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1.
Front Nutr ; 11: 1383725, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957871

RESUMO

Background and aim: Nutrition plays a vital role in maintaining and improving vision health. However, little is known about dietary intake habits and their correlation with vision health among adults in the Kingdom of Saudi Arabia (KSA). The present survey was aimed to assess dietary patterns and vision health among Saudi adults and to determine the association between dietary patterns and vision health. Methods: The present analytical study was carried out among 1,234 Saudi adults in the Makkah, Riyadh, and Qassim regions of KSA. We used the Arabic version of the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and the diet quality screener (DQS). We applied Mann-Whitney U and Kruskal-Wallis tests to determine the association between vision function score and demographic characteristics. Furthermore, the Spearman correlation test was used to determine the relationship between the DQS and the NEI VFQ-25. Results: Of the studied population, the highest score obtained through the NEI VFQ-25 was in the social function domain (mean ± SD = 76.64 ± 18.63), followed by the general vision domain (mean ± SD = 75.21 ± 15.16) and was negatively correlated with age. Regarding dietary patterns, the intake of lean protein sources per week was the highest, with a mean intake of 4.17 days per week, followed by that of whole grains and milk or dairy products, with a mean intake of around four days per week. There was a significant correlation between various dietary intakes and visual function scores. Conclusion: The present survey underscores the significance of understanding regional dietary patterns and their implications for vision health. Furthermore, our study's findings indicate a need for targeted nutritional intervention measures to improve the vision health of this population.

2.
Plants (Basel) ; 11(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36079668

RESUMO

Tomato brown rugose fruit virus (ToBRFV; genus, Tobamovirus, family, Virgaviridae) was first reported in 2015 infecting tomatoes grown under protected cropping in the Jordan Valley. Since then, ToBRFV has been detected in tomatoes grown in both protected and open fields across Jordan. The increased incidence of ToBRFV prompted this investigation of the potential role of natural weed hosts in the dissemination of ToBRFV. A survey was conducted in the Jordan Valley and highlands to determine possible reservoir hosts of ToBRFV in fields and greenhouse complexes in which tomatoes were grown. Detection of ToBRFV infection was made by double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) and further confirmation by reverse-transcription polymerase chain reaction (RT-PCR), followed by DNA cloning and sequencing, and bioassays. Thirty weed species belonging to twenty-six genera from sixteen families were tested. Twelve species belonging to eight families were infected of which ten species are newly reported hosts for ToBRFV. Seed transmission of ToBRFV in Solanum nigrum was confirmed in a grow-out experiment. To our knowledge, this is the first report of the natural occurrence of ToBRFV on weed hosts. Identification of natural reservoirs of ToBRFV can help to develop management practices focused on weed plant species to prevent ToBRFV transmission. The extent to which ToBRFV survives in diverse alternate weed host species outside tomato growing seasons in different world regions requires further research in order to establish the risk associated with the possible contribution of weeds as a reservoir for primary infections in tomato crops.

3.
Ann Med Surg (Lond) ; 72: 103046, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34824839

RESUMO

BACKGROUND: Participation in Colorectal cancer (CRC) screening programs is low in Saudi Arabia. Public awareness of CRC and knowledge of available screening tools are crucial for improving screening uptake. This study aimed to examine the level of awareness and knowledge of CRC among the Saudi population. MATERIALS AND METHODS: A survey-based study was conducted on 1912 residents of Riyadh, Saudi Arabia. The survey comprised 20 questions; these concerned the definition of the colon and rectum; the function of the colon; the incidence, risk factors, symptoms, screening methods, prevention methods, and treatment methods for CRC; and the value of early detection of CRC. RESULTS: Of the 1912 participants who completed the survey, only 51.7% knew that the colon was the large intestine, while 57% knew that the rectum was the end of the large intestine. Colonoscopy was the preferred screening tool (72.8%). Most respondents believed early detection of CRC through colonoscopy is associated with high survival rates. However, 65.7% of the participants reported that they would not like to undergo a CRC screening. Higher education level was also associated with knowledge that CRC can develop asymptomatically, with postgraduates most likely to know this (P = 0.032). CONCLUSIONS: There is a lack of knowledge regarding CRC among certain demographic groups in Saudi Arabia, and education and screening programs should target populations with the most limited knowledge.

4.
PLoS One ; 16(9): e0256853, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495997

RESUMO

The reconstruction of fire history is essential to understand the palaeoclimate and human history. Polycyclic aromatic hydrocarbons (PAHs) have been extensively used as a fire marker. In this work, the distribution of PAHs in Borneo peat archives was investigated to understand how PAHs reflect the palaeo-fire activity. In total, 52 peat samples were analysed from a Borneo peat core for the PAH analysis. Pyrogenic PAHs consist of 2-7 aromatic rings, some of which have methyl and ethyl groups. The results reveal that the concentration of pyrogenic PAHs fluctuated with the core depth. Compared to low-molecular-weight (LMW) PAHs, the high-molecular-weight (HMW) PAHs had a more similar depth variation to the charcoal abundance. This finding also suggests that the HMW PAHs were mainly formed at a local fire near the study area, while the LMW PAHs could be transported from remote locations.


Assuntos
Incêndios/história , Sedimentos Geológicos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo/química , Bornéu , Carvão Vegetal/análise , Biomarcadores Ambientais , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , História Medieval , Humanos , Peso Molecular , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/classificação
5.
Ann Saudi Med ; 40(5): 403-407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007172

RESUMO

BACKGROUND: Self-expanding metal stents (SEMS) are used as a bridge to surgery for colon cancer patients as an alternative to emergency surgery. Currently, there is a paucity of literature from Saudi Arabia on the preoperative usage of SEMS. OBJECTIVE: Determine whether SEMS are associated with a higher rate of complications. DESIGN: Retrospective cohort study SETTINGS: Tertiary care hospital in Saudi Arabia. PATIENTS AND METHODS: In patients diagnosed with obstructing colon cancer, up-front surgical resection was compared with insertion of SEMS followed by surgical resection between the years 2009 and 2013. MAIN OUTCOME MEASURES: Rate of stent-related short-term complications. Secondary endpoint, postoperative complications. SAMPLE SIZE: 65. RESULTS: Twenty-four (36.9%) patients underwent SEMS placement; 41 (63.1%) underwent primary surgery. The median (interquartile range) hospital stay was significantly higher among the SEMS group (13 [8.5] days versus 7 [3] days in the primary surgery group, P<.001). Five patients (20.8%) in the SEMS group developed complications: 2 (8.3%) perforations, 2 (8.3%) obstructions, and 1 (4.2%) stent migrations. CONCLUSION: SEMS is associated with longer hospital stays and short-term serious complications. Further research should be conducted, preferably with a larger sample size. LIMITATIONS: Retrospective design, small sample size. CONFLICT OF INTEREST: None.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Obstrução Intestinal , Neoplasias do Colo/complicações , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento
6.
J Family Med Prim Care ; 9(1): 221-228, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32110594

RESUMO

BACKGROUND: Breast cancer is having a major impact on women's health worldwide. Early detection is the best defense against the associated morbidity and mortality of the disease. OBJECTIVES: To assess the level of mammography uptake among working Saudi women and identify the obstacles and barriers that negatively affect it. In addition, to identify the most effective sources of breast-cancer-related information and early detection screening. METHOD: We conducted a cross-sectional study of women employees of King Saud University aged 40 years and above on March-May 2015 using a self-report questionnaire. RESULTS: A total of 229 participants were recruited from the female staff of King Saud University. Of the participants, 34% were aged 41 years or above, approximately 66% were married, 53.3% had a bachelor's degree, and 61.1% worked as administrators; further, 64.6% had a history of breastfeeding. The rate of mammography uptake was 51.5%. Univariate logistic regression indicated that age, education, and being single predict the rate of mammography uptake. However, multivariate logistic regression indicated that earlier age significantly predicts a higher risk of a low rate of mammography uptake. The main obstacle negatively affecting mammography uptake was ineligible criteria (21.8%). The main sources of information regarding breast cancer were awareness campaigns and television and radio (45.4% and 43.7%, respectively). CONCLUSION: The participants' rate of mammography uptake, awareness of mammograms, the risk factors, and signs of breast cancer were low. To improve breast-cancer mortality rates in Saudi Arabia, earlier detection of breast cancer through increasing awareness of mammograms is of paramount importance.

7.
Data Brief ; 25: 104214, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31372481

RESUMO

The data presented herein were collected from the Straits of Malacca, along the west coast of Peninsular Malaysia. A 3.9 m core sample was retrieved from the Straits of Malacca in 2001. This core was continuously sub-sampled at 5-cm intervals between selected core depths of 220 cm and 380 cm. The 32 sub-samples obtained were analysed to understand the species composition of benthic Foraminifera in them and the changes in lithology during the Holocene. The data available in this article include the raw counts of different species of Foraminifera and the weight percentages of sediment of different grain sizes and organic matter at different depth. In addition, the estimated ages of the sediment samples are also provided. The chronostratigraphic framework of the core was based on radiocarbon-14 Accelerator Mass Spectrometry (AMS) dates estimated from three selected sediment intervals. The results of carbon dating were calibrated to calendar years (cal BC/AD) and calibrated radiocarbon years (cal BP). Calibration was done using the INTCAL program with a Delta R value of -19 ± 70.

8.
Neurosciences (Riyadh) ; 24(1): 22-28, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30842396

RESUMO

OBJECTIVE: To study the frequency of multiple vascular risk factors and electrophysiological severity of carpal tunnel syndrome (CTS) in Saudi diabetic patients. METHODS: This retrospective cross-sectional study was conducted in Neurology Department, King Fahd Hospital of University, Al-Khobar, Kingdom of Saudi Arabia from April 2017 to March 2018 and included 200 patients with CTS. Body parameters, such as blood pressure (BP), weight, height, and body mass index (BMI), along with laboratory and median nerve electrophysiological parameters, of diabetic and non-diabetic patients were compared, and a p-value<0.05 was considered significant. RESULTS: Frequency of hypertension (HTN) and obesity was significantly higher in diabetic patients (p<0.05). Mean median nerve sensory amplitude (MNSA) was lower in diabetic patients (p<0.05).Non-recordable nerves, as well as bilateral and extremely severe CTS (p<0.05), were more frequently seen in diabetic patients. Age, BMI, systolic BP, low serum high density lipoprotein (HDL), high triglycerides, high fasting blood sugar, and high glycated hemoglobin (Hba1c) levels, known to affect the electrophysiological severity of CTS, had a statistically significant association with diabetes. CONCLUSION: Diabetes mellitus (DM) and obesity are the most commonly identified risk factors of CTS. Dyslipidemia, HTN and obesity are more frequently seen in diabetic patients with CTS. These concurrent risk factors are confounding the electrophysiological severity of CTS in these patients. Further larger-scale studies with the control of confounding factors are recommended.


Assuntos
Síndrome do Túnel Carpal/patologia , Complicações do Diabetes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome do Túnel Carpal/epidemiologia , Complicações do Diabetes/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Prevalência , Arábia Saudita
9.
J Clin Neurol ; 14(3): 359-365, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29971975

RESUMO

BACKGROUND AND PURPOSE: The objective of this study was to determine the frequencies of different clinical presentations and the phenotypic spectrum of multiple sclerosis (MS). METHODS: This cross-sectional study was performed in the Neurology Department of King Fahd Hospital of University Alkhobar in the Kingdom of Saudi Arabia (KSA). Data of 190 MS patients who fulfilled the McDonald criteria were retrieved from medical records and analyzed. RESULTS: The age at disease onset was 26.27±8.2 years (mean±SD) and disease duration was 6.38±5.10 years. The male-to-female ratio was 1:1.6. Optic neuritis and myelitis were the most-frequent first clinical presentations. Sensory (73.1%), motor (61%), and visual (58.4%) symptoms were the most-frequent established clinical symptoms. Relapsing-remitting multiple sclerosis (RRMS) was present in 75% of the cases. Supratentorial T2-weighted white-matter lesions and deep-gray-matter or juxtacortical lesions were the most-frequent magnetic resonance imaging (MRI) lesions, comprising 28% and 23.7% of all MRI lesions observed in 93.6% and 79.4% of the cases, respectively. The scores on the Expanded Disability Status Scale were within the range of 1.0-5.5 in 82.1% of the patients. There were 145 (76.3%) patients taking interferon ß therapy. CONCLUSIONS: MS presenting in the hospital setting is more common in KSA than reported previously, and the number of diagnosed cases in increasing. It is therefore an emerging and disabling neurological illness in KSA with clinical characteristics not dissimilar to those in other middle eastern countries. A decrease in the frequency of patients with secondary progressive multiple sclerosis (SPMS) indicates either that more new cases of RRMS are being diagnosed or that adequate treatments of RRMS are preventing the evolution to SPMS. Further larger and population-wide epidemiological and clinical studies with the long-term follow-up of MS patients are required to better assess the clinical spectrum of MS in KSA.

10.
Mar Pollut Bull ; 127: 654-663, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29475708

RESUMO

Study is made of the radioactivity in the beach sands of Langkawi island, a well-known tourist destination. Investigation is made of the relative presence of the naturally occurring radionuclide 40K and the natural-series indicator radionuclides 226Ra and 232Th, the gamma radiation exposure also being estimated. Sample quantities of black and white sand were collected for gamma ray spectrometry, yielding activity concentration in black sands of 226Ra, 232Th and 40K from 451±9 to 2411±65Bqkg-1 (mean of 1478Bqkg-1); 232±4 to 1272±35Bqkg-1 (mean of 718Bqkg-1) and 61±6 to 136±7Bqkg-1 (mean of 103Bqkg-1) respectively. Conversely, in white sands the respective values for 226Ra and 232Th were appreciably lower, at 8.3±0.5 to 13.7±1.4Bqkg-1 (mean of 9.8Bqkg-1) and 4.5±0.7 to 9.4±1.0Bqkg-1 (mean of 5.9Bqkg-1); 40K activities differed insubstantially from that in black sands, at 85±4 to 133±7Bqkg-1 with a mean of 102Bqkg-1. The mean activity concentrations of 226Ra and 232Th in black sands are comparable with that of high background areas elsewhere in the world. The heavy minerals content gives rise to elevated 226Ra and 232Th activity concentrations in all of black sand samples. Evaluation of the various radiological risk parameters points to values which in some cases could be in excess of recommendations providing for safe living and working. Statistical analysis examines correlations between the origins of the radionuclides, also identifying and classifying the radiological parameters. Present results may help to form an interest in rare-earth resources for the electronics industry, power generation and the viability of nuclear fuels cycle resources.


Assuntos
Radiação de Fundo , Praias/normas , Metais Terras Raras/química , Monitoramento de Radiação/métodos , Radioisótopos/análise , Poluentes Radioativos do Solo/análise , Humanos , Ilhas , Malásia , Dióxido de Silício/química
11.
Med Teach ; 38 Suppl 1: S66-72, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26984037

RESUMO

AIMS: To explore physical activity (PA) habits among the medical students and examine the correlation with their grade point average (GPA) achievement at College of Medicine, King Saud University, Riyadh, Saudi Arabia. METHODS: A cross-sectional study was conducted among the medical students (n = 409), during the academic year 2012-2013. Students' physical activity habits were self-reported. GPA, body mass index (BMI) and body fat percent (BF%) were collected and analyzed with SPSS software. RESULTS: Out of 409 students, 193 (47.2%) students reported being physically active. Our result showed a significant positive association between students' PA habits and high-GPA achievement (χ(2 )= 10.65, p = 0.001). The greatest odds ratio of high GPA was found among the fourth year students (OR = 3.08, CI: 1.15-8.28, p = 0.025) and fifth year students (OR = 5.07, CI: 1.48-17.31, p = 0.010). In addition, significant association was found between the normal BMI and high-GPA achievers (χ(2 )= 8.30; p = 0.016). However, no statistically, significant association was found between BF% and GPA. CONCLUSIONS: The present study showed a positive associations was found between PA habits and high academic achievement. In addition, positive association was found between PA, obese students and GPA achievement. Therefore, there is a need for the establishment of physical activity education and public health programs to promote importance of PA in Saudi population.


Assuntos
Escolaridade , Exercício Físico , Estudantes de Medicina , Adolescente , Adulto , Composição Corporal , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Arábia Saudita/epidemiologia , Adulto Jovem
12.
Pak J Pharm Sci ; 29(1): 221-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26826814

RESUMO

Nowadays,most of the pathogenic bacteria become resistant to antibiotics. Therefore,the pharmaceutical properties of the natural plant extracts have become of interest to researchers as alternative antimicrobial agents. In this study,antibacterial activities of extract gained from Acacia etbaica, Acacia laeta, Acacia origena and Acacia pycnantha have been evaluated against isolated pathogenic bacteria (Strains MFM-01, MFM-10 and AH-09) using agar well diffusion methods.The bacterial strains were isolated from infected individuals,and their exact identification was detected on the basis of 16S rRNA gene amplification and sequence determination. Alignment results and the comparison of 16 SrRN A gene sequences of the isolates to 16 SrRN A gene sequences available in Gen Bank data base as well as the phylogenetic analysis confirmed the accurate position of the isolates as Klebsiella oxytoca strain MFM-01, Staphylococcus aureus strain MFM-10 and Klebsiella pneumoniae strain AH-09. Except for cold water, all tested solvents (Chloroform, petroleum ether, methanol, diethyl ether, and acetone) showed variation in their activity against studied bacteria. GC-MS analysis of ethanol extracts showed that four investigated Acacia species have different phyto components. Eight important pharmaceutical components were found in the legume of Acacia etbaica, seven in the legume of Acacia laeta, fifteen in the legume of Acacia origena and nine in the leaves of Acacia pycnantha. A dendrogram was constructed based on chemical composition, revealed that Acacia laeta is more closely related to Acacia etbaica forming on eclade, whereas Acacia origena less similar to other species. Our results demonstrated that, investigated plants and chemical compounds present could be used as promising antibacterial agents.


Assuntos
Acacia , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acacia/química , Bactérias/classificação , Bactérias/genética , Análise por Conglomerados , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Testes de Sensibilidade Microbiana , Filogenia , RNA Ribossômico 16S/genética
13.
Pak J Pharm Sci ; 28(6): 2009-17, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26639478

RESUMO

In vitro antimicrobial efficacy of seven solvent extracts from leaves and hips of Saudi Arabian weed Rosa abyssinica against a variety of human pathogenic bacteria and Candida species have been evaluated using well diffusion methods. Phytochemicals present in the leaves and hips of Rosa abyssinica has been characterized using Gas Chromatogram Mass spectrometry analysis. The extracts comparative efficacy against tested microbes gained from the fresh and dry leaves exhibited more prominent activity than fresh and dry hips. The methanol, chloroform, petroleum ether, acetone and diethyl ether extracts have a greater lethal effect on pathogenic microbes than hot water extracts, while cold-water extracts showed no activity. Twenty-four phytochemicals have been characterized from ethanol extract of the leaves of Rosa abyssinica and fifteen from hips by GC-MS. The major compounds detected in the leaves were squalene (38.21%), ethane, 1,1-diethoxy- (9.65%), ß-D-glucopyranose, 1,6-anhydro- (8.55%), furfural (5.50%) and 2-furancarboxaldehyde 5-(hydroxymethyl)- (5.19%). The major compounds in the hips were 2-furancarboxaldehyde 5-(hydroxymethyl)- (51.27%), ß-D-glucopyranose, 1,6-anhydro- (8.18%), 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl- (7.42%), 2,5-furandione, dihydro-3-methylene- (6.79%) and furfural (5.99%). Current findings indicate that extract from leaves and hips of Rosa abyssinica and the bioactive components present could be used as pharmaceutical agents.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Rosa/química , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Frutas , Compostos Fitoquímicos/isolamento & purificação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Solventes/química
14.
BMJ Case Rep ; 20152015 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-26494713

RESUMO

We report a case of a 36-month-old Saudi girl who presented with recurrent episodes of unexplained hypoelectrolytaemia. Her cystic fibrosis CFTR (Cystic Fibrosis Transmembrane conductance Regulator) full gene sequence confirmed that she was homozygous for D579G mutation.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Desequilíbrio Hidroeletrolítico/etiologia , Pré-Escolar , Feminino , Homozigoto , Humanos , Mutação , Recidiva , Arábia Saudita
15.
Mol Biol Rep ; 38(4): 2603-10, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21107733

RESUMO

Killer cell immunoglobulin-like receptors (KIRs) influence the outcome of haematopoetic stem cell transplantation by modulating the cytotoxic ability of natural killer (NK) cells and a subset of T cells. KIRs are also highly polymorphic and could therefore be good population genetic markers, much like their human leukocyte antigen (HLA) ligands. This study represents the first report on distribution of 16 KIR genes in 162 unrelated healthy Saudi individuals. All the 16 KIR genes were observed in the studied population and the four framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1) were present in all individuals. Forty- one distinct KIR profiles were expressed in our population, 11 of which had not been previously described in other populations including the Middle Eastern population. AA1, the most common genotypic profile was observed at a frequency of 26.5%. The group A haplotype was more frequent (53%) in the Saudi population compared to the group B haplotype (47%). The pattern of the inhibitory KIR/HLA ligands were also analyzed and 52.3% of the Saudi population was found to express two pairs of the inhibitory KIR/HLA-C. The KIR gene frequencies suggests that the Saudi population shares common general features with the Middle Eastern and other populations, but still has its own unique frequencies of several KIR loci.


Assuntos
Variação Genética , Células Matadoras Naturais/imunologia , Fenótipo , Receptores KIR/genética , Feminino , Genótipo , Antígenos HLA-C/genética , Haplótipos/genética , Humanos , Masculino , Arábia Saudita
16.
Exp Hematol ; 37(7): 838-48, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19446661

RESUMO

OBJECTIVE: The purpose of this study was to examine the antitumor immune function of gammadelta T cells and to scan the granzyme B gene for the known single nucleotide polymorphism in breast cancer patients and normal controls. MATERIALS AND METHODS: Levels, cytotoxicity, and functional capacity of gammadelta T cells in peripheral blood mononuclear cells were assessed by flow cytometry, (51)Cr release, and ELISpot assays, respectively. Furthermore, sequence based typing was adopted to screen for granzyme B gene polymorphism. RESULTS: We have found that the frequency and function of gammadelta T cells are reduced both in peripheral blood mononuclear cells of 30 newly diagnosed breast cancer patients (2 [1.2, 3]), compared with 38 normal controls (3.2 [2.5, 5.7]) (p=0.02). In addition, resting gammadelta T cells from breast cancer patients produced significantly more interleukin-6 and tumor necrosis factor-alpha than normal controls. Moreover, ex vivo stimulation of gammadelta T cells with zoledronic acid and interleukin-2 compensated in part for this deficiency, as it stimulated the proliferation, cytokine production, and enhanced the expression of messenger RNA of granzyme B. Interestingly, when the known granzyme B gene polymorphism was screened, we found the prevalence of the mutated genotype RAH/RAH to be significantly (p<0.017) associated with breast cancer patients (14.30%) compared with normal donors (1.40%). Cytotoxicity exerted by gammadelta T cells on Daudi and MCF-7 was significantly higher in donors with the wild-type QPY/QPY (50%) compared with donors with RAH/RAH (21%). CONCLUSIONS: Our data suggest that reduction in the proportion of gammadelta T cells and granzyme B gene polymorphism leads to defective immune function in breast cancer patients. Treatment with zoledronic acid amend partially this fault. Further studies of gammadelta T cells function and granzyme B gene polymorphism in cancers, as well as the potential therapeutic use of zoledronic acid are warranted.


Assuntos
Neoplasias da Mama/genética , Granzimas/genética , Polimorfismo Genético , Receptores de Antígenos de Linfócitos T gama-delta/fisiologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Estudos de Coortes , Citotoxicidade Imunológica , Difosfonatos/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imidazóis/farmacologia , Imunofenotipagem , Interleucina-6/biossíntese , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Ácido Zoledrônico
17.
Cancer Res ; 68(15): 6350-9, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18676860

RESUMO

Compelling evidences indicate a key role for regulatory T cells (T(reg)) on the host response to cancer. The Wilms' tumor antigen (WT1) is overexpressed in several human leukemias and thus considered as promising target for development of leukemia vaccine. However, recent studies indicated that the generation of effective WT1-specific cytotoxic T cells can be largely affected by the presence of T(regs). We have generated T-cell lines and clones that specifically recognized a WT1-84 (RYFKLSHLQMHSRKH) peptide in an HLA-DRB1*0402-restricted manner. Importantly, they recognized HLA-DRB1*04-matched fresh leukemic cells expressing the WT1 antigen. These clones exerted a T helper 2 cytokine profile, had a CD4(+)CD25(+)Foxp3(+)GITR(+)CD127(-) T(reg) phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact. Priming of alloreactive T cells in the presence of T(regs) strongly inhibited the expansion of natural killer (NK), NK T, and CD8(+) T cells and had an inhibitory effect on NK/NK T cytotoxic activity but not on CD8(+) T cells. Furthermore, priming of T cells with the WT1-126 HLA-A0201-restricted peptide in the presence of T(regs) strongly inhibited the induction of anti-WT1-126 CD8(+) CTL responses as evidenced by both very low cytotoxic activity and IFN-gamma production. Moreover, these T(reg) clones specifically produced granzyme B and selectively induced apoptosis in WT1-84-pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells. Importantly, we have also detected anti-WT1-84 interleukin-5(+)/granzyme B(+)/Foxp3(+) CD4(+) T(regs) in five of eight HLA-DR4(+) acute myeloid leukemia patients. Collectively, our in vitro and in vivo findings strongly suggest important implications for the clinical manipulation of T(regs) in cancer patients.


Assuntos
Antígenos de Neoplasias/imunologia , Linfócitos T CD4-Positivos/imunologia , Imunoterapia , Tumor de Wilms/imunologia , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tumor de Wilms/terapia
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