Zinc in Soils and Crop Nutrition

Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.

https://www.mdpi.com/1660-4601/7/4/1342/pdf

The Essential Toxin: Impact of Zinc on Human Health

The beneficial effects of arbuscular mycorrhizal (AM) fungi on plant performance and soil health are essential for the sustainable management of agricultural ecosystems. Nevertheless, since the ‘first green revolution’, less attention has been given to beneficial soil microorganisms in general and to AM fungi in particular. Human society benefits from a multitude of resources and processes from natural and managed ecosystems, to which AM make a crucial contribution. These resources and processes, which are called ecosystem services, include products like food and processes like nutrient transfer. Many people have been under the illusion that these ecosystem services are free, invulnerable and infinitely available; taken for granted as public benefits, they lack a formal market and are traditionally absent from society’s balance sheet. In 1997, a team of researchers from the USA, Argentina and the Netherlands put an average price tag of US $33 trillion a year on these fundamental ecosystem services. The present review highlights the key role that the AM symbiosis can play as an ecosystem service provider to guarantee plant productivity and quality in emerging systems of sustainable agriculture. The appropriate management of ecosystem services rendered by AM will impact on natural resource conservation and utilisation with an obvious net gain for human society.

Agroecology: the key role of arbuscular mycorrhizas in ecosystem services.

The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer’s disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.

Fibrinogen as a key regulator of inflammation in disease

Metallic stents are used to promote revascularization and maintain patency of plaqued or damaged arteries following balloon angioplasty. To mitigate the long-term side effects associated with corrosion-resistant stents (i.e., chronic inflammation and late stage thrombosis), a new generation of so-called "bioabsorbable" stents is currently being developed. The bioabsorbable coronary stents will corrode and be absorbed by the artery after completing their task as vascular scaffolding. Research spanning the last two decades has focused on biodegradable polymeric, iron-based, and magnesium-based stent materials. The inherent mechanical and surface properties of metals make them more attractive stent material candidates than their polymeric counterparts. A third class of metallic bioabsorbable materials that are based on zinc has been introduced in the last few years. This new zinc-based class of materials demonstrates the potential for an absorbable metallic stent with the mechanical and biodegradation characteristics required for optimal stent performance. This review compares bioabsorbable materials and summarizes progress towards bioabsorbable stents. It emphasizes the current understanding of physiological and biological benefits of zinc and its biocompatibility. Finally, the review provides an outlook on challenges in designing zinc-based stents of optimal mechanical properties and biodegradation rate.

Biodegradable Metals for Cardiovascular Stents: from Clinical Concerns to Recent Zn‐Alloys

Objective – To review zinc physiology and pathophysiology and the importance of zinc toxicity and deficiency in veterinary patients.



Data Sources – A review of human and veterinary medical literature.



Human Data Synthesis – There is a significant amount of original research in humans and animals on the role of zinc in multiple organ systems. There is also significant data available on human patients with zinc abnormalities.



Veterinary Data Synthesis – Zinc deficiency has been studied in dogs with genetic disease and dietary deficiency leading to dermatological disease and immune deficiency. Zinc toxicity has been described after ingestion of metallic foreign bodies containing zinc.



Conclusions – Historically, the role of zinc in health and disease has been studied through patients with toxicity or severe deficiency with obvious clinical signs. As the ubiquitous contribution of zinc to structure and function in biological systems was discovered, clinically significant but subtle deficiency states have been revealed. In human medicine, mild zinc deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiency, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more. Determining the causal relationships between mild zinc deficiency and concurrent disease is complicated by the lack of sensitive or specific tests for zinc deficiency. The prevalence of zinc deficiency and its contribution to disease in veterinary patients is not well known. Continued research is warranted to develop more sensitive and specific tests to assess zinc status, to determine which patients are at risk for deficiency, and to optimize supplementation in health and disease.

The ubiquitous role of zinc in health and disease.

Objectives – To review the role of thrombin in physiology and clinical disease and to discuss the pharmacology of antithrombosis.



Data Sources – Original research articles, scientific reviews, textbooks.



Human Data Synthesis – Thrombin and thrombin receptors are involved in a variety of physiologic and pathologic processes resulting in a great deal of interest in thrombin-related pharmacologic intervention.



Veterinary Data Synthesis – Although there is little clinical research data available on thrombin specifically in veterinary patients, some of the original research on protease activated receptors was performed at veterinary institutions and many of the human molecular biology studies have been done on animals including dogs.



Conclusion – Thrombin plays a significant role in coagulation, anticoagulation, and fibrinolysis. Antithrombotic treatment is focused on preventing thrombosis while maintaining hemostasis. Pharmaceutical agents are selected for the specific component of the coagulation pathway associated with a specific disease process, for a proven prophylactic benefit with procedures that carry a risk of thromboembolism, for rapidity of onset and ease of reversibility, for limited monitoring requirements, and for oral formulation and bioavailablity. Recent insight into other aspects of thrombin physiology presents an opportunity for pharmacologic intervention in a variety of other processes such as inflammation and sepsis, peripheral blood cell activation and chemotaxis, vascular endothelial and smooth muscle activity, cellular development and tissue repair, mitogenesis, neoplasia, and the function of nervous tissue following injury.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-4431.2009.00383.x

Thrombin physiology and pathophysiology.

Objective – To review the human and veterinary literature on histamine physiology and pathophysiology and potential applications for clinical use in veterinary critical care.

Data Sources – Human and veterinary clinical studies, reviews, texts, and recent research in histamine receptor and antagonist therapy.

Human Data Synthesis – Recent progress in molecular biology has led to a more complete understanding of the enzymes involved in histamine metabolism and histamine receptor physiology. The past decade of research has confirmed the role of histamine in the classical functions (contraction of smooth muscle, increase in vascular permeability, and stimulation of gastric acid secretion) and has also elucidated newer ones that are now under investigation. Data on the roles of histamine in angiogenesis, circadian rhythm, bone marrow regeneration, bacterial eradication, and cancer are emerging in the literature. Newer histamine antagonists are currently in drug trials and are expected to advance the clinical field in treatment of allergic, gastrointestinal, and cognitive disorders.

Veterinary Data Synthesis – Veterinary histamine research is directed at identifying the effects of certain pharmacological agents on blood histamine concentrations and establishing the relevance in clinical disease states. Research demonstrates important species differences in regards to histamine receptor physiology and tissue response. Studies in the area of trauma, sepsis, anaphylaxis, allergy, and gastrointestinal disorders have direct applications to clinical veterinary medicine.

Conclusions – Histamine plays a key role in the morbidity and mortality associated with allergy, asthma, gastric ulcers, anaphylaxis, sepsis, hemorrhagic shock, anesthesia, surgery, cardiovascular disease, cancer, CNS disorders, and immune-mediated disease. Histamine antagonism has been in common use to block its adverse effects. With recent advances in the understanding of histamine receptor physiology, pharmaceutical agents targeting these receptors have increased the therapeutic options.

Histamine: metabolism, physiology, and pathophysiology with applications in veterinary medicine

Objective: To review phosphorus and phosphate metabolism and the importance of phosphate abnormalities in veterinary patients.



Data sources: A review of recent human and veterinary medical literature.



Human data synthesis: There is a significant amount of original research on human patients with phosphate abnormalities. Hypophosphatemia has been studied in patients with diabetic ketoacidosis (DKA), head trauma, refeeding syndrome, hypothermia and in ventilator patients that fail to wean. Hyperphosphatemia has been studied in patients with renal failure and malignancy. Phosphate levels have also been evaluated for prognostic value in sepsis and acute liver failure.



Veterinary data synthesis: Although animal models were used in early experimental research, fewer studies have been published on the effects of phosphate abnormalities in veterinary patients. Hypophosphatemia has been studied in animals with DKA, with refeeding syndrome and with hyperparathyroidism. Hyperphosphatemia has been studied in animals with renal failure and with secondary hypoparathyroidism.



Conclusion: Phosphorus and phosphate are important in many biological functions. This paper is a review of their role in normal metabolism and the clinical importance of phosphate imbalances for our emergency and critical care patients.

Phosphorus and phosphate metabolism in veterinary patients

Objective: To review the clinical spectrum and mechanisms of action of furosemide in human and small animal veterinary patients.

Data sources: Review of human and veterinary literature.

Data synthesis: Furosemide is used primarily for its properties as a loop diuretic; however, it has many other actions that may be clinically applicable. Furosemide has a vasodilatory effect that precedes diuresis that may confer its immediate benefit in patients with volume overload. Furosemide can be inhaled to relieve dyspnea in patients with bronchospasm. Furosemide also shows promise as an adjunct to antiseizure therapy to help control epilepsy, status epilepticus, and acute ischemic damage related to seizures. It has activity as an antioxidant, iodine depletive, and may increase thoracic lymph duct flow. Reported furosemide side effects include altered drug metabolism, electrolyte depletion, ototoxicity, mucociliary impairment, endocrine and exocrine pancreatic effects, delayed wound healing, sulfonamide toxicity, and thyroid binding interference. It is worthwhile to consider the implications of these effects when using furosemide either alone or in combination with other drugs.

Conclusions: Despite the research in animal models that demonstrates a wide spectrum of pharmacologic activity, furosemide has not been widely recognized or used clinically in veterinary medicine except as a loop diuretic.

Jan P. Kovacic

Papers

The ubiquitous role of zinc in health and disease.

Thrombin physiology and pathophysiology.

Histamine: metabolism, physiology, and pathophysiology with applications in veterinary medicine

Phosphorus and phosphate metabolism in veterinary patients

The pharmacologic spectrum of furosemide