Several species during evolution suffered random mutations in response to various environmental factors, which resulted in the formation of venom in phylogenetically distant species. The composition of the venom of most species is poorly known. Snake venom is well characterized while most species have poorly known composition. In contrast, snake venoms are well characterized which proteins and peptides are the main active and most abundant constituents. 42 protein families have been identified, including metalloproteins known as metalloproteinases. These macromolecules are enzymes with zinc in their active site derived from the disintegrin A and metalloproteinase (ADAM) cellular family and are categorized into three classes (PI, PII and PIII) according to their domain organization. The snake venom metalloproteinases (SVMP) are cytotoxic, neurotoxic, myotoxic and/or hematotoxic with a crucial role in the defense and restraint of prey. In this scenario envenoming represents a danger to human health and has been considered a neglected disease worldwide, particularly in tropical and subtropical countries. Nevertheless, recently advances in \"omics\" technologies have demonstrated interesting biological activities of SVMPs such as antimicrobial, anticancer, against cardiovascular diseases and nervous system disorders. Metalloproteins have the therapeutic potential to be converted into drugs as other components of the venom have undergone this process (e.g., captopril, tirefiban and eptifibatide). So, this chapter is focused on the metalloproteins found in the secretions of venomous species, highlight some aspects such as structure, biological activity, pharmacological therapeutic potential and on.

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Little is known about how pharmacological and toxicological knowledge evolves. The aim of this study was to investigate the changes in the presentation of the poison hydrogen cyanide in sixteen German-language pharmacology and toxicology textbooks from 1878 to 2020. The categories of structure, molecular mechanism of action, occurrence, effects, resorption, areas of application, lethal dose, acute symptoms of intoxication, treatment of hydrogen cyanide poisoning, and recommended therapeutic preparations were evaluated. The knowledge on the structure, lethal dosage, and occurrence of hydrogen cyanide has remained constant. In contrast, knowledge on molecular mechanism of action and recommended preparations of the poison has changed dramatically. Until 1944, the binding of hydrogen cyanide to hemoglobin was considered the mechanism of action, whereas from 1951 onwards, the interaction of hydrogen cyanide with the Fe3+ of cytochrome oxidase was described. The number of preparations containing hydrogen cyanide decreased into obsolescence until 1951. The areas of application of hydrogen cyanide also show a change, as from 1919 onwards, mainly industrial areas of application of the poison are described instead of medical ones, and from 1951 onwards, criminalistic areas of application are also mentioned. Thus, pharmacological and toxicological knowledge develops non-linearly, molecular mechanism and uses being the most dynamic areas, whereas the knowledge about hydrogen cyanide\'s chemical structure, lethal dose, and occurrence remained constant. Older pharmacology and toxicology textbooks were better than newer ones at discussing changes in scientific concepts. Pharmacology and toxicology textbooks also mostly failed to discuss the misuse of hydrogen cyanide (Zyklon B) during the Nazi regime, missing an important opportunity to showcase the ethical responsibility of pharmacology and toxicology. Thus, future pharmacology and toxicology textbooks should improve on discussing the development of pharmacological and toxicological concepts and the ethical responsibility of the discipline.

Carbon monoxide poisoning remains a leading cause of accidental poisoning worldwide (both at home and at work), and it is also a cause of suicidal poisoning. Such poisoning can arise following prolonged exposure to low levels of CO or following brief exposure to high concentrations of the gas. In fact, despite exposure limits, high safety standards, and the availability of CO alarms, nearly 50,000 people in the United States visit the emergency department each year due to poisoning. Additionally, CO poisoning in the United States causes up to 500 deaths each year. Despite the widespread nature of this form of poisoning, known about for centuries and whose damage mechanisms have been recognized (or rather hypothesized about) since the 1800s, early recognition, especially of late complications, and treatment remain a medical challenge. A well-designed therapeutic diagnostic process is necessary so that indication for hyperbaric or normobaric therapy is correctly made and so that patients are followed up even after acute exposure to diagnose late complications early. Furthermore, it is necessary to consider that in the setting of emergency medicine, CO poisoning can be part of a differential diagnosis along with other more frequent conditions, making its recognition difficult. The last thirty years have been marked by a significant increase in knowledge regarding the toxicity of CO, as well as its functioning and its importance at physiological concentrations in mammalian systems. This review, taking into account the significant progress made in recent years, aims to reconsider the pathogenicity of CO, which is not trivially just poisonous to tissues. A revision of the paradigm, especially as regards treatment and sequelae, appears necessary, and new studies should focus on this new point of view.

The impact of poisoning can differ significantly depending on the specific substance consumed. Identifying toxic substances in a patient is crucial to obtaining a thorough medical history. Frontline healthcare providers in the emergency department often handle patients presenting with poisoning. Their clinical presentation can vary depending on their dose, duration of exposure, and pre-existing medical conditions. Initially, poisoning management entails administering supportive care such as absorption and enhancing the elimination of poison with charcoal and antidote administration after identifying the poisoning substances. This article aims to provide a basic overview of the concepts involved in evaluating and managing these individuals.

β-Catenin is a well-established driver of many cancers; however, there are challenges in developing agents targeting β-catenin for clinical use. Recent progress has indicated that most of the pathological changes in β-catenin may be commonly caused by loss of protein homeostasis. Modulation of β-catenin homeostasis, especially by hyperactivation of β-catenin, potentially leads to robust antitumor outcomes. Here, we comprehensively dissect the protein homeostasis of β-catenin in terms of time, compartmentalization, supramolecular assemblies, and dynamics, with emphasis on changes in β-catenin homeostasis upon oncogenic mutations. We propose that altered β-catenin homeostasis could be deleterious for β-catenin-dependent cancers and that modulation of β-catenin homeostasis offers a novel avenue for targeting β-catenin for cancer therapy.

Ingestion of toxic bottle gourd juice, particularly the bitter one, may pose a significant risk to life if not treated in time. Notwithstanding its usefulness, people drink it routinely without concern for fruit quality, extraction hygiene, and mixture with other fruits. We report two cases of bottle gourd juice poisoning with severe abdominal pain and hematemesis. On evaluation, patients were hypotensive with associated esophagitis, pangastritis, and duodenitis. After conservative management, both were discharged after five days of hospitalisation. We conclude that the chances of bottle gourd juice poisoning are higher in water-stressed arid regions; hence, care should be taken on quality and quantity while consuming it.

Representatives of the Diodontidae family (porcupinefish) are known to have been fished by prehistoric Indo-Pacific populations; however, the antiquity of the use of this family is thus far unknown. We report here on the presence of Diodontidae in the archaeological sites of Bubog I, II, and Bilat in Mindoro, Philippines, dating back to c. 13,000 BP (Before Present). This evidence demonstrates the early exploitation by islanders of poisonous fish. Every part of porcupinefish can be toxic, but the toxicity is mostly concentrated in some organs, while other parts are edible. The continuous presence of Diodontidae remains throughout the stratigraphic record of these Philippines shell middens suggests that porcupinefish were prepared by human inhabitants of the sites to render them safe for consumption, indicating an advanced cultural knowledge of the preparation needed to separate the toxic principle from the edible parts. This constitutes one of the rare examples of poison processing by humans, aside from the contentious wooden stick poison applicator from Border Cave (South Africa).

The use of poison against predators is pervasive and negatively impacts biodiversity and ecosystem health globally. Little is known about the correlates of poison use as a lethal control method on small-livestock farmland. We used a mixed-methods approach to investigate commercial farmers\' experience with and perceived effectiveness of predation control methods, reported poison use and its correlates in the Central Karoo. Farmers perceived lethal methods to be cheaper and more effective than non-lethal methods in protecting their livestock from predation. They reported more experience with lethal methods, and over half reported having used poison. This is higher than other estimates in southern Africa and consistent with other survey-based evidence from the Karoo. Reported poison use was positively related to perceived efficacy, declining on-farm employment and perceived threats of predators. It was negatively related to terrain ruggedness. Our findings provide an understanding of the context and motivations shaping this illegal behavior.

Unlike many researchers of natural product chemistry, I was fortunate to have the opportunity to study phytochemical metabolites and isolates of microbial origin. I began my career isolating the active compound(s) from the medicinal plants. After obtaining a Ph.D. degree from Tohoku University, I flew to Chicago, College of Pharmacy, University of Illinois, where I carried out research on the chemistry of acronycine and discovered several interesting chemical reactions regarding this alkaloid. After returning to Japan, I began to work at the Kitasato Institute, to search for novel antitumor antibiotics. During this period, 27 new antibiotics were isolated, and the new chemical structures were elucidated. After rejoining the Pharmaceutical Institute at Tohoku University, I again began to work on the phytochemical substances, mainly alkaloids. These studies continued after I moved to Aomori University and finally to Nihon Pharmaceutical University. I was interested in the biosynthesis of the alkaloids and found that all alkaloids could be classified into 16 classes based on their method of biosynthesis. I wrote a book about this in Japanese, and subsequently the book was translated into English as \"ALKALOIDS-A Treasury of Poisons and Medicines.\" After completing the publication of this book, I had many chances to write books, mainly concerning poisons and medicines. Totally, I have been able to publish 26 books regarding on these fascinating topics until now. I am feeling very satisfied with my natural product chemistry contributions, especially those of alkaloids and poisons.