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1.
A familiar ring to it: biosynthesis of plant benzoic acids.
Widhalm, JR, Dudareva, N
Molecular plant. 2015;(1):83-97
Abstract
Plant benzoic acids (BAs) are building blocks or important structural elements for numerous primary and specialized metabolites, including plant hormones, cofactors, defense compounds, and attractants for pollinators and seed dispersers. Many natural products derived from plant BAs or containing benzoyl/benzyl moieties are also of medicinal or nutritional value to humans. Biosynthesis of BAs in plants is a network involving parallel and intersecting pathways spread across multiple subcellular compartments. In this review, a current overview on the metabolism of plant BAs is presented with a focus on the recent progress made on isolation and functional characterization of genes encoding biosynthetic enzymes and intracellular transporters. In addition, approaches for deciphering the complex interactions between pathways of the BAs network are discussed.
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2.
Breeding Vegetables with Increased Content in Bioactive Phenolic Acids.
Kaushik, P, Andújar, I, Vilanova, S, Plazas, M, Gramazio, P, Herraiz, FJ, Brar, NS, Prohens, J
Molecules (Basel, Switzerland). 2015;(10):18464-81
Abstract
Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. Major phenolic acids present in vegetables are derivatives of cinnamic acid and to a lesser extent of benzoic acid. A large diversity in phenolic acids content has been found among cultivars and wild relatives of many vegetable crops. Identification of sources of variation for phenolic acids content can be accomplished by screening germplasm collections, but also through morphological characteristics and origin, as well as by evaluating mutations in key genes. Gene action estimates together with relatively high values for heritability indicate that selection for enhanced phenolic acids content will be efficient. Modern genomics and biotechnological strategies, such as QTL detection, candidate genes approaches and genetic transformation, are powerful tools for identification of genomic regions and genes with a key role in accumulation of phenolic acids in vegetables. However, genetically increasing the content in phenolic acids may also affect other traits important for the success of a variety. We anticipate that the combination of conventional and modern strategies will facilitate the development of a new generation of vegetable varieties with enhanced content in phenolic acids.
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3.
Aceruloplasminaemia: a rare but important cause of iron overload.
Doyle, A, Rusli, F, Bhathal, P
BMJ case reports. 2015
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Abstract
We present a case of a 20-year-old man referred to our service with iron overload and mildly deranged liver biochemistry. Although liver histopathology was consistent with haemochromatosis, iron studies were not consistent with this diagnosis. Serum ceruloplasmin levels were undetectable, leading to a diagnosis of aceruloplasminaemia. Unlike other iron overload disorders, neurological complications are a unique feature of this illness, and often irreversible, once established. The patient was treated with iron chelation prior to the onset of neurological injury, and experienced progressive normalisation of his ferritin and liver biochemistry. This is one of the youngest diagnosed cases in the published literature and, crucially, was a rare case of diagnosis and treatment prior to the onset of neurological sequelae. This is presented alongside a review of previously published cases of aceruloplasminaemia, including responses to iron chelation therapy.
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[Treatment for acute promyelocytic leukemia].
Fujita, H
[Rinsho ketsueki] The Japanese journal of clinical hematology. 2014;(10):1817-26
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Deferasirox nephrotoxicity-the knowns and unknowns.
Díaz-García, JD, Gallegos-Villalobos, A, Gonzalez-Espinoza, L, Sanchez-Niño, MD, Villarrubia, J, Ortiz, A
Nature reviews. Nephrology. 2014;(10):574-86
Abstract
In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity is the most serious and frequent adverse effect of deferasirox treatment. This nephrotoxicity can present as an acute or chronic decrease in glomerular filtration rate (GFR). Features of proximal tubular dysfunction might also be present. In clinical trials and observational studies, GFR is decreased in 30-100% of patients treated with deferasirox, depending on dose, method of assessment and population studied. Nephrotoxicity is usually nonprogressive and/or reversible and rapid iron depletion is one of several risk factors. Scarce data are available on the molecular mechanisms of nephrotoxicity and the reasons for the specific proximal tubular sensitivity to the drug. Although deferasirox promotes apoptosis of cultured proximal tubular cells, the trigger has not been well characterized. Observational studies are required to track current trends in deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity in routine clinical practice, explore the effect on outcomes of various monitoring and dose-adjustment protocols and elucidate the long-term consequences of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be more common in the elderly; thus, specific efforts should be dedicated to investigate the effect of deferasirox use in this group of patients.
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Blood pressure variability over 24 h: prognostic implications and treatment perspectives. An assessment using the smoothness index with telmisartan-amlodipine monotherapy and combination.
Parati, G, Schumacher, H
Hypertension research : official journal of the Japanese Society of Hypertension. 2014;(3):187-93
Abstract
In-office blood pressure (BP) measurements have recognized limitations, including the inability to collect BP information over a long period of time, and during an individual's usual daily activities. Home or ambulatory BP monitoring (ABPM) may therefore be used to complement conventional office measurements, thereby improving prognostic value. Of particular relevance is the ability of 24 h ABPM to quantify the degree of BP variability over 24 h, which has been shown to be a significant and independent risk factor for cardiovascular (CV) morbidity and mortality. Twenty-four hour BP variability is indeed strongly associated with clinical outcomes, and the ability of ABPM to provide a quantification of BP throughout the 24-h period during an individual's normal daily routine is one of the reasons for its high prognostic value. The smoothness index (SI) provides a useful measure of antihypertensive treatment efficacy over the 24 h dosing period, its values being highest with antihypertensive agents that have large and consistent effects across 24 h. Telmisartan and amlodipine are long-acting antihypertensive drugs that, in combination, not only reduce 24 h mean BP more than the respective monotherapies but also provide a significantly greater SI. The provision of homogeneous 24 h BP control has important clinical implications. Maintaining smooth BP over the entire 24 h dosing period may contribute to the improvement of CV outcomes, and reductions in BP variability may decrease end organ damage, and reduce CV risk.
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A case report of deferasirox-induced kidney injury and Fanconi syndrome.
Murphy, N, Elramah, M, Vats, H, Zhong, W, Chan, MR
WMJ : official publication of the State Medical Society of Wisconsin. 2013;(4):177-80
Abstract
Cases of kidney injury associated with the use of deferasirox chelation therapy during the course of treatment for iron overload have been reported infrequently. We present the case of a patient treated with deferasirox who had biopsy-proven tubular injury in the setting of clinical Fanconi syndrome. The patient required hospitalization for metabolic acidosis, electrolyte abnormalities, and associated symptoms. With supportive care and cessation of chelation therapy he improved, but has yet to fully recover. This is the first known case reporting biopsy-proven tubular damage in the setting of deferasirox use.
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Effects of telmisartan therapy on interleukin-6 and tumor necrosis factor-alpha levels: a meta-analysis of randomized controlled trials.
Takagi, H, Mizuno, Y, Yamamoto, H, Goto, SN, Umemoto, T, ,
Hypertension research : official journal of the Japanese Society of Hypertension. 2013;(4):368-73
Abstract
A recent meta-analysis of randomized head-to-head trials suggests that therapy with telmisartan, an angiotensin II receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor-gamma, may increase adiponectin levels more strongly than other ARB therapies. Therefore, telmisartan would be expected to reduce interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-α). To determine whether telmisartan reduces IL-6 or TNF-α, we performed the first meta-analysis of randomized controlled trials of telmisartan therapy. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through November 2011. Eligible studies were prospective randomized controlled trials of telmisartan vs. unrestricted control therapy reporting IL-6 or TNF-α levels as an outcome. For each study, data regarding percent changes from baseline to final IL-6 or TNF-α levels in both the telmisartan and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Nine reports of randomized trials enrolling a total of 645 patients were identified. Pooled analysis of seven and five trials demonstrated a statistically significant reduction in percent changes of IL-6 (fixed-effects SMD, -0.385; 95% CI, -0.581 to -0.189; P<0.001; P for heterogeneity=0.073) and TNF-α levels (random-effects SMD, -0.627; 95% CI, -0.945 to -0.308; P<0.001; P for heterogeneity=0.029) with telmisartan relative to control therapy, respectively. In conclusion, based on a meta-analysis of nine randomized controlled trials, telmisartan therapy is likely effective in reducing IL-6 and TNF-α levels.
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Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials.
Maggio, A, Filosa, A, Vitrano, A, Aloj, G, Kattamis, A, Ceci, A, Fucharoen, S, Cianciulli, P, Grady, RW, Prossomariti, L, et al
Blood cells, molecules & diseases. 2011;(3):166-75
Abstract
The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized mean differences. Statistical heterogeneity was tested using χ2 (Q) and I2. Sources of bias and Grading of Recommendations Assessment, Development and Evaluation system (GRADE) were considered. Overall, 1520 patients were included. Only 7.4% of trials were free of bias. Overall measurements suggest low trial quality (GRADE). The meta-analysis suggests lower final liver iron concentrations during associated versus monotherapy treatment (p<0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treated groups (p<0.00001, p<0.00001, and p=0.002, respectively), but no statistically significant difference during DFX 30 mg/kg versus DFO (p=0.70), no statistically significant variations in heart T2* signal during associated or sequential versus mono-therapy treatment (p=0.46 and p=0.14, respectively), increases in urinary iron excretion during associated or sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively), and improved ejection fraction during associated or sequential versus monotherapy treatment (p=0.01 and p<0.00001, respectively). These findings do not support any specific chelation treatment. The literature shows risks of bias, and additional larger and longer trials are needed.
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Review article: cinnamon- and benzoate-free diet as a primary treatment for orofacial granulomatosis.
Campbell, HE, Escudier, MP, Patel, P, Challacombe, SJ, Sanderson, JD, Lomer, MC
Alimentary pharmacology & therapeutics. 2011;(7):687-701
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Abstract
BACKGROUND Orofacial granulomatosis is a rare chronic granulomatous inflammatory disease of the lips, face and mouth. The aetiology remains unclear but may involve an allergic component. Improvements have been reported with cinnamon- and benzoate-free diets. AIMS To explore the prevalence of compound and food sensitivity and examine the dietary treatments used in orofacial granulomatosis. METHODS A comprehensive literature search was carried out and relevant studies from January 1933 to January 2010 were identified using the electronic database search engines; AGRIS 1991-2008, AMED 1985-2008, British Nursing and Index archive 1985-2008, EMBASE 1980-2008, evidence based medicine review databases (e.g. Cochrane DSR), International Pharmaceutical and Medline 1950-2008. RESULTS Common sensitivities identified, predominantly through patch testing, were to benzoic acid (36%) food additives (33%), perfumes and flavourings (28%), cinnamaldehyde (27%), cinnamon (17%), benzoates (17%) and chocolate (11%). The cinnamon- and benzoate-free diet has been shown to provide benefit in 54-78% of patients with 23% requiring no adjunctive therapies. A negative or positive patch test result to cinnamaldehyde, and benzoates did not predict dietary outcome. The most concentrated source of benzoate exposure is from food preservatives. Use of liquid enteral formulas can offer a further dietary therapy, particularly in children with orofacial granulomatosis. CONCLUSION Management of orofacial granulomatosis is challenging but cinnamon- and benzoate-free diets appear to have a definite role to play.