RESUMO
OBJECTIVE: To combine non-contrast computerized tomography (NCCT)-based parameters with stone and patient characteristics that are already known to affect shock wave lithotripsy (SWL) success and assess this novel model's effectiveness in predicting SWL success for single ureteral stones in different locations. MATERIALS AND METHODS: Data of patients treated by SWL for a single ureteral stone between January 2017 and January 2019 were retrospectively reviewed. Demographic parameters of patients and stone characteristics were combined with NCCT-based parameters. NCCT-based parameters included the presence or absence of hydronephrosis, perinephric stranding, periureteral edema, diameter of the proximal ureter, ureteral wall thickness (UWT) at ureteral stone site. The logistic regression method was used for the development of a useful predictive model. Subsequently, the receiver operating curve was used to determine cut-off levels, and a scoring system was developed for prediction of SWL success. RESULTS: Stone-free rate was 77,1% (267/346) in the entire cohort. Univariate analysis revealed that age, stone volume, density, perinephric stranding, diameter of proximal ureter, and UWT, were associated with SWL success. In multivariate analysis, proximal ureteral stone location, stone volume, density, and UWT were independent predictors of SWL success. The formula used during logistic regression analysis was: 1/[1 + exp {-8.856 + 0.008 (stone volume) + 0.002 (stone density) + 0.673 (UWT) + 1026 (proximal ureteral stone)}]. The scores of 0, 1, 2, 3 and 4 were associated with 97,8%, 83,4%, 60,8%, 33,2% and 11,1% success rates, respectively, in the prediction model based on these parameters. CONCLUSION: We conclude that our model can facilitate decision-making for SWL treatment of ureteral stones in different locations.
Assuntos
Litotripsia , Cálculos Ureterais , Feminino , Humanos , Litotripsia/métodos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Cálculos Ureterais/complicações , Cálculos Ureterais/diagnóstico por imagem , Cálculos Ureterais/terapiaRESUMO
This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O6- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p = 0.02; OR: 0.662,95% CI: 0.430-1019, p = 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p = 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p = 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.
RESUMO
OBJECTIVE: To report three cases of severe skin reactions in patients treated with cladribine for multiple sclerosis. METHODS: Case study. RESULTS: Patients developed severe rash 3-192 days after receiving cladribine. All were effectively treated with steroids and antihistamines. Additional doses of cladribine were administered after pretreatment with steroids and anti-histamines. One patient developed mild recurrence following re-exposure, which resolved within three days, whilst another patient tolerated re-exposure without further adverse reaction. CONCLUSION: Severe skin reactions, well described in patients receiving cladribine for treatment of haematological conditions, may occur in patients treated with this compound for multiple sclerosis. Neurologists need to be aware of this rare, but significant adverse reaction. Re-exposure may be safe with standard pre-treatment against allergic reactions.
Assuntos
Cladribina , Imunossupressores , Esclerose Múltipla , Neoplasias , Cladribina/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , RecidivaRESUMO
Reactive oxygen species can bind protein, DNA, lipids, and carbohydrates and thus cause an oxidation reaction that induces various syndromes such as cardiovascular diseases, degenerative disease, and cancer types in the human body. Bioactive compounds, such as PUFA, EPA, DHA, and carotenoids in algae, have a chain ring and protect the tissue from chemical damage and reverse the symptoms of some diseases. Algal bioactives also have various biological properties such as anticoagulants, antiviral, antiangiogenic, antitumor, anti-inflammatory, antioxidant, antiproliferative, and immune modulation properties. This study aimed to show in vitro cytotoxic activity effect of Chlorella protothecoides and Nannochloropsis oculata microalgal extracts loaded nano-microparticles on A-172 (Homo sapiens brain glioblastoma) and HCT-116 (H. sapiens colon colorectal carcinoma) cell lines because of the increasing importance of algal biotechnology. MTT viability tests were performed on HUVEC, A172, and HCT 116 cells with particles obtained at optimum process parameters. The cell viability rates of encapsulated particles were also compared with pure algae extracts. Microalgal extracts loaded nano-micro particles showed very promising results for cytotoxic effect on cancer cells.
Assuntos
Antineoplásicos/farmacologia , Microalgas , Biotecnologia , Sobrevivência Celular/efeitos dos fármacos , Emulsões , Células HCT116 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Microalgas/química , Nanopartículas , Tamanho da PartículaRESUMO
BACKGROUND: Evidence suggests people with non-relapsing deteriorating ("progressive") multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices. METHODS: We report on two pwPMS, who were treated with subcutaneous cladribine undergoing CSF NfL testing, alongside MRI and clinical follow-up, before and after treatment. RESULTS: Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI detectable drop in disease activity. Disability mildly progressed in one, and remained stable in the other pwPMS. CONCLUSIONS: pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be a useful outcome in clinical trials targeting this patient group. Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option for pwPMS.
Assuntos
Cladribina/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla Crônica Progressiva/terapia , Adulto , Feminino , Humanos , Imunoterapia , Masculino , Esclerose Múltipla Crônica Progressiva/líquido cefalorraquidiano , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Absorção SubcutâneaRESUMO
1. The aim of the present study was to examine the effects of improving vitamin D status in broiler diets by supplementary 25-hydroxycholecalciferol (25OHD3), alone or in combination with calcium (Ca) and available phosphorus (aP), on live performance, sternum mineralisation and breast meat quality in broilers. 2. A total of 936 1-d-old Ross 308 broilers were used in the study. After gender determination at the hatchery, chicks from each sex were randomly distributed into three dietary treatments. The following dietary treatments were used in the experiment from hatch to 38 d: (1) A control diet formulated to meet all of the nutrient requirements of broiler chicks according to the management guide; (2) The control diet supplemented with 18.7-15.0 µg/kg of 25OHD3; and (3) The control diet supplemented with 18.7-15.0 µg/kg of 25OHD3 plus Ca + aP. 3. Improvement in vitamin D status by 25OHD3 supplementation, alone or in combination with Ca and aP, had no effect on body weight and feed conversion ratio of broilers. 4. The serum 25OHD3 concentration significantly increased with 25OHD3 and 25OHD3 plus Ca + aP supplementation (P < 0.05), whereas the ionised Ca and Mg concentrations remained unchanged. 5. Sternum absolute weight, ash content and the concentrations of Ca and P significantly increased (P < 0.01) with supplementation of 25OHD3, alone or in combination with Ca + aP. 6. Supplemental 25OHD3, alone or in combination with Ca + aP, slightly increased pH24 (P = 0.05) and decreased (P < 0.01) squeezable water loss in breast meat, whereas it had no significant effect on lightness, yellowness and sarcoplasmic protein solubility. 7. In conclusion, the results suggested that enhancing vitamin D status by 25OHD3 supplementation alone or in combination with Ca + aP may improve sternum structure and mineral accretion. Furthermore, supplemental 25OHD3, even in a nutritionally complete diet, may offer an effective way to improve protein solubility in female broilers.
Assuntos
Calcifediol/metabolismo , Cálcio da Dieta/metabolismo , Galinhas/fisiologia , Carne/análise , Fósforo na Dieta/metabolismo , Esterno/fisiologia , Ração Animal/análise , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Calcifediol/administração & dosagem , Cálcio da Dieta/administração & dosagem , Galinhas/sangue , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Masculino , Músculos Peitorais/fisiologia , Fósforo na Dieta/administração & dosagem , Distribuição Aleatória , Esterno/efeitos dos fármacos , Esterno/crescimento & desenvolvimentoRESUMO
BACKGROUND: Psoriasis is a common chronic inflammatory skin disease caused by genetic and epigenetic factors. There are conflicting results in the literature about the association between psoriasis and the methylenetetrahydrofolate reductase gene (MTHFR), ranging from strong linkage to no association. AIM: To investigate the association between the germline MTHFR polymorphisms C677T and A1298C with psoriasis risk in a Turkish population. METHODS: The study enrolled 84 patients with psoriasis and 212 healthy controls (HCs) without any history of psoriasis. DNA was extracted from peripheral blood samples of patients and HCs, and real-time PCR was used for genotyping. Results were compared by Pearson χ² test and multiple logistic regression models. RESULTS: The frequency of both the MTHFR 677TT and A1298C (homozygous) genotypes was statistically significantly different from HCs. Point mutations were detected in all patients with early-onset psoriasis (before the age of 20 years). The T allele of MTHFR 677 and the C allele of MTHFR 1298 increased psoriasis risk by 12.4- and 17.0-fold, respectively, in patients compared with HCs. CONCLUSION: A possible association was detected betweengermline MTHFR 677 C>T and 1298 A>C genotypes and psoriasis risk in a Turkish population. These results need to be confirmed in further studies with larger sample sizes.
Assuntos
Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Psoríase/genética , Adolescente , Adulto , Idoso , Alelos , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Prevalência , Psoríase/epidemiologia , Psoríase/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Turquia/epidemiologia , Adulto JovemRESUMO
There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.
Assuntos
Antineoplásicos Imunológicos/farmacologia , Cardiopatias/etiologia , Coração/efeitos da radiação , Lesões por Radiação/tratamento farmacológico , Trastuzumab/farmacologia , Animais , Antineoplásicos Imunológicos/administração & dosagem , Esquema de Medicação , Feminino , Ratos , Ratos Wistar , Volume Sistólico/efeitos da radiação , Trastuzumab/administração & dosagemRESUMO
AIM: To investigate the cause of morphology in non-ovoid multiple sclerosis (MS) lesions lacking a radial course and typical shape. MATERIALS AND METHODS: Non-ovoid atypical lesions without perpendicular extensions to the ventricle were investigated in 95 MS patients by retrospective examination of T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. The relationship between the morphology of these atypical lesions detected in 38 patients and central vein anatomy was examined using susceptibility-weighted imaging (SWI). RESULTS: A central venous structure was observed in 107 (65.6%) of 163 atypical lesions in 38 patients. The distribution of atypical lesions grouped by their shape was as follows: (1) V- or Y-shaped lesions (n=27, 48.6%) were observed where veins bifurcated; (2) crescent-shaped lesions (n=9, 8.4%) were observed where veins formed an arc; (3) patchy lesions comprised 48.6% (n=52) of the atypical lesions and involved multiple medullary veins or medullary veins showing a "caput medusae" distribution; (4) ovoid lesions with a non-radial course (n=19, 17.7%) were generally observed where medullary veins converged to form internal cerebral vein branches. CONCLUSION: Unlike typical MS plaques, non-ovoid atypical lesions make the differential diagnosis of MS challenging. Demonstration of the relationship between venous anatomy and lesion morphology in atypical lesions using SWI will aid in the differential diagnosis.
Assuntos
Encéfalo/irrigação sanguínea , Esclerose Múltipla/patologia , Veias/patologia , Adolescente , Adulto , Diagnóstico Diferencial , Suscetibilidade a Doenças , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p < 0.05), and the combination of both increased muscle strength (p < 0.05) in rats. In our histopathological evaluation, misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90, mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in TES and DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p < 0.05). In this study, blood oxidative stress marker malondialdehyde was increased slightly but not significantly in TES and DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups. These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats.
Assuntos
Androgênios/toxicidade , Desidroepiandrosterona/toxicidade , Coração/efeitos dos fármacos , Miocárdio , Estresse Oxidativo/efeitos dos fármacos , Testosterona/toxicidade , Androgênios/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Cardiotoxicidade , Desidroepiandrosterona/administração & dosagem , Relação Dose-Resposta a Droga , Ecocardiografia , Masculino , Atividade Motora/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Ratos Wistar , Testosterona/administração & dosagemRESUMO
BACKGROUND: Growing evidence demonstrates the neuroprotective effects of statins, and the risk to develop an intracerebral hemorrhage (ICH) using statins has been refuted. However, some controversy remains regarding their role in the acute phase after ICH onset. Therefore, we performed a systematic review to investigate this issue. METHODS: We searched in MEDLINE, Web of Knowledge, and Scopus databases for studies examining the outcome in patients with spontaneous ICH and statin use. The analysis was performed for short-term (≤3 months) and long-term outcome (≥6 months) and a further subanalysis considered studies seeking for the effects of the discontinuation of statin after ICH onset. A random-effect model was applied, and country was used as a cofactor for meta-regression; odds ratios (ORs) with 95% confidence intervals (CIs) are offered. RESULTS: A total of 17 studies were included, only 1 pseudo cohort trial assessed the new use of statin after ICH onset and 3 studies evaluated the suspension of statin after ICH onset, the rest of the studies focused on the effect of the regular use of statin before ICH onset. The number of patients with an ICH exposed and not exposed to statins were 3455 and 11,821, respectively. The absolute short-term mortality was 27.3% in statin users and 33% in nonusers that represented a significant risk reduction of mortality (OR, .73; 95% CI, .54-.97). For long-term mortality, the effect was less evident (OR, .71; 95% CI, .43-1.15). The analysis of the 3 studies assessing the discontinuation of statins suggested a reduction of mortality risk by continuing statin (OR, .14; 95% CI, .1-.20). CONCLUSIONS: The current evidence suggests that continuing statin after ICH onset might be highly related to improvement of the outcome of patients with ICH. Despite this strong suggestion, randomized controlled trials should be performed to further investigate this association.
Assuntos
Hemorragia Cerebral/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hemorragia Cerebral/mortalidade , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Humanos , Masculino , Razão de Chances , Resultado do TratamentoRESUMO
OBJECTIVE: Taurine is an abundant amino acid that is widely distributed in human and animal tissues. Pharmacodynamic studies show that taurine has hypotensive and myocardial protective effects. Studies in isolated tissue baths show that taurine relaxes precontracted arteries. This study aimed to show the effects of taurine on human internal mammary artery (IMA) in vitro and to explain the mechanisms of its effects. METHODS: The response in the IMA was recorded isometrically by a force displacement transducer in isolated organ baths. Taurine (20, 40, 80 mM) was added to organ baths after precontraction with KCl (45 mM) or serotonin (5-HT, 30 µM). Taurine-induced relaxations were also tested in the presence of the cyclooxygenase inhibitor indomethacin (10 µM), the nitric oxide synthase inhibitor L-NAME (100 µM), the large conductance Ca2+-activated K+ channel inhibitor tetraethylammonium (TEA, 1 mM), the ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 10 µM), the voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, 1 mM) and the inward rectifier K+ channel inhibitor barium chloride (BaCl2, 30 µM). RESULTS: Taurine did not affect the resting tone of IMA. However, it produced relaxation in the 5-HT and KCl -precontracted preparations. The relaxation to IMA was not affected by GLI, 4-AP, BaCl2, indomethacin and L-NAME. But, TEA inhibited taurine -induced relaxations significantly (p < 0.05). CONCLUSIONS: The preincubation of IMA with taurine antagonized KCl and 5-HT induced contractions in a concentration dependent manner, while it did not affect the resting tone. The relaxations to taurine were significantly antagonized by pretreatment with TEA. These results suggest that mechanism of vasodilator effect of taurine in IMA may be the activation of large conductance Ca2+-activated K+ channels.
Assuntos
Artéria Torácica Interna/efeitos dos fármacos , Canais de Potássio/agonistas , Taurina/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Glibureto/farmacologia , Humanos , Artéria Torácica Interna/fisiologia , Técnicas de Cultura de Órgãos , Canais de Potássio/fisiologia , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Vasodilatadores/farmacologiaRESUMO
The aim of this study was to determine the independent risk factors, morbidity, and mortality of central nervous system (CNS) infections caused by Listeria monocytogenes. We retrospectively evaluated 100 episodes of neuroinvasive listeriosis in a multinational study in 21 tertiary care hospitals of Turkey, France, and Italy from 1990 to 2014. The mean age of the patients was 57 years (range, 19-92 years), and 64% were males. The all-cause immunosuppression rate was 54 % (54/100). Forty-nine (49 %) patients were referred to a hospital because of the classical triad of symptoms (fever, nuchal rigidity, and altered level of consciousness). Rhombencephalitis was detected radiologically in 9 (9 %) cases. Twenty-seven (64 %) of the patients who had cranial magnetic resonance imaging (MRI) performed had findings of meningeal and parenchymal involvement. The mean delay in the initiation of specific treatment was 6.8 ± 7 days. Empiric treatment was appropriate in 52 (52 %) patients. The mortality rate was 25 %, while neurologic sequelae occurred in 13 % of the patients. In the multivariate analysis, delay in treatment [odds ratio (OR), 1.07 [95 % confidence interval (CI), 1.01-1.16]] and seizures (OR, 3.41 [95 % CI, 1.05-11.09]) were significantly associated with mortality. Independent risk factors for neurologic sequelae were delay in treatment (OR, 1.07 [95 % CI, 1.006-1.367]) and presence of bacteremia (OR, 45.2 [95 % CI, 2.73-748.1]). Delay in the initiation of treatment of neuroinvasive listeriosis was a poor risk factor for unfavorable outcomes. Bacteremia was one of the independent risk factors for morbidity, while the presence of seizures predicted worse prognosis. Moreover, the addition of aminoglycosides to ampicillin monotherapy did not improve patients' prognosis.
Assuntos
Listeria monocytogenes/isolamento & purificação , Meningite por Listeria/diagnóstico , Meningite por Listeria/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Coortes , Feminino , França , Humanos , Itália , Masculino , Meningite por Listeria/epidemiologia , Meningite por Listeria/patologia , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Turquia , Adulto JovemRESUMO
The RUNX1/ETO (RE) fusion protein, which originates from the t(8;21) chromosomal rearrangement, is one of the most frequent translocation products found in de novo acute myeloid leukemia (AML). In RE leukemias, activated forms of the c-KIT tyrosine kinase receptor are frequently found, thereby suggesting oncogenic cooperativity between these oncoproteins in the development and maintenance of t(8;21) malignancies. In this report, we show that activated c-KIT cooperates with a C-terminal truncated variant of RE, REtr, to expand human CD34+ hematopoietic progenitors ex vivo. CD34+ cells expressing both oncogenes resemble the AML-M2 myeloblastic cell phenotype, in contrast to REtr-expressing cells which largely undergo granulocytic differentiation. Oncogenic c-KIT amplifies REtr-depended clonogenic growth and protects cells from exhaustion. Activated c-KIT reverts REtr-induced DNA damage and apoptosis. In the presence of activated c-KIT, REtr-downregulated DNA-repair genes are re-expressed leading to an enhancement of DNA-repair efficiency via homologous recombination. Together, our results provide new mechanistic insight into REtr and c-KIT oncogenic cooperativity and suggest that augmented DNA repair accounts for the increased chemoresistance observed in t(8;21)-positive AML patients with activated c-KIT mutations. This cell-protective mechanism might represent a new therapeutic target, as REtr cells with activated c-KIT are highly sensitive to pharmacological inhibitors of DNA repair.
Assuntos
Apoptose , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Dano ao DNA , Células-Tronco Hematopoéticas/citologia , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Antígenos CD34/metabolismo , Benzamidas/administração & dosagem , Ciclo Celular , Separação Celular , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Clonagem Molecular , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Reparo do DNA , Regulação para Baixo , Inibidores Enzimáticos/química , Citometria de Fluxo , Células HEK293 , Humanos , Mesilato de Imatinib , Mutação , Proteínas de Fusão Oncogênica/genética , Fenótipo , Piperazinas/administração & dosagem , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/administração & dosagem , Proteína 1 Parceira de Translocação de RUNX1 , Translocação Genética , Células U937RESUMO
Monoamine oxidase (MAO) inhibitors are generally used in the treatment of depressive disorders and some neurodegenerative illnesses, such as Parkinson's disease and Alzheimer's disease. The aim of this preliminary study was to investigate the MAO [MAO (E.C.1.4.3.4)] inhibiting effect of various apitherapeutic products, such as chestnut honey, pollen and propolis. Extracts' MAO inhibition was measured using peroxidase-linked spectrophotometric assay in enzyme isolated from rat liver microsomes, and the values are expressed as the inhibition concentration (IC50) causing 50% inhibition of MAO. The antioxidant activity of the bee products was also determined in terms of total phenolic content (TPC) and ferric reducing/antioxidant power in aquatic extracts. All samples exhibited substantial inhibition of MAO, propolis having the highest. Inhibition was related to samples' TPCs and antioxidant capacities. These results show that bee products possess a sedative effect and may be effective in protecting humans against depression and similar diseases.
Assuntos
Antioxidantes/farmacologia , Fagaceae/química , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a Droga , Mel , Microssomos Hepáticos/enzimologia , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Pólen/química , Própole/química , Ratos , Relação Estrutura-AtividadeRESUMO
BACKGROUND-OBJECTIVE: Several factors might affect the adherence to treatment in patients with asthma and COPD. Among these factors, the effect of religious beliefs and behaviours has been less studied so far. In this study, the effect of fasting on drug use behaviours of patients with asthma and COPD were comparatively analysed. METHODS: A total of 150 adult patients with asthma and 150 adult patients with COPD were consecutively enrolled into this cross-sectional study. The patients were asked whether they fast during Ramadan and if the answer was yes, they were kindly asked to respond to further questions related to use of inhaled medications during that particular time. RESULTS: The majority of the cases from both groups [98 (65.3%) of asthma patients and 139 (92.6%) of COPD] were fasting during Ramadan. The majority of the patients with COPD (n=126; 90.6%) reported that they quitted their regular therapy basis during Ramadan. On the other hand, the majority of asthma patients used their controller inhaled medications during Ramadan and preferred to use them on iftar and sahur times (n=81, 82.6%). CONCLUSION: Our results showed that in a Muslim population, the patients with asthma and COPD do not feel their diseases to be an inhibitory factor for fasting during Ramadan. However, fasting seems to be an important determining factor in medication compliance by modifying the drug use behaviours in each group in a different way. Therefore, the patients should be informed about the effects of fasting on their disease and the allowed drugs during fasting.
Assuntos
Asma/tratamento farmacológico , Jejum , Islamismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Religião , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TurquiaRESUMO
PURPOSE: Preoperative chemoradiotherapy (pre-CRT) followed by total mesorectal excision (TME) is the recommended therapy for patients with locally advanced rectal cancer (LARC). The primary aim of this study was to compare the rates of local and distant recurrence and overall survival (OS) in LARC patients who received pre-CRT vs postoperative (post) CRT. METHODS: The medical records of 158 rectal cancer patients with clinical stage T3, T4 or N positive disease who received either pre-CRT or post-CRT between 2000-2009 were retrospectively analysed. Pre-CRT employed protracted 5-fluorouracil (5FU) infusion, whereas post-CRT included bolus 5FU and leucovorin concurrently with radiation therapy (RT). Radiation dose was 50.4 Gy in 82% and 45 Gy in 18% of the patients. RESULTS: 158 patients (65 females, 93 males) were analysed. Median age was 56.5 years (range 19-78). Fifty-three (34%) patients received pre-CRT and 105 (66%) post-CRT. Median follow-up was 43.3 months (range 8-182) and 47.6 months (range 9-194) in pre-CRT and post-CRT patients, respectively. After pre-CRT, significant downstaging was achieved. However, the type of surgical resection was not influenced by the administration of pre-CRT in tumors ≥5 cm distant from the anal verge (p=0.3). Pathologic complete response was achieved in 20% of the patients in the pre-CRT group. Local recurrence free survival (LRFS) at 5-years was 89.2% in the pre-CRT and 74.8% in the post-CRT group (p=0.04). Distant recurrence free survival (DRFS) at 5-years was 81.7% and 68.5 % in pre-CRT and post-CRT groups, respectively (p=0.1). OS was similar in the two groups (71.4 vs 64.4%, p=0.9). CONCLUSION: Treatment of LARC with pre-CRT followed by surgery improved LRFS as compared to surgery followed by post-CRT, but failed to improve DRFS or OS in our patient population.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Doses de Radiação , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Asthma symptoms can be triggered by a variety of factors commonly referred to as "triggers". Some of these factors can also induce severe asthma exacerbations. Thus, it can be assumed that actions taken against such triggers may prevent the progression of the disease. However, limited data exist on the clinical importance of these triggers in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To compare the effect of triggers on symptoms and actions taken against certain modifiable triggers in patients with asthma and COPD. METHODS: The study was conducted in a university hospital between June 2009 and June 2010. Patients with asthma and COPD were asked to complete a questionnaire in which both the factors triggering symptoms and the actions taken against several triggers were assessed. RESULTS: Three hundred consecutive adult patients (150 asthma, 150 COPD) were enrolled to the study. The frequency of triggering factors was similar in both groups. Vaccination rates for influenza and pneumococcus were significantly higher in patients with COPD. However, such anti-allergic approaches as the use of strategies to decrease dust exposure, the use of anti-mite bed sheets, and the removal of pets from the home were more commonly employed by asthmatic patients. CONCLUSION: This study revealed that certain triggers affected COPD and asthma patients to the same degree. Therefore, triggers and strategies for controlling modifiable triggers should be more concentrated on during education in both groups. However, the preventive effect of these strategies on disease progression, particularly in patients with COPD, needs clarification.
Assuntos
Asma/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Adulto , Asma/complicações , Estudos Transversais , Progressão da Doença , Poeira , Exposição Ambiental/efeitos adversos , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Inquéritos e QuestionáriosRESUMO
Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with which a variety of neuropathic disorders have been associated. Among these, the acute inflammatory demyelinating polyradiculoneuropathy variant of Guillain-Barré syndrome has been well established. However, acute axonal lumbosacral polyradiculoneuropathy accompanied by albuminocytological dissociation in the cerebrospinal fluid has been extremely rarely reported in SLE. We report on a 47-year-old woman with discoid lupus presenting with acute onset of flaccid paraplegia. Extensive investigations suggested the diagnoses of axonal lumbosacral polyradiculoneuropathy and SLE. Treatment with intravenous methylprednisolone and cyclophosphamide resulted in clinical recovery. Development of immune-mediated polyneuropathy in a patient with discoid lupus should forewarn the clinician regarding transformation into the systemic form of the disease.