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1.
Acta Physiol (Oxf) ; : e14160, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747650

RESUMO

AIM: Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. METHODS: We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines. RESULTS: The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2-8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels. CONCLUSION: Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.

3.
Toxicon ; 241: 107661, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38408526

RESUMO

Mushroom poisonings caused by Amanita phalloides are the leading cause of mushroom-related deaths worldwide. Alpha-Amanitin (α-AMA), a toxic substance present in these mushrooms, is responsible for the resulting hepatotoxicity and nephrotoxicity. The objective of our study was to determine the distribution of α-AMA in Balb/c mice by labeling with Iodine-131. Mice were injected with a toxic dose (1.4 mg/kg) of α-AMA labeled with Iodine-131. The mice were sacrificed at the 1st, 2nd, 4th, 8th, 24th, and 48th hours under anesthesia. The organs of the mice were removed, and their biodistribution was assessed in all experiments. The percent injected dose per gram (ID/g %) value for kidney, liver, lung, and heart tissues at 1st hour were 1.59 ± 0.07, 1.25 ± 0.33, 3.67 ± 0.80 and 1.07 ± 0.01 respectively. This study provides insights into the potential long-term effects of α-AMA accumulation in specific organs. Additionally, this study has generated essential data that can be used to demonstrate the impact of antidotes on the biological distribution of α-AMA in future toxicity models.


Assuntos
Alfa-Amanitina , Intoxicação Alimentar por Cogumelos , Animais , Camundongos , Alfa-Amanitina/toxicidade , Distribuição Tecidual , Radioisótopos do Iodo , Amanita
4.
NPJ Genom Med ; 8(1): 37, 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925498

RESUMO

Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, and schizophrenia, which may bias the numbers. As to NDD-associated mutations, in most cases, they are germline while cancer mutations are sporadic, emerging during life. However, somatic mosaicism can spur NDDs, and cancer-related mutations can be germline. NDDs and cancer share proteins, pathways, and mutations. Here we ask (i) exactly which features they share, and (ii) how, despite their commonalities, they differ in clinical outcomes. To tackle these questions, we employed a statistical framework followed by network analysis. Our thorough exploration of the mutations, reconstructed disease-specific networks, pathways, and transcriptome levels and profiles of autism spectrum disorder (ASD) and cancers, point to signaling strength as the key factor: strong signaling promotes cell proliferation in cancer, and weaker (moderate) signaling impacts differentiation in ASD. Thus, we suggest that signaling strength, not activating mutations, can decide clinical outcome.

5.
Biophys Rev ; 15(2): 163-181, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37124926

RESUMO

Neurodevelopmental disorders (NDDs) and cancer share proteins, pathways, and mutations. Their clinical symptoms are different. However, individuals with NDDs have higher probabilities of eventually developing cancer. Here, we review the literature and ask how the shared features can lead to different medical conditions and why having an NDD first can increase the chances of malignancy. To explore these vital questions, we focus on dysregulated PI3K/mTOR, a major brain cell growth pathway in differentiation, and MAPK, a critical pathway in proliferation, a hallmark of cancer. Differentiation is governed by chromatin organization, making aberrant chromatin remodelers highly likely agents in NDDs. Dysregulated chromatin organization and accessibility influence the lineage of specific cell brain types at specific embryonic development stages. PAK1, with pivotal roles in brain development and in cancer, also regulates MAPK. We review, clarify, and connect dysregulated pathways with dysregulated proliferation and differentiation in cancer and NDDs and highlight PAK1 role in brain development and MAPK regulation. Exactly how PAK1 activation controls brain development, and why specific chromatin remodeler components, e.g., BAF170 encoded by SMARCC2 in autism, await clarification.

6.
Niger J Clin Pract ; 25(4): 509-515, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35439912

RESUMO

Aims: The aim of this study was to investigate the effects of an antioxidant on the bleaching-induced reduction in the penetration depth of infiltrant resins. Materials and Methods: White spot lesions (WSLs) were created on 105 bovine tooth samples, each measuring 6 × 4 × 4 mm. Five samples were randomly selected for the examination of lesion characteristics. The remaining 100 samples were then divided into four groups (n = 25). In Group I, the WSLs were treated with resin infiltration (RI) only. RI was performed on Group II immediately after bleaching. In Group III, an antioxidant was applied for 2 h after bleaching, and this was immediately followed by RI. The Group IV samples were treated with RI at the end of a 1-week waiting period after bleaching. The penetration depths were evaluated through confocal laser scanning microscopy. Results: The lowest penetration rate, which was approximately 57%, was observed in Group II. This was followed by Group III (87%), Group IV (90%), and Group I (92%). Group II, in which the samples were infiltrated immediately after bleaching, had the lowest mean penetration percentage. All the bleached groups exhibited significantly lower penetration percentages than the nonbleached group (Group I) (P < 0.05). Antioxidant application increased the penetration significantly (P < 0.05). Conclusion: Application of sodium ascorbate was found to reverse the reduced resin penetration depth and penetration percentages resulting from bleaching. The postponement of adhesive procedures after bleaching yielded similar results.


Assuntos
Colagem Dentária , Clareamento Dental , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Bovinos , Resinas Compostas , Humanos , Hidrogéis , Clareamento Dental/métodos
7.
Front Mol Biosci ; 8: 666705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676243

RESUMO

Beyond the list of molecules, there is a necessity to collectively consider multiple sets of omic data and to reconstruct the connections between the molecules. Especially, pathway reconstruction is crucial to understanding disease biology because abnormal cellular signaling may be pathological. The main challenge is how to integrate the data together in an accurate way. In this study, we aim to comparatively analyze the performance of a set of network reconstruction algorithms on multiple reference interactomes. We first explored several human protein interactomes, including PathwayCommons, OmniPath, HIPPIE, iRefWeb, STRING, and ConsensusPathDB. The comparison is based on the coverage of each interactome in terms of cancer driver proteins, structural information of protein interactions, and the bias toward well-studied proteins. We next used these interactomes to evaluate the performance of network reconstruction algorithms including all-pair shortest path, heat diffusion with flux, personalized PageRank with flux, and prize-collecting Steiner forest (PCSF) approaches. Each approach has its own merits and weaknesses. Among them, PCSF had the most balanced performance in terms of precision and recall scores when 28 pathways from NetPath were reconstructed using the listed algorithms. Additionally, the reference interactome affects the performance of the network reconstruction approaches. The coverage and disease- or tissue-specificity of each interactome may vary, which may result in differences in the reconstructed networks.

8.
J Fr Ophtalmol ; 43(8): 753-760, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32620412

RESUMO

PURPOSE: The objective of this study is to evaluate the preoperative and short- and long-term postoperative results in terms of visual acuity, refractive error, and corneal wavefront aberrations in patients with myopia and myopic astigmatism undergoing small incision lenticule extraction (SMILE). METHODS: Seventy-nine eyes of 52 myopes with or without astigmatism (41 right and 38 left) were enrolled in this retrospective study. The measurements included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SE) and wavefront aberrations. All the measurements before and after SMILE surgery were systematically recorded. RESULTS: Mean preoperative UDVA was 1.19±0.24 logMAR and improved to 0.06±0.17 logMAR at the 3-year postoperative follow-up. At the conclusion of the 3-year follow-up, UDVA was better than or equal to 20/20 and 20/25 in 73% and 84% of eyes, respectively. At 1 month postoperatively, CDVA was 0.05±0.23 logMAR and significantly lower than the preoperative CDVA, 0.02±0.04 log MAR (P>0.05). However, at 1 year and 3 years after surgery, CDVA showed a significant increase compared to preoperative CDVA. At the conclusion of the 3-year follow-up, SE was -0.47 D, and 69.6% and 83.5% of the eyes were within±0.50 D and±1.00 D, respectively, of the intended correction. HOA's, coma, and spherical aberration increased significantly. No significant change in trefoil was detected. CONCLUSION: This study showed that SMILE produces a stable, safe outcome for surgical treatment of myopia and myopic astigmatism.


Assuntos
Astigmatismo/cirurgia , Cirurgia da Córnea a Laser/efeitos adversos , Microcirurgia/efeitos adversos , Miopia/cirurgia , Adulto , Astigmatismo/complicações , Astigmatismo/epidemiologia , Astigmatismo/patologia , Córnea/patologia , Córnea/cirurgia , Cirurgia da Córnea a Laser/métodos , Topografia da Córnea , Aberrações de Frente de Onda da Córnea/epidemiologia , Aberrações de Frente de Onda da Córnea/etiologia , Feminino , Humanos , Lasers de Excimer/efeitos adversos , Masculino , Microcirurgia/métodos , Microcirurgia/estatística & dados numéricos , Pessoa de Meia-Idade , Miopia/complicações , Miopia/epidemiologia , Miopia/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Refração Ocular/fisiologia , Erros de Refração/epidemiologia , Erros de Refração/etiologia , Estudos Retrospectivos , Ferida Cirúrgica/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento , Acuidade Visual/fisiologia , Adulto Jovem
9.
Chemosphere ; 252: 126644, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32443284

RESUMO

Pendimethalin, one of the dinitroaniline group herbicides, is applied for controlling weeds in cereals, legumes and vegetable crops, and has been classified as possible human carcinogen. It is indicated that pendimethalin should arise risks of developing some cancer types; however, there is no data on the effects of pendimethalin on pancreatic cancer-induced inflammation. Injuries resulting from by acute pancreatitis attacks and inflammation are significant factors in the development of pancreatic cancer. Therefore, we investigated whether pendimethalin triggers inflammation as a mechanism of pancreatic cancer development. Parameters related to pancreatic activation, oxidative stress, and inflammation were measured in the human pancreatic (PANC-1) cell line. In the range of 0-100 µM, the levels of chymotrypsin decreased. It should be indicated that the reason for the decrease in chymotrypsin may be the high rates of cell death (20%) observed in the high concentration levels. We observed that pendimethalin significantly induced oxidative damage, while levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) did not change. The obtained results may draw attention to the usage and possible toxic effect of pendimethalin due to oxidative damage induction; however, detailed inflammation mechanisms and other cancer pathways should be investigated.


Assuntos
Compostos de Anilina/toxicidade , Carcinógenos/toxicidade , Herbicidas/toxicidade , Neoplasias Pancreáticas/induzido quimicamente , Doença Aguda , Carcinógenos/metabolismo , Herbicidas/metabolismo , Humanos , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo
10.
Hum Exp Toxicol ; 39(3): 328-337, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31726883

RESUMO

Alpha-amanitin (α-AMA), the primary toxin of Amanita phalloides, is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant-antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group (p < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group (p < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms.


Assuntos
Alfa-Amanitina/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Glutationa Peroxidase , Rim/metabolismo , Malondialdeído , Camundongos , Camundongos Endogâmicos BALB C , Oxidantes/metabolismo , Superóxido Dismutase
11.
Indian J Pharmacol ; 47(4): 436-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26288478

RESUMO

OBJECTIVES: The aim of this study was to evaluate the short and long-term impact of pharmacovigilance (PV) training on the 5th year medical students' knowledge about definitions and on the awareness of the regulatory aspects in PV. MATERIALS AND METHODS: In academic year 2010/11, the students completed structured, questionnaire before and just after training. They also completed the same questionnaire 1-year after the training. RESULTS: The students' knowledge about PV significantly increased after training in the short term (P < 0.001). However, the improvement decreased significantly in the long-term (P < 0.001). Although long-term scores were higher than the baseline score, the difference was not statistically significant. Total scores were 17.5 ± 2.0, 20.8 ± 2.0 and 18.0 ± 2.5; before, at short and long-term after the training. CONCLUSION: PV training increased the students' knowledge significantly. However, in the long-term, the impact of the training is limited. Repeated training of PV should be planned.


Assuntos
Educação de Graduação em Medicina/métodos , Conhecimentos, Atitudes e Prática em Saúde , Farmacovigilância , Estudantes de Medicina , Adulto , Avaliação Educacional , Feminino , Humanos , Masculino , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
12.
Transplant Proc ; 47(2): 343-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25769570

RESUMO

BACKGROUND: Endothelial dysfunction can be detected at early stages of chronic kidney disease. Although endothelial functions improve after successful renal transplantation, renal transplant recipients have still worse endothelial functions compared to healthy subjects. Vitamin D deficiency and high fibroblast growth factor-23 (FGF-23) levels may have a role on endothelial dysfunction in chronic kidney disease patients. The aim of this study is to investigate the association between endothelial functions, vitamin D, and FGF-23 levels in renal transplant recipients. METHODS: One hundred nine renal transplant recipients (71 male, 38 female) underwent brachial flow-mediated dilatation (FMD), serum 25-OH vitamin D, and FGF-23 level measurements. Vitamin D and FGF-23 levels were compared between patients with normal and abnormal endothelial functions. Correlations between FMD, vitamin D, and FGF-23 were also investigated. RESULTS: Endothelial functions were abnormal in 72.5% of the patients. Prevalence of vitamin D deficiency was 80.7%. Vitamin D levels were significantly lower in patients with endothelial dysfunction compared to patients with normal endothelial functions (12.6 ± 6.6 µg/L vs 17.3 ± 10.0 µg/L respectively, P = .02). FGF-23 levels were not different between the two groups. 25-OH vitamin D levels had a significant positive correlation with amount of FMD (r = 0.218 and P = .02) and were an independent predictor of FMD after adjusting for potential confounding factors including age, transplantation duration, body mass index, mean blood pressure, glomerular filtration rate, proteinuria, hemoglobin, and FGF-23 in multivariate regression analysis (beta = 0.194, P = .04). FGF-23 levels were not predictive of FMD in this model (beta: -0.125, P = .197) CONCLUSION: Vitamin D deficiency is associated with endothelial dysfunction in renal transplant recipients. Further clinical and experimental studies are necessary to define a causal relationship between the parameters, discover the potential mechanisms, and observe the effect of vitamin D replacement on endothelial functions in renal transplant recipients.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Transplante de Rim , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/cirurgia , Doenças Vasculares/sangue , Deficiência de Vitamina D/epidemiologia , Adulto , Feminino , Fator de Crescimento de Fibroblastos 23 , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/complicações , Doenças Vasculares/complicações , Doenças Vasculares/fisiopatologia , Vasodilatação/fisiologia , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/fisiopatologia
13.
Transplant Proc ; 47(2): 363-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25769574

RESUMO

BACKGROUND: Increased allograft mass in living donor kidney transplantation has been recognized as a predictor factor of better short-term allograft function. We evaluated whether donor kidney volume adjusted for recipient body weight is associated with long-term allograft function in living donor kidney transplantation. METHODS: We analyzed 67 living donors and their recipients who underwent transplantation between 2003 and 2007. Estimated glomerular filtration rate (eGFR) and serum creatinine levels at 1, 2, 3, 4, and 5 years post-transplantation were recorded for all recipients. Transplanted kidney volumes were measured using 3-D helical computed tomography scanning. A transplant kidney volume-recipient body weight (Vol/Wt) ratio was calculated for each donor-recipient pair. The subjects were divided into tertiles according to Vol/Wt ratios: low (<2.16), medium (2.16-2.88), and high (>2.88). RESULTS: Vol/Wt ratio significantly correlated with recipient eGFR and serum creatinine levels at 1, 2, 3, and 4 years post-transplantation (r = .48, P < .0001; r = .46, P < .0001; r = .47, P < .0001; r = .26, P = .037, respectively, for eGFR; r = -.53, P < .0001; r = -.50, P < .0001; r = -.44, P < .0001; r = -.37, P = .003, respectively, for serum creatinine) but not at 5 years (r = .12, P = .406 for eGFR; r = -.21, P = .110 for serum creatinine). Whereas recipient eGFR increased significantly in a graded fashion among low to high Vol/Wt ratio groups during 1 to 3 years post-transplantation, there was no difference in eGFR values between Vol/Wt ratio groups at 4 and 5 years (P = .21 and .71, respectively). CONCLUSION: Vol/Wt ratio is not associated with long-term allograft function in living donor kidney transplantation.


Assuntos
Transplante de Rim/métodos , Rim/anatomia & histologia , Doadores Vivos , Adulto , Aloenxertos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Rim/fisiologia , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Fatores de Tempo
14.
J Dairy Sci ; 98(3): 1604-24, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25547308

RESUMO

Exopolysaccharide (EPS)-producing starter cultures are preferred for the manufacture of fermented milk products to improve rheological and technological properties. However, no clear correlation exists between EPS production and the rheological and technological properties of fermented milk products such as the yogurt drink ayran. In this study, 4 different strain conditions (EPS- and EPS+ Streptococcus thermophilus strains) were tested as a function of incubation temperature (32, 37, or 42°C) and time (2, 3, or 4 h) to determine the effect of culture type and in situ EPS production on physicochemical, rheological, sensory, and microstructural properties of ayran. Furthermore, we assessed the effect of fermentation conditions on amounts of EPS production by different EPS-producing strains during ayran production. A multifactorial design of response surface methodology was used to model linear, interaction, and quadratic effects of these variables on steady shear rheological properties of ayran samples and in situ EPS production levels. The physicochemical and microbiological characteristics of ayran samples altered depending on incubation conditions and strain selection. Steady shear tests showed that ayran samples inoculated with EPS+ strains exhibited pseudoplastic flow behavior. Production of ayran with EPS- strain (control sample) resulted in the lowest apparent viscosity values (η50), whereas those produced with the combination of 2 EPS+ strains yielded ayran with notably increased η50 values. We concluded that incubation time was the variable with the greatest effect on η50, consistency coefficient (K), and flow behavior index (n) values. In situ EPS production was also affected by these conditions during ayran fermentation in which strain-specific metabolism conditions were found to be the most important factor for EPS production. In addition, these findings correlated the amount of in situ EPS produced with the rheological properties of ayran. Scanning electron microscopy images of the samples showed differences in structural features, revealing a prominent network strand structure in the ayran samples inoculated with the admixture of 2 EPS-producing strains incubated at 37°C for 3 h. These results provide useful information for large-scale production of ayran by the dairy industry.


Assuntos
Produtos Fermentados do Leite/química , Polissacarídeos Bacterianos/biossíntese , Paladar , Iogurte/análise , Animais , Fenômenos Químicos , Cor , Produtos Fermentados do Leite/microbiologia , Fermentação , Microscopia Eletrônica de Varredura , Modelos Teóricos , Odorantes/análise , Reologia , Streptococcus thermophilus/metabolismo , Temperatura , Viscosidade , Iogurte/microbiologia
15.
Indian J Pharmacol ; 45(1): 4-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23543821

RESUMO

OBJECTIVES: In this study we aimed to evaluate the impact of Rational Pharmacotherapy (RPT) course program, reinforced by video footages, on the rational pharmacotherapy skills of the students. MATERIALS AND METHODS: RPT course program has been conducted in Dokuz Eylul University School of Medicine since 2008/9. The course has been organised in accordance with World Health Organisation (WHO) Good Prescribing Guide. The aim of the course was to improve the problem solving skills (methodology for selection of the (p)ersonel-drug, prescription writing and informing patient about his illness and drugs) and communication skills of students. The impact of the course has been measured by pre/post-test design by an objective structured clinical examination (OSCE). In academic year 2010/11, to further improve OSCE score of the students we added doctor-patient communication video footages to the RPT course programme. During training, the students were asked to evaluate the doctor-patient communication and prescription on two video footages using a checklist followed by group discussions. RESULTS: Total post-test OSCE score was significantly higher for 2010/11 academic year students (n = 147) than it was for 2009/10 year students (n = 131). The 2010/11 academic year students performed significantly better than the 2009/10 academic year students on four steps of OSCE. These steps were "defining the patient's problem", "specifying the therapeutic objective", "specifying the non-pharmacological treatment" and "choosing a (drug) treatment, taking all relevant patient characteristics into account". CONCLUSIONS: The present study demonstrated that the implementation of video footages and group discussions to WHO/Good Prescribing Method improved the fourth-year medical students' performance in rational pharmacotherapy skills.


Assuntos
Competência Clínica/normas , Tratamento Farmacológico/métodos , Educação de Graduação em Medicina/métodos , Avaliação Educacional/métodos , Comunicação , Humanos , Relações Médico-Paciente , Estudantes de Medicina , Gravação de Videoteipe
16.
Transplant Proc ; 45(1): 77-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23375277

RESUMO

BACKGROUND: The proposed mechanism by which nephron underdosing contributes to graft failure is hyperfiltration damage leading to proteinuria and nephron loss. We evaluated whether proteinuria had an impact on the relationship between graft size and outcome in living donor kidney transplantation. METHODS: We analyzed 69 living donors and their recipients who underwent transplantation between 2003 and 2007. Transplanted kidney volumes were measured by 3-D helical computed tomography scanning. A transplant kidney volume-recipient body weight (Vol/Wt) ratio was calculated for each donor-recipient pair. The subjects were divided into tertiles according to Vol/Wt ratios: low (<2.0), medium (2.0-2.7) and high (>2.7). RESULTS: Recipient glomerular filtration rate (GFR) positively correlated with Vol/Wt ratio at 6, 12, and 24 months posttransplantation (r = .49, P < .001; r = .47, P < .001; r = .42, P < .001, respectively). Mean GFR increased significantly in graded fashion from low to high Vol/Wt ratio groups at 6, 12, and 24 months posttransplantation. Proteinuria did not differ between the three groups during 24 months after transplantation. Upon multivariate analysis, donor age, recipient age, and Vol/Wt ratio showed significant impacts on graft function. CONCLUSION: Vol/Wt ratio displayed a significant independent effect on graft function in living donor kidney transplantation. This close association did not appear to be related to the degree of proteinuria during 24 months.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim/métodos , Rim/fisiopatologia , Doadores Vivos , Proteinúria/patologia , Adulto , Peso Corporal , Feminino , Taxa de Filtração Glomerular , Humanos , Imageamento Tridimensional , Rim/anatomia & histologia , Falência Renal Crônica/cirurgia , Falência Renal Crônica/urina , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Análise de Regressão , Fatores de Tempo , Tomografia Computadorizada por Raios X , Adulto Jovem
17.
Int Urol Nephrol ; 45(1): 265-73, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23065433

RESUMO

PURPOSE: Hyponatremia is a common electrolyte disorder in hospitalized patients. Clinical features, outcome and cost of hyponatremia-associated admission and hospitalization in elderly and very elderly patients are not well known. METHODS: Elderly (>64 years) patients admitted to the emergency department (ED) and hospitalized between January 1, 2010, and December 31, 2010, were evaluated. Hyponatremia was defined as serum sodium level below 135 mmol/L. Hyponatremic patients were divided into two groups: group 1 (n = 150, 65-74 years old) and group 2 (n = 103, >74 years old). RESULTS: A total of 4,960 patients above 65 years of age admitted to ED and hospitalized were included. Prevalence of ED in group 1 and group 2 was 4.1 % (150/3,651) and 7.8 % (103/1,309), respectively (p < 0.001). Vomiting and diarrhea were the most important complaints. A total of 111 (43.8 %) patients were being treated with renin-angiotensin system (RAS) blockers. Mortality, morbidity and hospital cost increased in parallel to decrease in serum Na(+) level and increase in age. Group 2 subjects had not only higher intensive care need (p < 0.01) and mortality rates (p < 0.01), but also higher hospital cost burden (p < 0.05) compared to group 1. Alzheimer's disease was one of the most common co-morbidity in patients, particularly in group 2 (5.3 % vs. 21.3 %, p < 0.001). CONCLUSION: Hyponatremia-associated hospitalization is an important and potentially lethal condition in elderly and very elderly patients. Clinicians should be careful when prescribing RAS blockers and diuretics in elderly patients.


Assuntos
Custos Hospitalares/estatística & dados numéricos , Hiponatremia/etiologia , Hiponatremia/mortalidade , Injúria Renal Aguda/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Bacteriemia/epidemiologia , Cuidados Críticos/estatística & dados numéricos , Diarreia/complicações , Serviço Hospitalar de Emergência/estatística & dados numéricos , Humanos , Hiponatremia/economia , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Sódio/sangue , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Estatísticas não Paramétricas , Fatores de Tempo , Turquia/epidemiologia , Vômito/complicações
18.
Hum Exp Toxicol ; 32(3): 316-22, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22653689

RESUMO

OBJECTIVE: We investigated both the effects of the endothelin type B (ETB) receptor antagonist, BQ-788, on amitriptyline-induced cardiotoxicity and the role of ETB receptors on amitriptyline-induced cardiovascular depression. METHODS: Male Wistar rats were anaesthetized with urethane/chloralose. Mean arterial pressure (MAP), heart rate (HR) and QRS duration were recorded. Toxicity was induced by amitriptyline infusion (0.94 mg/kg per min) until the 50% inhibition of MAP. In the first protocol, 5% dextrose or BQ-788 bolus was administered to control or experimental group animals, respectively. In the second protocol, after incubation with BQ-788 or 5% dextrose, amitriptyline was infused. RESULTS: Amitriptyline caused a significant decrease in MAP, prolonged QRS duration and decreased HR for both the groups. BQ-788 administration improved MAP (5, 10 and 15 min), shortened the prolonged QRS (5 and 10 minutes) and increased HR (5, 10 and 15 min) compared with dextrose group. While all the amitriptyline-infused rats survived in BQ-788 group, all the amitriptyline-infused rats died within 20 min in dextrose group. In the second protocol, BQ-788 incubation did not cause any statistically significant change in amitriptyline-induced cardiovascular depression. CONCLUSION: BQ-788 may have beneficial effects in amitriptyline-induced cardiovascular changes via a physiologic antagonism. ETB receptor antagonists may be the promising antidotes for the cardiovascular toxicity with hypotension and bradycardia.


Assuntos
Antídotos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Antagonistas do Receptor de Endotelina B , Oligopeptídeos/uso terapêutico , Piperidinas/uso terapêutico , Amitriptilina , Animais , Antídotos/farmacologia , Pressão Arterial/efeitos dos fármacos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Oligopeptídeos/farmacologia , Piperidinas/farmacologia , Ratos , Ratos Wistar
19.
Eur J Clin Nutr ; 66(11): 1214-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22909578

RESUMO

BACKGROUND/OBJECTIVES: In this study, we hypothesized that dietary salt intake may be related with inflammation and albuminuria independently from blood pressure (BP) in non-diabetic hypertensive patients. SUBJECTS/METHODS: A total of 224 patients with primary hypertension were included in the study. Serum C-reactive protein (CRP) levels, 24-h urine sodium and albumin excretion were measured in all patients. The subjects were divided into tertiles according to the level of 24-h urinary sodium excretion: low-salt-intake group (n = 76, mean urine sodium: 111.7 ± 29.1 mmol/24 h), medium-salt-intake group (n = 77, mean urine sodium: 166.1 ± 16.3 mmol/24 h) and high-salt-intake group (n = 71, mean urine sodium: 263.6 ± 68.3 mmol/24 h). RESULTS: Systolic and diastolic BP measurements of patients were similar in the three salt-intake groups. CRP and urinary albumin levels were significantly higher in high-salt-intake group compared with medium- and low-salt-intake groups (P = 0.0003 and P = 0.001, respectively). CRP was positively correlated with 24-h urinary sodium excretion (r = 0.28, P = 0.0008) and albuminuria, whereas albuminuria was positively correlated with 24-h urinary sodium excretion (r = 0.21, P = 0.0002). Multiple regression analysis revealed that urinary sodium excretion was an independent predictor of both CRP and albuminuria. CONCLUSIONS: These findings suggest that high salt intake is associated with enhanced inflammation and target organ damage reflected by increased albuminuria in treated hypertensive patients independent of any BP effect.


Assuntos
Albuminúria/etiologia , Proteína C-Reativa/metabolismo , Dieta/efeitos adversos , Hipertensão/patologia , Inflamação/etiologia , Cloreto de Sódio na Dieta/efeitos adversos , Sódio/efeitos adversos , Adulto , Albuminúria/urina , Feminino , Humanos , Hipertensão/complicações , Hipertensão/metabolismo , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Sódio/urina , Cloreto de Sódio na Dieta/urina
20.
Hum Exp Toxicol ; 31(6): 533-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21665922

RESUMO

OBJECTIVE: The aim of this study was to analyse the caustic and household detergent exposure cases were admitted to the Department of Emergency Medicine at Dokuz Eylul University Hospital (EMDEU) between 1993 and 2008. METHODS: Age, sex, reason of exposure, clinical signs, rate of endoscopy in oral exposures, treatment attempts, length of hospital stay and outcome were evaluated. A chi-square test was used to analyse statistical differences. RESULTS: Caustic exposures accounted for 8.5% (1160 cases) and 4.1% (1988 cases) of all poisonings in children and adults, respectively. Female/male ratio of caustic exposure poisonings was 0.8. Most of the exposures were unintentional (158, 86.8%). Intentional exposures were common in cases between 19 and 29 years old (χ(2) = 25.685, p < 0.001). The most common caustic substance was alkaline (106, 58.3%) followed by acidic (47, 25.8%) and other household detergents (28, 15.4%). Vomiting (35.7%), nausea (14.8%) and sore throat (13.1%) were the most common clinical signs. The patients who had endoscopy, the most frequent finding was first-degree damage (58.7%). A 48-year-old man died from intentional hydrochloric acid ingestion. CONCLUSION: Because of the large number of unintentional caustic exposures, parent education is very important to decrease the caustic exposures in children.


Assuntos
Queimaduras Químicas/epidemiologia , Cáusticos/toxicidade , Detergentes/toxicidade , Serviços Médicos de Emergência/estatística & dados numéricos , Esôfago/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Queimaduras Químicas/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Ácido Clorídrico/intoxicação , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Turquia/epidemiologia , Adulto Jovem
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