There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Several years ago, as editor-in-chief of theAmerican Journal of Surgical Pathology, Dr Sternberg inaugurated a series of articles under the same heading as his book's title,Histology for Pathologists. These articles have now been considerably augmented and incorporated into this large, almost 1000-page, comprehensive text, whose 80 authors comprise an international cast of experts. Inevitably, the chapters vary in their quality, to an extent that reflects either inadequate editorial surveillance or adherence to a very tight deadline. I would assume that the instruction to contributors was to write on pure and applied histology, with the level of detail required by a practicing pathologist. As Dr Sternberg mentions in his preface, there are many histology books in existence, but none contains the detail and variations from normal that form a baseline for estimating the presence of disease. The papers originally published in theAmerican Journal of Surgical Pathologyare strictly

Histology for Pathologists

The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria-xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and mycotoxicosis.

Mycotoxin: Its Impact on Gut Health and Microbiota.

Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantities of the microbial flora exist in the gut of the vertebrates. These microorganisms frequently exchange materials with the host. Melatonin isomers, which are produced by these organisms inevitably enter the host’s system. The origins of melatonin and its isomers can be traced back to photosynthetic bacteria and other primitive unicellular organisms. Since some of these bacteria are believed to be the precursors of mitochondria and chloroplasts these cellular organelles may be the primary sites of melatonin production in animals or in plants, respectively. Phylogenic analysis based on its rate-limiting synthetic enzyme, serotonin N-acetyltransferase (SNAT), indicates its multiple origins during evolution. Therefore, it is likely that melatonin and its isomer are also present in the domain of archaea, which perhaps require these molecules to protect them against hostile environments including extremely high or low temperature. Evidence indicates that the initial and primary function of melatonin and its isomers was to serve as the first-line of defence against oxidative stress and all other functions were acquired during evolution either by the process of adoption or by the extension of its antioxidative capacity.

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Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin’s synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland.

Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo (group C, n = 9) over a period of six weeks. The pigs were sacrificed after one, three, or six weeks of the treatment (12 pigs per each time-point). Histological investigations revealed an increase in the mucosal thickness and the crypt depth as well as a decrease in the ratio of the villus height to the crypt depth in groups D and M after six weeks of exposure to the mycotoxins. The number of goblet cells in the villus epithelium was elevated in groups Z and M after one week and in group D after three weeks. The administration of ZEN increased the lymphocyte number in the villus epithelium after 1 week and the plasma cell quantity in the lamina propria after one, three, and six weeks of the experiment. DON treatment resulted in an increase in the lymphocyte number in the villus epithelium and the lamina propria after six weeks, and in the plasma cell quantity in the lamina propria after one, three, and six weeks of exposure. In group M, lymphocyte counts in the epithelium and the lamina propria increased significantly after six weeks. Neither mycotoxin induced significant adverse changes in the ultrastructure of the mucosal epithelium and the lamina propria or in the intestinal barrier permeability. Our results indicate that immune cells are the principal target of low doses of ZEN and DON.

The Effects of Low Doses of Two Fusarium Toxins, Zearalenone and Deoxynivalenol, on the Pig Jejunum. A Light and Electron Microscopic Study

Histological structure of duodenum in gilts receiving low doses of zearalenone and deoxynivalenol in feed

The contamination of feed with mycotoxins results in reduced growth, feed refusal, immunosuppression, and health problems. Deoxynivalenol (DON) and zearalenone (ZEN) are among the most important mycotoxins. The aim of the study was to examine the effects of low doses of these mycotoxins on the histological structure and ultrastructure of the large intestine in the pig. The study was performed on 36 immature gilts of mixed breed (White Polish Big × Polish White Earhanging), which were divided into four groups administrated per os with ZEN at 40 µg/kg BW, DON at 12 µg/kg BW, a mixture of ZEN (40 µg/kg BW) and DON (12 µg/kg BW) or a placebo. The pigs were killed by intravenous overdose of pentobarbital after one, three, and six weeks of treatment. The cecum, ascending and descending colon samples were prepared for light and electron microscopy. Administration of toxins did not influence the architecture of the mucosa and submucosa in the large intestine. ZEN and ZEN + DON significantly decreased the number of goblet cells in the cecum and descending colon. The mycotoxins changed the number of lymphocytes and plasma cells in the large intestine, which usually increased in number. However, this effect differed between the intestine segments and toxins. Mycotoxins induced some changes in the ultrastructure of the mucosal epithelium. They did not affect the expression of proliferative cell nuclear antigen and the intestinal barrier permeability. The obtained results indicate that mycotoxins especially ZEN may influence the defense mechanisms of the large intestine.

The Effects of Deoxynivalenol and Zearalenone on the Pig Large Intestine. A Light and Electron Microscopy Study.

The pineal organs of 14-week-old domestic geese were investigated with light and electron microscopy. The pineals consisted of a wide distal part and a narrow middle-proximal one. The glands were attached to the intercommissural region via the choroid plexus. The pineal parenchyma was formed by round or elongated follicles. The follicular wall was composed predominantly by cells immunoreactive with antibodies against hydroxyindolo-O-methyltransferase (HIOMT) or glial fibrillary acid protein (GFAP). They formed two or more layers. HIOMT-positive elements were represented by elongated cells bordering the follicular lumen and oval cells located in the external layer of the follicular wall. These cells were identified in ultrastructural studies as rudimentary-receptor pinealocytes and secretory pinealocytes, respectively. Among rudimentary-receptor pinealocytes two types of cells, designed as A and B, were distinguished due to structural differences. Type A cells extended through the whole follicular wall and showed regular stratified distribution of organelles in well-recognizable zones with rough endoplasmic reticulum, the Golgi apparatus and mitochondria. Type B cells, like type A pinealocytes, contacted the pineal lumen and showed polarity of their internal structure. However, they were markedly shorter than the cells of type A and lacked stratified distribution of organelles. Secretory pinealocytes contained irregularly dispersed organelles. A prominent feature of all types of goose pinealocytes was the presence of numerous dense core vesicles. The population of GFAP-positive cells consisted of ependymal-like supporting cells and astrocyte-like cells.

Histology and ultrastructure of the pineal organ in the domestic goose.

Objective The study was performed to analyze structural changes of the turkey pineal during the post-hatching development. Material and methods The pineals were collected from male turkeys at the age of 1 day, 2, 8, 22, 56 weeks and subjected to histological investigations including morphometrical analyses. The pinealocytes were identified immunohistochemically using antiserum against hydroxyinolo-O-methyltransferase (HIOMT). Results and conclusions Independently of age, the pineal consisted of a narrow proximal part and a club-shaped top. The narrow part extended into the stalk attached to the diencephalon. The pineal parenchyma was formed by the follicles, surrounded by the connective tissue. The caudal part of the organ contained the pineal lumen, which prolonged into the stalk lumen. Up to the age of two weeks the stalk lumen was open to the third ventricle, later--closed. The proximal part of the stalk showed age-dependent reduction. During the investigated period of life, the pineal increased in size due to creation of new follicles, enlargement of the follicles and development of the stroma. In immature turkeys, the follicular wall was formed by elongated cells bordering the lumen and sparse, peripherally localized, round cells. This pseudostratified organization was transformed during ontogenesis into thick, multilayer structure (characteristic for 22- and 56-week-old turkeys) composed by the layer of elongated cells and several layers of round cells, located peripherally. The rudimentary-receptor and secretory pinealocytes were demonstrated based on HIOMT-immunoreactivity. The secretory pinealocytes were sparse in young birds and predominated in mature turkeys. Intra-pineal calcified concrements occurred in 56-week-old turkeys.

Magdalena Prusik

Papers

The Effects of Low Doses of Two Fusarium Toxins, Zearalenone and Deoxynivalenol, on the Pig Jejunum. A Light and Electron Microscopic Study

Histological structure of duodenum in gilts receiving low doses of zearalenone and deoxynivalenol in feed

The Effects of Deoxynivalenol and Zearalenone on the Pig Large Intestine. A Light and Electron Microscopy Study.

Histology and ultrastructure of the pineal organ in the domestic goose.

Post-hatching development of the turkey pineal organ: histological and immunohistochemical studies.