Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects.

BACKGROUND: Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. OBJECTIVE AND METHODS: To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: "sars cov 2", "covid 19", "subacute thyroiditis", "atypical thyroiditis", "chronic thyroiditis", "hashimoto's thyroiditis", "graves' disease", "thyroid nodule", "differentiated thyroid cancer", "medullary thyroid cancer", "methimazole", "levothyroxine", "multikinase inhibitor", "remdesivir", "tocilizumab". Data were collected, analyzed, and discussed to answer the following clinical questions: "What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?"; "Could medical management of thyroid diseases influence the clinical course of COVID-19?"; "Does medical management of COVID-19 interfere with thyroid function?"; "Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?". RESULTS: SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. DISCUSSION: Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.

Nanoparticle delivery of grape seed-derived proanthocyanidins to airway epithelial cells dampens oxidative stress and inflammation.

BACKGROUND: Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins. METHODS: Plain, 6-coumarin (6-Coum), DiR- and GSE-loaded SLN were produced with the melt-emulsion method. Physicochemical characterization of all prepared SLN was determined by photon correlation spectroscopy and laser Doppler anemometry. MTT assay (spectrophotometry) and propidium iodide (PI) assay (cytofluorimetry) were used to assess cell viability. Flow cytometry coupled with cell imaging was performed for assessing apoptosis and necrosis by Annexin V/7-AAD staining (plain SLE), cell internalization (6-Coum-SLN) and reactive oxygen species (ROS) production (SLN-GSE). NF-κB nuclear translocation was studied by immunofluorescence. In vivo bio-imaging was used to assess lung deposition and persistence of aerosolized DiR-loaded SLN. RESULTS: Plain SLN were not cytotoxic when incubated with H441 airway epithelial cells, as judged by both PI and MTT assays as well as by apoptosis/necrosis evaluation. 6-Coum-loaded SLN were taken up by H441 cells in a dose-dependent fashion and persisted into cells at detectable levels up to 16 days. SLN were detected in mice lungs up to 6 days. SLN-GSE possessed 243 nm as mean diameter, were negatively charged, and stable in size at 37 °C in Simulated Lung Fluid up to 48 h and at 4 °C in double distilled water up to 2 months. The content of SLN in proanthocyanidins remained unvaried up to 2 months. GSE-loaded SLN determined a significant reduction in ROS production when added 24-72 h before the stimulation with hydrogen peroxide. Interestingly, while at 24 h free GSE determined a higher decrease of ROS production than SLN-GSE, the contrary was seen at 48 and 72 h. Similar results were observed for NF-κB nuclear translocation. CONCLUSIONS: SLN are a biocompatible drug delivery system for natural anti-oxidants obtained from grape seed in a model of oxidative stress in airway epithelial cells. They feature stability and long-term persistence inside cells where they release proanthocyanidins. These results could pave the way to novel anti-oxidant and anti-inflammatory therapies for chronic respiratory diseases.

Liver melanomacrophage centres as indicators of Atlantic bluefin tuna, Thunnus thynnus L. well-being.

Melanomacrophage centres (MMCs), located in different organs of non-mammalian vertebrates, play a role in the destruction, detoxification or recycling of endogenous and exogenous materials. Cytochrome P450 monoxygenase 1A (CYP1A) is involved in xenobiotics biotransformation, and its liver expression is considered as a biomarker for detecting exposure to environmental pollutants. Atlantic bluefin tuna (ABFT), Thunnus thynnus L., liver samples were collected from: wild animals caught in the eastern Atlantic; juveniles reared in the central Adriatic; juveniles reared in the northern Adriatic; adults reared in the western Mediterranean. The samples were processed for basic histology, histochemistry and for CYP1A immunodetection. An unexpected high density of MMCs, containing ferric iron and lipofuscin-ceroids, was detected in the juveniles sampled in the northern Adriatic Sea. These individuals showed also a strong anti-CYP1A immunopositivity in hepatocytes and in the epithelium of bile ducts. This study supports the utility of MMCs as biomarkers of fish 'health status' and gives concern for a potential contaminant accumulation in ABFT.

Immunopathogenesis of neurodegenerative diseases: current therapeutic models of neuroprotection with special reference to natural products.

Parkinson disease (PD) and Alzheimer disease (AD) are neurodegenerative processes whose frequency is dramatically increasing in the western world. Both diseases share a common pathogenic denominator characterized by an exaggerated activation of the systemic and cerebral immune system, respectively. For instance, lipopolysaccharides in PD and amyloid beta in AD trigger microglia and astrocytes to release reactive oxygen species (ROS) and proinflammatory cytokines. Infiltrating peripheral T cells once activated in the central nervous system also contribute to the neurodegenerative process. Besides innovative biotherapy, nutraceuticals or functional foods are currently investigated for their neuroprotective activities. Especially, vitamin D and polyphenols, seem to be promising therapeutic tools for inhibiting ROS formation and arresting cytokine-mediated neuroinflammation in PD and AD.

Potential application of dietary polyphenols from red wine to attaining healthy ageing.

Polyphenols are ubiquitous compounds present in the vegetal kingdom and endowed with an array of beneficial activities to human health. In this review, the effects of dietary polyphenols on the prevention and/or mitigation of cancer, neurodegenerative diseases, obesity, metabolic syndrome and atherosclerosis will be illustrated. Moreover, emphasis will be placed on our own data concerning the in vitro effects performed by polyphenols from an Italian red wine "Negroamaro" on human healthy peripheral blood mononuclear cells. Particularly, production of nitric oxide and maintenance of the inflammatory/anti-inflammatory cytokine network will be discussed also in relation to potential application to human age-related diseases. In conclusion, polyphenols in virtue of the plethora of protective effects manifested in various experimental models and clinical trials seem to be appropriate as dietary supplements for preventing the functional decline of organs with age.

Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement.

Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and age-related diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling age-related low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing.

Administration of a synbiotic to free-living elderly and evaluation of serum cytokines. A pilot study.

Ten free-living elderly were administered with a synbiotic [fermented milk containing Lactobacillus rhamnosus Gorbach and Goldin (LGG)] and oligofructose as a prebiotic for one month. Serum cytokines were evaluated before (T(0)) and after (T(1)) synbiotic administration. At T(0), values of Interleukin (IL)-12, IL-6, IL-10, IL-1beta and Tumor Necrosis Factor (TNF)-alpha were lower than normal controls, with the exception of IL-8, thus confirming previous results on the impairment of both innate and adaptive responses in elderly. At T(1), the synbiotic was able to significantly increase, depressed values of IL-1, IL-6 and IL-8 with a trend to a modest increase for the restant cytokines. In conclusion, the synbiotic used in this study seems to be very beneficial to elderly for its capacity to maintain the immune homeostasis, even if an increase in dosage and prolongation of administration time are required for a better modulation of the aged adaptive immune response.

Donkey and goat milk intake and modulation of the human aged immune response.

In a group of 14 healthy aged subjects, donkey and goat milk was administered respectively, for a period of one month. Cytokine profile [interleukin (IL)-12, IL-10, IL-1beta, IL-8, IL-6 and Tumor Necrosis Factor (TNF)-alpha] was assessed before and after milk intake by means of a cytometric bead array test. Data demonstrated that IL-12 was undetectable, while IL-10, IL-1beta and TNF-alpha were released in very low amounts. Quite interestingly, IL-8 was increased by donkey milk administration, while same cytokine was dramatically decreased following goat milk intake. Same pattern of response was noted with IL-6 even if levels of these cytokine were lower than those detectable in the case of IL-8. Taken together, these findings indicate that administration of donkey milk in the aged host is able to upregulate the immune response, while goat milk seems to reduce the exaggerated acute phase response in elderly.

Ability of goat milk to modulate healthy human peripheral blood lymphomonocyte and polymorphonuclear cell function: in vitro effects and clinical implications.

The in vitro effects of goat's milk from different sources (Jonica, Saanen, and Priska breeds plus a commercial preparation) on healthy human peripheral blood mononuclear cells (PBMCs) were evaluated in terms of nitric oxide (NO) and cytokine release. According to the incubation time (24 h or 48 h) used all milks could induce release of NO from monocytes. In this context, however, in the presence of a commercial milk preparation inhibition of lypopolysaccharide (LPS)-induce NO generation was evident. Also polymorphonuclear cells stimulated with the various milks released detectable amounts of NO. In the case of Priska milk inhibition of LPS-mediated NO generation was observed. Despite a broad array of cytokines tested [Interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, Tumor Necrosis Factor (TNF)-alpha, Transforming Growth Factor-beta and Granulocyte Colony Stimulating Factor] only IL-10, TNF-alpha, and IL-6 were released by PBMCs upon stimulation with various milks. Taken together, these data indicate that goat's milk for its capacity to produce NO may exert a cardioprotective and anti-atherogenic effect in consumers. Moreover, induction of proinflammatory (TNF-alpha and IL-6) and anti-inflammatory (IL-10) cytokines suggests the ability of this milk to maintain immune homeostasis in the immunocompromised host (e.g., aged people).

Effects of a hypocaloric diet on obesity biomarkers: prevention of low-grade inflammation since childhood.

Body mass index (BMI), serum cytokines and serum obesity markers were evaluated in 33 obese children before, during and after a hypocaloric diet. The cytometric bead array "human inflammatory kit" was used for the evaluation of serum interleukin (IL)-1beta, IL-6, IL-10 and tumor necrosis factor-alpha. On the other hand, the following obesity biomarkers were evaluated by means of a flowcytomix-human obesity 9 plex kit: Soluble Isoform of CD40 Ligand; Soluble Intercellular Adhesion Molecule-1; Leptin; Monocyte Chemoattractant Protein 1; Myeloperoxidase; Osteoprotegerin; Resistin and Soluble TNF-receptors. Actually, throughout the study modifications of BMI were negligible and, therefore, serum cytokines and obesity markers did not show any significant changes in comparison with baseline values. On the other hand, at the different time points considered the majority of obesity markers were higher than normal controls, thus indicating a low grade inflammation in childhood obesity. Therefore, attempts at reducing this inflammatory status in children which predisposes to the metabolic syndrome outcome are discussed.

Polyphenols from red wine modulate immune responsiveness: biological and clinical significance.

Many studies have been conducted on the effects of red wine polyphenols on certain diseases, primarily, coronary heart disease (CHD) and, in this respect, evidence has been demonstrated that intake of red wine is associated with a reduction of CHD symptomatology. In this framework, the purpose of this review is to illustrate the effects of polyphenols on immune cells from human healthy peripheral blood. Data will show that polyphenols are able to stimulate both innate and adaptive immune responses. In particular, the release of cytokines such as interleukin (IL)-12, interferon (IFN)-gamma, and IL-10 as well as immunoglobulins may be important for host protection in different immune related disorders. Another important aspect pointed out in this review is the release of nitric oxide (NO) from peripheral blood mononuclear cells (PBMC), stimulated by red wine polyphenols despite the fact that the majority of studies have reported NO production only by endothelial cells. Release of NO from PBMC may play an important role in cardiovascular disease, because it is known that this molecule acts as an inhibitor of platelet aggregation. On the other hand, NO exerts a protective role against infectious organisms. Finally, some molecular cytoplasmatic pathways elicited by polyphenols able to regulate certain immune responses will also be discussed. In particular, it seems that p38, a molecule belonging to the MAPK family, is involved in the release of IFN-gamma and, therefore, in NO production. All these data confirm the beneficial effects of polyphenols in some chronic diseases.

Elicitation of immune responsiveness against antigenic challenge in age-related diseases: effects of red wine polyphenols.

Polyphenols contained in red wine possess a broad array of properties which seem to be beneficial to human and animal health. We have investigated the ability of red wine polyphenols to promote the in vitro release of both proinflammatory and antiinflammatory cytokines from human healthy mononuclear cells, as well as of immunoglobulins from B cells. Following red wine (Negroamaro) pretreatment of lymphomonocytes, results will show a production of regulatory [Interleukin(IL)-12], proinflammatory (IL-1 beta and IL-6), and anti-inflammatory (IL-10) cytokines, as well as of IgA and IgG. The fine balance between inflammation and antiinflammation, as well as the role of humoral immune response either systemic or mucosal will be discussed as a consequence of red wine intake. Finally, since ageing is characterized by a decline of many immune functions, our results suggest that moderate use of red wine may be beneficial in age-related disorders where the host immune response is very often not effective against a variety of antigens.

Molecular effects elicited in vitro by red wine on human healthy peripheral blood mononuclear cells: potential therapeutical application of polyphenols to diet-related chronic diseases.

Red wine represents a source of polyphenols which exhibit a number of biological effects on various systems. In this respect, there is evidence that red wine polyphenols constitute one of the ingredients of the Mediterranean diet which is associated to a reduced risk of coronary heart disease according to current literature. Here, we have evaluated in vitro the molecular mechanisms elicited by polyphenols from red wine (Negroamaro) on human healthy mononuclear cells. In particular, we have investigated the involvement of polyphenols in the activation of p38 and ERK1/2 molecules belonging to the MAPK kinase family and on the expression of I kappaB alpha and p65/NF kappaB. Results will demonstrate that in cells both the expression of p38 and ERK1/2 augments in the presence of red wine polyphenols, but their expression drops in the presence of polyphenols plus lipopolysaccharides (LPS). This indicates that in Gram-negative infections polyphenols may attenuate triggering of inflammatory mediators as a response to LPS stimulation. Finally, the regulatory role of polyphenols on I kappaB alpha and p65/NF kappaB expression is discussed, pointing out that red wine might favor anti-atherogenic mechanisms in the course of cardiovascular disease.

Inflammation in fish as seen from a morphological point of view with special reference to the vascular compartment.

Modern bony fishes or teleosts are increasingly being used as model organisms for human diseases. Ambitious mapping programmes have revealed parts of or entire genomes of several species. This information suggests that there are several similarities between the mammalian and teleost immune systems, but also important differences. These differences are especially evident in the anatomical and functional constructions. However, compared to mammals, morphological studies of the immune system and in particular the inflammatory responses in fish are scarce, much due to a general lack of good cell markers. This review seeks to give an overview of the current knowledge of the teleost immune system related to inflammation and morphological research. The emphasis is placed on coronary changes which may be observed in salmonids over the size of 10 cm. Here, the immunopathological picture has some resemblance to that observed in similar changes in humans.

Immunological properties of donkey's milk: its potential use in the prevention of atherosclerosis.

Donkey's milk is the best substitute of human milk for its content in lactose, proteins, minerals, and omega-3 fatty acids. Here, we have evaluated the effects of colostrum and milk from donkeys (Martina Franca breed) on the function of human peripheral blood mononuclear cells (PBMCs) at different intervals from lactation. Colostrum induced more IgA responses, while milk induced predominantly more IgG responses. Both milk and colostrum induced expression of CD25 and CD69 on PBMCs. The ability to induce release of interleukins (IL) (IL-12, IL-1 beta and IL-10) and tumor necrosis factor-alpha was confined only to milk, while colostrum was devoid of this capacity. Finally, both colostrum and milk induced nitric oxide (NO) release from PBMCs but milk exhibited a greater capacity than colostrum in NO generation. Taken together, these immunological activities exerted by both colostrum and milk from donkeys may be useful in the treatment of human immune-related diseases. In particular, NO induction by donkey's milk may be very useful in the prevention of atherosclerosis, being a strong vasodilator and an effective antimicrobial agent since pathogens and/or their products may play a proatherogenic role.

Red wine consumption and prevention of atherosclerosis: an in vitro model using human peripheral blood mononuclear cells.

Evidence has been provided that red wine possesses antiatherogenic activities in virtue of its content in polyphenols (flavonoids and non-flavonoids substances). Here, some red wines (Negroamaro, Primitivo and Lambrusco) were tested for their ability to trigger nitric oxide (NO) production from human healthy peripheral blood mononuclear cells (PBMC). Negroamaro was the strongest inducer of NO from PBMC and deprivation of polyphenols did not influence its NO generation capacity. This fact supports the involvement of polyphenols in the NO production even in the absence of alcohol, which also per se does not exert any significant activity. These results are also corroborated by the evidence that PBMC inducible-nitric oxide synthase expression occurred by the effect of samples containing polyphenols but this expression was very weak when polyphenols were removed from the whole Negroamaro. In synthesis, flavonoids and resveratrol, major constituents of red wine, once absorbed at intestinal level, enter circulation and trigger monocytes for NO production. To the best of our knowledge, this is the first demonstration of a direct effect of red wine on monocytes for NO release to occur. On the other hand, also the macrophage contingent from gut-associated lymphoid tissue can contribute to NO generation, besides the aliquot produced by endothelial cells, as previously demonstrated by various authors. Taken together, these results support the concept that moderate intake of red wine can prevent atherosclerosis via production of NO, a potent vasodilator of terminal vessels.

New insights into the biological and clinical significance of fecal calprotectin in inflammatory bowel disease.

Nowadays, calprotectin, a cytoplasmatic protein, released by activated neutrophilic polymorphonuclear cells (PMN) and/or monocytes-macrophages (MØ), is considered a good indicator of inflammation in several diseases. Accordingly, fecal calprotectin represents a good predictor of clinical relapse in ulcerative colitis (UC) patients, whereas conflicting results have been reported in Crohn's disease (CD) patients. In our study, in 76 IBD patients (29 CD and 47 UC) fecal calprotectin has been evaluated by a commercial ELISA kit. Results demonstrate that levels of this protein in the stool are significantly more elevated in active CD and UC patients than in normal volunteers. In quiescent CD and UC a trend to higher levels of calprotectin than in the normal counterpart is, however, evident. These data suggest that a low-grade inflammation of the intestinal wall is always present in CD and UC patients, which may predict a clinical relapse risk. In the same group of patients calprotectin levels also were analyzed according to sex and age. A trend to higher values of calprotectin was present in male patients with active or quiescent CD than in their female counterparts. Only in UC patients in remission a trend to calprotectin increase was more marked in the male group than in the female counterpart. When CD and UC patients were divided up according to age, calprotectin positivity peaked between 30-39 years in active CD patients, while in quiescent CD maximum positivity was between 40 and 49 years. However, in both active and quiescent UC patients, calprotectin positivity increased with age. The more precocious detectability of fecal calprotectin in CD patients, as a marker of intestinal mucosa inflammation, may be related to the different histopathology of the two diseases (CD versus UC). However, reduced PMN and/or MØ trafficking from peripheral blood to intestinal mucosa with age by effects of chronic treatment should not be ignored in CD patients.

Ablation of T-helper 1 cell derived cytokines and of monocyte-derived tumor necrosis factor-alpha in hereditary hemorrhagic telangiectasia: immunological consequences and clinical considerations.

Experimental evidences on the adaptive immune response in patients with hereditary hemorragic telagiectasia (HHT) are lacking. Here, we report in 9 patients with HHT a multiple deficit involving the intracellular expression of T helper (h)1-derived cytokines [Interferon (IFN)-gamma, Interleukin (IL)-2 and Tumor Necrosis Factor (TNF)-alpha] and of monocyte-derived TNF-alpha. On the other hand, percentages of Th2-derived cytokines (IL-4, IL-5 and IL-10) were normal or, in some cases, above normality. Quite interestingly, monocyte-derived IL-10 was detectable in 5 out of 9 patients in a percentage of cells comparable to controls or exceeding normal levels. Taken together, these data point out, in HHT, an ablation of Th1-responses, while Th2-type cytokines are preserved, thus exerting either a suppressive effect on Th1-cells (via IL-4 and IL-10) or an antiinflammatory response on monocyte-derived TNF-alpha (via IL-10). Furthermore, monocyte-derived IL-10 may also contribute to the antiinflammatory activity seen in HHT. According to current literature even if patients with HHT do not exhibit certain diseases, such as autoimmune diseases, cancer and abnormal responses to pathogens, the observed immune deficits need to be diagnosed and therapeutically corrected.

Involvement of the transforming growth factor beta in the pathogenesis of hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel alterations such as dilatation of postcapillary venules and arterio-venous communications, which account for the major clinical manifestations of the disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively, depending the former on endoglin mutations and the latter on activin receptor-like kinase 1 (ALK-1) mutations. Both endoglin and ALK-1 bind to the transforming growth factor (TGF) superfamily which, physiologically, regulates the activities of endothelial cells and also those related to the extracellular matrix. In this review, the salient features of TGF-beta will be outlined with special reference to its activity on the immune system and on tumorigenesis. Furthermore, the involvement of TGF-beta in the pathogenesis of some gastrointestinal diseases will be discussed and, in particular, in the course of liver disease, Helicobacter pylori infection and inflammatory bowel disease. In the light of these data and of animal model of HHT, the potential risk of developing other diseases in HHT patients will be discussed.

Do fish thrombocytes play an immunological role? Their cytoenzymatic profiles and function during an accidental piscine candidiasis in aquarium.

Fish (F) thrombocytes (THRs) from healthy trouts were studied in terms of cytoenzyme expression. FTHRs were positive to acid periodic of shiff (PAS) and acid phosphatase (ac. phos.) without tartaric acid (-TA) stainings, as well to alkaline phosphatase. However, when compared with autologous macrophages (M psi's), they were negative to naphthol cloroacetate esterase (AS-D), alpha-naphthyl acetate esterase (Anae), peroxidase (perox) and control ac. phos. with tartaric acid (+TA) stainings, thus indicating a lack of typical lysosomial enzymes. This evidence supports the notion that FTHRs are not true digesting cells. Quite interestingly, trouts and human M psi's were positive for PAS, AS-D, Anae, and perox stainings, thus confirming that cellular cytochemistries are maintained across evolution as their phagocytic functions. Additionally, blood films from trouts, accidentally infected with Candida albicans in aquarium, were morphologically analyzed. Actually, FTHRs interact with erythrocytes, potentiating the formation of rosettes around a central Mpsi. Polymorph nuclear cells and lymphocytes are present in these cellular aggregates, thus suggesting that FTHRs may represent a link between innate and adaptive immunity.