https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)60937-X.pdf

Maternal and child undernutrition and overweight in low-income and middle-income countries

This review is written with the goal of informing public health concerns related to nanoscience, while raising awareness of nanomaterials toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to nanoparticles and dust from natural sources and human activities, the recent development of industry and combustion-based engine transportation profoundly increasing anthropogenic nanoparticulate pollution. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function. Among diseases associated with nanoparticles are asthma, bronchitis, lung cancer, neurodegenerative diseases (such as Parkinson`s and Alzheimer`s diseases), Crohn`s disease, colon cancer. Nanoparticles that enter the circulatory system are related to occurrence of arteriosclerosis, and blood clots, arrhythmia, heart diseases, and ultimately cardiac death. We show that possible adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape, and agglomeration state. The faster we will understand their causes and mechanisms, the more likely we are to find cures for diseases associated with nanoparticle exposure. We foresee a future with better-informed, and hopefully more cautious manipulation of engineered nanomaterials, as well as the development of laws and policies for safely managing all aspects of nanomaterial manufacturing, industrial and commercial use, and recycling.

Nanomaterials and nanoparticles: Sources and toxicity

This review is presented as a common foundation for scientists interested in nanoparticles, their origin, activity, and biological toxicity. It is written with the goal of rationalizing and informing public health concerns related to this sometimes-strange new science of “nano,” while raising awareness of nanomaterials’ toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to tiny particles via dust storms, volcanic ash, and other natural processes, and that our bodily systems are well adapted to protect us from these potentially harmful intruders. The reticuloendothelial system, in particular, actively neutralizes and eliminates foreign matter in the body, including viruses and nonbiological particles. Particles originating from human activities have existed for millennia, e.g., smoke from combustion and lint from garments, but the recent development of industry and combustion-based engine transportation has profoundly increased anthropogenic particulate pollution. Significantly, technological advancement has also changed the character of particulate pollution, increasing the proportion of nanometer-sized particles-“nanoparticles”-and expanding the variety of chemical compositions. Recent epidemiological studies have shown a strong correlation between particulate air pollution levels, respiratory and cardiovascular diseases, various cancers, and mortality. Adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape, agglomeration state, and electromagnetic properties. Animal and human studies show that inhaled nanoparticles are less efficiently removed than larger particles by the macrophage clearance mechanisms in the lungs, causing lung damage, and that nanoparticles can translocate through the circulatory, lymphatic, and nervous systems to many tissues and organs, including the brain. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function. Examples of toxic effects include tissue inflammation, and altered cellular redox balance toward oxidation, causing abnormal function or cell death. The manipulation of matter at the scale of atoms, “nanotechnology,” is creating many new materials with characteristics not always easily predicted from current knowledge. Within the nearly limitless diversity of these materials, some happen to be toxic to biological systems, others are relatively benign, while others confer health benefits. Some of these materials have desirable characteristics for industrial applications, as nanostructured materials often exhibit beneficial properties, from UV absorbance in sunscreen to oil-less lubrication of motors. A rational science-based approach is needed to minimize harm caused by these materials, while supporting continued study and appropriate industrial development. As current knowledge of the toxicology of “bulk” materials may not suffice in reliably predicting toxic forms of nanoparticles, ongoing and expanded study of “nanotoxicity” will be necessary. For nanotechnologies with clearly associated health risks, intelligent design of materials and devices is needed to derive the benefits of these new technologies while limiting adverse health impacts. Human exposure to toxic nanoparticles can be reduced through identifying creation-exposure pathways of toxins, a study that may someday soon unravel the mysteries of diseases such as Parkinson’s and Alzheimer’s. Reduction in fossil fuel combustion would have a large impact on global human exposure to nanoparticles, as would limiting deforestation and desertification. While nanotoxicity is a relatively new concept to science, this review reveals the result of life’s long history of evolution in the presence of nanoparticles, and how the human body, in particular, has adapted to defend itself against nanoparticulate intruders.

https://avs.scitation.org/doi/pdf/10.1116/1.2815690

https://www.doils.net/v1/links/836150.pdf

n−3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases

Nutritional deprivation suppresses immune function The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight Circulating levels of this adipocyte-derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob) or its receptor (db/db), has never been explained Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans Indeed, malnutrition predisposes to death from infectious diseases We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells Leptin increased Th1 and suppressed Th2 cytokine production Administration of leptin to mice reversed the immunosuppressive effects of acute starvation Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation

Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression

Zinc and small babies.

Two cases of scleroderma and primary biliary cirrhosis are described One had systemic sclerosis with primary biliary cirrhosis of six years' duration at the stage of ductular proliferation The other had the CRST syndrome (calcinosis, Raynaud's phenomenon, sclerodactyly, and telangiectases) with primary biliary cirrhosis at the florid stage Several similar cases were found in a review of other reports, and it is suggested that the association may be due to a common "autoimmune" process

https://www.bmj.com/content/bmj/3/5717/258.full.pdf

Scleroderma and Primary Biliary Cirrhosis

Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation.

https://gut.bmj.com/content/gutjnl/38/3/390.full.pdf

Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue

A number of the activities currently ascribed to the mediator interleukin 1 (IL-1) are relevant to chronic inflammatory bowel disease. Using the mouse thymocyte stimulation assay, lymphocyte-activating factor (LAF) activity was measured in plasma samples and supernatants from cultures of peripheral blood mononuclear cells from 16 patients with Crohn's disease, six with ulcerative colitis, and 10 healthy subjects. Results were compared with disease activity, drug therapy, granulocyte count, and plasma levels of zinc and C-reactive protein (CRP). Very low levels of LAF were detected in a few plasma samples from each of the subject groups. Mononuclear cells from healthy subjects produced LAF only when cultured with lipopolysaccharide, but stimulated cells from patients produced greater amounts. Moreover, cells from six patients with Crohn's disease, not receiving steroids, produced LAF spontaneously. Crohn's disease patients also had low plasma zinc but elevated levels of CRP and granulocytes. This enhanced production of LAF in vitro may reflect a primary cellular defect in Crohn's disease, or a secondary consequence of monocyte activation.

R. P. H. Thompson

Papers

Zinc and small babies.

Scleroderma and Primary Biliary Cirrhosis

Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue

Interleukin 1 in Crohn's disease.

Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease