Exercise training in aging and diseases.

Sedentary lifestyle along with high blood pressure, abnormal values for blood lipids, smoking, and obesity are recognized risk factors for cardiovascular diseases and for many other chronic diseases, such as diabetes, osteoporosis, breast and colon cancer. Several studies conducted on large cohort of individuals have documented the protective effects of physical activity for both vascular and nonvascular syndromes. Exercise training is an integral part of cardiac rehabilitation, a complex therapeutic approach, effective both in young and elderly patients. Despite the number of evidences underling the benefits associated with physical fitness, the cardiac rehabilitation is still an underused medical resource. The molecular mechanism behind physical activity protective effect is presently unresolved, and further studies are also needed to establish the best protocol in terms of specificity, volume and duration of the training

Exercise training in aging and diseases

Sedentary lifestyle along with high blood pressure, abnormal values for blood lipids, smoking, and obesity are recognized risk factors for cardiovascular diseases and for many other chronic diseases, such as diabetes, osteoporosis, breast and colon cancer. Several studies conducted on large cohort of individuals have documented the protective effects of physical activity for both vascular and nonvascular syndromes. Exercise training is an integral part of cardiac rehabilitation, a complex therapeutic approach, effective both in young and elderly patients. Despite the number of evidences underling the benefits associated with physical fitness, the cardiac rehabilitation is still an underused medical resource. The molecular mechanism behind physical activity protective effect is presently unresolved, and further studies are also needed to establish the best protocol in terms of specificity, volume and duration of the training

Aerobic training workload affects human endothelial cells redox

Moderate aerobic exercise reduces oxidative stress, intense physical activity may produce the opposite result. At present, the effects of different exercise loads on oxidative stress markers and the response of human cells to different exercise volumes have not been fully elucidated. In this research human (Eahy-926) endothelial cells (ECs), exposed or not exposed to oxidative stress, were conditioned with sera from two groups of triathletes practising at different workloads. Although no differences in functional and hemodynamic variables were observed between the two groups of triathletes, significant changes in some markers for oxidative stress were found in their sera. Thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) activity were similar, but triathletes practicing the sport at lower volume (T1) had higher serum Nitric Oxide (NO) and lower catalase activity than triathletes performing the training at greater load (T2). The ECs conditioned with serum from T1 (T1-ECs) showed higher survival and proliferation rates and lower senescence levels than the ECs supplemented with T2 (T2-ECs) serum both before and after oxidative stress induction. These effects depended on catalase as demonstrated via enzyme activity inhibition using 3-amino-1,2,4-triazole (ATZ). After oxidative stress induction, Sirt1 activity, a regulator of the oxidative stress response, was significantly increased in the T1-ECs but not in the T2-ECs. Moreover, the T1-ECs required less catalase activity than the T2-ECs to counteract an equal amount of TBARS after H2O2 administration. In conclusion, this study demonstrates that the beneficial effects of aerobic exercise are eliminated when the training is performed at a greater workload. Moreover, we suggest an oxidative stress marker, serum catalase activity, as a valid tool to use in the supervision of changes to exercise volume

Aerobic training workload affects human endothelial cells redox

Moderate aerobic exercise reduces oxidative stress, intense physical activity may produce the opposite result. At present, the effects of different exercise loads on oxidative stress markers and the response of human cells to different exercise volumes have not been fully elucidated. In this research human (Eahy-926) endothelial cells (ECs), exposed or not exposed to oxidative stress, were conditioned with sera from two groups of triathletes practising at different workloads. Although no differences in functional and hemodynamic variables were observed between the two groups of triathletes, significant changes in some markers for oxidative stress were found in their sera. Thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) activity were similar, but triathletes practicing the sport at lower volume (T1) had higher serum Nitric Oxide (NO) and lower catalase activity than triathletes performing the training at greater load (T2). The ECs conditioned with serum from T1 (T1-ECs) showed higher survival and proliferation rates and lower senescence levels than the ECs supplemented with T2 (T2-ECs) serum both before and after oxidative stress induction. These effects depended on catalase as demonstrated via enzyme activity inhibition using 3-amino-1,2,4-triazole (ATZ). After oxidative stress induction, Sirt1 activity, a regulator of the oxidative stress response, was significantly increased in the T1-ECs but not in the T2-ECs. Moreover, the T1-ECs required less catalase activity than the T2-ECs to counteract an equal amount of TBARS after H2O2 administration. In conclusion, this study demonstrates that the beneficial effects of aerobic exercise are eliminated when the training is performed at a greater workload. Moreover, we suggest an oxidative stress marker, serum catalase activity, as a valid tool to use in the supervision of changes to exercise volume

Opposite Response to Vitamin K Antagonists: A Report of Two Cases and Systematic Review of Literature

Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose–response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events

Multidosing Intramuscular Administration of Methotrexate in Interstitial Pregnancy With Very High Levels of β-hCG: A Case Report and Review of the Literature

Ectopic pregnancy (EP) is the implantation of an embryo outside the endometrial cavity of the uterus. Signs and symptoms of EP may arise between the 6th and the 8th week of gestation and include vaginal bleeding, lower abdominal and pelvic pain. Frequently EPs implant in the fallopian tubes. A rare EP is the interstitial pregnancy, a life-threatening condition being responsible for nearly 20% of all deaths caused by EPs. Because of its unique location, the diagnosis is difficult and based on signs and specific criteria together with measuring of serum β-hCG. Usually, EP is treated by surgical approach, which is associated with increased morbidity, decreased fertility and increased likelihood of hysterectomy and uterine rupture in a subsequent pregnancy. Early diagnosis is crucial to life saving and allowing alternative therapeutic interventions such as pharmacological treatments. Methotrexate (MTX) represents the mainstay therapy. There is no standard care for the interstitial pregnancy for what concerns either surgical or pharmacological approaches. We reported a case of a 36-year-old woman admitted to the Hospital of Salerno-Italy with a value of serum β-hCG of 35,993 IU/L. Transvaginal ultrasonography revealed an empty uterine cavity and a mass of 35.7 mm in diameter characterized by a hypoechoic central area. The patient was in stable haemodynamic condition and no haematologic, renal and hepatic impairments were recorded. Despite the high serum β-hCG levels, a pharmacological approach was preferred to a surgical one. The patient was treated with intramuscular administration of MTX in daily dose of 1 mg/Kg alternated with 0.1 mg/kg folinic acid for 5 days. The patient remained hospitalized for 20 days and no side effects were reported. The decrease of the serum β-hCG was monitored and more than 15% reduction was detected between the 4th and the 7th day after the beginning of the treatment. The serum β-hCG became undetectable 35 days after. A multidosing intramuscular administration of MTX was effective and safe even in the presence of very high serum β-hCG levels. Together with similar cases reported in literature, the present results can contribute to improve the decision making in the treatment of the interstitial pregnancy

Chemical risk in hospital settings: Overview on monitoring strategies and international regulatory aspects

Chemical risk in hospital settings is a growing concern that health professionals and supervisory authorities must deal with daily. Exposure to chemical risk is quite different depending on the hospital department involved and might origin from multiple sources, such as the use of sterilizing agents, disinfectants, detergents, solvents, heavy metals, dangerous drugs, and anesthetic gases. Improving prevention procedures and constantly monitoring the presence and level of potentially toxic substances, both in workers (biological monitoring) and in working environments (environmental monitoring), might significantly reduce the risk of exposure and contaminations. The purpose of this article is to present an overview on this subject, which includes the current international regulations, the chemical pollutants to which medical and paramedical personnel are mainly exposed, and the strategies developed to improve safety conditions for all healthcare workers.&nbsp

Regulation of inflammation and oxidative stress by formyl peptide receptors in cardiovascular disease progression

G protein-coupled receptors (GPCRs) are the most important regulators of cardiac function and are commonly targeted for medical therapeutics. Formyl-Peptide Receptors (FPRs) are members of the GPCR superfamily and play an emerging role in cardiovascular pathologies. FPRs can modulate oxidative stress through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) production whose dysregulation has been observed in different cardiovascular diseases. Therefore, many studies are focused on identifying molecular mechanisms of the regulation of ROS production. FPR1, FPR2 and FPR3 belong to the FPRs family and their stimulation triggers phosphorylation of intracellular signaling molecules and nonsignaling proteins that are required for NADPH oxidase activation. Some FPR agonists trigger inflammatory processes, while other ligands activate proresolving or anti-inflammatory pathways, depending on the nature of the ligands. In general, bacterial and mitochondrial formylated peptides activate a proinflammatory cell response through FPR1, while Annexin A1 and Lipoxin A4 are anti-inflammatory FPR2 ligands. FPR2 can also trigger a proinflammatory pathway and the switch between FPR2-mediated pro- and anti-inflammatory cell responses depends on conformational changes of the receptor upon ligand binding. Here we describe the detrimental or beneficial effects of the main FPR agonists and their potential role as new therapeutic and diagnostic targets in the progression of cardiovascular diseases

Environmental and biological monitoring of formaldehyde inside a hospital setting: a combined approach to manage chemical risk in workplaces

Background: The safety of healthcare workers exposed to formaldehyde remains a great matter of concern for healthcare management units. This work aimed at describing the results of a combined monitoring approach (environmental and biological) to manage occupational exposure to formaldehyde in a hospital setting.Design and Methods: Environmental monitoring of working spaces and biological monitoring of urinary formaldehyde in 16 exposed healthcare workers of the Anatomic Pathology Unit of a University Hospital in Southern Italy was performed on a four-year timescale (2016-2019).Results: Values of aero-dispersed formaldehyde identified were on average low; although workers' urinary formaldehyde levels were also minimal, the statistical analysis highlighted a slight weekly accumulation.Conclusions: Our data confirm that both environmental and biological monitoring are important to identify risk situations, in particular when values of hazardous compounds are below the accepted occupational exposure levels

Concomitant Administration of Capecitabine and Folate Supplements: Need to Encourage Medication Reconciliation

Hand-Foot syndrome (HFS) and diarrhoea are dose-limiting Adverse Drug Reactions (ADRs) of capecitabine-based chemotherapy. Four polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene, encoding the DPD enzyme responsible for the metabolism of fluoropyrimidines, such as capecitabine, are strongly associated with severe ADRs, and their screening should be performed before starting treatment. Moreover, capecitabine-related toxicity may worsen due to drug-drug and drug-supplement interactions. Here we investigated factors responsible for severe HFS and diarrhoea presented by two patients, non-carriers of the recommended DPYD single nucleotide polymorphisms (SNPs) but carriers of other genetic variants suggested to increase the risk of capecitabine-related ADRs. Through careful therapy recognition, we demonstrated that, unbeknownst to the oncologists, the patients were taking folic acid during the treatment with capecitabine at a dosage higher than 2000 mg/m(2), which is the maximum tolerated dose when folate is administered. To resolve the ADRs, the therapy had to be drastically changed. In one case, dose reduction of capecitabine and discontinuation of lipid-lowering agents were carried out. In the other case, discontinuation of capecitabine and folic acid and capecitabine re-administration were performed after a month. Genetic and environmental factors should be considered good predictors of severe capecitabine-related toxicity. Medication reconciliation should be encouraged to avoid the harmful consequences of inappropriate treatments