Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 69
Filter
1.
Ergonomics ; 66(10): 1465-1476, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36437777

ABSTRACT

Chair design features are typically compared using multiple seats, which can lead to confounding effects. Using a single chair, configurable to four designs (control, lumbar support, seat pan tilt and scapular relief), we investigated the effect of chair design on spine posture and movement, muscle activity and perceived pain in a sample of 31 asymptomatic adults. A total of 39% of the population were classified as pain developers, having significantly higher peak pain levels across most body regions. The lumbar support and seat pan tilt condition resulted in more neutral spine and pelvic postures. Greater muscle activity was found in the seat pan condition and non-pain developers displayed lower spine muscle activation levels overall. Despite some improvements in spine posture, sitting-induced pain was present in the study sample at similar proportions to those reported previously. Future studies may consider investigating interventions targeted to sitting-induced pain developers as opposed to the general population. Practitioner summary: Four office chair configurations were tested. The lumbar support and seat pan tilt conditions resulted in the most neutral back posture but did not mitigate the clinically significant levels of sitting-induced pain experienced by a large portion of the tested sample. Future work should target interventions to these individuals.


Subject(s)
Back Muscles , Low Back Pain , Adult , Humans , Low Back Pain/etiology , Low Back Pain/prevention & control , Spine/physiology , Lumbar Vertebrae/physiology , Posture/physiology , Pain Perception
2.
Chiropr Man Therap ; 30(1): 62, 2022 12 30.
Article in English | MEDLINE | ID: mdl-36585725

ABSTRACT

BACKGROUND: Spinal manipulation has been shown to affect muscle activity, posture, and pain. To date, no studies have examined the effect of manipulation on biomechanical factors during sitting. Therefore, the purpose of this study was to investigate the immediate effect of lumbar spinal manipulation on trunk muscle activation, spine posture and movements, and perceived ratings of transient pain in asymptomatic adults during prolonged office sitting. METHODS: Twenty healthy adults were recruited for a single laboratory session that included a standardized office sitting/data entry protocol (120 min total, 3 blocks of 40 min). Data were collected between July and August 2012. The first block (baseline) was immediately followed by two experimental blocks. Prior to the start of each experimental block, participants were transferred to a therapy plinth and placed side lying (right side down), and a random presentation of either a control or high velocity low amplitude thrust directed at L4/L5 was delivered. Continuous measures of muscle activity, spine posture, and spine movements were recorded throughout the sitting trials. Perceived transient pain was measured by visual analogue scale at 10-min intervals (including immediately before and after the randomized maneuvers). RESULTS: There were no significant differences in spine or pelvic posture or perceived back pain following either the manipulation or control maneuvers. Significantly reduced muscle activity and increased shifts of the lumbar spine angle were identified in the block following manipulation compared to both baseline and post control blocks. CONCLUSIONS: Spinal manipulation does not appear to have an immediate impact on spine or pelvic posture in healthy adults but does appear to reduce muscle activity and increase spine movement during sitting. Future work should replicate this study with a larger population in a field setting. It may be worthwhile to explore the implication of reduced muscle activation and increased spine movements during prolonged sitting for office workers that receive manipulations or mobilizations during their workday.


Subject(s)
Manipulation, Spinal , Sitting Position , Adult , Humans , Cross-Sectional Studies , Muscle, Skeletal/physiology , Lumbar Vertebrae , Back Pain
3.
Appl Ergon ; 97: 103546, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34399370

ABSTRACT

This study investigates the effects of a dynamic seat pan design on sitting biomechanics, perceived pain and seat movement compared to a control. Thirty male participants were recruited for two experimental sessions consisting of a 2-h sitting exposure (standardized typing task). Spine angles, back muscle activity, perceived pain and calf circumference were measured pre and post exposure. Sitting in the dynamic condition resulted in lower pain ratings (p = 0.031), decreased calf circumference (p < 0.001), lower average seat pressure (p < 0.001), and greater seat contact area (p = 0.003) compared to the control. Spine angles and low back EMG for all 6 muscles showed no significant differences between chair conditions. These results suggest this dynamic seat pan design is effective at decreasing several negative components associated with sitting for the occupant. Future work should examine the longer-term effects of dynamic office chair features in the field setting with a more generalizable population.


Subject(s)
Low Back Pain , Posture , Biomechanical Phenomena , Ergonomics , Humans , Male , Pain Perception , Spine
4.
J Electromyogr Kinesiol ; 58: 102545, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33756279

ABSTRACT

Viscoelastic creep of spine tissue, induced by submaximal spine flexion in sitting, can delay the onset of the flexion-relaxation phenomenon (FRP) and low back reflexes (LBR). Theoretically, these two outcome measures should be correlated; however, no studies have investigated this. This study aims to determine whether 30 min of near-maximal spine flexion will affect the onset of FRP and LBR in the lumbar erector spinae (LS) and lumbar multifidus (LM), and to examine the relation between these parameters. 15 participants were recruited (9F, 6M). Spine angle (between L1 and S2) was monitored synchronously with bilateral muscle activity in the LS (L1) and the LM (L4). FRP onset and LBR were measured in a randomized order before and after 30 min of slouched sitting. No significant difference was found for any muscle LBR onset time between pre and post-sitting (p > 0.05). A significant increase in FRP onset was found in the RLM (p = 0.016) following sitting. No significant correlation was found between the FRP and the LBR for any muscle. These results suggest that the LBR onset might not be as sensitive as an outcome measure to investigate shorter exposures of sitting as FRP.


Subject(s)
Muscle Relaxation , Paraspinal Muscles/physiology , Reflex , Sitting Position , Adult , Humans , Lumbosacral Region/physiology , Range of Motion, Articular
5.
Physiotherapy ; 104(4): 408-416, 2018 12.
Article in English | MEDLINE | ID: mdl-30477678

ABSTRACT

OBJECTIVES: To compare the effects of two similar 6-month protocols of high-intensity exercise training, in water and on land, in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Randomised controlled trial. SETTING: University-based outpatient clinic. PARTICIPANTS: Thirty-six patients with predominantly moderate-to-severe COPD completed the study. INTERVENTION: Patients were evaluated at baseline, at 3 months and at the end of the programme (i.e. 6 months). For both groups, the 6-month protocol consisted of high-intensity endurance and strength exercises with gradual increase in time and/or workload, totalling 60 sessions. MAIN OUTCOMES: Objective monitoring of physical activity in daily life (PADL, primary outcome), lung function, peripheral and respiratory muscle strength, body composition, maximal and submaximal exercise capacity, functional status, quality of life, and symptoms of anxiety and depression. RESULTS: After 6 months of training, a significant improvement in PADL was seen for both groups [mean difference (95% confidence interval): land group 993 (358 to 1628) steps/day; water group 1669 (404 to 2934) steps/day]. Significant improvements were also seen in inspiratory, expiratory and peripheral muscle strength; maximal and submaximal exercise capacity; quality of life and functional status for both groups. There were no significant improvements in lung function, body composition, and symptoms of anxiety and depression for either group. No difference was found in the magnitude of improvement between the two types of training for any outcome. CONCLUSION: High-intensity exercise training in water generates similar effects compared with training on land in patients with moderate-to-severe COPD, rendering it an equally beneficial therapeutic option for this population. CLINICAL TRIAL REGISTRATION NUMBER: NCT01691131.


Subject(s)
Exercise Therapy/methods , Pulmonary Disease, Chronic Obstructive/rehabilitation , Water , Activities of Daily Living , Aged , Aged, 80 and over , Body Composition , Comorbidity , Female , Humans , Male , Middle Aged , Muscle Strength , Physical Endurance , Quality of Life , Spirometry , Trauma Severity Indices
6.
Transplant Proc ; 50(3): 728-736, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29661425

ABSTRACT

BACKGROUND: Pretransplantation soluble CD30 (sCD30) has been shown to be a good predictor of acute rejection (AR) and graft loss. This study aimed to evaluate the effectiveness of sCD30 measured pretransplant and up to 6 months after transplantation as a predictor of AR, graft loss, and survival at 5 years post-transplantation. Subjects were patients receiving living donor renal transplants at Bonsucesso Federal Hospital (Rio de Janeiro) in 2006 and between August 2010 and May 2011. METHODS: sCD30 was analyzed in samples collected pretransplantation and 7, 14, and 21, 28 days and 3, 4, 5, and 6 months post-transplantation from 73 kidney recipients. RESULTS: Patients in the AR group did not present a positive correlation with the sCD30 levels pretransplant (P = .54); in the post-transplant period, the 7- to 14-day samples showed patients with AR had higher levels of this biomarker (P = .036). The graft survival in 5 years of follow-up was not different between groups. CONCLUSIONS: The best time to predict AR using sCD30 is the 7- to 14-day sample; however, identifying and following the decrease of this biomarker from pre- to post-transplant seems to be better than just 1 measurement. The sCD30 post-transplant is another tool that may be used in monitoring patients after renal transplantation.


Subject(s)
Graft Rejection/blood , Graft Survival/physiology , Ki-1 Antigen/blood , Kidney Transplantation/adverse effects , Adult , Biomarkers/blood , Female , Humans , Male , Middle Aged , Postoperative Period , Predictive Value of Tests , Preoperative Period , Time Factors
7.
Environ Monit Assess ; 190(2): 77, 2018 Jan 10.
Article in English | MEDLINE | ID: mdl-29322345

ABSTRACT

Total mercury (THg) concentrations measured in two freshwater shrimp species (Macrobrachium depressimanum and Macrobrachium jelskii) showed a relationship with the location of artisanal and small-scale gold mining (ASGM) from the Madeira River Basin, Western Amazon. Between August 2009 and May 2010, 212 shrimp samples were collected in the confluence of the Madeira River with three of its tributaries (Western Amazon). THg concentration was quantified in the exoskeleton, hepatopancreas and muscle tissue of the shrimps by cold vapor atomic absorption spectrophotometry. There were no significant differences between the two shrimp species when samples came from the Madeira River, but Hg concentrations were significantly lower in a tributary outside the influence of the gold mining area. Average THg concentrations were higher in the hepatopancreas (up to 160.0 ng g-1) and lower in the exoskeleton and muscle tissue (10.0-35.0 ng g-1 and < 0.9-42.0 ng g-1, respectively). Freshwater shrimps from the Madeira River respond to local environmental levels of Hg and can be considered as biomonitors for environmental Hg at this spatial scale. These organisms are important for moving Hg up food webs including those that harbor economic significant fish species and thus enhancing human exposure.


Subject(s)
Gold , Mercury/analysis , Mining , Palaemonidae , Water Pollutants, Chemical/analysis , Animal Shells/chemistry , Animals , Brazil , Environmental Monitoring , Hepatopancreas/chemistry , Muscles/chemistry , Rivers
8.
Bone Marrow Transplant ; 52(10): 1384-1389, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28737776

ABSTRACT

Individual therapeutic monitoring of busulfan (BU) minimizes its toxicity and improves the therapeutic outcomes during hematopoietic stem cell transplantation (HSCT). For individual dose adjustment, several blood collections are performed that are uncomfortable for patients. The aim of this pilot study was to validate a laboratory method for quantification of BU in saliva and to present the results obtained using this protocol in HSCT patients. We performed analyses of selectivity, precision and accuracy of saliva with standard concentrations of BU using ultra-high-performance liquid chromatography with diode array detection. We also determined salivary and plasmatic concentrations of BU in six HSCT patients. Saliva exhibited excellent selectivity, precision and accuracy for quantification of BU. In the patient samples, significant correlations were noted between plasmatic and salivary concentrations of BU (r=0.97, P<0.001 in the test dose; r=0.93, P<0.001 in the adjusted dose). Passing &Bablok regression revealed good agreement between the two methods (R2=0.956 for test dose; R2=0.927 for adjusted dose). In conclusion, the saliva is safe for laboratory BU measurement. The good agreement with plasma encourages further clinical studies using saliva for BU therapeutic monitoring.


Subject(s)
Busulfan/administration & dosage , Busulfan/pharmacokinetics , Hematopoietic Stem Cell Transplantation , Saliva/metabolism , Transplantation Conditioning , Adult , Allografts , Female , Humans , Male , Middle Aged , Pilot Projects
9.
Ann Dermatol Venereol ; 143(11): 691-696, 2016 Nov.
Article in French | MEDLINE | ID: mdl-27646571

ABSTRACT

BACKGROUND: The clinical polymorphism of syphilis leads to diagnostic issues. We report a case of secondary syphilis revealed by skin and mucosal erosions, and responsible for sensorineural hearing loss and asymptomatic papillitis. PATIENTS AND METHODS: A 55-year-old man presented oral and peri-anal erosions as the initial symptoms of secondary syphilis. He reported hypoacusis and a pure-tone audiogram revealed bilateral sensorineural hearing loss. Ophthalmological investigation revealed isolated right papillitis and superior temporal scotoma with blind-spot enlargement. TPHA-VDRL serology was strongly positive for plasma (TPHA 1/10,240 and VDRL 1/64) but doubtful for cerebrospinal fluid. For his hearing and eye disorders, considered as related to neurosyphilis, the patient received a 14-day course of intravenous penicillin G, associated with systemic corticosteroids with gradual reduction over a period of fifteen weeks. The patient's skin and mucosal erosions resolved, as did his papillitis. His hearing loss remained stable. Serological monitoring at three months showed a sixteen-fold decrease in VDRL titre. DISCUSSION: The re-emergence of syphilis has led to increasing incidence of related ophthalmological and otological disorders. This report highlights the first-line role of the dermatologist in systematic diagnosis and in screening for associated involvement.


Subject(s)
Anus Diseases/microbiology , Hearing Loss, Sensorineural/microbiology , Mouth Mucosa/microbiology , Papilledema/microbiology , Syphilis/diagnosis , Humans , Male , Middle Aged
10.
Environ Sci Pollut Res Int ; 23(10): 9640-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26846239

ABSTRACT

Damming rivers to construct hydroelectric reservoirs results in a series of impacts on the biogeochemical Hg cycle. For example, modifying the hydrodynamics of a natural watercourse can result in the suspension and transport of Hg deposits in the water column, which represents an exposure risk for biota. The objective of this study was to evaluate the influences of seasonality on the dispersion of total Hg in the Hydroelectric Power Plant (HPP)-Samuel Reservoir (Porto Velho/Brazil). Sampling campaigns were performed during the three following hydrological periods characteristic of the region: low (Oct/2011), ebbing (May/2012), and high (Feb/2013) water. Sediment profiles, suspended particulate matter (SPM), and aquatic macrophytes (Eicchornia crassipes and Oryza spp.) were collected, and their Hg concentrations and isotopic and elemental C and N signatures were determined. The drainage basin significantly influenced the SPM compositions during all the periods, with a small autochthonous influence from the reservoir during the low water. The highest SPM Hg concentrations inside the reservoir were observed during the high water period, suggesting that the hydrodynamics of this environment favor the suspension of fine SPM, which has a higher Hg adsorption capacity. The Hg concentrations in the sediment profiles were ten times lower than those in the SPM, indicating that large particles with low Hg concentrations were deposited to form the bottom sediment. Hg concentrations were higher in aquatic macrophyte roots than in their leaves and appeared to contribute to the formation of SPM during the low water period. In this environment, Hg transport mainly occurs in SPM from the Jamari River drainage basin, which is the primary source of Hg in this environment.


Subject(s)
Geologic Sediments/analysis , Mercury/analysis , Particulate Matter/analysis , Power Plants , Rivers/chemistry , Water Pollutants, Chemical/analysis , Brazil , Environmental Monitoring , Geologic Sediments/chemistry , Mercury/chemistry , Particulate Matter/chemistry
11.
Neuroscience ; 313: 36-45, 2016 Jan 28.
Article in English | MEDLINE | ID: mdl-26601772

ABSTRACT

The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Most of the studies involving the role of the LC in hypercapnic ventilatory responses have been performed in males. Since ovarian steroids modulate the activity of LC neurons and females have a different respiratory response to CO2 than males, we evaluated the activity of LC noradrenergic neurons during normocapnia and hypercapnia in female and male rats with distinct sex hormone levels. Ovariectomized (OVX), estradiol (E2)-treated ovariectomized (OVX+E2) and female rats on the diestrous day of the estrous cycle were evaluated. Concurrently, males were investigated as gonad-intact, orchidectomized (ORX), testosterone (T)-treated ORX (ORX+T), and E2-treated ORX (ORX+E2). Activation of LC neurons was determined by double-label immunohistochemistry to c-Fos and tyrosine hydroxylase (TH). Hypercapnia induced by 7% CO2 increased the number of c-Fos/TH-immunoreactive (ir) neurons in the LC of all groups when compared to air exposure. Hypercapnia-induced c-Fos expression did not differ between diestrous females and intact male rats. In the OVX+E2 group, there was attenuation in the c-Fos expression during normocapnia compared with OVX rats, but CO2 responsiveness was not altered. Moreover, in ORX rats, neither T nor E2 treatments changed c-Fos expression in LC noradrenergic neurons. Thus, in female rats, E2 reduces activation of LC noradrenergic neurons, whereas in males, sex hormones do not influence the LC activity.


Subject(s)
Gonadal Steroid Hormones/metabolism , Hypercapnia/physiopathology , Locus Coeruleus/physiology , Sex Characteristics , Air , Animals , Carbon Dioxide/administration & dosage , Carbon Dioxide/metabolism , Castration , Disease Models, Animal , Female , Gonadal Steroid Hormones/administration & dosage , Immunohistochemistry , Male , Neurons/physiology , Proto-Oncogene Proteins c-fos/metabolism , Rats, Wistar , Tyrosine 3-Monooxygenase/metabolism
12.
Am J Transplant ; 13(12): 3155-63, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24266969

ABSTRACT

Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. In this multicenter, randomized, open-label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. Of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). The primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. Of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. In the intention-to-treat population there were no differences in eGFR (66.2 ± 25.3 vs. 70.7 ± 25.1, p = 0.817) or in the severity of chronic sclerosing lesions scores in 24-month protocol biopsies. Higher mean urinary protein-to-creatinine ratio (0.36 ± 0.69 vs. 0.15 ± 0.53, p = 0.03) and higher incidence of treated acute rejection between months 3-24 (13.4% vs. 4.7%, p = 0.047) were observed in SRL compared to TAC group. In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months.


Subject(s)
Graft Rejection/prevention & control , Kidney Transplantation , Renal Insufficiency/therapy , Sirolimus/administration & dosage , Tacrolimus/administration & dosage , Adult , Biopsy , Creatinine/blood , Female , Glomerular Filtration Rate , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Prednisone/administration & dosage , Prospective Studies , Sirolimus/adverse effects , Tacrolimus/adverse effects , Treatment Outcome
13.
J Fish Biol ; 83(3): 671-6, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23991882

ABSTRACT

This study distinguished hybrids of surubim or pintado Pseudoplatystoma corruscans and cachara Pseudoplatystoma reticulatum from pure strains using a set of eight microsatellite markers and population assignment methods. Applications of this molecular tool range from certification of hybrid-free breeders in restocking conservation programmes to the identification of fish products lacking traditional morphological characteristics.


Subject(s)
Catfishes/genetics , Hybridization, Genetic , Microsatellite Repeats , Alleles , Animals , Brazil , Chimera/genetics , Conservation of Natural Resources , Gene Frequency , Genetic Loci , Principal Component Analysis
14.
Int J Tuberc Lung Dis ; 17(4): 499-504, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23394127

ABSTRACT

SETTING: Isoniazid (INH) is related to the development of hepatotoxicity in some patients. OBJECTIVE: To investigate the role of N-acetyl transferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) in the hepatotoxicity of patients treated with INH in an Amazonian Brazilian population. DESIGN: Patients undergoing anti-tuberculosis treatment were investigated. Hepatotoxicity was defined as an increase of more than three times the upper limit of normal in serum alanine aminotransferase levels after treatment. NAT2 genotypes were identified by sequencing, whereas CYP2E1 alleles were detected using polymerase chain reaction based methods. RESULTS: Of the 270 individuals included in the study, 18 (6.7%) developed drug-related hepatotoxicity. A high association was found between slow acetylators and hepatotoxicity, particularly with regard to allele *5. The adjusted risk of developing hepatotoxicity was significant in individuals carrying two slow acetylation alleles (P = 0.036, OR 3.05, 95%CI 1.07-8.64). In all of the CYP2E1 markers examined, wild homozygous genotypes were more prevalent in subjects with hepatotoxicity than in controls; however, the difference was not statistically significant. Joint evaluation of the genes revealed a high risk of developing hepatotoxicity in slow acetylators with CYP2E1 wild alleles (adjusted OR 4.26; 95%CI 1.47-12.37, P = 0.008). CONCLUSIONS: Large-scale screening for NAT2 and CYP2E1 genotypes can prove useful in predicting the risk of adverse effects.


Subject(s)
Antitubercular Agents/adverse effects , Arylamine N-Acetyltransferase/genetics , Chemical and Drug Induced Liver Injury/genetics , Cytochrome P-450 CYP2E1/genetics , Isoniazid/adverse effects , Polymorphism, Single Nucleotide , Acetylation , Adult , Alanine Transaminase/blood , Antitubercular Agents/metabolism , Arylamine N-Acetyltransferase/metabolism , Biomarkers/blood , Brazil/epidemiology , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/enzymology , Chemical and Drug Induced Liver Injury/epidemiology , Chi-Square Distribution , Cytochrome P-450 CYP2E1/metabolism , Female , Gene Frequency , Genetic Predisposition to Disease , Heterozygote , Homozygote , Humans , Isoniazid/metabolism , Logistic Models , Male , Middle Aged , Odds Ratio , Phenotype , Polymerase Chain Reaction , Prevalence , Risk Assessment , Risk Factors , Up-Regulation , Young Adult
15.
Curr Mol Med ; 13(2): 296-304, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23228130

ABSTRACT

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts a cancer cell-specific pro-apoptotic activity. This property made the TRAIL associated pathway one of the most promising strategies aimed at inducing tumor-selective death. In fact, several approaches have been considered to explore this pathway for cancer therapy, such as recombinant TRAIL, agonist antibodies for TRAIL receptors, and adenoviral TRAIL. However, all of these approaches have certain disadvantages that limit their clinical use. Our recent discovery that the complex PRAME/EZH2 is able to repress TRAIL expression, in a cancer-specific manner, suggests an alternative approach for combined cancer therapy. A genetic or pharmacological inhibition of TRAIL repressors in cancer cells could restore endogenous TRAIL expression, thereby overcoming some of the limitations of and/or cooperating with previous approaches.


Subject(s)
Antigens, Neoplasm/genetics , Gene Expression Regulation, Neoplastic/drug effects , Neoplasm Proteins/genetics , Neoplasms/genetics , Polycomb Repressive Complex 2/genetics , TNF-Related Apoptosis-Inducing Ligand/genetics , Antigens, Neoplasm/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Enhancer of Zeste Homolog 2 Protein , Humans , Molecular Targeted Therapy , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Polycomb Repressive Complex 2/antagonists & inhibitors , Polycomb Repressive Complex 2/metabolism , Protein Binding/drug effects , RNA, Small Interfering/genetics , Signal Transduction/drug effects , TNF-Related Apoptosis-Inducing Ligand/agonists , TNF-Related Apoptosis-Inducing Ligand/metabolism
16.
Oncogene ; 30(2): 223-33, 2011 Jan 13.
Article in English | MEDLINE | ID: mdl-20838376

ABSTRACT

Tumor necrosis factor-related apoptosis-inducing ligand-TNFSF10 (TRAIL), a member of the TNF-α family and a death receptor ligand, was shown to selectively kill tumor cells. Not surprisingly, TRAIL is downregulated in a variety of tumor cells, including BCR-ABL-positive leukemia. Although we know much about the molecular basis of TRAIL-mediated cell killing, the mechanism responsible for TRAIL inhibition in tumors remains elusive because (a) TRAIL can be regulated by retinoic acid (RA); (b) the tumor antigen preferentially expressed antigen of melanoma (PRAME) was shown to inhibit transcription of RA receptor target genes through the polycomb protein, enhancer of zeste homolog 2 (EZH2); and (c) we have found that TRAIL is inversely correlated with BCR-ABL in chronic myeloid leukemia (CML) patients. Thus, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is upregulated in BCR-ABL cells and is associated with the progression of disease in CML patients. There is a positive correlation between PRAME and BCR-ABL and an inverse correlation between PRAME and TRAIL in these patients. Importantly, knocking down PRAME or EZH2 by RNA interference in a BCR-ABL-positive cell line restores TRAIL expression. Moreover, there is an enrichment of EZH2 binding on the promoter region of TRAIL in a CML cell line. This binding is lost after PRAME knockdown. Finally, knocking down PRAME or EZH2, and consequently induction of TRAIL expression, enhances Imatinib sensibility. Taken together, our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML.


Subject(s)
Antigens, Neoplasm/metabolism , DNA-Binding Proteins/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , TNF-Related Apoptosis-Inducing Ligand/metabolism , Transcription Factors/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Antigens, Neoplasm/analysis , Antineoplastic Agents/therapeutic use , Benzamides , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Carcinoma/drug therapy , Carcinoma/genetics , Carcinoma/metabolism , Cell Line , DNA-Binding Proteins/analysis , Disease Progression , Enhancer of Zeste Homolog 2 Protein , Fusion Proteins, bcr-abl/analysis , Fusion Proteins, bcr-abl/metabolism , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Melanoma/drug therapy , Melanoma/genetics , Melanoma/metabolism , Piperazines/therapeutic use , Polycomb Repressive Complex 2 , Promoter Regions, Genetic , Pyrimidines/therapeutic use , RNA Interference , TNF-Related Apoptosis-Inducing Ligand/analysis , TNF-Related Apoptosis-Inducing Ligand/genetics , Transcription Factors/analysis , Tumor Cells, Cultured , Up-Regulation
17.
Transplant Proc ; 42(5): 1659-66, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20620495

ABSTRACT

The safety and efficacy of concentration-controlled use of sirolimus (SRL) and cyclosporine (CsA) followed by CsA minimization (CsAm) or elimination (CsAe) beginning at week 13 was compared in a phase 4, open-label, randomized (1:1) trial of renal transplant recipients enrolled between March 2004 and November 2005. The primary endpoint was renal function, measured at 12 months using the Nankivell formula, in patients remaining on therapy. Though a total enrollment of 140 patients in each group was planned to provide an 80% power to detect a difference in means, only 207 subjects were enrolled in this study. Demographic characteristics were similar between groups, with 98.1% recipients of first grafts, 69.1% from living donors, and 7.2% diabetics. At 12 months, there were no differences in renal function (61.08 vs 65.24 mL/min, P = .132); incidence of biopsy-confirmed acute rejection (14.3% vs 22.5%, P = .152); and patient (89.5% vs 92.2%, P = .632), graft (87.6% vs 88.2%, P = .999), and death-censored graft (98.1% vs 94.1%, P = .166) survivals between CsAm and CsAe groups, respectively. There were no differences in the overall rate of study-drug discontinuation (32.4% vs 36.3%, P = .562) but more patients discontinued because of lack of efficacy/graft loss in the CsAe group (4.8% vs 14.7%, P = .018). This study was underpowered to demonstrate the superiority of one regimen over the other. In summary, SRL immunotherapy combined with CsA minimization or elimination showed comparative safety and efficacy. Both regimens offer potential treatment options for de novo renal allograft recipients.


Subject(s)
Cyclosporine/therapeutic use , Kidney Transplantation/immunology , Sirolimus/therapeutic use , Adult , Cadaver , Cyclosporine/adverse effects , Dose-Response Relationship, Drug , Drug Therapy, Combination , Ethnicity , Female , Histocompatibility Testing , Humans , Immunosuppressive Agents/therapeutic use , Kidney Function Tests , Kidney Transplantation/mortality , Kidney Transplantation/physiology , Living Donors , Male , Patient Selection , Tissue Donors , Transplantation, Homologous , Treatment Failure , Treatment Outcome
18.
Cell Biol Toxicol ; 25(6): 523-32, 2009 Dec.
Article in English | MEDLINE | ID: mdl-18975118

ABSTRACT

Purified phospholipase A2 (PLA2) enzymes from Bothrops jararacussu snake venom were examined to evaluate NIH 3T3 and COS7 fibroblast cytotoxicity, as well as muscle myotoxic and inflammatory activities. Separation of fractions Bj-VII (from BthTX-I; a Lys49 PLA2 homolog) and 6-1 and 6-2 (from BthTX-II; an Asp49 PLA2) from B. jararacussu snake venom by SDS-PAGE in tricine buffer in the absence and presence of dithiothreitol revealed a homodimer with an estimated molecular mass of approximately 30 kDa (monomer mass approximately 15 kDa). This finding indicates that these toxins form dimeric complexes-a previously reported tendency among PLA2s. These toxins were assayed for viability with the MTT assay, which is used to examine the effects of phospholipases on the mitochondrial viability of cells. The toxins were also assayed for cytolysis of the fibroblast cell lines NIH 3T3 and COS7 by quantification of lactate dehydrogenase released into the medium. The results indicate that the PLA2s 6-1, 6-2 and the Bj-VII PLA2 homolog studied here induce moderate footpad edema and local myotoxicity. Moreover, exposure to these phospholipases led to a reduction in fibroblast viability; at the 1 muM dose of PLA2 tested, a reduction of 50% in cell viability was observed. The present findings indicate that the inflammatory activity observed in envenomation may be correlated with the cytotoxicity observed in fibroblasts.


Subject(s)
Bothrops , Cell Survival/drug effects , Crotalid Venoms , Edema/chemically induced , Fibroblasts/drug effects , Group II Phospholipases A2/isolation & purification , Group II Phospholipases A2/toxicity , Mitochondria/drug effects , Muscles/drug effects , Reptilian Proteins/toxicity , Animals , COS Cells , Chlorocebus aethiops , Hindlimb , Inflammation/chemically induced , Mice , NIH 3T3 Cells , Protein Structure, Quaternary , Sequence Homology, Amino Acid , Snake Bites
19.
Rev Neurol ; 43(2): 74-7, 2006.
Article in Spanish | MEDLINE | ID: mdl-16838253

ABSTRACT

INTRODUCTION: Carbamazepine (CBZ) is a pharmacological agent used to control epileptic syndromes. In refractory epilepsy patients, however, a second anticonvulsive drug such as lamotrigine (LTG) is often added. This association can reduce the frequency of the epileptic seizures and favour control over them. AIMS: This study was conducted to evaluate the plasma concentration of CBZ throughout a period of mono and polytherapy. Furthermore, tests were also carried out to determine whether any alterations were caused in the haematological parameters or in plasma concentrations by adding LTG to the therapy with CBZ. PATIENTS AND METHODS: This study involved a sample of refractory epilepsy patients who were following monotherapy with CBZ and who had a wholly unsatisfactory control over their bouts of seizures. LTG was thus added to these patients' treatment in an attempt to improve their control over the seizures. RESULTS AND CONCLUSIONS: On ending the study, we found that LTG did not interfere with the plasma concentrations of CBZ or give rise to any kind of alteration in the haematological parameters of any of the patients. Nevertheless, one patient did break out in a rash, which shows that therapeutic monitoring may be a key tool, especially when the treatment that is prescribed includes two drugs with a narrow therapeutic range.


Subject(s)
Anticonvulsants/therapeutic use , Carbamazepine/therapeutic use , Drug Interactions , Epilepsy/drug therapy , Triazines/therapeutic use , Adolescent , Adult , Anticonvulsants/blood , Carbamazepine/blood , Dose-Response Relationship, Drug , Epilepsy/blood , Humans , Lamotrigine , Middle Aged , Triazines/blood
20.
Transplant Proc ; 37(6): 2746-7, 2005.
Article in English | MEDLINE | ID: mdl-16182798

ABSTRACT

To evaluate the frequency of delayed graft function (DGF) in kidney transplant centers in Brazil, we sent a questionnaire requesting information on the number of cadaveric donor kidney transplants performed during the years 2000, 2001, and 2002, the number of early nonfunctioning grafts, and the number of patients on dialysis during the first posttransplant week with subsequent recovery. Among all centers performing more than 50 kidney transplants during the last year of evaluation, 6, performing 612 cadaveric kidney transplants during the study period, replied to the questionnaire. Sixty procedures (9.7%) resulted in nonfunctioning grafts, while 312 (55.6%) patients required dialysis during the first Ptx week: 216 (53.9%) in 2000, 189 (62.3%) in 2001, and 216 (51.6%) in 2002. The frequency of DGF during the study period was higher than that noted by several previous foreign studies. To better evaluate the possible causes of this finding, a more extensive and focused study is warranted.


Subject(s)
Kidney Transplantation/physiology , Brazil , Cadaver , Humans , Kidney Transplantation/statistics & numerical data , Retrospective Studies , Surveys and Questionnaires , Tissue Donors , Treatment Failure , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...