•Sarcopenia is frequently combined with obesity.•Oxidative stress may represent a pathophysiological link between sarcopenia and obesity.•Circulating oxidative stress markers are increased in ...sarcopenia.•Circulating oxidative stress is related to cardiovascular risk in sarcopenic obesity.
To define whether circulating markers of oxidative stress correlate with sarcopenia in terms of glutathione balance and oxidative protein damage, and whether these biomarkers are associated with risk of cardiovascular disease (CVD).
Population-based cross-sectional study. 115 out of 347 elderly subjects were classified as non-sarcopenic non-obese (NS-NO), sarcopenic non-obese (S-NO), non-sarcopenic obese (NS-O), and sarcopenic obese (S-O).
Sarcopenia was defined as a relative skeletal muscle mass index (RASM) <7.25kg/m2 for men or <5.67kg/m2 for women, while obesity was diagnosed in those presenting with% fat >27 for men or >38 for women. The CVD risk was estimated by the carotid intima-media thickness (IMT) and the Framingham score. Blood reduced glutathione (GSH), oxidized glutathione (GSSG), plasma malondialdehyde-(MDA) and 4-hydroxy-2,3-nonenal-(HNE) protein adducts were analyzed.
Significantly greater blood GSSG/GSH ratio and plasma MDA/HNE protein adducts were observed in sarcopenic than in non-sarcopenic patients. A logistic regression model showed a close relationship between serum HNE and MDA adducts and sarcopenia (OR=1.133, 95% CI 1.057–1.215, and OR=1.592, 95% CI 1.015–1.991, respectively). Linear and logistic regression analysis evidenced strong associations between the IMT or the Framingham CVD risk category and blood GSSG/GSH or serum HNE protein adducts in the S-O group.
Circulating markers of oxidative stress are increased in sarcopenia and related to CVD risk in sarcopenic obesity, suggesting that redox balance analysis would be a useful part of a multidimensional evaluation in aging. Further research is encouraged to support interventional strategies to correct redox imbalance, which might contribute to the prevention or at least limitation of sarcopenia and its co-morbidities.
Metabolic reprogramming is critically involved in the development and progression of cancer. In particular, lipid metabolism has been investigated as a source of energy, micro-environmental ...adaptation, and cell signalling in neoplastic cells. However, the specific role of lipid metabolism dysregulation in hepatocellular carcinoma (HCC) has not been widely described yet. Alterations in fatty acid synthesis, β-oxidation, and cellular lipidic composition contribute to initiation and progression of HCC. The aim of this review is to elucidate the mechanisms by which lipid metabolism is involved in hepatocarcinogenesis and tumour adaptation to different conditions, focusing on the transcriptional aberrations with new insights in lipidomics and lipid zonation. This will help detect new putative therapeutic approaches in the second most frequent cause of cancer-related death.
A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta‐lactam (BL) hypersensitivity ...demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost‐effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross‐reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, and diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (ie, occurring within 1‐6 hours after the last administered dose) or nonimmediate (ie, occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low‐risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus.
Alzheimer's disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) ...deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.
Background Studies regarding the cross-reactivity and tolerability of alternative cephalosporins in large samples of subjects with an IgE-mediated hypersensitivity to cephalosporins are lacking. ...Objective We sought to evaluate the possibility of using alternative cephalosporins in subjects with cephalosporin allergy who especially require them. Methods One hundred two subjects with immediate reactions to cephalosporins and positive skin test results to the responsible drugs underwent serum specific IgE assays with cefaclor and skin tests with different cephalosporins. Subjects were classified in 4 groups: group A, positive responses to 1 or more of ceftriaxone, cefuroxime, cefotaxime, cefepime, cefodizime, and ceftazidime; group B, positive responses to aminocephalosporins; group C, positive responses to cephalosporins other than those belonging to the aforementioned groups; and group D, positive responses to cephalosporins belonging to 2 different groups. Group A subjects underwent challenges with cefaclor, cefazolin, and ceftibuten; group B participants underwent challenges with cefuroxime axetil, ceftriaxone, cefazolin, and ceftibuten; and group C and D subjects underwent challenges with some of the aforementioned cephalosporins selected on the basis of their patterns of positivity. Results There were 73 subjects in group A, 13 in group B, 7 in group C, and 9 in group D. Challenges with alternative cephalosporins (ceftibuten in 101, cefazolin in 96, cefaclor in 82, and cefuroxime axetil and ceftriaxone in 22 subjects) were well tolerated. Conclusions Cephalosporin hypersensitivity does not seem to be a class hypersensitivity. Subjects with cephalosporin allergy who especially require alternative cephalosporins might be treated with compounds that have side-chain determinants different from those of the responsible cephalosporins and have negative pretreatment skin test responses.
Oxidative stress and aging Romano, Antonino D; Serviddio, Gaetano; de Matthaeis, Angela ...
Journal of nephrology,
2010 Sep-Oct, Letnik:
23 Suppl 15
Journal Article
Recenzirano
The fountain of youth has always been a myth for mankind. Aging is a physiologic state in which a progressive decline of organ functions is accompanied with the development of age-related diseases. ...The causes of aging remain unknown, probably being related to a multifactorial process. To date, the free radical and mitochondrial theories seem to be the 2 most prominent theories on aging and have survived the test of time. Such theories claim that oxidative stress within mitochondria can lead to a vicious cycle in which damaged mitochondria produce increased amounts of reactive oxygen species, leading in turn to progressive augmentation in damage. If aging results from oxidative stress, it may be corrected by environmental, nutritional and pharmacological strategies. This review summarizes the role of free radicals and oxidative stress in developing aging in kidney and human pathologies.
The present review points out the role of oxidative stress in aging and the potential therapeutic targets of modern antioxidant therapies. Mitochondria are essential for several biological processes ...including energy production by generating ATP through the electron transport chain (ETC) located on the inner mitochondrial membrane. Due to their relevance in cellular physiology, defects in mitochondria are associated with various human diseases. Moreover, several years of research have demonstrated that mitochondria have a pivotal role in aging. The oxidative stress theory of aging suggests that mitochondria play a key role in aging as they are the main cellular source of reactive oxygen species (ROS), which indiscriminately damage macromolecules leading to an age-dependent decline in biological function. In this review we will discuss the mitochondrial dysfunction occurring in aging. In particular, we will focus on the novel mitochondria targeted therapies and the new selective molecules and nanocarriers technology as potentially effective in targeting mitochondrial dysfunction and diseases involving oxidative stress and metabolic failure.
Total serum IgE result from the combination of specific and non-specific pools. High specific/total IgE ratio may reflect high level of allergen-specific IgE on mast cells. No data regarding its ...applications to drug allergies is available. One hundred seventy-one patients with a history of immediate reactions to β-lactams, confirmed by positive skin testing, and 122 control subjects tolerant to β-lactams, were studied. CAP System was used for the detection of serum total and specific IgE antibodies. The specific/total IgE ratio was tested for diagnostic accuracy compared with conventional criteria. We finally performed a simulation study to expand our investigation of the performance of the specific/total IgE ratio index in a scenario in which the new CAP detection threshold is lowered further. Specific/total IgE ratio values ≥0.002 were observed more frequently in reactive than in controls. Seventy-four of 80 subjects with values ≥0.002 were allergic to β-lactams, yielding a positive predictive value of 92.5%. The application of specific/total IgE ratio significantly improves the positive likelihood ratio and the overall diagnostic performance. In addition, we showed the capability of this new criterion to identify true reactive patients even among subjects with high levels of total IgE (>200 kU/L). Significant increase in both receiver operator characteristic (ROC) curve and sensitivity were observed in imputed case of the simulation study. The β-lactams-specific/total IgE ratio may be an additional index compared to the common criterion of positivity to a single hapten in the allergological work-up of patients with β-lactams immediate adverse reactions.
Adverse drug reactions (ADRs) are an area of concern for pharmaceutical drug development. Among these, drug hypersensitivity reactions are neither dose-dependent nor predictable, and affect only ...predisposed individuals. Clinical and immunological studies suggest that IgE-mediated (type I) and cell-mediated (type-IV) pathogenic mechanisms are involved in many immediate (i.e., occurring within 1 hour after the last drug administration) and non-immediate (i.e., occurring more than 1 hour after the last drug administration) hypersensitivity reactions, respectively. Skin prick, patch, and intradermal tests are the most readily available tools for the evaluation of hypersensitivity drug reactions. The diagnostic value of skin tests for many drugs still has not been fully established. Reliable skin test procedures for the diagnosis of drug hypersensitivity have been defined, and test concentrations have been validated for many drugs. Skin tests should be carried out according to the clinical features of ADRs. In immediate drug reactions, an IgE-mediated mechanism can be demonstrated by a positive skin prick and/or intradermal test after 20 minutes, whereas in non-immediate reactions, a T-cell involvement can be found by a positive patch test and/or a late-reading intradermal test. The predictive value of skin tests varies with the drug tested and is especially high with beta-lactams, muscle relaxants, insulins, platinum salts, streptokinase, and chymopapain. Further diagnostic tests are required in the assessment of drug hypersensitivity reactions. However, skin tests can provide information about the culprit drug and the mechanism involved in certain reactions. The present review addresses literature data regarding the diagnosis of drug hypersensitivity reactions by skin tests.
Diagnosis and management of drug hypersensitivity reactions Romano, Antonino, MD; Torres, Maria J., MD, PhD; Castells, Mariana, MD, PhD ...
Journal of allergy and clinical immunology,
03/2011, Letnik:
127, Številka:
3
Journal Article, Conference Proceeding
Recenzirano
The present article addresses the advances in the diagnosis and management of drug hypersensitivity reactions that were discussed in the 4th Drug Hypersensitivity Meeting held in Rome in April 2010. ...Such reactions can be classified as immediate or nonimmediate according to the time interval between the last drug administration and onset. Immediate reactions occur within 1 hour, and nonimmediate reactions occur after more than 1 hour. Clinical and immunologic studies suggest that type-I (IgE-mediated) and type-IV (T cell–mediated) pathogenic mechanisms are involved in most immediate and nonimmediate reactions, respectively. In diagnosis prick, patch, and intradermal tests are the most readily available tools. Determination of specific IgE levels is still the most common in vitro method for diagnosing immediate reactions. New diagnostic tools, such as the basophil activation test, the lymphocyte activation test, and enzyme-linked immunospot assays for analysis of the frequency of antigen-specific, cytokine-producing cells, have been developed for evaluating either immediate or nonimmediate reactions. The sensitivity of allergologic tests is not 100%; therefore in selected cases provocation tests are necessary. In the diagnosis of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs, the provocation test with the suspected drug still represents the “gold standard.” However, there was no consensus regarding the use of this test in subjects with histories of hypersensitivity reactions to 1 (single reactors) or more (multiple reactors) nonsteroidal anti-inflammatory drugs. With regard to management, desensitization allows patients to be treated with irreplaceable chemotherapy agents, such as taxanes, platinum salts, and mAbs, to which they have presented hypersensitivity reactions. Desensitization also permits the use of aspirin in aspirin-sensitive patients undergoing revascularization and in subjects with aspirin-exacerbated respiratory disease.
PDF
