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1.
J Adolesc ; 96(2): 251-265, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37985148

RESUMO

INTRODUCTION: At-risk youth are those who are currently or potentially exposed to physical, mental, or emotional danger. The Friendship Online Intervention Program (FOIP) was created to encourage physical activity (PA) and reduce risky behavior among vocational secondary-school youth in Israel. We wanted to evaluate the effect of FOIP on PA, substance abuse, and psychological factors, including psychosomatic symptoms and well-being. METHODS: From October 2021 to June 2022, nonrandom sampling was employed to select at-risk youth from vocational secondary schools for participation in the FOIP. Before and after the intervention, questionnaires were administered to the intervention and control groups. The effects of FOIP were evaluated by univariate and multivariable analyses. RESULTS: The intervention (n = 103) and control (n = 77) groups showed similar levels of PA, cigarette smoking, and alcohol consumption at the beginning of the study. At follow-up, the intervention group showed a 57% increase in PA versus no change for the control group and decreased levels of smoking compared to the control group (p < .001). Similarly, in the intervention group, the number of psychosomatic symptoms decreased (effect size = 1.68) and life satisfaction increased (effect size = 0.86). Group assignment (intervention or control group) significantly predicted PA level, cigarette smoking, psychosomatic symptoms, and life satisfaction (adjusted R2 = .46, .20, .08, and .28, respectively) with participants in the intervention group showing more favorable results compared with the control group. CONCLUSIONS: FOIP was effective in increasing PA and decreasing risky behaviors among youth. FOIP may help at-risk youth build resilience and promote their physical and mental health.


Assuntos
Intervenção Baseada em Internet , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Amigos , Exercício Físico/psicologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Psicofisiológicos/psicologia
2.
Healthcare (Basel) ; 11(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38132038

RESUMO

Regular toothbrushing is the primary self-care method to prevent the most common dental diseases and is considered an important public health indicator. This retrospective observational study aimed to examine cross-national time trends in adolescent toothbrushing behaviour and its association with sociodemographic factors between 1994 and 2018. We studied data from 20 countries that conducted seven surveys of the Health Behaviour in School-aged Children (HBSC) study. Adolescents aged 11, 13 and 15 years responded to questions on their toothbrushing frequency, family affluence and structure. Altogether, reports of 691,559 students were analysed using descriptive statistics and binominal logistic regression. The findings showed an overall positive trend in the prevalence of more-than-once-a-day toothbrushing frequency during the entire study period mainly due to a noticeable increase from 1994 to 2010 (except Denmark and Sweden); this trend continued significantly thereafter in 12 of 20 countries. Across all countries, girls and adolescents from more affluent families were more likely to brush their teeth regularly. These relationships remained unchanged throughout the study period, whereas the age-related difference in toothbrushing prevalence decreased noticeably, and the negative relationship between toothbrushing and living in a non-intact family became evident. While the prevalence of regular toothbrushing among adolescents has increased in recent decades, it is still far behind the recommended level of twice-daily brushing for everyone across all countries. The promotion of toothbrushing needs to start at an early age, with a special focus on boys and adolescents from low-affluence and non-intact families.

3.
Eur J Investig Health Psychol Educ ; 13(10): 2082-2094, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37887148

RESUMO

The Bedouin community is a minority disadvantaged population in Israel that suffers from a variety of health and socioeconomic disparities and limited access to higher education. The current study aimed to examine perceptions, successes, and challenges experienced by Bedouin students during their studies and to assess an internship program developed on the principles of a community-based participatory research approach to public health. In-depth interviews were conducted with 34 Bedouin students studying in the public health academic track between January and April 2023. Grounded Theory was used to analyze the data. Three main themes emerged from the analysis: (1) facilitators for the decision to pursue higher education in public health, (2) challenges and coping strategies, and (3) experiences of success. The internship program included eleven Bedouin students who conducted six community intervention projects covering a range of topics with different target Bedouin populations. Higher education is crucial for empowering minorities, producing leadership, and reducing socioeconomic and health gaps. The field internship enabled the necessary alignment between academia and public health practice. It is important to further reflect on the integration of minority groups in public health studies and its role in decreasing health inequity.

4.
Minerva Surg ; 78(3): 254-260, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36472585

RESUMO

BACKGROUND: Severe obesity and metabolic syndrome are common long-term complications after liver transplantation (LT). Metabolic bariatric surgery (MBS) is the essential treatment for severe obesity with laparoscopic sleeve gastrectomy (SG) being the most commonly performed procedure. METHODS: This is a retrospective analysis of all LT patients who underwent MBS between January 2006 and December 2020 in a single tertiary center. RESULTS: During the study period, a total of 226 LTs were performed. Four patients (1.8%) underwent SG following LT. Time interval from LT to SG ranged 11-72 months. The median Body Mass Index (BMI) before LT and SG was 38.8(±6.5) and 41.8(±2.7) kg/m2, respectively. All patients suffered from type II diabetes mellitus (T2DM) with a median A1c level of 5.9% (±1) under medications. All patients were consuming immunosuppressants perioperatively. All surgeries were approached laparoscopically, the median operative time was 65.5 minutes (±47.6), there were no intra-operative complications, and no conversions to open surgery. There were no early (30-day) major complications. The median length of stay was 3.5 days (±3.6). The median range of follow-up was 61.6 months (±18.2), there were no late (>30 day) complications. The median BMI at 24, and 60 months was 29.61(±3.9) and 31.10(±2.6) kg/m2, respectively. The median percentage of total weight loss at 24, and 60 months was 29.18 (±5.2) and 28.87(±3.7), respectively. The median percentage of excess weight loss at 24 and 60 months was 60.5% (±13) and 58.57% (±11.7), respectively. Three patients had T2DM resolution. CONCLUSIONS: SG following LT is associated with low perioperative morbidity and satisfactory long-term results.


Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Fígado , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Seguimentos , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Resultado do Tratamento , Obesidade/complicações , Obesidade/cirurgia , Redução de Peso , Gastrectomia/efeitos adversos , Gastrectomia/métodos
5.
Transplantation ; 107(1): 172-180, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36042543

RESUMO

BACKGROUND: The occurrence of acute liver failure (ALF) in pregnant women due to an etiology unrelated to pregnancy (pregALF) that leads to liver transplantation (LT) has rarely been reported. The objective was to report the outcome of pregnant women and fetus and propose a strategy for the timing of delivery and of LT in these patients. METHODS: Five consecutive pregnant patients with ALF were admitted to our center between 1986 and 2018 and underwent an LT. A systematic review of case reports concerning patients with pregALF who underwent LT was extracted from the literature. RESULTS: Three with gestational ages (GA) at admission of 15, 22, and 31 weeks of gestation (WG) were transplanted after delivery (n = 1) or intrauterine demise (n = 2) and 2 with GA of 16 and 23 WG before delivery. One infant survived in each group. Among the 32 cases published previously, 11 (34%) had been transplanted after delivery (median GA:31 [28-33]); 10 of these 11 infants were alive at birth. The other 21 mothers were transplanted before delivery (GA:21 WG [18-22]). The median GA at delivery was 30 WG [27.75-37]. Twelve of 21 infants were alive at birth. One-year survival among the ALF patients in our series and in the literature was 100%. Overall, the perinatal survival rate was low (64.8%). CONCLUSIONS: In pregnant patients presenting with ALF not related to the pregnancy, the LT lifesaving procedure had an excellent outcome. Overall, 65% of the infants were alive at delivery with major mortality in those fetus <22 WG despite continued pregnancy.


Assuntos
Falência Hepática Aguda , Transplante de Fígado , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Transplante de Fígado/métodos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/cirurgia , Taxa de Sobrevida , Idade Gestacional
6.
Artigo em Inglês | MEDLINE | ID: mdl-36360994

RESUMO

Active travel (AT) is a core physical activity (PA) indicator for children and youth; contributing to health and wellbeing, at both the individual and societal levels. This analysis explores patterns of adolescent active school travel (AST) and cycling and associations with different PA measures. Secondary analysis of the cross-sectional 2018-2019 Health Behaviour in School Age Children study in Israel included an extended PA module with walking, cycling and e-cycling modes. The nationally representative sample includes students in grades 6-12 (n = 4407). Analysis of weighted data included descriptive analyses, inferential statistics, and regression analyses. AST was reported by 61.9% of adolescents; 39.3% reported 20 min or more daily AST; 27.1% reported habitual cycling (HC) and 17.4% reported habitual e-cycling (HEC). There are mixed results for socio-economic status and environment. AST and HC were associated with less sedentary hours daily (odds ratio [OR] = 1.190 and 1.397, respectively); HC was associated with positive sports self-rating (OR = 2.394). Stepwise regression analysis found that lower AST duration, time in minutes, was associated with watching television with the family. Promotion of adolescent AT may be associated with increased PA and joint parent-adolescent AT, and was utilized across different socio-demographic groups in Israel.


Assuntos
Exercício Físico , Instituições Acadêmicas , Criança , Adolescente , Humanos , Estudos Transversais , Israel , Caminhada , Viagem , Meios de Transporte
7.
Artigo em Inglês | MEDLINE | ID: mdl-36429957

RESUMO

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are often co-transmitted. Viral coinfection results in worse outcomes. Persons who inject drugs (PWIDs) face barriers to medical treatment, but HCV treatment is indicated and effective even with ongoing active drug use. We aimed to assess access to HCV care and treatment results in patients coinfected with HIV-HCV. This is a real-world retrospective single-center study of patients followed in the HIV clinic between 2002 and 2018. Linkage to care was defined as achieving care cascade steps: (1) hepatology clinic visit, (2) receiving prescription of anti-HCV treatment, and (3) documentation of sustained virologic response (SVR). Of 1660 patients with HIV, 254 with HIV-HCV coinfection were included. Only 39% of them achieved SVR. The rate limiting step was the engagement into hepatology care. Being a PWID was associated with ~50% reduced odds of achieving study outcomes, active drug use was associated with ~90% reduced odds. Older age was found to facilitate treatment success. Once treated, the rate of SVR was high in all populations. HCV is undertreated in coinfected young PWIDs. Further efforts should be directed to improve access to care in this marginalized population.


Assuntos
Coinfecção , Usuários de Drogas , Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Coinfecção/epidemiologia , Coinfecção/tratamento farmacológico , Hepacivirus , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Estudos Retrospectivos , Antivirais/uso terapêutico , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , HIV
8.
Int J Qual Stud Health Well-being ; 17(1): 2130508, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36226383

RESUMO

PURPOSE: Active travel (AT) incorporates physical activity into daily living, critical for healthy adolescent development. We explore adolescent and parent attitudes and behaviours related to motivations for adolescent AT and effects of the COVID-19 pandemic. METHODS: We conducted semi-structured Zoom interviews with 25 adolescent-parent dyads in communities across Israel during early stages of the COVID-19 pandemic. Thematic content analysis was used to develop categories and themes. RESULTS: We identified key themes related to adolescent AT: Fostering independence enables adolescent AT; Pampering and safety concerns inhibit adolescent AT; Family and community norms influence adolescent travel modes; Personal enjoyment and positive attitudes facilitate AT; Peers and social networks promote adolescent AT and PA; Built environment and transport options influence AT choices. Interestingly, adolescents indicate AT is an opportunity for peer-to-peer communication without screen distraction, yet they use social media to promote AT and PA. CONCLUSIONS: The findings point to the influence of positive parent perceptions, active and supportive family and community norms on adolescent AT. Peer norms and social networks as well as features of the built environment also have the potential to influence AT. The COVID-19 pandemic encouraged use of AT and provided a setting for positive AT experiences.


Assuntos
COVID-19 , Adolescente , Liberdade , Humanos , Motivação , Pandemias , Pais
9.
J Phys Act Health ; 19(11): 700-728, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36280233

RESUMO

BACKGROUND: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children's and adolescents' (5-17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. METHODS: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders' top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. RESULTS: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. CONCLUSIONS: The Global Matrix 4.0 represents the largest compilation of children's and adolescents' PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.


Assuntos
COVID-19 , Exercício Físico , Criança , Adolescente , Humanos , Promoção da Saúde/métodos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Política de Saúde , Relatório de Pesquisa
10.
J Safety Res ; 78: 115-128, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399907

RESUMO

INTRODUCTION: There has been a significant increase in online purchasing and product safety problems have been identified in e-commerce. This study examines consumer behavior and safety perceptions among parents purchasing child products online. METHOD: A mixed methods approach, including focus groups and a survey with parents, identified key characteristics and behaviors. Cluster analysis was used to determine different population segments (including "Informed," "Uninformed," and "Infrequent" consumer groups) based on their frequency of online shopping and search for product information. "Safe" and "Unsafe" behavior groups were identified related to their search for safety information on child products. Logistic regression analysis was used to study the effects of consumer type groups and demographic variables on the chances of being a safer consumer. RESULTS: Findings indicate that child product safety considerations are not a priority for parents when shopping online. Only 62% of the survey respondents indicated that they search for information prior to buying a child product online, of which only 13% of the respondents noted that they search for information on product safety. Risky consumer behaviors were identified including the purchase of imitation products (counterfeit or knockoff products) and autonomous checks for product safety in lieu of safety standards. The logistic regression analysis found that being an "Uninformed Consumer" increases the odds of an individual being an "Unsafe Consumer" by 8.4 times (χ2(11) = 97.33, p < .001). Practical Applications: Design of a social marketing campaign that targets these different population segments to change perceptions and promote safe online purchasing is recommended.


Assuntos
Comércio , Comportamento do Consumidor , Criança , Feminino , Humanos , Pais , Gravidez , Assunção de Riscos , Inquéritos e Questionários
11.
J Hepatol ; 75(2): 435-438, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33892006

RESUMO

BACKGROUND & AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p <0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p <0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group. CONCLUSION: LT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: The Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina/imunologia , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Transplante de Fígado/métodos , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Terapia de Imunossupressão/métodos , Israel/epidemiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/imunologia , Testes Sorológicos/métodos , Testes Sorológicos/estatística & dados numéricos , Vacinação/efeitos adversos , Vacinação/métodos
12.
Traffic Inj Prev ; 21(7): 453-458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32615804

RESUMO

OBJECTIVE: Research indicates that hands-on instruction on installation and use of child restraint systems (CRSs) is an effective method to reduce misuse. However, use of these services is low. The objective of the Awareness and Availability of Child Passenger Safety Information Resources (AACPSIR) Survey was to estimate the degree of awareness caregivers have of CRS inspection stations. The survey also evaluated the relationships among caregiver confidence and risk perceptions as well as potential barriers and facilitators to inspection station use. METHODS: The AACPSIR was a web-based cross-sectional survey targeting a nationally representative sample of adults who drove with children aged 0-9 at least twice a month. An address-based sample was selected using a cluster sample design. Caregivers who reported driving frequently with child passengers answered questions on awareness and use of inspection stations, confidence related to CRS use, and barriers and facilitators to inspection station use. RESULTS: Data were collected from 1,565 households. In all, 66.9% of respondents were aware of inspection stations, but only 44.2% reported that they had used these services. Most caregivers indicated that they were confident (91.7%) that the car seat was installed correctly. A quarter of the respondents indicated a reason that might prevent them from using an inspection station was that they "don't think it's necessary". A long wait time (66.5%), distance (65.2%), and schedule conflicts (63.9%) were also frequently indicated as potential barriers. Conversely, among inspection station users, most did not need to make an appointment (73%), and over half indicated that the station was five miles or less from their home and within a 15-minute drive. CONCLUSIONS: The AACPSIR Survey results suggest a segment of caregivers share a positive safety culture, including knowledge of CPS services and use of those services. Of concern are caregivers who did not access an inspection station because they indicated it was not necessary, they already knew how to install the CRS, or pointed to other inconveniences. Future intervention programs that target caregivers unfamiliar with inspection stations or believe that the services are not necessary have the potential to improve child passenger safety.


Assuntos
Cuidadores/psicologia , Sistemas de Proteção para Crianças , Falha de Equipamento/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Cuidadores/estatística & dados numéricos , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Inquéritos e Questionários
13.
Accid Anal Prev ; 122: 36-47, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30308329

RESUMO

Children are more vulnerable as pedestrians due to their cognitive, physical and behavioral traits. However, walking is one of the main forms of travel for children, particularly during leisure hours. Child pedestrian injury primarily occurs in urban areas, with a significant share at crosswalks. This study observed child pedestrian behaviors at crosswalks of urban intersections aiming to characterize their behavior patterns and identify risk factors that may lead to injury. Crossing behaviors of children and adolescents up to age 18, during leisure hours, were video-recorded at 29 crosswalks, on signalized and un-signalized intersections situated on collector roads. Some children used pedestrian crosswalks while riding a bicycle or other non-motorized means; they were also included in the sample. Behaviors of 2930 young road users were encoded and compared by age groups. Multivariate logistic regression models were adjusted to identify factors associated with crossing on red and with non-checking vehicle traffic at un-signalized crosswalks. The findings pointed to different behavior patterns for the various child age groups. Risk-taking behaviors are higher for older children; adolescents aged 14-17 cross more on red, without checking traffic, outside crosswalk boundaries and while distracted. At all types of sites, a fifth of children over the age of 9 crossed by riding, the probability of crossing on red and of non-checking traffic prior to crossing at an un-signalized crosswalk was higher for children riding an electric bicycle or kick-scooter. The non-checking of traffic was also higher when a child is distracted by a mobile phone or other electronic gadget, or carries a big object. Children under age 9 were usually accompanied by adults but still exhibited risk-taking behaviors that apparently mirrored those of the adults. Risk-taking behaviors of young road users should be taken into account in the development of injury prevention programs focusing on child and parent education and training, and by adapting the urban environment to better meet their needs.


Assuntos
Acidentes de Trânsito/prevenção & controle , Pedestres/psicologia , Adolescente , Ciclismo/lesões , Ciclismo/psicologia , Ambiente Construído , Criança , Feminino , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Assunção de Riscos , População Urbana/estatística & dados numéricos , Gravação em Vídeo , Caminhada/lesões , Caminhada/psicologia
14.
Kidney Blood Press Res ; 42(2): 201-208, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28478454

RESUMO

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is an endothelium-specific peptide that stimulates angiogenesis via two receptor tyrosine kinases, Flt-1 and KDR. Endothelial nitric oxide synthase (eNOS) plays a major role in VEGF signaling. Delivery of arginine to membrane bound eNOS by the cationic amino acid transporter-1 (CAT-1) has been shown to modulate eNOS activity. The current studies were designed to test the hypothesis that VEGF enhances eNOS activity via modulation of arginine transport by CAT-1. METHODS: Using radio-labeled arginine, {[3H] L-arginine} uptake was determined in human umbilical vein endothelial cells (HUVEC) following incubation with VEGF with and without silencing the VEGF receptors Flt-1 or KDR. Subsequently, western blotting for CAT-1, PKCα, ERK 1/2, JNK, and their phosphorylated forms were performed. NO generation was measured by the Griess reaction. RESULTS: VEGF (50 and 100 ng/ml) significantly augmented endothelial arginine transport in a time dependent manner, an effect which was prevented by Sunitinib (2 µM), a multi targeted receptor tyrosine kinase inhibitor. The increase in arginine transport velocities by VEGF was not affected by silencing Flt-1 while silencing KDR abrogated VEGF effect. Furthermore, incubating cells with 50 and 100 ng of VEGF for 30 minutes significantly augmented CAT-1 abundance. The expression of PKC-α, JNK, and ERK1/2 and their phosphorylated forms were unchanged following incubation of HUVEC with VEGF. The concentration of NO2/NO3 following incubation with VEGF was significantly higher than from untreated cells. This increase was significantly attenuated by silencing KDR. CONCLUSIONS: VEGF increases arginine transport via modulation of CAT-1 in endothelial cells. This effect is exclusively dependent on KDR rather than Flt-1.


Assuntos
Arginina/metabolismo , Transporte Biológico/efeitos dos fármacos , Óxido Nítrico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Óxido Nítrico Sintase Tipo III/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Am J Physiol Renal Physiol ; 306(4): F449-56, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24338824

RESUMO

Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide synthase (eNOS) activity is a crucial parameter characterizing ECD. Decreased activity of cationic amino acid transporter-1 (CAT-1), the selective arginine transporter of eNOS, has been shown to inhibit eNOS in uremia. Recently, we failed to demonstrate a decrease in glomerular arginine transport in uremic female rats (Schwartz IF, Grupper A, Soetendorp H, Hillel O, Laron I, Chernichovski T, Ingbir M, Shtabski A, Weinstein T, Chernin G, Shashar M, Hershkoviz R, Schwartz D. Am J Physiol Renal Physiol 303: F396-F404, 2012). The current experiments were designed to determine whether sexual dimorphism which characterizes glomerular arginine transport system in uremia involves the systemic vasculature as well and to assess the effect of L-arginine in such conditions. Contractile and vasodilatory responses, ultrastructural changes, and measures of the L-arginine-NO system were performed in thoracic aortas of female rats subjected to 5/6 nephrectomy. The contractile response to KCl was significantly reduced, and acetylcholine-induced vasodilation was significantly impaired in aortas from CRF dames compared with healthy rats. Both of these findings were prevented by the administration of arginine in the drinking water. The decrease in both cGMP generation, a measure of eNOS activity, and aortic eNOS and phosphorylated eNOS abundance observed in CRF rats was completely abolished by l-arginine, while arginine transport and CAT-1 protein were unchanged in all experimental groups. Arginine decreased both serum levels of advanced glycation end products and the asymmetrical dimethylarginine/arginine ratio and restored the endothelial ultrastructure in CRF rats. In conclusion. arginine administration has a profound beneficial effect on ECD, independently of cellular arginine uptake, in CRF female rats.


Assuntos
Aorta/efeitos dos fármacos , Arginina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Falência Renal Crônica/fisiopatologia , Animais , Aorta/metabolismo , Aorta/fisiopatologia , Arginina/metabolismo , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Rim/metabolismo , Rim/fisiopatologia , Falência Renal Crônica/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos
16.
Am J Nephrol ; 37(6): 613-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23796541

RESUMO

BACKGROUND: The spectrum of cardiovascular toxicity by cyclosporine (CsA) includes hypertension, accelerated atherosclerosis, and thrombotic microangiopathy, all of which are the result of endothelial cell dysfunction. Endothelial cell dysfunction is characterized by decreased endothelial nitric oxide synthase (eNOS) activity. Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter for eNOS. CsA has been shown to attenuate nitric oxide (NO) generation. However, the mechanism remains elusive. We hypothesize that CsA inhibits eNOS activity through modulation of its selective arginine supplier CAT-1. METHODS: We studied the effect of CsA on arginine uptake, NO2/NO3 generation, and CAT-1, protein kinase Cα (PKCα), and phosphorylated PKCα protein expression in human umbilical vein endothelial cell cultures (HUVEC) in the absence and presence of L-arginine. RESULTS: CsA (0.5-2 µg/ml) significantly attenuated arginine transport in a dose- and time-dependent manner, a phenomenon which was prevented by co-incubation with L-arginine (1 mM). The aforementioned findings were accompanied by increased protein nitration, a measure for peroxynitrite accumulation. In contrast, no changes were observed in NO2/NO3 generation. CsA significantly decreased the abundance of CAT-1 protein, an effect that was attenuated by L-arginine. PKCα and phosphorylated PKCα (CAT-1 inhibitors) protein contents were not affected by CsA. CONCLUSION: CsA inhibits arginine transport and induces protein nitration in HUVEC through modulation of CAT-1.


Assuntos
Arginina/efeitos dos fármacos , Transportador 1 de Aminoácidos Catiônicos/efeitos dos fármacos , Ciclosporina/farmacologia , Células Endoteliais/efeitos dos fármacos , Imunossupressores/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Arginina/metabolismo , Transporte Biológico/efeitos dos fármacos , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Nitratos/metabolismo , Óxido Nítrico/biossíntese , Nitritos/metabolismo , Proteína Quinase C-alfa/efeitos dos fármacos , Proteína Quinase C-alfa/metabolismo
17.
Traffic Inj Prev ; 14(2): 194-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23343029

RESUMO

OBJECTIVE: Because the rate of injury and mortality from car crashes among Arab children is higher than among Jewish children in Israel, this study assesses the patterns of age-appropriate child restraint system (CRS) use in Arab towns in Israel. METHODS: From October 2010 to September 2011, 4396 children ages 0 to 14 were observed while seated in vehicles in 9 Arab towns and villages in Israel. RESULTS: Among infants aged 0 to 1 year old, 31.2 percent were observed in an age-appropriate restraint, whereas among children aged 1 to 4 years, only 12.4 percent were age-appropriately restrained. Children aged 5 to 9 were observed to have the lowest levels of age-appropriate restraint use (1.3%). The variation between the various villages was large and dependent on the age of the child. CONCLUSIONS: The low rates of CRS use may explain to some degree the high rates of injury and mortality of Arab children in car crashes. These low rates indicate that previous interventions have not been successful in increasing restraint use in the Arab community in Israel and there is a need to plan targeted interventions specifically for this population. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.


Assuntos
Árabes , Sistemas de Proteção para Crianças/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Israel
18.
J Bacteriol ; 195(7): 1475-83, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23335417

RESUMO

Upon nutrient deprivation, Bacillus subtilis initiates the developmental process of sporulation by integrating environmental and extracellular signals. These signals are channeled into a phosphorelay ultimately activating the key transcriptional regulator of sporulation, Spo0A. Subsequently, phosphorylated Spo0A regulates the expression of genes required for sporulation to initiate. Here we identified a group of genes whose transcription levels are controlled by Spo0A during exponential growth. Among them, three upregulated genes, termed sivA, sivB (bslA), and sivC, encode factors found to inhibit Spo0A activation. We furthermore show that the Siv factors operate by reducing the activity of histidine kinases located at the top of the sporulation phosphorelay, thereby decreasing Spo0A phosphorylation. Thus, we demonstrate the existence of modulators, positively controlled by Spo0A, which inhibit inappropriate entry into the costly process of sporulation, when conditions are favorable for exponential growth.


Assuntos
Bacillus subtilis/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Esporos Bacterianos/crescimento & desenvolvimento , Bacillus subtilis/citologia , Bacillus subtilis/genética , Bacillus subtilis/fisiologia , Proteínas de Bactérias/metabolismo , Perfilação da Expressão Gênica , Histidina Quinase , Proteínas Quinases/metabolismo , Transdução de Sinais , Esporos Bacterianos/citologia , Esporos Bacterianos/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica
19.
Mol Microbiol ; 69(4): 1018-28, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18573177

RESUMO

A fundamental challenge in developmental biology is to elucidate the regulatory events that trigger cellular differentiation. Sporulation in the Gram-positive bacterium Bacillus subtilis serves as a simple experimental model system to address this challenge. The hallmark of sporulation is the formation of an asymmetrically positioned septum that divides the cell into unequally sized progeny. Here we describe the role of an ABC transporter, comprising the FtsE and FtsX proteins, in the initiation of spore formation. We discovered that in the absence of this transporter, entry into sporulation is delayed and an atypical symmetric septum is formed instead of a polar one. We show that this phenotype can be suppressed by artificially activating the master regulator of sporulation, Spo0A, or by activating the histidine kinases that function upstream of Spo0A. Our data indicate that the FtsEX transporter is one of the top components in the hierarchy of factors required to initiate sporulation, and thus it is essential for establishing proper temporal activation of the process.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Bacillus subtilis/citologia , Bacillus subtilis/fisiologia , Proteínas de Bactérias/metabolismo , Diferenciação Celular , Transportadores de Cassetes de Ligação de ATP/genética , Bacillus subtilis/genética , Proteínas de Bactérias/genética , Diferenciação Celular/genética , Divisão Celular/genética , Esporos Bacterianos/citologia , Esporos Bacterianos/genética , Esporos Bacterianos/fisiologia
20.
J Biol Chem ; 283(13): 8564-72, 2008 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-18195007

RESUMO

The interaction of the Arf1-directed GTPase-activating protein ArfGAP1 with the Golgi apparatus depends on motifs in its noncatalytic part that are unstructured in solution but are capable of folding into amphipathic helices in vitro upon interaction with poorly packed lipids. In previous studies a few hydrophobic residues that are critical for lipid binding and Golgi localization were identified, but the precise topology of the amphipathic motifs has not been determined. Here we present a detailed analysis of the Golgi targeting and in vitro folding features of the region encompassing the amphipathic motifs (residues 199-294). Point mutation analysis revealed that most hydrophobic residues within this region contribute to Golgi localization, whereas analysis by proline replacements and alanine insertions revealed that Golgi interaction depends on folding into two amphipathic helices with a short interrupting sequence. Analysis of splice isoforms containing 10-residue in-frame insertions within their first amphipathic motifs revealed that the insertion causes a truncation of the amphipathic helix that does not extend beyond the insertion sequence. Lastly, a lysine replacement mutant recently reported to bind to negatively charged liposomes in a curvature-independent manner showed normal cellular distribution, suggesting that Golgi targeting of Arf-GAP1 may involve factors other than sensing lipid packing.


Assuntos
Processamento Alternativo/genética , Proteínas Ativadoras de GTPase/química , Proteínas Ativadoras de GTPase/metabolismo , Complexo de Golgi/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Dicroísmo Circular , Citosol/metabolismo , Proteínas Ativadoras de GTPase/genética , Células HeLa , Humanos , Lipossomos , Dados de Sequência Molecular , Mutação/genética , Ligação Proteica , Dobramento de Proteína , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transporte Proteico , Eletricidade Estática
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