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1.
Med Oncol ; 41(6): 158, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761317

RESUMO

Nimbolide, one of the main ingredients constituent of Azadirachta indica (neem) leaf extract, has garnered attention for its potential as an anticancer agent. Its efficacy against various cancers and chemopreventive action has been demonstrated through numerous in vivo and in vitro studies. This updated review aims to comprehensively explore the chemopreventive and anticancer properties of nimbolide, emphasizing its molecular mechanisms of action and potential therapeutic applications in oncology. The review synthesizes evidence from various studies that examine nimbolide's roles in apoptosis induction, anti-proliferation, cell death, metastasis inhibition, angiogenesis suppression, and modulation of carcinogen-metabolizing enzymes. Nimbolide exhibits multifaceted anticancer activities, including the modulation of multiple cell signaling pathways related to inflammation, invasion, survival, growth, metastasis, and angiogenesis. However, its pharmacological development is still in the early stages, mainly due to limited pharmacokinetic and comprehensive long-term toxicological studies. Nimbolide shows promising anticancer and chemopreventive properties, but there is need for systematic preclinical pharmacokinetic and toxicological research. Such studies are essential for establishing safe dosage ranges for first-in-human clinical trials and further advancing nimbolide's development as a therapeutic agent against various cancers. The review highlights the potential of nimbolide in cancer treatment and underscores the importance of rigorous preclinical evaluation to realize its full therapeutic potential.


Assuntos
Limoninas , Neoplasias , Humanos , Limoninas/farmacologia , Limoninas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Azadirachta/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
2.
Funct Plant Biol ; 50(8): 623-632, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37231613

RESUMO

Copper (Cu) is an abundant essential micronutrient element in various rocks and minerals and is required for a variety of metabolic processes in both prokaryotes and eukaryotes. However, excess Cu can disturb normal development by adversely affecting biochemical reactions and physiological processes in plants. However, organic soil is rich in micronutrients and can assist plants to tolerate toxicity by promoting growth and biomass. This study explored the potential of organic and Cu-contaminated soil on fibrous jute (Corchorus capsularis ). Plants were grown in the organic soil, natural soil (normal soil) and Cu-contaminated soil for 60days, and we studied different growth, physiological and ultra-structure alterations in the plant. Results showed that the addition of organic acid in the soil showed a remarkable increase in seed germination, plant height, fresh biomass, photosynthetic pigment and gas exchange parameters, and decreased the malondialdehyde (MDA) concentration in the tissues when compared to the plants grown in the natural soil. In contrast, plants grown in the Cu-contaminated soil significantly (P <0.05) decreased the seed germination, plant height, fresh biomass, photosynthetic pigment and gas exchange parameters, and increased MDA content, proline concentration and the activities of various antioxidant compounds; i.e. peroxidase (POD) and superoxidase dismutase (SOD). In addition, Cu toxicity also destroyed many membrane bounded organelles especially the chloroplast, which was revealed from transmission electron microscopy (TEM). We concluded that Cu toxicity affected growth and physiological attributes in C. capsularis , while addition of organic soil increased plant growth and biomass.


Assuntos
Antioxidantes , Solo , Antioxidantes/metabolismo , Biodegradação Ambiental , Estresse Oxidativo/fisiologia , Cobre/toxicidade , Cobre/análise , Cobre/metabolismo , Plantas/metabolismo
3.
J Ayub Med Coll Abbottabad ; 34(Suppl 1)(4): S928-S931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36550646

RESUMO

Background: Evidence on performance of Rapid Antigen Detection Tests to recognize SARS-CoV-2 symptomatic patients in our context is limited. This study was aimed to evaluate Panbio™ COVID-19 Ag Rapid Test Device (Abbott Diagnostics, Jena, Germany) in identifying SARS-CoV-2 infection in comparison with RT-PCR test. Methods: This cross-sectional validation study was carried out at Margalla Hospital, Taxila from October, 2020 to March, 2021. Three hundred and eighty-two participants of both gender and all ages, symptomatic for 3-4 days were included in this study. For each participant, two nasopharyngeal swabs were collected by trained lab technicians according to SOPs, one for Rapid Antigen Test and other for RT-PCR.Covid-19 antibodies were checked 4-6 weeks after symptoms among 77 randomly selected participants to further evaluate the performance of Rapid Antigen Test. Data was analyzed using SPSS-26. Results: The mean age of the participants was 43.1 years (SD=15.9). More than half of participants were males (n=213%=55.8) and 169 (44.2%) were females. Sensitivity of Rapid Antigen Test was calculated to be 94.3%, whereas the specificity was 39.7%. Out of 34 RT-PCR negatives that were initially detected positive on Rapid Antigen Test, 33 demonstrated presence of COVID-19 antibodies. Conclusion: Panbio™ COVID-19 Ag Rapid Test was found to have 93.4% overall sensitivity and relatively low overall specificity (37.9%). Rapid antigen testing using Panbio™ COVID-19 Ag Rapid Test Device can be effectively used to scale up mass testing to interrupt transmissibility of COVID-19 infection by generating quick result.


Assuntos
COVID-19 , SARS-CoV-2 , Feminino , Masculino , Humanos , Adulto , Recém-Nascido , COVID-19/diagnóstico , Estudos Transversais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Hospitais , Sensibilidade e Especificidade
4.
Am J Kidney Dis ; 78(5): 640-648, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34144104

RESUMO

RATIONALE & OBJECTIVE: Prior studies of patients receiving maintenance hemodialysis have shown that, on average, blood pressure (BP) measured predialysis is higher than BP measured at home. We hypothesized that a subset of hemodialysis patients has BP that is higher when measured at home than when measured predialysis and this subgroup of patients has a higher prevalence of left ventricular hypertrophy. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 97 hypertensive hemodialysis patients enrolled in the Blood Pressure in Dialysis Study (BID), a randomized trial of comparing target predialysis BP ≤140/90 to 155-165/90 mm Hg. EXPOSURE: Differences between predialysis and next-day home systolic BP measured ≥6 times over 1 year. OUTCOME: Left ventricular mass index (LVMI) by cardiac magnetic resonance imaging. ANALYTICAL APPROACH: A hierarchical clustering analysis divided patients into 3 clusters based on the average and variability of differences in systolic predialysis and home BP. Clusters were compared with respect to clinical factors and LVMI. RESULTS: Mean differences between predialysis and home systolic BP were 19.1 (95% CI, 17.0 to 21.1) mm Hg for cluster 1 ("home lower"), 3.7 (95% CI, 1.6 to 5.8) mm Hg for cluster 2 ("home and predialysis similar"), and -9.7 (95% CI, -12.0 to -7.4) mm Hg for cluster 3 ("home higher"). Systolic BP declined during dialysis in clusters 1 and 2 but increased in cluster 3. Interdialytic weight gains did not differ. After adjusting for sex and treatment arm, LVMI was higher in cluster 3 than in clusters 1 and 2: differences in means of 10.6 ± 4.96 (SE) g/m2 (P = 0.04) and 12.0 ± 5.08 g/m2 (P = 0.02), respectively. LIMITATIONS: Limited statistical power. CONCLUSIONS: Nearly one-third of participants had home BPs higher than predialysis BPs. These patients had LVMI higher than those with similar or lower BPs at home, indicating that their BP may have been undertreated.


Assuntos
Hipertensão , Diálise Renal , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Estudos de Coortes , Humanos , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Estudos Prospectivos
5.
GM Crops Food ; 12(1): 292-302, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33648412

RESUMO

Gossypium arboreum (Desi Cotton) holds a special place in cotton industry because of its inherent ability to withstand drought, salinity, and remarkable resistance to sucking pests and cotton leaf curl virus. However, it suffers yield losses due to weeds and bollworm infestation. Genetic modification of G. arboreum variety FBD-1 was attempted in the current study to combat insect and weedicide resistance by incorporating cry1Ac, cry2A and cp4-EPSPS genes under control of 35S promoter in two different cassettes using kanamycin and GUS as markers through Agrobacterium-mediated shoot apex cut method of cotton transformation. The efficiency of transformation was found to be 1.57%. Amplification of 1700 bp for cry1Ac, 167 bp for cry2A and 111 bp for cp4-EPSPS confirmed the presence of transgenes in cotton plants. The maximum mRNA expression of cry1Ac and cp4-EPSPS was observed in transgenic cotton line L3 while minimum in transgenic cotton line L1. The maximum protein concentrations of Cry1Ac, Cry2A and Cp4-EPSPS of 3.534 µg g-1, 2.534 µg g-1 and 3.58 µg-g-1 respectively were observed for transgenic cotton line L3 as compared to control cotton line. On leaf-feed-based insect bioassay, almost 99% mortality was observed for Helicoverpa armigera on the transgenic cotton plant (L3). It completely survived the 1900 ml hectare-1 glyphosate spray assay as compared to non-transgenic cotton plants. The necrotic spots appeared on the third day, leading to the complete death of control plants on the fifth day of assay. The successful multiple gene-stacking in G. arboreum FBD-1 variety could be further used for qualitative improvement of cotton fiber through plant breeding techniques.


Assuntos
Gossypium , Mariposas , Animais , Proteínas de Bactérias/genética , Endotoxinas , Gossypium/genética , Proteínas Hemolisinas/genética , Melhoramento Vegetal , Plantas Geneticamente Modificadas
6.
Plant Cell Rep ; 40(4): 707-721, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33634360

RESUMO

KEY MESSAGE: Second generation Bt insecticidal toxin in comibination with Allium sativum leaf agglutinin gene has been successfully expressed in cotton to develop sustainable resistance against major chewing and sucking insects. The first evidence of using the Second-generation Bt gene in combination with Allium sativum plant lectin to develop sustainable resistance against chewing and sucking insects has been successfully addressed in the current study. Excessive use of Bt δ-endotoxins in the field is delimiting its insecticidal potential. Second-generation Bt Vip3Aa could be the possible alternative because it does not share midgut receptor sites with any known cry proteins. Insecticidal potential of plant lectins against whitefly remains to be evaluated. In this study, codon-optimized synthetic Bt Vip3Aa gene under CaMV35S promoter and Allium sativum leaf agglutinin gene under phloem-specific promoter were transformed in a local cotton variety. Initial screening of putative transgenic cotton plants was done through amplification, histochemical staining and immunostrip assay. The mRNA expression of Vip3Aa gene was increased to be ninefold in transgenic cotton line L6P3 than non-transgenic control while ASAL expression was found to be fivefold higher in transgenic line L34P2 as compared to non-transgenic control. The maximum Vip3Aa concentration was observed in transgenic line L6P3. Two copy numbers in homozygous form at chromosome number 9 and one copy number in hemizygous form at chromosome number 10 was observed in transgenic line L6P3 through fluorescent in situ hybridization. Significant variation was observed in transgenic cotton lines for morphological characteristics, whereas physiological parameters of plants and fiber characteristics (as assessed by scanning electron microscopic) remained comparable in transgenic and non-transgenic cotton lines. Leaf-detach bioassay showed that all the transgenic lines were significantly resistant to Helicoverpa armigera showing mortality rates between 78% and 100%. Similarly, up to 95% mortality of whiteflies was observed in transgenic cotton lines when compared with non-transgenic control lines.


Assuntos
Proteínas de Bactérias/genética , Gossypium/genética , Insetos , Lectinas de Plantas/genética , Plantas Geneticamente Modificadas/fisiologia , Aglutininas/genética , Animais , Fibra de Algodão , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Alho/genética , Dosagem de Genes , Gossypium/fisiologia , Hemípteros , Controle de Insetos , Mariposas , Regiões Promotoras Genéticas
7.
Artigo em Inglês | MEDLINE | ID: mdl-33641094

RESUMO

The purpose of this study is to examine the relationship between renewable energy sources and sustainable economic growth of the South Asian Association for Regional Cooperation (SAARC) countries. This study uses three main renewable energy sources such as geothermal, hydro and wind. This study collects dataset from SAARC countries from 1995 to 2018. This study applies a fixed-effect test and panel vector error correction model (PVECM) test for data analysis. The overall results show that all three renewable energy sources have positively significant impacts on economic development among SAARC countries' economies. Moreover, the hydropower renewable energy source has more effects and influences on economic growth as relatively compared with the rest of the two individual sources of renewable energy.

8.
J Anim Physiol Anim Nutr (Berl) ; 105(2): 354-363, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33381881

RESUMO

Recent studies have demonstrated a strong relationship between the intestinal microbiota and the host health. As such, consumers are increasingly becoming more concerned about the potential effect of certain foods/feeds, particularly of transgenic origin on the gut microbiota. Although the European Food Safety Authority has recommended in their guidelines, to study the effect of transgenic food/feed on host-microbiota, yet, few studies have focused on the evaluation of such effects mainly due to culturing difficulties. Therefore, this study was intended to evaluate the potential adverse effects of transgenic diet consumption on some specific gut microflora (Lactobacillus group, Bifidobacterium genus, Escherichia coli subgroup and Enterococcus genus) of rabbits. A total of forty-eight rabbits were randomly assigned into four groups and fed a diet containing a variable proportion of transgenic cottonseeds at 0, 20, 30 and 40% inclusion level, respectively. Changes in the specific or total faecal bacterial population were monitored at five different experimental stages (i.e. 0, 45, 90, 135 and 180 days) using both the traditional plate count method (TM) and quantitative real-time PCR (qPCR). No significant differences (p > .05) were observed concerning numbers of specific bacteria or total bacteria between the control and experimental groups, though qPCR showed numerically higher values in terms of 16S rRNA gene copies as compared to the values obtained from TM. However, such numerical differences were biologically insignificant (p > .05). Similarly, no significant variations were noticed in the calculated B/E (log10 copies of Bifidobacterium per g faces/log10 copies of E. coli genome per g faeces) ratios in all the groups. All the ratios were in the range of 1.24 to 1.30 throughout the experiment, indicating a good balance of intestinal microflora and greater resistance to intestinal disorders. It is therefore concluded that feeding transgenic cottonseeds could not adversely affect the gut microflora of rabbits during a long-term study.


Assuntos
Escherichia coli , Microbiota , Animais , Bifidobacterium , Fezes , RNA Ribossômico 16S , Coelhos
9.
Sci Rep ; 10(1): 8958, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488033

RESUMO

Whitefly infestation of cotton crop imparts enormous damage to cotton yield by severely affecting plant health, vigour and transmitting Cotton Leaf Curl Virus (CLCuV). Genetic modification of cotton helps to overcome both the direct whitefly infestation as well as CLCuV based cotton yield losses. We have constitutively overexpressed asparaginase (ZmASN) gene in Gossypium hirsutum to overcome the cotton yield losses imparted by whitefly infestation. We achieved 2.54% transformation efficiency in CIM-482 by Agrobacterium-mediated shoot apex transformation method. The relative qRT-PCR revealed 40-fold higher transcripts of asparaginase in transgenic cotton line vs. non-transgenic cotton lines. Metabolic analysis showed higher contents of aspartic acid and glutamic acid in seeds and phloem sap of the transgenic cotton lines. Phenotypically, the transgenic cotton lines showed vigorous growth and height, greater number of bolls, and yield. Among six representative transgenic cotton lines, line 14 had higher photosynthetic rate, stomatal conductance, smooth fiber surface, increased fiber convolutions (SEM analysis) and 95% whitefly mortality as compared to non-transgenic cotton line. The gene integration analysis by fluorescence in situ hybridization showed single copy gene integration at chromosome number 1. Collectively, asparaginase gene demonstrated potential to control whitefly infestation, post-infestation damages and improve cotton plant health and yield: a pre-requisite for farmer's community.


Assuntos
Asparaginase/genética , Gossypium/genética , Plantas Geneticamente Modificadas/genética , Animais , Asparaginase/metabolismo , Begomovirus/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas/genética , Hemípteros/genética , Hemípteros/patogenicidade , Inseticidas/metabolismo , Doenças das Plantas/genética
10.
J Ayub Med Coll Abbottabad ; 32(2): 228-233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32583999

RESUMO

BACKGROUND: The study was conducted at Army Medical College, Rawalpindi to explore the factors in Case Based Learning (CBL) session responsible for promoting deep learning approach in medical students. METHODS: A mix method research methodology with explanatory sequential design was adopted. In the quantitative part, the data was collected through a survey of second year medical students in which learning approaches were assessed using the Approaches and Study Skills Inventory for Students (ASSIST). Students were scored separately for the three approaches: surface, strategic and deep approach. In qualitative part; semi structured interviews were conducted with deep learners to explore the factors which help in promoting deep learning through Case-Based Leaning (CBL) guided inquiry approach. Interview data was transcribed, coded and thematic analysis was carried out. All quality assurance procedures of qualitative research such as credibility, trustworthiness, transferability, dependability and confirmability were ensured during the research. RESULTS: Deep learners were identified by analyzing the ASSIST-inventory results. Qualitative analysis has revealed six main themes: active participation of the students in the CBL session, relevance of the case with their clinical practice, complexity of the case for future practice, intrinsic motivation, guided inquiry approach with tutor's involvement, role playing and changes in learning approaches of the students were found responsible for inculcating deep learning approach in medical students in their pre-clinical years. CONCLUSIONS: The study concluded that by ensuring the factors that promote "deep learning approach" in medical students through Case Based Learning; it can be used as an effective strategy in teaching the content of basic science subjects during the pre-clinical years of medical students.


Assuntos
Aprendizagem , Estudantes de Medicina , Humanos , Paquistão , Testes Psicológicos , Pesquisa Qualitativa
11.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936325

RESUMO

Runaway pacemaker is phenomenon in which pacemaker induces ventricular tachycardia as a result of some malfunction in the device. This entity is not very common in clinical practice. Normally, the pacemaker perceives the inherent cardiac impulse and hence averting the delivery of pacemaker stimulus in susceptible period of cardiac cycle. This is a case of a pacemaker-induced tachycardia (named as runaway pacemaker) in a patient with a history of Single Chamber Ventricular (VVI) pacemaker. A 75-year-old man was admitted with 3 days history of fluttering in the chest, shortness of breath, central chest and epigastric pain which radiated to the back. His medical history includes pacemaker implantation in 1996 with lead complication following which he was managed with VVI pacemaker, and the last procedure was generator change 4 years ago with no complication. Examination revealed ventricular tachycardia with ECG showing paced rhythm with ventricular pacing at the rate of 200-150/min. His pacemaker-induced ventricular tachycardia was immediately aborted after putting magnet on the device which restored his baseline rhythm with heart rate of 60/min. Pacemaker was explanted urgently with replacement of new pulse generator. The patient was discharged home with VVI pacemaker showing excellent parameters.


Assuntos
Arritmias Cardíacas/terapia , Sistema de Condução Cardíaco/cirurgia , Marca-Passo Artificial/efeitos adversos , Implantação de Prótese , Taquicardia Ventricular/etiologia , Idoso , Fontes de Energia Bioelétrica , Remoção de Dispositivo , Eletrocardiografia , Desenho de Equipamento , Falha de Equipamento , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/cirurgia , Resultado do Tratamento
13.
Curr Diab Rep ; 18(4): 18, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29497863

RESUMO

PURPOSE OF REVIEW: Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment. RECENT FINDINGS: In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes. Two recent multicenter randomized control trials, Preventing Early Renal Function Loss in Diabetes (PERL) and FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER), were recently designed to assess if uric acid lowering slows progression of CKD. We review the evidence supporting a role for uric acid in the pathogenesis of CKD in people with diabetes and the putative benefits of uric acid lowering.


Assuntos
Nefropatias Diabéticas/etiologia , Insuficiência Renal Crônica/etiologia , Ácido Úrico/metabolismo , Nefropatias Diabéticas/metabolismo , Progressão da Doença , Humanos
14.
J Am Soc Nephrol ; 29(1): 307-316, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29212839

RESUMO

The optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110-140 mmHg (intensive arm) or 155-165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4-12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of -0.84 (-17.1 to 10.0) g and 1.4 (-11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.


Assuntos
Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Diálise Renal , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Anastomose Cirúrgica , Anti-Hipertensivos/uso terapêutico , Artérias/cirurgia , Peso Corporal , Doenças Cardiovasculares/etiologia , Feminino , Hospitalização , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Sístole , Trombose/etiologia , Veias/cirurgia
15.
Nat Commun ; 8(1): 1975, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-29213047

RESUMO

Decoration of phytochemicals contributes to the majority of metabolic diversity in nature, whereas how this process alters the biological functions of their precursor molecules remains to be investigated. Flavones, an important yet overlooked subclass of flavonoids, are most commonly conjugated with sugar moieties by UDP-dependent glycosyltransferases (UGTs). Here, we report that the natural variation of rice flavones is mainly determined by OsUGT706D1 (flavone 7-O-glucosyltransferase) and OsUGT707A2 (flavone 5-O-glucosyltransferase). UV-B exposure and transgenic evaluation demonstrate that their allelic variation contributes to UV-B tolerance in nature. Biochemical characterization of over 40 flavonoid UGTs reveals their differential evolution in angiosperms. These combined data provide biochemical insight and genetic regulation into flavone biosynthesis and additionally suggest that adoption of the positive alleles of these genes into breeding programs will likely represent a potential strategy aimed at producing stress-tolerant plants.


Assuntos
Flavonas/genética , Flavonas/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Oryza/genética , Oryza/metabolismo , Tolerância a Radiação/genética , Tolerância a Radiação/fisiologia , Flavonoides/classificação , Flavonoides/genética , Genes de Plantas , Variação Genética , Genoma de Planta , Glicosiltransferases/metabolismo , Cinética , Magnoliopsida/genética , Magnoliopsida/metabolismo , Oryza/enzimologia , Oryza/efeitos da radiação , Fenótipo , Filogenia , Melhoramento Vegetal , Proteínas Recombinantes , Raios Ultravioleta
16.
Hemodial Int ; 21 Suppl 2: S27-S32, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29064178

RESUMO

INTRODUCTION: Modifiable hemodialysis treatment parameters may impact patient reported outcomes, including recovery time. Answers to the recovery question may predict the impact of treatment parameters on clinical outcomes and health related quality of life. However, the reliability of answers to the recovery question after consecutive and nonconsecutive dialysis treatments in diverse populations has not been established. OBJECTIVE: To assess the reliability of this instrument and to determine if recovery time was associated with modifiable dialysis parameters, we conducted a quality assurance project in which we asked, "How long did it take you to recover from your last dialysis session?" after consecutive and nonconsecutive treatments. METHODS: We asked patients the recovery question ≤ seven times. We computed polychoric correlations to assess within patient correlations. We used random intercept ordinal logistic regression models to test for associations of recovery time with patient variables. RESULTS: We obtained answers to the recovery question in association with 1572 treatments in 364 patients. Recovery time was <2 hours in 52.1%; 2 to 7 hours in 20.9%; and >7 hours in 27.0% of treatments. Polychoric correlations demonstrated highly reliable responses within individual patients between consecutive and nonconsecutive treatments. Prolonged recovery was associated with a dialysate potassium of 1 vs. 2 mEq/L (odds ratio [OR] 2.25 {95% confidence interval [CI] 1.43-3.55}) and 1 vs. 3 mEq/L (OR 1.88 [95% CI 1.06-3.33]); vintage >6 months (OR 2.43 [95% CI 1.42-4.16]), body mass index >35 kg/m2 (OR 1.94 [95% CI 1.18-3.20]), post-dialysis systolic blood pressure (SBP) <115 mmHg (OR 1.57 [95% CI 1.04-2.37]) and intradialytic cramps (OR 1.76 [95% CI 1.09-2.86]). There were no associations with gender, race, age, ESRD etiology, intradialytic SBP <90 mmHg, serum sodium or potassium, dialysate sodium, bicarbonate or temperature, blood flow rate, or ultrafiltration rate. CONCLUSIONS: Responses to the recovery question were reliable and low dialysate potassium was associated with prolonged recovery.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Soluções para Diálise/efeitos adversos , Potássio/sangue , Qualidade de Vida/psicologia , Diálise Renal/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
18.
Kidney Int ; 91(5): 1005-1007, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28407875

RESUMO

Previous studies have demonstrated an association of serum uric acid with kidney disease. However, it is unknown whether this relationship is causal. Mendelian randomization takes advantage of allele randomization at birth to assess causation. Using this technique Ahola et al. found strong evidence against causation in Finnish Caucasians with type 1 diabetes mellitus. However, replication in other populations is needed to further assess a potential causal role for hyperuricemia in kidney disease.


Assuntos
Nefropatias Diabéticas , Ácido Úrico/sangue , Diabetes Mellitus Tipo 1 , Humanos , Hiperuricemia/sangue , Distribuição Aleatória
19.
Curr Opin Nephrol Hypertens ; 25(6): 545-550, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27606498

RESUMO

PURPOSE OF REVIEW: This review focuses on recent advances in our understanding of intradialytic hypotension (IDH) and measures that may reduce its frequency. RECENT FINDINGS: The frequency and severity of IDH predict the risk for adverse clinical outcomes. The highest mortality risks associated with IDH were observed when the intradialytic systolic blood pressure (SBP) nadirs were <90 and <100 mmHg and the predialysis SBP were ≤159 mmHg or ≥160 mmHg, respectively. Interdialytic weight gain (IDWG) ≥3 kg occurs more frequently among patients with IDH. Prolonged and possibly more frequent dialysis, use of biofeedback devices, dialysate cooling and limiting sodium loading are useful measures to reduce the frequency of IDH. SUMMARY: Frequent IDH is associated with high IDWGs and a poor prognosis. Studies on prolonged dialysis, biofeedback devices and cooled dialysate have yielded promising results. Intradialytic relative blood volume monitoring devices have been investigated in preventing IDH but results are mixed. Administration of a sodium/hydrogen exchange isoform 3 inhibitor increases stool sodium but has not been shown to decrease IDWG. IDH continues to be a significant dialysis complication deserving of further investigation.


Assuntos
Pressão Sanguínea , Hipotensão/etiologia , Hipotensão/prevenção & controle , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Soluções para Diálise , Humanos , Fatores de Risco , Aumento de Peso
20.
Am J Kidney Dis ; 67(3): 439-45, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26776538

RESUMO

BACKGROUND: There is controversy regarding the optimal dialysate sodium concentration for hemodialysis patients. Dialysate sodium concentrations of 134 to 138 mEq/L may decrease interdialytic weight gain and improve hypertension control, whereas a higher dialysate sodium concentration may offer protection to patients with low serum sodium concentrations and hypotension. We conducted a quality improvement project to explore the hypothesis that prescribed and delivered dialysate sodium concentrations may differ significantly. STUDY DESIGN: Cross-sectional quality improvement project. SETTING & PARTICIPANTS: 333 hemodialysis treatments in 4 facilities operated by Dialysis Clinic, Inc. QUALITY IMPROVEMENT PLAN: Measure dialysate sodium to assess the relationships of prescribed and measured dialysate sodium concentrations. OUTCOMES: Magnitude of differences between prescribed and measured dialysate sodium concentrations. MEASUREMENTS: Dialysate sodium measured pre- and late dialysis. RESULTS: The least square mean of the difference between prescribed minus measured dialysate sodium concentration was -2.48 (95% CI, -2.87 to -2.10) mEq/L. Clinics with a greater number of different dialysate sodium prescriptions (clinic 1, n=8; clinic 2, n=7) and that mixed dialysate concentrates on site had greater differences between prescribed and measured dialysate sodium concentrations. Overall, 57% of measured dialysate sodium concentrations were within ±2 mEq/L of the prescribed dialysate sodium concentration. Differences were greater at higher prescribed dialysate sodium concentrations. LIMITATIONS: We only studied 4 facilities and dialysate delivery machines from 2 manufacturers. Because clinics using premixed dialysate used the same type of machine, we were unable to independently assess the impact of these factors. Pressures in dialysate delivery loops were not measured. CONCLUSIONS: There were significant differences between prescribed and measured dialysate sodium concentrations. This may have beneficial or deleterious effects on clinical outcomes, as well as confound results from studies assessing the relationships of dialysate sodium concentrations to outcomes. Additional studies are needed to identify factors that contribute to differences between prescribed and measured dialysate sodium concentrations. Quality assurance and performance improvement (QAPI) programs should include measurements of dialysate sodium.


Assuntos
Soluções para Diálise , Falência Renal Crônica , Diálise Renal , Sódio , Estudos Transversais , Soluções para Diálise/análise , Soluções para Diálise/farmacologia , Humanos , Hipertensão/etiologia , Hipertensão/prevenção & controle , Hiponatremia/etiologia , Hiponatremia/prevenção & controle , Hipotensão/etiologia , Hipotensão/prevenção & controle , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Rins Artificiais , Melhoria de Qualidade , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Diálise Renal/métodos , Sódio/sangue , Sódio/farmacologia
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