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1.
Actas urol. esp ; 46(2): 114-121, mar. 2022. ilus, tab
Article in Spanish | IBECS | ID: ibc-203562

ABSTRACT

ObjetivoIncorporar los parámetros basados en la tomografía computarizada sin contraste (TCSC) a las características de los cálculos y de los pacientes comúnmente asociadas con el éxito de la litotricia por ondas de choque (LEOCH) para evaluar la efectividad de este nuevo modelo en la predicción del éxito de LEOCH en cálculos ureterales únicos situados en diferentes localizaciones.Materiales y métodosSe revisaron retrospectivamente los datos de los pacientes tratados con LEOCH por un único cálculo ureteral entre enero de 2017 y enero de 2019. Los parámetros basados en la TCSC se evaluaron junto con los parámetros demográficos de los pacientes y las características de los cálculos. Los parámetros basados en TCSC incluyeron la presencia o ausencia de hidronefrosis, trabeculación de la grasa perirrenal, edema periureteral, diámetro del uréter proximal, grosor de la pared ureteral (GPU) en el sitio del cálculo ureteral. Se utilizó el método de regresión logística para desarrollar un modelo predictivo útil. Posteriormente, se utilizó la curva ROC para determinar los puntos de corte, y se desarrolló un sistema de puntuación para la predicción del éxito de LEOCH.ResultadosLa tasa libre de cálculos fue del 77,1% (267/346) en toda la cohorte. El análisis univariante reveló que la edad, el volumen de los cálculos, la densidad, la trabeculación perirrenal, el diámetro del uréter proximal y el GPU se asociaron con el éxito de la LEOCH. En el análisis multivariante, la localización del cálculo ureteral proximal, el volumen del cálculo, la densidad y el GPU fueron predictores independientes del éxito de la LEOCH. La fórmula utilizada en el análisis de regresión logística fue: 1/[1+exp {-8,856+0,008(volumen del cálculo)+0,002 (densidad del cálculo)+0,673 (GPU)+1026 (cálculo ureteral proximal)}]. Las puntuaciones de 0, 1, 2, 3 y 4 se asociaron con un 97,8%, 83,4%, 60,8%, 33,2% y 11,1% de éxito, respectivamente, en el modelo de predicción basado en estos parámetros.


ObjectiveTo 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 methodsData 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.ResultsStone-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.ConclusionWe conclude that our model can facilitate decision-making for SWL treatment of ureteral stones in different locations (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Lithotripsy/methods , Ureteral Calculi/diagnostic imaging , Ureteral Calculi/therapy , Predictive Value of Tests , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
2.
Actas Urol Esp (Engl Ed) ; 46(2): 114-121, 2022 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-35184987

ABSTRACT

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.


Subject(s)
Lithotripsy , Ureteral Calculi , Female , Humans , Lithotripsy/methods , Male , Predictive Value of Tests , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , Ureteral Calculi/complications , Ureteral Calculi/diagnostic imaging , Ureteral Calculi/therapy
3.
Balkan J Med Genet ; 23(1): 33-41, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32953407

ABSTRACT

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.

4.
Mult Scler Relat Disord ; 43: 102140, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32454296

ABSTRACT

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.


Subject(s)
Cladribine , Immunosuppressive Agents , Multiple Sclerosis , Neoplasms , Cladribine/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Multiple Sclerosis/drug therapy , Recurrence
5.
Biotechnol Prog ; 35(6): e2876, 2019 11.
Article in English | MEDLINE | ID: mdl-31237985

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/pharmacology , Microalgae , Biotechnology , Cell Survival/drug effects , Emulsions , HCT116 Cells , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Microalgae/chemistry , Nanoparticles , Particle Size
6.
Mult Scler Relat Disord ; 24: 20-27, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29860198

ABSTRACT

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.


Subject(s)
Cladribine/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis, Chronic Progressive/therapy , Adult , Female , Humans , Immunotherapy , Male , Multiple Sclerosis, Chronic Progressive/cerebrospinal fluid , Multiple Sclerosis, Chronic Progressive/diagnostic imaging , Neurofilament Proteins/cerebrospinal fluid , Subcutaneous Absorption
7.
Br Poult Sci ; 58(4): 452-461, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28494164

ABSTRACT

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.


Subject(s)
Calcifediol/metabolism , Calcium, Dietary/metabolism , Chickens/physiology , Meat/analysis , Phosphorus, Dietary/metabolism , Sternum/physiology , Animal Feed/analysis , Animals , Bone Development/drug effects , Calcifediol/administration & dosage , Calcium, Dietary/administration & dosage , Chickens/blood , Diet/veterinary , Dietary Supplements/analysis , Female , Male , Pectoralis Muscles/physiology , Phosphorus, Dietary/administration & dosage , Random Allocation , Sternum/drug effects , Sternum/growth & development
8.
Hum Exp Toxicol ; 36(11): 1121-1130, 2017 Nov.
Article in English | MEDLINE | ID: mdl-27932539

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Immunological/pharmacology , Heart Diseases/etiology , Heart/radiation effects , Radiation Injuries/drug therapy , Trastuzumab/pharmacology , Animals , Antineoplastic Agents, Immunological/administration & dosage , Drug Administration Schedule , Female , Rats , Rats, Wistar , Stroke Volume/radiation effects , Trastuzumab/administration & dosage
9.
Clin Exp Dermatol ; 42(1): 8-13, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28028860

ABSTRACT

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.


Subject(s)
Genetic Predisposition to Disease , Germ-Line Mutation , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic , Psoriasis/genetics , Adolescent , Adult , Aged , Alleles , Child , Child, Preschool , DNA Mutational Analysis , Female , Gene Frequency , Genotype , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2)/metabolism , Middle Aged , Prevalence , Psoriasis/epidemiology , Psoriasis/metabolism , Real-Time Polymerase Chain Reaction , Risk Factors , Turkey/epidemiology , Young Adult
10.
Clin Radiol ; 71(5): 418-26, 2016 May.
Article in English | MEDLINE | ID: mdl-26966086

ABSTRACT

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.


Subject(s)
Brain/blood supply , Multiple Sclerosis/pathology , Veins/pathology , Adolescent , Adult , Diagnosis, Differential , Disease Susceptibility , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multiple Sclerosis/diagnosis , Retrospective Studies , Young Adult
11.
Hum Exp Toxicol ; 35(5): 562-72, 2016 May.
Article in English | MEDLINE | ID: mdl-26199281

ABSTRACT

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.


Subject(s)
Androgens/toxicity , Dehydroepiandrosterone/toxicity , Heart/drug effects , Myocardium , Oxidative Stress/drug effects , Testosterone/toxicity , Androgens/administration & dosage , Animals , Body Weight/drug effects , Cardiotoxicity , Dehydroepiandrosterone/administration & dosage , Dose-Response Relationship, Drug , Echocardiography , Male , Motor Activity/drug effects , Muscle Strength/drug effects , Myocardium/metabolism , Myocardium/pathology , Rats, Wistar , Testosterone/administration & dosage
13.
J Stroke Cerebrovasc Dis ; 24(11): 2521-6, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26387046

ABSTRACT

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.


Subject(s)
Cerebral Hemorrhage/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cerebral Hemorrhage/mortality , Databases, Bibliographic/statistics & numerical data , Female , Humans , Male , Odds Ratio , Treatment Outcome
14.
Eur Rev Med Pharmacol Sci ; 19(8): 1498-504, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25967726

ABSTRACT

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.


Subject(s)
Mammary Arteries/drug effects , Potassium Channels/agonists , Taurine/pharmacology , Vasoconstriction/drug effects , Vasodilation/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Glyburide/pharmacology , Humans , Mammary Arteries/physiology , Organ Culture Techniques , Potassium Channels/physiology , Vasoconstriction/physiology , Vasodilation/physiology , Vasodilator Agents/pharmacology
15.
Eur J Clin Microbiol Infect Dis ; 34(6): 1213-21, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25698311

ABSTRACT

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.


Subject(s)
Listeria monocytogenes/isolation & purification , Meningitis, Listeria/diagnosis , Meningitis, Listeria/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Female , France , Humans , Italy , Male , Meningitis, Listeria/epidemiology , Meningitis, Listeria/pathology , Middle Aged , Mortality , Prognosis , Retrospective Studies , Risk Factors , Survival Analysis , Tertiary Care Centers , Treatment Outcome , Turkey , Young Adult
16.
Leukemia ; 29(2): 279-89, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24897507

ABSTRACT

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.


Subject(s)
Apoptosis , Core Binding Factor Alpha 2 Subunit/metabolism , DNA Damage , Hematopoietic Stem Cells/cytology , Oncogene Proteins, Fusion/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Antigens, CD34/metabolism , Benzamides/administration & dosage , Cell Cycle , Cell Separation , Chromosomes, Human, Pair 21 , Chromosomes, Human, Pair 8 , Cloning, Molecular , Core Binding Factor Alpha 2 Subunit/genetics , DNA Repair , Down-Regulation , Enzyme Inhibitors/chemistry , Flow Cytometry , HEK293 Cells , Humans , Imatinib Mesylate , Mutation , Oncogene Proteins, Fusion/genetics , Phenotype , Piperazines/administration & dosage , Protein Structure, Tertiary , Proto-Oncogene Proteins c-kit/genetics , Pyrimidines/administration & dosage , RUNX1 Translocation Partner 1 Protein , Translocation, Genetic , U937 Cells
17.
Allergol. immunopatol ; 42(2): 115-119, mar.-abr. 2014. tab, graf
Article in English | IBECS | ID: ibc-121009

ABSTRACT

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


No disponible


Subject(s)
Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/drug therapy , Medication Adherence , Religion and Medicine , Fasting
18.
Allergol Immunopathol (Madr) ; 42(2): 115-9, 2014.
Article in English | MEDLINE | ID: mdl-23265268

ABSTRACT

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.


Subject(s)
Asthma/drug therapy , Fasting , Islam , Pulmonary Disease, Chronic Obstructive/drug therapy , Religion , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Turkey
19.
J Enzyme Inhib Med Chem ; 29(5): 690-4, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24156742

ABSTRACT

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.


Subject(s)
Antioxidants/pharmacology , Fagaceae/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase/metabolism , Plant Extracts/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/isolation & purification , Dose-Response Relationship, Drug , Honey , Microsomes, Liver/enzymology , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Pollen/chemistry , Propolis/chemistry , Rats , Structure-Activity Relationship
20.
J BUON ; 18(2): 385-90, 2013.
Article in English | MEDLINE | ID: mdl-23818350

ABSTRACT

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.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Neoadjuvant Therapy , Neoplasm Recurrence, Local/prevention & control , Rectal Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/adverse effects , Chi-Square Distribution , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoplasm Invasiveness , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Proportional Hazards Models , Radiation Dosage , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
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