Publications by authors named "Anna Teresa Palatucci"

14 Publications

  • Page 1 of 1

Effect of a Weight Loss Program on Biochemical and Immunological Profile, Serum Leptin Levels, and Cardiovascular Parameters in Obese Dogs.

Front Vet Sci 2020 6;7:398. Epub 2020 Aug 6.

Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.

This study aimed to investigate the effects of a weight loss program (WLP) on biochemical and immunological profile, and cardiovascular parameters in a cohort of dogs with naturally occurring obesity. Eleven obese dogs [body condition scoring (BCS), ≥7/9] were enrolled into the study and underwent clinical and cardiovascular examination, and blood testing before (T0) and after 6 months (T1) of WLP. Eleven normal weight (BCS, 4/5) healthy dogs were used as a control (CTR) group. Compared to the CTR group, at T0 obese dogs expressed higher serum leptin concentrations ( < 0.0005) that significantly decreased after weight loss ( < 0.005) but remained higher than the CTR group. Furthermore, obese dogs showed considerably lower levels ( < 0.0005) of regulatory T cell (Treg) compared to the CTR group, but they did not change after weight loss at T1. In obese dogs, tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations were substantially reduced at T1 ( < 0.0001 and < 0.005). Regarding the cardiovascular parameters, only one obese dog was hypertensive at T0, and systolic blood pressure values showed no significant differences at the end of the WLP. The ratio of interventricular septal thickness in diastole to left ventricle internal diameter in diastole (IVSd/LVIDd) was significantly greater in obese dogs at T0 than in the CTR group ( < 0.005). It decreased after weight loss ( < 0.05). In obese dogs, troponin I level significantly reduced with weight loss ( < 0.05), while endothelin-1 level did not differ statistically. The results suggest that the immune dysregulation in the presence of high leptin levels and reduced number of Treg could affect obese dogs as well as humans. Based on our findings, we may speculate that a more complete immune-regulation restore could be obtained by a greater reduction in fat mass and a longer-term WLP. Finally, left ventricular remodeling may occur in some obese dogs. However, in canine species, further studies are needed to investigate the impact of obesity and related WLP on cardiovascular system.
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http://dx.doi.org/10.3389/fvets.2020.00398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424025PMC
August 2020

T1D progression is associated with loss of CD3CD56 regulatory T cells that control CD8 T cell effector functions.

Nat Metab 2020 02 17;2(2):142-152. Epub 2020 Feb 17.

Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale G. Salvatore, Consiglio Nazionale delle Ricerche, Naples, Italy.

An unresolved issue in autoimmunity is the lack of surrogate biomarkers of immunological self-tolerance for disease monitoring. Here, we show that peripheral frequency of a regulatory T cell population, characterized by the co-expression of CD3 and CD56 molecules (T), is reduced in subjects with new-onset type 1 diabetes (T1D). In three independent T1D cohorts, we find that low frequency of circulating T cells is associated with reduced β-cell function and with the presence of diabetic ketoacidosis. As autoreactive CD8 T cells mediate disruption of insulin-producing β-cells, we demonstrate that T cells can suppress CD8 T cell functions by reducing levels of intracellular reactive oxygen species. The suppressive function, phenotype and transcriptional signature of T cells are also altered in T1D children. Together, our findings indicate that T cells constitute a regulatory cell population that controls CD8 effector functions, whose peripheral frequency may represent a traceable biomarker for monitoring immunological self-tolerance in T1D.
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http://dx.doi.org/10.1038/s42255-020-0173-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272221PMC
February 2020

Clinical and Immunological Response in Dogs Naturally Infected by Treated with a Nutritional Supplement.

Animals (Basel) 2019 Jul 30;9(8). Epub 2019 Jul 30.

Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, 80138 Napoli NA, Italy.

The use of nutraceuticals as immunomodulators in the treatment of visceral leishmaniasis has generated interest in the current approaches to treat the disease. In this clinical and immunological study, we investigated whether the administration of a nutritional supplement mediates the immune-modulatory response in canine leishmaniosis (CL) and improves the clinical outcome of the disease. With this purpose, we analysed T lymphocyte subsets in peripheral blood (PB) of 12 dogs naturally infected by , following treatment with a nutritional supplement. The regulatory T (Treg) cells and the T helper (Th) 1 population were specifically evaluated. The animals underwent complete clinical examination and blood sample collection for haematological, biochemical, serological and immunological analysis before treatment (T0), one month (T30) and 3 months (T90) after the onset of the nutraceutical supplementation. We observed that nutraceutical supplementation was associated with immunomodulation of Th1 response and significant clinical improvement of the animals. No side effects were observed. Therefore, a potential supportive role for the nutraceutical supplement during canine leishmaniasis is proposed.
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http://dx.doi.org/10.3390/ani9080501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721201PMC
July 2019

Circulating regulatory T cells (Treg), leptin and induction of proinflammatory activity in obese Labrador Retriever dogs.

Vet Immunol Immunopathol 2018 Aug 7;202:122-129. Epub 2018 Jul 7.

Dipartimento di Scienze, Università della Basilicata, Via Nazario Sauro 85, 85100, Potenza, Italy; Dipartimento di Scienze Mediche Traslazionali, Università Federico II, Via Pansini 5, 80131, Napoli, Italy.

Over-nutrition and obesity have been associated with impaired immunity and low-grade inflammation in humans and mouse models. In this context, a causal role for unbalanced T regulatory cell (Treg)-dependent mechanisms has been largely suggested. Obesity is the most common nutritional disorder in dogs. However, it is not defined whether canine obesity may influence circulating Treg as well as if their number variation might be associated with the occurrence of systemic inflammation. The present study investigated the immune profile of healthy adult obese dogs belonging to the Labrador Retriever breed, in comparison with the normal weight counterpart. Indeed, obesity has been described as particularly evident in this dogs. With this purpose, 26 healthy dogs were enrolled and divided into two groups based on body condition score (BCS): controls (CTR: BCS 4-5) and obeses (OB: BCS ≥ 7). Our data indicate that adult obese Labrador Retrievers are characterised by the inverse correlation between leptin serum concentration and circulating Treg (CD4CD25Foxp3) levels. In addition, an increased number of cytotoxic T cell effectors (CD3CD8) and a higher IFN-γ production by cytotoxic T lymphocytes were observed in OB group. These results may provide new insights into the immunological dysregulation frequently associated to obesity in humans and still undefined in dogs.
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http://dx.doi.org/10.1016/j.vetimm.2018.07.004DOI Listing
August 2018

Oxytetracycline induces DNA damage and epigenetic changes: a possible risk for human and animal health?

PeerJ 2017 27;5:e3236. Epub 2017 Apr 27.

Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.

Background: Oxytetracycline (OTC), which is largely employed in zootechnical and veterinary practices to ensure wellness of farmed animals, is partially absorbed within the gastrointestinal tract depositing in several tissues. Therefore, the potential OTC toxicity is relevant when considering the putative risk derived by the entry and accumulation of such drug in human and pet food chain supply. Despite scientific literature highlights several OTC-dependent toxic effects on human and animal health, the molecular mechanisms of such toxicity are still poorly understood.

Methods: Here, we evaluated DNA damages and epigenetic alterations by quantitative reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, chromatin immuno-precipitation and Western blot analysis.

Results: We observed that human peripheral blood mononuclear cells (PBMCs) expressed DNA damage features (activation of ATM and p53, phosphorylation of H2AX and modifications of histone H3 methylation of lysine K4 in the chromatin) after the exposure to OTC. These changes are linked to a robust inflammatory response indicated by an increased expression of Interferon (IFN)- and type 1 superoxide dismutase (SOD1).

Discussion: Our data reveal an unexpected biological activity of OTC able to modify DNA and chromatin in cultured human PBMC. In this regard, OTC presence in foods of animal origin could represent a potential risk for both the human and animal health.
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http://dx.doi.org/10.7717/peerj.3236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410137PMC
April 2017

In Vitro Effects of Some Botanicals with Anti-Inflammatory and Antitoxic Activity.

J Immunol Res 2016 15;2016:5457010. Epub 2016 Aug 15.

Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy; Department of Science, University of Basilicata, 85100 Potenza, Italy.

Several extrinsic factors, like drugs and chemicals, can foster autoimmunity. Tetracyclines, in particular oxytetracycline (OTC), appear to correlate with the emergence of immune-mediated diseases. Accumulation of OTC, the elective drug for gastrointestinal and respiratory infectious disease treatment in broiler chickens, was reported in chicken edible tissues and could represent a potential risk for pets and humans that could assume this antibiotic as residue in meat or in meat-derived byproducts. We investigated the in vitro anti-inflammatory properties of a pool of thirteen botanicals as a part of a nutraceutical diet, with proven immunomodulatory activity. In addition, we evaluated the effect of such botanicals in contrasting the in vitro proinflammatory toxicity of OTC. Our results showed a significant reduction in interferon- (INF-) γ production by human and canine lymphocytes in presence of botanicals ((⁎) p < 0.05). Increased INF-γ production, dependent on 24-hour OTC-incubation of T lymphocytes, was significantly reduced by the coincubation with Haematococcus pluvialis, with Glycine max, and with the mix of all botanicals ((⁎) p < 0.05). In conclusion, the use of these botanicals was shown to be able to contrast OTC-toxicity and could represent a new approach for the development of functional foods useful to enhance the standard pharmacological treatment in infections as well as in preventing or reducing the emergence of inflammatory diseases.
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http://dx.doi.org/10.1155/2016/5457010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002466PMC
March 2017

An immune-modulating diet increases the regulatory T cells and reduces T helper 1 inflammatory response in Leishmaniosis affected dogs treated with standard therapy.

BMC Vet Res 2015 Dec 3;11:295. Epub 2015 Dec 3.

Department of Translational Medical Sciences, University of Naples Federico II, Via Pansini, 5, 80131, Naples, Italy.

Background: Clinical appearance and evolution of Canine Leishmaniosis (CL) are the consequence of complex interactions between the parasite and the genetic and immunological backgrounds. We investigated the effect of an immune-modulating diet in CL. Dogs were treated with anti- Leishmania pharmacological therapy combined with standard diet (SD Group) or with the immune-modulating diet (IMMD Group). CD3+ CD4+ Foxp3+ Regulatory T cells (Treg) and CD3+ CD4+ IFN-γ + T helper 1 (Th1) were analyzed by flow cytometry.

Results: All sick dogs showed low platelet number at diagnosis (T0). A platelet increase was observed after six months (T6) SD Group, with still remaining in the normal range at twelve months (T12). IMMD Group showed an increase in platelet number becoming similar to healthy dogs at T6 and T12. An increase of CD4/CD8 ratio was revealed in SD Group after three months (T3), while at T6 and at T12 the values resembled to T0. The increase in CD4/CD8 ratio at T3 was maintained at T6 and T12 in IMMD Group. A reduction in the percentage of Treg of all sick dogs was observed at T0. A recovery of Treg percentage was observed only at T3 in SD Group, while this effect disappeared at T6 and T12. In contrast, Treg percentage became similar to healthy animals in IMDD Group at T3, T6 and T12. Sick dogs showed an increase of Th1 cells at T0 as compared with healthy dogs. We observed the occurrence of a decrease of Th1 cells from T3 to T12 in SD Group, although a trend of increase was observed at T6 and T12. At variance, IMMD Group dogs showed a progressive decrease of Th1 cells, whose levels became similar to healthy controls at T6 and T12.

Conclusion: The immune-modulating diet appears to regulate the immune response in CL during the standard pharmacological treatment. The presence of nutraceuticals in the diet correlates with the decrease of Th1 cells and with the increase of Treg in sick dogs. Therefore, the administration of the specific dietary supplement improved the clinical response to the standard treatment in a model of CL.
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http://dx.doi.org/10.1186/s12917-015-0610-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669625PMC
December 2015

Use of larvae of the wax moth Galleria mellonella as an in vivo model to study the virulence of Helicobacter pylori.

BMC Microbiol 2014 Aug 27;14:228. Epub 2014 Aug 27.

Department of Molecular Medicine, Human Physiology Section, University of Pavia Medical School, Pavia, Italy.

Background: Helicobacter pylori is the first bacterium formally recognized as a carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized by the bacterium. H. pylori-induced gastroduodenal disease depends on the inflammatory response of the host and on the production of specific bacterial virulence factors. The study of Helicobacter pylori pathogenic action would greatly benefit by easy-to-use models of infection.

Results: In the present study, we examined the effectiveness of the larvae of the wax moth Galleria mellonella as a new model for H. pylori infection. G. mellonella larvae were inoculated with bacterial suspensions or broth culture filtrates from either different wild-type H. pylori strains or their mutants defective in specific virulence determinants, such as VacA, CagA, CagE, the whole pathogenicity island (PAI) cag, urease, and gamma-glutamyl transpeptidase (GGT). We also tested purified VacA cytotoxin. Survival curves were plotted using the Kaplan-Meier method and LD50 lethal doses were calculated. Viable bacteria in the hemocoel were counted at different time points post-infection, while apoptosis in larval hemocytes was evaluated by annexin V staining. We found that wild-type and mutant H. pylori strains were able to survive and replicate in G. mellonella larvae which underwent death rapidly after infection. H. pylori mutant strains defective in either VacA, or CagA, or CagE, or cag PAI, or urease, but not GGT-defective mutants, were less virulent than the respective parental strain. Broth culture filtrates from wild-type strains G27 and 60190 and their mutants replicated the effects observed using their respective bacterial suspension. Also, purified VacA cytotoxin was able to kill the larvae. The killing of larvae always correlated with the induction of apoptosis in hemocytes.

Conclusions: G. mellonella larvae are susceptible to H. pylori infection and may represent an easy to use in vivo model to identify virulence factors and pathogenic mechanisms of H. pylori. The experimental model described can be useful to screen a large number of clinical H. pylori strain and to correlate virulence of H. pylori strains with patients' disease status.
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http://dx.doi.org/10.1186/s12866-014-0228-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148543PMC
August 2014

T cell activation induces CuZn superoxide dismutase (SOD)-1 intracellular re-localization, production and secretion.

Biochim Biophys Acta 2014 Feb 31;1843(2):265-74. Epub 2013 Oct 31.

Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy. Electronic address:

Reactive oxygen species (ROS) behave as second messengers in signal transduction for a series of receptor/ligand interactions. A major regulatory role is played by hydrogen peroxide (H2O2), more stable and able to freely diffuse through cell membranes. Copper-zinc superoxide dismutase (CuZn-SOD)-1 is a cytosolic enzyme involved in scavenging oxygen radicals to H2O2 and molecular oxygen, thus representing a major cytosolic source of peroxides. Previous studies suggested that superoxide anion and H2O2 generation are involved in T cell receptor (TCR)-dependent signaling. Here, we describe that antigen-dependent activation of human T lymphocytes significantly increased extracellular SOD-1 levels in lymphocyte cultures. This effect was accompanied by the synthesis of SOD-1-specific mRNA and by the induction of microvesicle SOD-1 secretion. It is of note that SOD-1 increased its concentration specifically in T cell population, while no significant changes were observed in the "non-T" cell counterpart. Moreover, confocal microscopy showed that antigen-dependent activation was able to modify SOD-1 intracellular localization in T cells. Indeed, was observed a clear SOD-1 recruitment by TCR clusters. The ROS scavenger N-acetylcysteine (NAC) inhibited this phenomenon. Further studies are needed to define whether SOD-1-dependent superoxide/peroxide balance is relevant for regulation of T cell activation, as well as in the functional cross talk between immune effectors.
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http://dx.doi.org/10.1016/j.bbamcr.2013.10.020DOI Listing
February 2014

Regulatory T cells, Cytotoxic T lymphocytes and a T(H)1 cytokine profile in dogs naturally infected by Leishmania infantum.

Res Vet Sci 2013 Dec 22;95(3):942-9. Epub 2013 Aug 22.

Department of Veterinary Medicine and Animal Productions, Division of Internal Medicine, University of Naples Federico II, Via Delpino, 1, 80137 Naples, Italy.

Canine leishmaniasis caused by the protozoan parasite Leishmania infantum is a chronic systemic disease endemic in Mediterranean basin. The aim of the study is to investigate the immune profile of dogs naturally infected by Leishmania infantum. In order to address such issue, CD4(+) and CD8(+) lymphocyte T cell subsets, peripheral CD4(+)CD3(+)Foxp3(+) (Treg) levels and the presence of pro-inflammatory T cells have been assessed, in 45 infected dogs and in 30 healthy animals, by using immunofluorescence and flow cytometry detection. Animals were categorised according to their clinical-pathological status and their antibody titer at diagnosis. Results showing a significant increase of CD8(+)CD3(+) T lymphocytes, a reduced percentage of the T regulatory CD4(+)CD3(+)Foxp3(+) subset and a significant increase of T(H)1 cells, characterise the infected dogs, regardless of their antibody titer or the occurrence of clinical symptomatic disease. These data may provide new insights into the pathogenesis of immune-mediated alterations associated with canine leishmaniasis.
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http://dx.doi.org/10.1016/j.rvsc.2013.08.005DOI Listing
December 2013

Natural killer expansion, human leukocyte antigens-E expression and CD14(+) CD56(+) monocytes in a myelodysplastic syndrome patient.

Eur J Haematol 2013 Sep 28;91(3):265-9. Epub 2013 Jun 28.

Department of Science, University of Basilicata, Potenza, Italy; Department of Translational Medical Sciences, University of Naples "Federico II", Naples, Italy.

Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and possible evolution to acute leukemia. Occurrence of stem cell defects and of immune-mediated mechanisms was evidenced as relevant for pathophysiology of MDS. Here, we described one case of MDS patient carrying CD14(+) CD56(+) monocytes in bone marrow (BM), in the presence of a defective human leukocyte antigen (HLA)-E expression on peripheral blood (PB) cells and of natural killer (NK) cell expansion in PB and BM. The defective HLA-E expression and the NK expansion are proposed to be relevant for the pathogenesis of myelodysplasia in those patients showing CD14(+) CD56(+) monocytes in BM.
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http://dx.doi.org/10.1111/ejh.12152DOI Listing
September 2013

HLA-E and HLA class I molecules on bone marrow and peripheral blood polymorphonuclear cells of myelodysplatic patients.

Leuk Res 2013 Feb 3;37(2):169-74. Epub 2012 Oct 3.

Dipartimento di Scienze, Università della Basilicata, Potenza, Italy.

Relevance of immune-dysregulation for emergence, dominance and progression of dysplastic clones in myelodysplastic syndromes (MDS) was suggested, but valuable or predictive criteria on this involvement are lacking. We previously reported that reduced T-regulatory cells (Treg) and high CD54 expression on T cell identify a sub-group of patients in whom an immune-pathogenesis might be inferred. Here, we suggest the occurrence of immune-selection of dysplastic clones in a subgroup of MDS patients, with reduced HLA-I and HLA-E on PMN, and propose that an altered immune profile might represent a valuable criterion to classify Low/Int-1 patients on the basis of immune-pathogenesis of MDS.
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http://dx.doi.org/10.1016/j.leukres.2012.09.015DOI Listing
February 2013