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1.
Folia Biol (Praha) ; 66(1): 36-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32512657

RESUMO

This study investigated whether kaempferol could inhibit ovarian cancer (OC) by activation of endoplasmic reticulum (ER) stress and autophagy, and tested its effect on the sensitivity of OC cells to cisplatin (cis-diamminedichloroplatinum, DPP). To study the effect of kaempferol on activation of ER stress and autophagy and find out whether its mechanism of action involves calcium (Ca2+), A2780 OC cells were cultured in DMEM/F12 for 24 h with or without kaempferol (40 µmol/l) in the presence or absence of autophagy or ER stress inhibitors or a calcium chelator. To study the effect of kaempferol on the sensitivity of OC cells to DPP and the potential involvement of modulation of protein kinase B (Akt) expression, A2780 OC were incubated with kaempferol and increasing concentrations of DPP (0-20 µmol/l) and then with kaempferol at its predetermined IC50 (6.8 µmol/l). Compared to control cells, kaempferol increased cell apoptosis (158 %) and decreased viability (53.17 %) and proliferation (49.17 %) of A2780 OC cells. Concomitantly, it increased the protein levels of GRP78, PERK, ATF6, IRE-1, LC3II, beclin 1, and caspase 4, thus suggesting activation of cytotoxic autophagy. This was mediated by increasing intracellular Ca+2 levels. In addition, kaempferol increased the sensitivity of A2780 cells to DPP (IC50 from 6.867 ± 0.99 to 3.73 ± 0.59 µmol/l) by decreasing the protein levels of p-Akt (0.31 ± 0.09 vs 0.12 ± 0.005). In conclusion, the findings of this study encourage the use of kaempferol alone or in combination with DPP to inhibit tumorigenesis of ovarian cells.


Assuntos
Autofagia , Cisplatino/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Quempferóis/farmacologia , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Apoptose , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
2.
Int Nurs Rev ; 65(4): 559-566, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30239998

RESUMO

AIM: This study investigated the spiritual climate of a hospital in Saudi Arabia as perceived by nurses. BACKGROUND: A spiritually conducive environment improves patient, nurse and organizational outcomes. Despite being important, no studies have investigated this area in the Muslim-dominated Middle Eastern countries. INTRODUCTION: A snapshot on the degree of spiritual climate perception may provide insight into the aspects that may need improvement and may become basis for the creation of health and nursing policies directed towards creating a spiritually-accepting and respecting clinical workplace. METHOD: A sample of 219 nurses employed in a 500-bed capacity hospital in Saudi Arabia was included in this cross-sectional study utilizing the spiritual climate scale. RESULTS: The nurses perceived their hospital's spiritual climate to be fair. The item 'I am encouraged to express spirituality in this clinical area' received the lowest mean, whereas the item 'My spiritual views are respected in this clinical area' received the highest mean. Being Saudi, having less total experience as a nurse, and having greater total experience as a nurse in Saudi Arabia and in the present hospital positively influenced the perception of the spiritual climate among nurses. CONCLUSION: The findings stress the need to improve the spiritual climate in the hospital. IMPLICATIONS FOR NURSING AND NURSING POLICY: Hospitals are recommended to create policies to implement interventions geared towards creating a spiritually-friendly environment. Hospitals are encouraged to create a safe place where nurses can freely express their spirituality regardless of preference or religious denomination. Spiritual education may be provided by hospitals as part of continuing education. Managers may also focus on the existential spirituality of nurses, especially for spiritually-sensitive environments such as Saudi Arabia.


Assuntos
Atitude do Pessoal de Saúde , Recursos Humanos de Enfermagem Hospitalar , Cultura Organizacional , Espiritualidade , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Arábia Saudita , Inquéritos e Questionários , Local de Trabalho
3.
Eur Rev Med Pharmacol Sci ; 27(20): 10082-10093, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916379

RESUMO

OBJECTIVE: Protein tyrosine kinases (TKs) play a critical role in the regulation of various functions of a cell, including cellular proliferation, differentiation, and growth, and inhibitors of TKs have emerged as next-generation therapeutic agents in various types of cancer. Nilotinib, one of the TK inhibitors used to treat chronic myeloid leukemia, has been poorly investigated for its potential impact on memory function despite its ability to cross the blood-brain barrier (BBB). Thus, in this study, we investigated the effect of nilotinib on hippocampal-dependent cognitive functions and its potential mechanisms. MATERIALS AND METHODS: Wistar albino male rats were divided into three groups of 10 each. The animals of group I (normal control) received drinking water only, while groups II and III were treated with nilotinib at doses of 15 mg/kg and 30 mg/kg, p.o. respectively, once daily for two weeks. The animals were subjected to behavioral tests after completion of drug treatment for the assessment of cognitive function using the Y-maze, novel object recognition (NOR) test, and elevated plus maze (EPM). The animals were euthanized after the estimation of blood glucose, and hippocampal tissues were dissected for the estimation of markers of oxidative stress. RESULTS: Nilotinib produced impairment of memory function on the Y-maze, NOR test, and EPM. These results were also supported by a significant increase in glutathione (GSH), malondialdehyde (MDA), Akt, glycogen synthase kinase-3 beta (GSK3ß), and total antioxidant capacity (TAC) in hippocampal tissue without altering the blood glucose level. CONCLUSIONS: Nilotinib treatment produced significant impairment of cognitive function by inducing oxidative stress in the hippocampal tissue of rats.


Assuntos
Glicemia , Disfunção Cognitiva , Ratos , Animais , Ratos Wistar , Glicemia/metabolismo , Estresse Oxidativo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Pirimidinas/farmacologia , Hipocampo/metabolismo , Glutationa/metabolismo
4.
Eur Rev Med Pharmacol Sci ; 27(15): 6972-6984, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37606107

RESUMO

OBJECTIVE: Decreased expression of the mitochondrial protein frataxin is the cause of the neurodegenerative disorder Friedreich's ataxia. In patients with cardiac disorders, the death rate of this disease is very high, up to 66%. In order to combat Friedreich ataxia, which is a potentially toxic disorder, de novo drug discovery and design have been created utilizing the approach of compound engineering with halogens. This study aimed to investigate the potential for effective treatment of Friedreich ataxia. MATERIALS AND METHODS: The screening of twenty different agonist compounds was carried out in order to find the most promising agonist compound that may be used for molecular docking prediction against the Frataxin Protein. The compound with the lowest binding energies is then optimized by halogens. The final candidate's drug-like properties are identified through Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling. Lipinski's rule of five was checked. Molecular dynamic stimulations were evaluated. RESULTS: The most potent agonist compound was identified out of twenty different compounds utilizing a docking approach against the Frataxin Protein. The compound with the lowest binding energies was next subjected to optimization by halogens. The optimized agonist 9-[1-[(1S, 5R)-8, 8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]triazol-4-yl]fluoren-9-ol  has higher binding energy of -10.4Kcal/mol with molecular weight of 705.63 g/mol. Drug-like properties are identified through ADMET profiling, having water solubility of about -7.59, skin permeation -7.08 cm/s, bioavailability score 0.17, and high GI absorption. The candidate fulfills the Lipinski rule of five and portrays efficient molecular dynamic stimulations. CONCLUSIONS: The selected agonist is one of the most potent compounds in increasing Frataxin protein expression. Furthermore, optimization with halogens can be a productive approach to improve the candidate's drug efficacy. The development of effective medications for the treatment of Friedreich ataxia would be aided by the results of these computational investigations.


Assuntos
Ataxia de Friedreich , Humanos , Ataxia de Friedreich/tratamento farmacológico , Ataxia de Friedreich/genética , Halogênios , Simulação de Acoplamento Molecular , Proteínas de Ligação ao Ferro/genética , Frataxina
5.
Eur Rev Med Pharmacol Sci ; 27(14): 6785-6791, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37522689

RESUMO

OBJECTIVE: Cervical intraepithelial neoplasia (CIN) is a type of abnormal cervical epithelial development that can lead to cervical malignancy. Thus, the purpose of this study was to examine the cytological pattern of cervical smears from a group of Saudi women who visited a single gynecologic center. PATIENTS AND METHODS: From May 2020 to May 2021, 300 women were referred to the cytopathology laboratory and their cytological materials were collected. Because of gynecologic concerns, the women in the study were referred for Pap smears. As part of the obligatory investigations in conjunction with the clinical assessment, a Pap smear is requested. RESULTS: CIN of various grades was found in 11% of the women. High-grade Squamous Intraepithelial Lesions (HSIL) were the most detected modifications, followed by Atypical Squamous Cells of Undetermined Significance (ASUS) and Low-grade Squamous Intraepithelial Lesions (LSIL), accounting for 36.4%, 33.3%, and 30.3%, respectively. In 23.7% of the women, inflammatory cell infiltrations were found. Infection with Candida Albicans was identified in 2.3% of the women. In 15.8% of the patients, cytological evidence of bacterial infection was found. CONCLUSIONS: The prevalence of CIN has been growing in Saudi Arabia in recent years, implying a probable involvement in the spread of HPV. Most CIN cases associated with middle age point to HPV infection at a younger age. There is no link between estrogen and/or progesterone levels and CIN.

6.
Braz J Biol ; 83: e270256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37018800

RESUMO

Cobalt metal is considered as an essential trace element for the animals. Present investigation was undertaken in the peri-urban area to analyze the cobalt availability in animal food chain by using different indices. Cow, buffalo and sheep samples along with forage and soil samples were collected from the three different sites of District Jhang and analyzed through atomic absorption spectrophotometer. Cobalt values differed in soil samples as 0.315-0.535 mg/kg, forages as 0.127-0.333 mg/kg and animal samples as 0.364-0.504 mg/kg. Analyzed cobalt concentration in soil, forage and animal samples was found to be deficient in concentration with respect to standard limits. Soil showed the minimum cobalt level in Z. mays while maximum concentration was examined in the forage C. decidua samples. All indices examined in this study has values lesser than 1, representing the safer limits of the cobalt concentration in these samples. Enrichment factor (0.071-0.161 mg/kg) showed the highly deficient amount of cobalt enrichment in this area. Bio-concentration factor (0.392-0.883) and pollution load index (0.035-0.059 mg/kg) values were also lesser than 1 explains that plant and soil samples are not contaminated with cobalt metal. The daily intake and health risk index ranged from 0.00019-0.00064 mg/kg/day and 0.0044-0.0150 mg/kg/day respectively. Among the animals, cobalt availability was maximum (0.0150 mg/kg/day) in the buffaloes that grazed on the C. decidua fodder. Results of this study concluded that cobalt containing fertilizers must be applied on the soil and forages. Animal feed derived from the cobalt containing supplements are supplied to the animals, to fulfill the nutritional requirements of livestock.


Assuntos
Cobalto , Poluentes do Solo , Feminino , Bovinos , Animais , Ovinos , Solo , Cadeia Alimentar , Poluentes do Solo/análise , Ração Animal/análise , Búfalos
7.
Eur Rev Med Pharmacol Sci ; 16(13): 1834-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23208968

RESUMO

BACKGROUND: Multidrug resistant Acinetobacter baumannii, (MRAB) is an important cause of hospital acquired infection. AIM: To document the emergence of MRAB in an Intensive Care Unit (ICU); and to characterize its hospital-wide outbreak by investigating antibiotypes and genotypes. MATERIALS AND METHODS: A six-month prospective study for the presence of MRAB infection or colonization on inpatients, health care workers and environmental sites was done at an ICU in Fahd Hospital, Saudi Arabia. For all the collected specimens, microbiological analysis and antimicrobial susceptibility testing using an automated system (Phoenix, Becton Dickinson, USA) were performed. Pulsed-Field Gel Electrophoresis (PFGE) analysis was done to determine the clonal relationship between isolates. RESULTS: A total 18 MRAB were isolated from 12 patients and 3 environmental samples. The risk factors for the acquisition of infection were age less than 60 years, mechanical ventilation, surgical interference and co-morbidity. Five PFGE profiles; pulsotype A to E, were identified. Pulsotype C isolates were further separated into 5 subtypes with predominance of subtype C3. CONCLUSIONS: The study revealed a causal link between the contaminated ventilator and the subsequent MRAB. A correct antibiotic strategy should be addressed; and strict compliance with basic and potential control measures for the containment of infection should be achieved.


Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/efeitos dos fármacos , Infecção Hospitalar/epidemiologia , Adolescente , Adulto , Idoso , Farmacorresistência Bacteriana Múltipla , Eletroforese em Gel de Campo Pulsado , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Eur Rev Med Pharmacol Sci ; 26(17): 6259-6264, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36111945

RESUMO

OBJECTIVE: Serval modifiable risk factors have been linked to stroke and myocardial infarction, including chronic Kendy disease. This study aimed to assess the prevalence of stroke and myocardial infarction among patients with deteriorated GFR (GFR < 60 mL/min). PATIENTS AND METHODS: A total of 1185 Saudi participants were enrolled during a cross-sectional survey conducted in Hai'l region, Northern Saudi Arabia. Volunteers were enrolled based on their GFR estimation. Only those with Stage III, Stage IV, or Stage V CKD   were included. RESULTS: The overall prevalence of stroke was 2.4%. The risk of stroke associated with deteriorated GFR, the relative risk (RR) and the 95% confidence interval (95% CI), RR (95% CI) = 2.1371 (0.9804-4.6584), p = 0.0561. The prevalence rates of males and females were 3.7% and 1.2%, respectively. The overall prevalence of myocardial infarctions was 3.2% (4.7% in males and 2% in females). CONCLUSIONS: Deteriorated GFR <60 mL/min is significantly associated with stroke and myocardial infarction. Stroke and MI are more prevalent among men than women. Stroke and MI are more prevalent in middle-aged adults and older individuals.


Assuntos
Infarto do Miocárdio , Acidente Vascular Cerebral , Adulto , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/complicações
9.
Eur Rev Med Pharmacol Sci ; 26(9): 3325-3333, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35587085

RESUMO

OBJECTIVE: An increase in life expectancy has been attributed to better access to health care and viable treatment options for diseases where there were none before. However, a multiple-drug regimen increases the risk of inappropriate prescription and drug-related problems. This study aimed to investigate polypharmacy and inappropriate prescription among elderly patients in the Qassim region of Saudi Arabia. PATIENTS AND METHODS: This was a retrospective study wherein the electronic files of patients aged ≥ 60 years were reviewed and investigated for polypharmacy and inappropriate drug prescription using Beer's criteria 2019. RESULTS: The 1123 patients who met the eligibility criteria were between 60-102 years of age (mean age: 71.9 years). 387 patients (34.46%) used five medications, while the remaining patients used more than five medications. The prevalence of potentially inappropriate medications (PIMs) was 66.25%. The most commonly prescribed PIMs were non-steroidal anti-inflammatory drugs, baclofen, proton pump inhibitors, diuretics, and aspirin (11.3%, 10.6%, 10.1%, 8.46%, and 5.6%, respectively). CONCLUSIONS: This study showed a high prevalence of polypharmacy, which consequently led to a high prevalence of PIMs. This is a serious health problem in the elderly population and should be prevented or tackled with caution.


Assuntos
Prescrição Inadequada , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Hospitais , Humanos , Prescrição Inadequada/prevenção & controle , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita/epidemiologia
10.
Eur Rev Med Pharmacol Sci ; 26(17): 6367-6373, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36111939

RESUMO

OBJECTIVE: HPV is responsible for over 90% of cervical cancer worldwide. HPV has numerous subtypes with great variety distribution in different geographical regions. Thus, the present study aimed at assessing Human Papillomavirus (HPV) genotypes associated with cervical intraepithelial lesions among Saudi women. PATIENTS AND METHODS: The current study collected cervical smears from 300 women transferred to a cytopathology laboratory between May 2020 and May 2021. The studied women were referred to do Pap smear because of gynecologic complaints. RESULTS: Positive HPV testing was established in 4.7%. Most positive cases were identified in the age range of 14-50 years, followed by 51-60 years, representing 50% and 35.7%, respectively. The risk of HPV infection was significantly high in the age between 40-50 years, the odds ratio (OR), 95% confidence interval (95% CI), OR (95% CI) = 3.0137 (1.0228 to 8.8797), p = 0.0454, z statistic = 2.001. About 57% of the cases of HPV were found with cytological atypia. The risk of HPV in inducing cytological atypia, the OR (95%CI) = 1.8546 (2.9386 to 27.0952), p = 0.0001, z statistic = 3.862. Inflammatory cells infiltrate was identified in 43% of HPV-positive cases. The risk of HPV in inducing inflammatory changes, the OR (95% CI) = 2.6423 (0.8850 to 7.8887), p = 0.0817, z statistic = 1.741. CONCLUSIONS: The prevalence of High-risk human papillomavirus is relatively low in the AL-Madinah area, Saudi Arabia. Cervical cytological atypia corresponds to the positive HR-HPV findings. HR-HPV infection or cervical cytological atypical changes induce inflammatory cell infiltrates. HR-HPV infection is more common among elderly Saudi women.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Adolescente , Adulto , Idoso , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Arábia Saudita/epidemiologia , Adulto Jovem
11.
Oxid Med Cell Longev ; 2019: 1486232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467629

RESUMO

Ionizing radiation-induced cardiovascular diseases (CVDs) have been well documented. However, the mechanisms of CVD genesis are still not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to gamma irradiation at different doses ranging from 0.2 Gy to 5 Gy. Cell viability, migration ability, permeability, oxidative and nitrosative stresses, inflammation, and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway activation were evaluated postirradiation. It was found that gamma irradiation at doses ranging from 0.5 Gy to 5 Gy inhibited the migration ability of HUVECs without any significant effects on cell viability at 6 h and 24 h postirradiation. The decreased transendothelial electrical resistance (TEER), increased permeability, and disruption of cellular junctions were observed in HUVECs after gamma irradiation accompanied by the lower levels of junction-related proteins such as ZO-1, occludin, vascular endothelial- (VE-) cadherin, and connexin 40. The enhanced oxidative and nitrosative stresses, e.g., ROS and NO2 - levels and inflammatory cytokines IL-6 and TNF-α were demonstrated in HUVECs after gamma irradiation. Western blot results showed that protein levels of mitogen-activated protein kinase (MAPK) pathway molecules p38, p53, p21, and p27 increased after gamma irradiation, which further induced the activation of the NF-κB pathway. BAY 11-7085, an inhibitor of NF-κB activation, was demonstrated to partially block the effects of gamma radiation in HUVECs examined by TEER and FITC-dextran permeability assay. We therefore concluded that the gamma irradiation-induced disruption of cellular junctions in HUVECs was through the inflammatory MAPK/NF-κB signaling pathway.


Assuntos
Raios gama/efeitos adversos , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Humanos
12.
J Family Med Prim Care ; 7(5): 957-962, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30598940

RESUMO

CONTEXT: Women should consume folic acid (FA) during pregnancy to prevent neural tube defects (NTDs) in their children. Awareness of FA use, dosage, and administration can affect the risk of child malformations and other pregnancy complications. AIMS: The primary objective of this study was to assess knowledge about the role of FA intake among Saudi women of reproductive age. The secondary objective was to ascertain the use of FA supplements in Saudi Arabia and the age of gestation at which FA is taken. SETTINGS AND DESIGN: This cross-sectional study used a simple random sampling method for selecting Saudi women attending outpatient clinics at King Fahad Medical City in Riyadh, Saudi Arabia. MATERIALS AND METHODS: A random sample of 600 Saudi women aged 18-45 years was evaluated for their awareness of FA use. Participants completed a questionnaire comprising 16 questions. Six questions were demographic, and the remaining 10 fulfilled the study aims. RESULTS: Women had high awareness about FA. Survey responses showed that 42.2% of women knew that FA should be taken before pregnancy, and 80.1% were aware that it prevents NTDs. A total of 46.8% women took FA during preconception. Healthcare professionals provided the information in 69.7% of the cases. CONCLUSION: We concluded that the lower number of deformities in Saudi Arabia is due to greater awareness of the importance of FA, which can likely be attributed to better education. Doctors and nurses should continue to encourage women to take FA supplements when planning their pregnancies.

13.
Gait Posture ; 43: 170-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26455475

RESUMO

BACKGROUND: Although there is evidence that stroke survivors have reduced gait adaptability, the underlying mechanisms and the relationship to functional recovery are largely unknown. We explored the relationships between walking adaptability and clinical measures of balance, motor recovery and functional ability in stroke survivors. METHODS: Stroke survivors (n=42) stepped to targets, on a 6m walkway, placed to elicit step lengthening, shortening and narrowing on paretic and non-paretic sides. The number of targets missed during six walks and target stepping speed was recorded. Fugl-Meyer (FM), Berg Balance Scale (BBS), self-selected walking speed (SWWS) and single support (SS) and step length (SL) symmetry (using GaitRite when not walking to targets) were also assessed. Stepwise multiple-linear regression was used to model the relationships between: total targets missed, number missed with paretic and non-paretic legs, target stepping speed, and each clinical measure. RESULTS: Regression revealed a significant model for each outcome variable that included only one independent variable. Targets missed by the paretic limb, was a significant predictor of FM (F(1,40)=6.54, p=0.014,). Speed of target stepping was a significant predictor of each of BBS (F(1,40)=26.36, p<0.0001), SSWS (F(1,40)=37.00, p<0.0001). No variables were significant predictors of SL or SS asymmetry. DISCUSSION: Speed of target stepping was significantly predictive of BBS and SSWS and paretic targets missed predicted FM, suggesting that fast target stepping requires good balance and accurate stepping demands good paretic leg function. The relationships between these parameters indicate gait adaptability is a clinically meaningful target for measurement and treatment of functionally adaptive walking ability in stroke survivors.


Assuntos
Adaptação Fisiológica , Avaliação da Deficiência , Transtornos Neurológicos da Marcha/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Transtornos Neurológicos da Marcha/reabilitação , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral
14.
Curr Mol Med ; 15(10): 961-74, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26592245

RESUMO

Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model were investigated using whole-genome microarrays. Gene expression profiles were compared between infected THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx) or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential upregulation of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4), transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the tolllike receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B. pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment of human macrophages infected with B. pseudomallei.


Assuntos
Burkholderia pseudomallei/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Proteínas/farmacologia , Transcriptoma , Venenos de Víboras/química , Animais , Burkholderia pseudomallei/crescimento & desenvolvimento , Burkholderia pseudomallei/ultraestrutura , Ceftazidima/farmacologia , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno , Humanos , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/ultraestrutura , Análise em Microsséries , NF-kappa B/genética , NF-kappa B/metabolismo , Fator Plaquetário 4/genética , Fator Plaquetário 4/metabolismo , Proteínas/isolamento & purificação , Transdução de Sinais , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Viperidae
15.
Comp Immunol Microbiol Infect Dis ; 18(3): 171-7, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7554818

RESUMO

Skin allograft rejection in Balb/c and C57BL/6J mice following experimental infection with 300 larvae of Trichinella spiralis or Trichinella pseudospiralis was studied. Skin grafts from normal C57BL/6J mice were transplanted to infected Balb/c mice and vice versa at days 3, 10, 20 and 30 post-infection. The clinical criteria for graft rejection, scarring and graft falling, were followed. The results indicated that T. spiralis and T. pseudospiralis infections induced a significant delay in graft rejection when compared to the control groups. A maximum rejection time of 24 days was observed in T. spiralis infected C57BL/6J mice which received skin grafts from Balb/c mice on day 3 post-infection. The rejection in the uninfected control group was on day 7 post transplant. The mean rejection times for transplants on various days post-infection, with both species were very similar. Also, the rejection profiles in Balb/c mice were comparable to that observed in C57BL/6J mice, with a maximum delay of 26 days to rejection again obtained in mice transplanted on day 3 post-infection, for both species. When the skin grafts were performed 5 or 10 days prior to infection, the rejection occurred on day 7, as in the control group. The effect of T. spiralis and T. pseudospiralis soluble larval extracts (TSE or TPE) on graft rejection was also examined. Four intraperitoneal injections of 50 micrograms each of TSE or TPE every 48 h for 7 days did not induce any significant delay in graft rejection. In contrast, secretory antigens prepared from cultured larvae in vitro induced significant delays in graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Tolerância Imunológica , Transplante de Pele/imunologia , Trichinella spiralis , Triquinelose/imunologia , Animais , Antígenos de Helmintos/administração & dosagem , Quimiotaxia/imunologia , Rejeição de Enxerto/imunologia , Larva/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Fatores de Tempo , Transplante Homólogo , Trichinella spiralis/imunologia
16.
Trop Biomed ; 31(4): 616-32, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25776587

RESUMO

A total of 157 environmental samples were collected from 11 ecological regions across Saudi Arabia to isolate native Bacillus thuringiensis (Bt) strains. Bt isolates (n=103) were recovered by the 50% (v/v) ethanol treatment method with Bt index range of 0.01 to 0.4. Most of Bt isolates showed spherical crystals (54%), while, irregular, bi-pyramidal, and spore-attached crystal constituted 27, 16 and 3% respectively. PCR analysis with eight general and specific dipteran primers of Cry and Cyt genes, revealed positive amplification for cry4 & cyt1, and cry4A, cry4B and cyt2, and cry 10 and cry 11 genes in 28%, 26%, 22%, and 25% of tested strains respectively; whereas cry2 gene was not detected except with the reference Bt kurstaki HD-1 strain. Bioassays against Aedes caspuis and Culex pipiens larvae indicated that 11 strains displayed better larvicidal activity compared with Bacillus thuringiensis H14 (Bti) reference (LC50 0.6 µg/ml) strain against Ae. caspuis, but only two strains (620A & 633R1, LC50 of 0.09 µg/ml & 0.064 µg/ml) that gave significant enhancement. Additionally, one strain (633R1) showed LC50 similar to that of Bti H14 (LC50 0.064 µg/ml) against Cx. pipiens. With the exception of cyt primers, sequenced DNA of all positive primers amplicons revealed 95 to 99% identity in GenBank with Bacillus thuringiensis subsp. israelensis plasmid pBtoxis and also correlated with its SDS-PAGE expressed protein profiles analysis. It is hoped that our wild bio-insecticide Bt strains can be explored in future in the control of mosquito-vector borne diseases in Saudi Arabia.


Assuntos
Aedes/efeitos dos fármacos , Bacillus thuringiensis/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Culex/efeitos dos fármacos , Endotoxinas/genética , Endotoxinas/farmacologia , Microbiologia Ambiental , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/farmacologia , Inseticidas/farmacologia , Aedes/fisiologia , Animais , Bacillus thuringiensis/genética , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/isolamento & purificação , Bioensaio , Culex/fisiologia , DNA Bacteriano/genética , Eletroforese em Gel de Poliacrilamida , Endotoxinas/isolamento & purificação , Genes Bacterianos , Proteínas Hemolisinas/isolamento & purificação , Reação em Cadeia da Polimerase , Arábia Saudita , Análise de Sequência de DNA , Análise de Sobrevida
17.
Clin Immunol Immunopathol ; 32(2): 224-33, 1984 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6234119

RESUMO

Head injury and multiple trauma patients were evaluated for mitogen responsiveness and lymphocyte subset frequencies within the first few days after injury. The profile obtained was compared to the patient's clinical course to see if there was a relation between early immune abnormalities and the subsequent development of unanticipated sepsis. Lymphocytes from multiple trauma patients were generally hyporesponsive to in vitro stimulation with a suboptimal dose of the mitogen phytohemagglutinin (PHA). In contrast, the response of head injured patients was comparable to that of the control group. There was a significant decrease in the relative number of multiple trauma patient's T4 (29.3 vs 48.6%) and T11 (48.9 vs 74.7%) positive populations (P less than 0.01). There was no change in the percentage of T8-positive cells (19.0 vs 20.5%). Patients with head injuries also had a decrease in T4-positive cells (35.9%). The percentage of cells with B cell and natural killer (NK) markers remained normal. Thus trauma patients appeared to have an increase in null cells. Six patients whose PHA responses were among the lowest developed sepsis early after trauma. The changes in subset distributions although possibly contributing to a decreased responsiveness did not predict the ability to respond to PHA or the development of sepsis.


Assuntos
Sepse/etiologia , Linfócitos T/classificação , Ferimentos e Lesões/imunologia , Adulto , Idoso , Anticorpos Monoclonais , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Sepse/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Ferimentos e Lesões/complicações
18.
Eur J Immunogenet ; 23(1): 67-70, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8834924

RESUMO

This study is the first to assess the prevalence of HLA B27 in Kuwaiti patients with ankylosing spondylitis (AS) or related spondyloarthropathies compared to healthy controls. Positive HLA B27 was found in nine (25.7%) of 35 patients, but only in 22 (4%) of 544 controls (P = 0.000). A significant difference in Cw2 and Cw6 between patients and controls was also found (P < 0.01 and 0.000, respectively), suggesting a linkage disequilibrium between B27 and Cw2 (P < 0.000) in the Kuwaiti population. These findings suggest that B27-positive Kuwaitis are at high risk of developing AS and spondyloarthropathies, especially if they carry Cw2 and Cw6: The importance of HLA Cw loci is becoming increasingly apparent in disease association studies.


Assuntos
Antígeno HLA-B27/imunologia , Espondilite Anquilosante/imunologia , Adolescente , Adulto , Feminino , Antígeno HLA-B27/classificação , Antígenos HLA-C/classificação , Antígenos HLA-C/imunologia , Antígenos de Histocompatibilidade Classe I/classificação , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Kuweit , Masculino , Pessoa de Meia-Idade
19.
J Helminthol ; 68(4): 273-6, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7706672

RESUMO

Groups of C57BL/6J mice, orally infected with 300 larvae each of Trichinella spiralis or T. pseudospiralis were injected with [3H]-alanine, tyrosine, tryptophan or glycine. The incorporation of isotope labelled amino acids into larval proteins was measured at 2, 6, and 12 months post-infection. It was shown that there is a significant increase in the in vivo uptake of isotope labelled amino acids with time by the larvae of T. spiralis and T. pseudospiralis. The level of uptake was highest for tyrosine followed by tryptophan, alanine and then glycine, for both species. The in vivo uptake of amino acids by T. pseudospiralis larvae was always higher than T. spiralis or the host at 6 and 12 months post-infection. At 2 months post-infection, T. spiralis uptake of these amino acids was higher, except for tyrosine. This may be related to the special needs of these larvae during the process of encystation. The higher metabolic requirements of T. pseudospiralis may be related to the higher energy needs of these non encapsulated, highly motile and mobile muscle larvae.


Assuntos
Aminoácidos/metabolismo , Proteínas de Helminto/biossíntese , Trichinella/metabolismo , Triquinelose/parasitologia , Alanina/metabolismo , Animais , Transporte Biológico , Glicina/metabolismo , Larva , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo , Trichinella spiralis/metabolismo , Trítio , Triptofano/metabolismo , Tirosina/metabolismo
20.
Clin Diagn Virol ; 2(6): 323-9, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15566778

RESUMO

BACKGROUND: Rotaviruses are the single most important causative agent of acute neonatal enteritis in most avian and mammalian species including humans. Rotaviruses infections have also been shown to be associated with the elderly, immunocompromised individuals and more recently with epidemic diarrheal illness in adults. OBJECTIVES: To study the incidence and the effect of seasonality on the prevalence of rotaviruses in Al-Ain, United Arab Emirates. STUDY DESIGN: A total of 650 stool samples submitted to the laboratories of two University Teaching Hospitals (Al-Ain and Tawam) and a private hospital (Oasis) were examined for the presence of rotaviruses from January 1990-December, 1992, using a commercially available latex agglutination assay. The meteorological data (temperature, relative humidity and rainfall) recorded during the sampling period was analyzed statistically to examine the effect of seasonality on the prevalence of rotavirus cases in Al-Ain, United Arab Emirates. RESULTS: Rotavirus was detected in 21.4% of the samples examined. The predominant number of positive cases (35%) were in the 7-12 months age group. It was interesting to find rotavirus-positive cases in as low an age group as < 3 months (3.6%) and as high as 10 years (8.04%). There was no significant difference on infection rates between male and female groups in the study. However, there was a significant difference between the national (38.18%) and non-national children (61.28%). The higher rate of the latter may be due to import of infections. There appeared to be a seasonal pattern of rotavirus occurrence in the cases studied, with a marked increase in the number of positive cases during the months when the relative humidity was low (25-45%) and there was no rainfall. CONCLUSIONS: Rotavirus was detected in all age groups with a predominance in 7-12 month age groups, and a higher incidence in non-nationals. There was a marked increase in the number of positive cases during the months when the relative humidity was low (25-45%) and there was no rainfall. These findings are discussed in relation to the epidemiology and prophylaxis of rotavirus infections.

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