , Pleurotus , Species Specificity
14.
Cell Mol Life Sci ; 62(7-8): 731-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15868398

ABSTRACT

Poly(ADP-ribosyl)ation of proteins is involved in the regulation of basal cellular processes and seems to be crucial for genomic integrity and cell survival. Several nuclear poly(ADP-ribose) polymerases (PARPs) are known which interact with various proteins involved in DNA metabolism. These proteins can be targets of poly(ADP-ribosyl)ation, which generally downregulates their activities. Accordingly, PARPs have been implicated in numerous processes involving chromosomal DNA, such as the regulation of chromatin structure, DNA repair, replication and transcription. PARP-1, the major cellular PARP, and PARP-2 are activated by DNA strand breaks. These enzymes have been shown to participate in DNA repair. PARP-1 has also been associated with DNA replication and recombination. Another outstanding feature of PARP-1 is its impact on the activities of transcription factors and on gene expression. Two other nuclear PARP enzymes, tankyrase-1 and tankyrase-2, are important for telomere maintenance.


Subject(s)
Chromatin/metabolism , DNA Repair/physiology , DNA Replication/physiology , Poly(ADP-ribose) Polymerases/metabolism , Telomere/metabolism , Animals , Humans , Recombination, Genetic/physiology
15.
Virchows Arch ; 446(4): 360-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15756591

ABSTRACT

During pregnancy, the placenta produces a variety of proteins that are responsible for the establishment of the foeto-maternal tolerance and circulation. The aim of this study was to investigate the expression of glycodelin A (formerly named PP14) in decidual tissue of placentas with intrauterine growth restriction (IUGR), preeclamptic patients, hemolysis, elevated liver, low-platelet (HELLP) patients and normal decidual tissue. Slides of paraffin-embedded decidual tissue of patients with IUGR, preeclamptic patients, HELLP patients and normal-term placentas were incubated with either polyclonal or monoclonal antibodies against glycodelin A. Staining reaction was performed with the ABC reagent. Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score. In addition, expression of glycodelin mRNA was analysed by in situ hybridisation. Expression of glycodelin A was significantly reduced in decidual cells of placentas with IUGR and HELLP, as investigated with both monoclonal and polyclonal antibodies and in situ hybridisation. However, preeclamptic decidual tissue showed no significantly different expression of intensity of glycodelin mRNA compared with normal placental tissue controls. A reduced expression of glycodelin A by decidual cells seems to be related to IUGR and HELLP. Therefore, glycodelin A might play an important role in the pathogeneses of these diseases.


Subject(s)
Decidua/metabolism , Fetal Growth Retardation/metabolism , Glycoproteins/metabolism , HELLP Syndrome/metabolism , Pre-Eclampsia/metabolism , Pregnancy Proteins/metabolism , Adult , Biomarkers/metabolism , Cell Count , Decidua/pathology , Female , Fetal Growth Retardation/pathology , Glycodelin , Glycoproteins/genetics , HELLP Syndrome/pathology , Humans , Image Processing, Computer-Assisted , Immunoenzyme Techniques , In Situ Hybridization , Pre-Eclampsia/pathology , Pregnancy , Pregnancy Proteins/genetics , RNA, Messenger/metabolism
16.
Clin Neuropathol ; 23(5): 223-31, 2004.
Article in English | MEDLINE | ID: mdl-15581025

ABSTRACT

OBJECTIVE: Dysembryoplastic neuroepithelial tumors (DNT) are relatively benign brain lesions that often cause medically intractable epilepsy. There is mounting evidence that multidrug transporters such as P-glycoprotein (P-gp) or multidrug resistance-associated proteins (MRP) play an important role in the development of resistance to antiepileptic drugs (AED). MATERIAL AND METHODS: In the present study, we examined the expression of several multidrug transporters in 14 cases of DNT. The peritumoral brain tissue as well as 9 cases of arteriovenous malformations (AVM) served as controls. P-gp, MRP2, MRP5 and breast cancer resistance protein (BCRP) expression was evaluated qualitatively and quantitatively using immunohistochemistry. RESULTS: All transporters were overexpressed quantitatively in DNT, but each revealed a different labeling pattern. P-gp and BCRP were predominantly located in the endothelium of brain vessels. MRP5 was detected primarily in endothelial cells, but notably also in neurons. The expression of P-gp, MRP2 and MRP5 was low in AVM, whereas BCRP demonstrated strong staining. Examination of MDR1 gene polymorphisms revealed no correlation with P-gp expression whereas the MRP2 exon 10 G1249A polymorphism was associated with different MRP2 labelling. CONCLUSIONS: Our results show that multidrug transporters are overexpressed in DNT. This finding supports the view that several of these transport proteins may play an important role in the mechanisms of drug resistance in epileptic brain tissue.


Subject(s)
Brain Neoplasms/metabolism , Epilepsy/etiology , Multidrug Resistance-Associated Proteins/biosynthesis , Neoplasms, Neuroepithelial/metabolism , Adolescent , Adult , Brain Neoplasms/blood supply , Brain Neoplasms/complications , Child , Drug Resistance/physiology , Endothelial Cells/metabolism , Female , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Intracranial Arteriovenous Malformations/metabolism , Male , Middle Aged , Neoplasms, Neuroepithelial/blood supply , Neoplasms, Neuroepithelial/complications , Polymorphism, Genetic , Reverse Transcriptase Polymerase Chain Reaction
17.
Naunyn Schmiedebergs Arch Pharmacol ; 368(6): 463-9, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14618298

ABSTRACT

A promising development in tumor therapy is the application of non-toxic prodrugs from which the active cytostatic is released by endogenous enzymes such as beta-glucuronidase (beta-gluc). Regulation of beta-gluc expression is one crucial factor modulating bioactivation of prodrugs. Recent experiments in rats indicate regulation of beta-gluc activity by the calcium channel blocker verapamil. To further explore this phenomenon, we investigated the effect of verapamil on beta-gluc enzyme activity, protein (western blot) and mRNA expression (RT-PCR) as well as the underlying mechanisms (effects of verapamil metabolites; promoter activity) in the human hepatoma cell line HepG2. Treatment of HepG2 cells with verapamil revealed down-regulation of beta-gluc activity, protein, and mRNA level down to 50% of the control with EC(50) values of 25 microM. Effects were similar for both enantiomers. Moreover, it was demonstrated that reduced promoter activity contributes to the observed effects. In summary, our data demonstrate regulation of human beta-glucuronidase expression by verapamil. Based on our findings we hypothesize that coadministration of verapamil may effect cleavage of glucuronides by beta-glucuronidase.


Subject(s)
Glucuronidase/biosynthesis , Hymecromone/analogs & derivatives , RNA, Messenger/biosynthesis , Verapamil/pharmacology , Blotting, Western , Calcium Channel Blockers/chemistry , Calcium Channel Blockers/metabolism , Calcium Channel Blockers/pharmacology , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Down-Regulation/drug effects , Genes, Reporter , Glucuronidase/genetics , Glucuronidase/metabolism , Glyceraldehyde-3-Phosphate Dehydrogenases/biosynthesis , Humans , Hymecromone/metabolism , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Promoter Regions, Genetic , Stereoisomerism , Time Factors , Transfection , Verapamil/analogs & derivatives , Verapamil/metabolism
18.
Water Res ; 36(8): 2133-9, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12092588

ABSTRACT

Toxic effects and microcystin content from various extracts of a Planktothrix agardhii bloom and two different strains of Planktothrix agardhii, HUB 076, and NIVA 34 were investigated. Extracts were obtained with solvents of different polarity such as hexane, dichloromethane, methanol, and water. Additionally, different pre-treatments were used to break the cells before extraction. Acute toxicity was determined with the fairy shrimp Thamnocephalus platyurus, subchronic effects were detected in embryos and larvae of the zebrafish Danio rerio. The extracts affected the test species to a different extent. Effects were severe in polar extracts (water and methanol) of all strains tested. Although the strain NIVA 34 did not contain any microcystins, aqueous extracts of this strain showed the highest acute toxicity to the crustacean species tested (LC50= 0.08 mg ml(-1)). In contrast aqueous extracts of the Planktothrix bloom containing high amounts of microcystins were less acutely toxic (LC50 = 0.46 mg ml(-1)). Our results indicate the existence of further toxic metabolites in different Plankorothrix agardhii strains.


Subject(s)
Cyanobacteria/pathogenicity , Eutrophication , Peptides, Cyclic/toxicity , Animals , Decapoda , Lethal Dose 50 , Microcystins
19.
Appl Occup Environ Hyg ; 16(10): 967-72, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11599546

ABSTRACT

The evaporation of formaldehyde from cadavers in gross anatomy laboratories can produce high exposures among students and instructors. To understand the system that produces exposures and to plan for implementing control options, the generation of formaldehyde vapors must be characterized. A gross anatomy laboratory with 47 dissecting tables was studied during 15 lab sessions over a period of 16 weeks. Area concentrations were measured using National Institute of Occupational Safety and Health (NIOSH) method 3500. Average daily area concentrations in the laboratory ranged from 0.635 to 1.82 mg/m3. The ventilation was characterized on three separate days. The laboratory had a general ventilation rate of 9.8 air changes per hour. There was no local exhaust ventilation. The concentration measurements were used in a mass balance model along with ventilation rates to determine formaldehyde emission rates. The daily average formaldehyde emission rate from all sources in the laboratory ranged from 95.2-274 mg/min, with an average of 148 mg/min over the course of the study. This total emission rate was used along with the number of dissecting tables to develop an emission factor of 3.15 mg/min per table. The emission factor is a generalizable tool that can be used in laboratories of various sizes to predict emission rates and develop control strategies. This emission factor is applicable where the cadavers are prepared with similar embalming fluid consisting of approximately 10 percent formaldehyde.


Subject(s)
Air Pollutants, Occupational/analysis , Air Pollution, Indoor/analysis , Formaldehyde/analysis , Occupational Exposure/analysis , Anatomy , Cadaver , Humans , Laboratories , National Institute for Occupational Safety and Health, U.S. , United States , Ventilation
20.
Psychol Bull ; 127(5): 673-97, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11548973

ABSTRACT

The dynamic nature of the predictor-criterion relationship has long been a concern in psychology, especially with regard to the deterioration of validity over time. The authors examine P. L. Ackerman's ( 1987, 1988) hypothesized relationships between different types of predictors and criteria over time using data from previous longitudinal studies. Expert ratings categorized predictors and criteria according to P. L. Ackerman's model. Regression results support the predicted negative curvilinear relationship between cognitive ability and consistent and inconsistent task performance but do not support the predicted relationships between perceptual speed ability and psychomotor ability and consistent and inconsistent task performance. Deterioration of validity was more ubiquitous than has been suggested previously, and the pervasive form of deterioration was cubic with a negative trend. Findings are discussed in the context of catastrophe-chaos models.


Subject(s)
Psychometrics , Psychomotor Performance , Reaction Time , Humans , Models, Statistical , Nonlinear Dynamics , Reproducibility of Results
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