Dried Blood Spot Technique Applied in Therapeutic Drug Monitoring of Anticancer Drugs: a Review on Conversion Methods to Correlate Plasma and Dried Blood Spot Concentrations

Pharmaceutical Research - Anticancer drugs are notoriously characterized by a low therapeutic index, the introduction of therapeutic drug monitoring (TDM) in oncologic clinical practice could...     

Age-dependent alteration in muscle regeneration: the critical role of tissue niche

Although adult skeletal muscle is composed of fully differentiated fibers, it retains the capacity to regenerate in response to injury and to modify its contractile and metabolic properties in response to changing demands. The major role in the growth, remodeling and regeneration is played by satellite cells, a quiescent population of myogenic precursor cells that reside between the basal lamina and plasmalemma and that are rapidly activated in response to appropriate stimuli. However, in pathologic conditions or during aging, the complete regenerative program can be precluded by fibrotic tissue formation and resulting in functional impairment of the skeletal muscle. Our study, along with other studies, demonstrated that although the regenerative program can also be impaired by the limited proliferative capacity of satellite cells, this limit is not reached during normal aging, and it is more likely that the restricted muscle repair program in aging is presumably due to missing signals that usually render the damaged muscle a permissive environment for regenerative activity.     

Health Implications of PAH Release from Coated Cast Iron Drinking Water Distribution Systems in the Netherlands

Background: Coal tar and bitumen have been historically used to coat the insides of cast iron drinking water mains. Polycyclic aromatic hydrocarbons (PAHs) may leach from these coatings into the drinking water and form a potential health risk for humans.Objective: We estimated the potential human cancer risk from PAHs in coated cast iron water mains.Method: In a Dutch nationwide study, we collected drinking water samples at 120 locations over a period of 17 days under various operational conditions, such as undisturbed operation, during flushing of pipes, and after a mains repair, and analyzed these samples for PAHs. We then estimated the health risk associated with an exposure scenario over a lifetime.Results: During flushing, PAH levels frequently exceeded drinking water quality standards; after flushing, these levels dropped rapidly. After the repair of cast iron water mains, PAH levels exceeded the drinking water standards for up to 40 days in some locations.Conclusions: The estimated margin of exposure for PAH exposure through drinking water was > 10,000 for all 120 measurement locations, which suggests that PAH exposure through drinking water is of low concern for consumer health. However, factors that differ among water systems, such as the use of chlorination for disinfection, may influence PAH levels in other locations.     

Prevalent cardiac,renal and cardiorenal damage in patients with advanced abdominal aortic aneurysms

Chronic kidney disease (CKD), cardiac damage (CD) and the combination of the two are associated with increased morbidity and death in patients admitted to vascular surgery units. We assessed the prevalence of cardiac and renal damage and cardiorenal syndrome (CRS) in 563 patients with abdominal aortic aneurysms (AAA) who underwent cardiac screening before either an endovascular procedure (EVAR) or open surgery (OS) for aneurysm repair. CD was defined by ≥stage B as per the ACC/AHA classification of congestive heart failure (CHF), while CKD was defined by estimated GFR <60 mL/min/1.73 m² (CKD-EPI). Anemia [World Health Organization (WHO) guidelines] and iron deficiency (ID) (criteria for CHF patients) were also calculated. AAA patients were stratified into the following groups: CD, CKD, CRS or none of these conditions [no risk factors (NoRF)]. The prevalence of isolated cardiac and renal structural damage, of combined cardiorenal damage and of ID was 24.1, 15.0, 20.6 and 23.4 %, respectively. The frequency of anemia (mostly unrecognized) among the groups increased from NoRF (12.8 %)/CKD (19 %)/CD (25 %) up to CRS (38.8 %). This large-scale observational study provides clues for the increased CD/CKD risk profiles of unselected AAA patients, and underlines the need for better identification of ID/anemia and for appropriate treatment of CKD and CD before these patients undergo EVAR/OS.     

Juvenile paracoccidioidomycosis in urban area: report of two cases

We present two cases of juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis frequently found in rural areas, whose prognosis is poor in children and young adults. They are a 14-year-old boy and a 25-year-old woman, both residents in an urban area in São Paulo – Brazil, without any history of travelling to an endemic area. They have been admitted to the hospital due to fever, weight loss and lymphadenopathy. The diagnosis was confirmed by serologic and histopathologic study. Patients have recovered after therapy with oral itraconazole and were discharged from hospital, maintaining outpatient visits. In this article, the authors discuss the unusual presentation of PCM in an urban area.     

Emerging roles of fibronectin in thrombosis

Fibronectin (FN) is a glycoprotein recognized originally in the 1940's as a contaminant of fibrinogen in Cohn fraction I of plasma. Decades of research demonstrated FN synthesis by a variety of cells and defined FN as an essential component of the extracellular matrix with roles in embryogenesis, development, and wound healing. More recently, FN has emerged as player in platelet thrombus formation and diseases associated with thrombosis including vascular remodeling, atherosclerosis, and cardiac repair following a myocardial infarct. We discuss the mechanisms by which this might occur and conclude that FN may have a unique role in thrombosis without affecting normal hemostasis and therefore may be a reasonable therapeutic target for the prevention of thrombotic diseases.     

Are adolescents who moderate their cannabis use at lower risk of later regular and dependent cannabis use?

Aims   To examine whether moderation of cannabis use among adolescent cannabis users is associated with reductions in cannabis use frequency and risk of dependence in young adulthood.
Design   Ten-year representative cohort study with six surveys in adolescence (mean age 14.9–17.4 years) and two in young adulthood (mean age 20.7 and 24.1 years).
Participants   Inception cohort of 1943 Victorian secondary school students (96% response rate), with 1520 (78% of adolescent participants) interviewed in the final wave.
Measurements   Participants were classified into six groups according to the maximum level of adolescent use and the extent of subsequent moderation in such use: non-users, occasional to abstinence, occasional persisting, weekly to abstinence, weekly to occasional and weekly persisting. Outcome measures were weekly+ cannabis use and DSM-IV cannabis dependence at 20 and 24 years.
Findings   Thirty-one per cent reported cannabis use during adolescence. Most adolescent users had moderated their use: from occasional to abstinence (71% of occasional users), weekly to abstinence or weekly to occasional (28% and 48% of weekly+ users, respectively). By age 24, both occasional use groups were at similar, elevated risk of regular and dependent cannabis use compared to non-users. Weekly+ adolescent users were at greatest risk of these outcomes, although the weekly to abstinence group exhibited lower risk than those in the weekly persisting and weekly to occasional groups, who were at similar risk.
Conclusions   While many young people have dynamic cannabis use patterns, a pattern of moderating adolescent cannabis use was associated with less risk of later problematic use than among those persisting, but risks were still elevated substantially compared with never-users.