The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Agrochemicals have enabled to more than duplicate food production during the last century, and the current need to increase food production to feed a rapid growing human population maintains pressure on the intensive use of pesticides and fertilizers. However, worldwide surveys have documented the contamination and impact of agrochemical residues in soils, and terrestrial and aquatic ecosystems including coastal marine systems, and their toxic effects on humans and nonhuman biota. Although persistent organic chemicals have been phased out and replaced by more biodegradable chemicals, contamination by legacy residues and recent residues still impacts on the quality of human food, water, and environment. Current and future increase in food production must go along with production of food with better quality and with less toxic contaminants. Alternative paths to the intensive use of crop protection chemicals are open, such as genetically engineered organisms, organic farming, change of dietary habits, and development of food technologies. Agro industries need to further develop advanced practices to protect public health, which requires more cautious use of agrochemicals through prior testing, careful risk assessment, and licensing, but also through education of farmers and users in general, measures for better protection of ecosystems, and good practices for sustainable development of agriculture, fisheries, and aquaculture. Enhanced scientific research for new developments in food production and food safety, as well as for environmental protection, is a necessary part of this endeavor. Furthermore, worldwide agreement on good agriculture practices, including development of genetically modified organisms (GMOs) and their release for international agriculture, may be urgent to ensure the success of safe food production.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/fes3.108

Pesticides, environment, and food safety

the broad sense of ‘non-genetic’. The exposome, therefore, complements the genome by providing a comprehensive description of lifelong exposure history. Remaining focused on the element of application (to epidemiology) is a key to ensuring that the exposome is translated from concept to utility for better delineating the causes and prevention of human disease. At the time of the original proposal, it was recognized that whereas exquisite tools had been developed to sequence the human genome and to interrogate individual susceptibility through genome-wide association studies (GWAS), there was a relative paucity of comparable tools, or indeed investment, in relation to exposure assessment. Given that cancer and other chronic diseases develop predominantly from a combination of environmental exposures played out on a particular genetic background, the inability to measure one part of the gene:environment combination with anything approaching the precision of the other will stymie progress. This becomes particularly acute as epidemiology aims to tease out relatively modest effect sizes associated with specific environmental exposures. This commentary seeks to further define the exposome and to describe how its realisation may be achieved in epidemiological studies. The commentary focuses on cancer but many of the concepts are applicable to other chronic diseases.

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The exposome: from concept to utility

Molecular and ionic mimicry and the transport of toxic metals.

Statistics for analytical chemistry

http://www.auburn.edu/academic/classes/biol/5090/boyd/DDT_toxicology_review.pdf

Persistent organochlorinated pesticides and mechanisms of their toxicity

Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

Toward an "omic" physiopathology of reactive chemicals: thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds.

Mercury, cadmium, arsenic and lead are among priority metals for toxicological studies due to the frequent human exposure and to the significant burden of disease following acute and chronic intoxication. Among their common characteristics is chemical affinity to proteins and non-protein thiols and their ability to generate cellular oxidative stress by the best-known Fenton mechanism. Their health effects are however diverse: kidney and liver damage, cancer at specific sites, irreversible neurological damages with metal-specific features. Mechanisms for the induction of oxidative stress by interaction with the cell thiolome will be presented, based on literature evidence and of experimental findings.

/pdf/toxicity-of-glutathione-binding-metals-a-review-of-targets-17thx5zhbf.pdf

Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms

The continuous introduction of new antineoplastic drugs and their use as complex mixture emphasize the need to carry out correct health risk assessment. The aim of this study was to evaluate genotoxic effects of antineoplastic drugs in nurses ( n  = 25) and pharmacy technicians ( n  = 5) employed in an oncology hospital. The nurses administered antineoplastic drugs in the day-care hospital ( n  = 12) and in the wards ( n  = 13), and pharmacy technicians prepared the drugs in the central pharmacy. We performed the micronucleus (MN) test with lymphocytes and exfoliated buccal cells and conducted traditional analysis of chromosomal aberrations (CA). Thirty healthy subjects were selected as controls. Monitoring of surface contamination with cyclophosphamide, 5-fluorouracil, ifosfamide, cytarabine, and gemcitabine showed the presence of detectable levels only for cyclophosphamide, 5-fluorouracil and ifosfamide. In addition, we measured the 5-fluorouracil metabolite α-F-βalanine in the urine of all subjects and found significant concentrations only in 3 out of 25 nurses. The micronucleus assay with lymphocytes did not show significant differences between exposed and control groups, while the same test with exfoliated buccal cells found higher values in nurses administering antineoplastic drugs than in pharmacy employees. In the CA analysis, we detected in exposed groups a significant increase (about 2.5-fold) of structural CA, particularly breaks (up to 5.0-fold). Our results confirm the genotoxic effect of antineoplastic drugs in circulating blood lymphocytes. Moreover, in exfoliated buccal cells the data show more consistent genetic damage induced during administration of the antineoplastic drugs than during their preparation. The data also stress the use of this non-invasive sampling, to assess occupational exposure to mixture of chemicals at low doses.

Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees.

Federico Maria Rubino

Papers

Persistent organochlorinated pesticides and mechanisms of their toxicity

Toward an "omic" physiopathology of reactive chemicals: thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds.

Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms

Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees.

Volatile organic compounds produced during the aerobic biological processing of municipal solid waste in a pilot plant.