RESUMO
Gender is an important risk factor for adverse drug reactions. Women report significantly more adverse drug reactions than men. There is a growing consensus that gender differences in drug PK is a main contributor to higher drug toxicity in women. These differences stem from physiological differences (body composition, plasma protein concentrations, and liver and kidney function), drug interactions, and comorbidities. Contrast agents are widely used to enhance diagnostic performance in computed tomography and magnetic resonance imaging. Despite their broad use, these contrast agents can lead to important adverse reactions including hypersensitivity reactions, nephropathy, and hyperthyroidism. Importantly, female gender is one of the main risk factors for contrast agent toxicity. As these adverse reactions may be related to gender differences in PK, this perspective aims to describe distribution and elimination pathways of commonly used contrast agents and to critically discuss gender differences in these processes.
RESUMO
Significance: Chronic diabetic wounds on the lower extremities (diabetic foot ulcers, DFU) are one of the most prevalent and life-threatening complications of diabetes, responsible for significant loss of quality of life and cost to the health care system. Available pharmacologic treatments fail to achieve complete healing in many patients. Recent studies and investigational treatments have highlighted the potential of modulating wound pH in DFU. Recent Advances: Data from in vitro, preclinical, and clinical studies highlight the role of pH in the pathophysiology of DFU, and topical administration of pH-lowering agents have shown promise as a therapeutic strategy for diabetic wounds. In this critical review, we describe the role of pH in DFU pathophysiology and present selected low-molecular-weight and hydrogel-based pH-modulating systems for wound healing and infection control in diabetic wounds. Critical Issues: The molecular mechanisms leading to pH alterations in diabetic wounds are complex and may differ between in vitro models, animal models of diabetes, and the human pathophysiology. Wound pH-lowering bandages for DFU therapy must be tested in established animal models of diabetic wound healing and patients with diabetes to establish a comprehensive benefit-risk profile. Future Directions: As our understanding of the role of pH in the pathophysiology of diabetic wounds is deepening, new treatments for this therapeutic target are being developed and will be tested in preclinical and clinical studies. These therapeutic systems will establish a target product profile for pH-lowering treatments such as an optimal pH profile for each wound healing stage. Thus, controlling wound bed pH could become a powerful tool to accelerate chronic diabetic wound healing.
