Ochratoxin A (OTA) is a mycotoxin produced by secondary metabolism of several fungi belonging to the genera Aspergillus and Penicillium. OTA is potentially nephrotoxic, neurotoxic, immunotoxic and carcinogenic in several animal species and in humans. This toxin has been detected in several human food and animal feed. The aim of this study was to determine OTA in blood samples of healthy and affected by chronic kidney disease (CKD) dogs. CKD group showed higher incidence of OTA-positivity than healthy dogs (96 vs. 56%) and a significantly higher median value of OTA plasma concentration (0.008 vs. 0.144 ng/ml). No significant correlation was observed between OTA levels and creatinine values in CKD dogs. This is the first study regarding OTA detection in plasma samples of healthy and CKD dogs; the presence of this toxin is higher in nephropatic patients but is not yet clear, if it is correlated with progression of the disease.
Ochratoxin A (OTA) is a secondary toxic metabolite synthesized by Aspergillus or Penicillium species, which can contaminate various crops. The International Agency for Research on Cancer (IARC) classified OTA as a group 2B possible human carcinogen. The aim of the present study was to assess OTA concentrations in tissues of wild boar (Sus scrofa L.) from Tuscany (Italy). Over a period of 2 years, samples of muscle, liver, and kidney from 48 wild boars were collected and concentrations of OTA were determined by enzymatic digestion (ED) coupled to high-performance liquid chromatography with a fluorescence detector (HPLC-FLD). The highest concentrations of OTA were found in the kidneys of the 48 wild boars analyzed. No difference in concentrations was found based on years of collection and sex while a significantly higher OTA concentration was found in the kidney of the young wild boars with respect to the adult one. Monitoring the quality of meat destined for transformation is a priority in order to decrease the possibility of toxin carry-over to humans. The present study showed that contamination of wild boar meat products by OTA represents a potential emerging source of OTA.
The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.
The growing emergence of drug-resistant bacterial strains is an issue to treat severe infections, and many efforts have identified new pharmacological agents. The inhibitors of β-lactamases (BLI) have gained a prominent role in the safeguard of beta-lactams. In the last years, new β-lactam–BLI combinations have been registered or are still under clinical evaluation, demonstrating their effectiveness to treat complicated infections. It is also noteworthy that the pharmacokinetics of BLIs partly matches that of β-lactams companions, meaning that some clinical situations, as well as renal impairment and renal replacement therapies, may alter the disposition of both drugs. Common pharmacokinetic characteristics, linear pharmacokinetics across a wide range of doses, and known pharmacokinetic/pharmacodynamic parameters may guide modifications of dosing regimens for both β-lactams and BLIs. However, comorbidities (i.e., burns, diabetes, cancer) and severe changes in individual pathological conditions (i.e., acute renal impairment, sepsis) could make dose adaptation difficult, because the impact of those factors on BLI pharmacokinetics is partly known. Therapeutic drug monitoring protocols may overcome those issues and offer strategies to personalize drug doses in the intensive care setting. Further prospective clinical trials are warranted to improve the use of BLIs and their β-lactam companions in severe and complicated infections.
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