Castelnovo ne'Monti, Italy
Castelnovo ne'Monti, Italy

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De Luca C.,Institute Krasoty Na Arbate | Gugliandolo A.,Messina University | Calabro C.,Messina University | Curro M.,Messina University | And 3 more authors.
Mediators of Inflammation | Year: 2015

Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A -2.5 kb (CCTTT)as well as Ser608Leu and NOS3 -786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 -786T>C polymorphisms. Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A -2.5 kb (CCTTT)allele represents a genetic determinant for FM/CFS, and the (CCTTT)allele discriminates MCS from SMCS patients. Instead, the (CCTTT)allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5 kb (CCTTT)polymorphism may be useful for differential diagnosis of various IEI. © 2015 Chiara De Luca et al.


PubMed | Active Longevity Clinic Institute Krasoty na Arbate, Dermatology Institute IDI IRCCS and Messina University
Type: | Journal: Mediators of inflammation | Year: 2015

Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A -2.5kb (CCTTT) n as well as Ser608Leu and NOS3 -786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 -786T>C polymorphisms. Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A -2.5kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5kb (CCTTT) n polymorphism may be useful for differential diagnosis of various IEI.


De Luca C.,Dermatology Institute IDI IRCCS | Scordo M.G.,Uppsala University Hospital | Cesareo E.,Dermatology Institute IDI IRCCS | Pastore S.,Dermatology Institute IDI IRCCS | And 11 more authors.
Toxicology and Applied Pharmacology | Year: 2010

Background: Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I/phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined. Objectives: We sought for genetic, immunological, and metabolic markers in MCS. Methods: We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy controls for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST, glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined. Results: Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased. Conclusions: Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS. © 2010 Elsevier Inc.


De Luca C.,Active Longevity Clinic Institute Krasoty Na Arbate | Chung Sheun Thai J.,39 Health | Raskovic D.,Dermatology Institute IDI IRCCS | Cesareo E.,Dermatology Institute IDI IRCCS | And 3 more authors.
Mediators of Inflammation | Year: 2014

Growing numbers of "electromagnetic hypersensitive" (EHS) people worldwide self-report severely disabling, multiorgan, non-specific symptoms when exposed to low-dose electromagnetic radiations, often associated with symptoms of multiple chemical sensitivity (MCS) and/or other environmental "sensitivity-related illnesses" (SRI). This cluster of chronic inflammatory disorders still lacks validated pathogenetic mechanism, diagnostic biomarkers, and management guidelines. We hypothesized that SRI, not being merely psychogenic, may share organic determinants of impaired detoxification of common physic-chemical stressors. Based on our previous MCS studies, we tested a panel of 12 metabolic blood redox-related parameters and of selected drug-metabolizing-enzyme gene polymorphisms, on 153 EHS, 147 MCS, and 132 control Italians, confirming MCS altered (P<0.05-0.0001) glutathione-(GSH), GSH-peroxidase/S-transferase, and catalase erythrocyte activities. We first described comparable - though milder - metabolic pro-oxidant/proinflammatory alterations in EHS with distinctively increased plasma coenzyme-Q10 oxidation ratio. Severe depletion of erythrocyte membrane polyunsaturated fatty acids with increased ω6/ω3 ratio was confirmed in MCS, but not in EHS. We also identified significantly (P=0.003) altered distribution-versus- control of the CYP2C191/2 SNP variants in EHS, and a 9.7-fold increased risk (OR: 95% C.I.=1.3-74.5) of developing EHS for the haplotype (null)GSTT1 + (null)GSTM1 variants. Altogether, results on MCS and EHS strengthen our proposal to adopt this blood metabolic/genetic biomarkers' panel as suitable diagnostic tool for SRI. © 2014 Chiara De Luca et al.


Daniela L.,Dermatology Institute IDI IRCCS | Alla P.,Dermatology Institute IDI IRCCS | Alla P.,Belarusian National Technical University | Maurelli R.,Dermatology Institute IDI IRCCS | And 8 more authors.
Mediators of Inflammation | Year: 2012

Edelweiss (Leontopodium alpinum Cass.) is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with leontopodic acid representing 55 ± 2 of the total phenolic fraction (ECC55), was characterized for anti-inflammatory properties in primary human keratinocytes (PHKs) and endotheliocytes (HUVECs). Inflammatory responses were induced by UVA+UVB, lipopolysaccharide (LPS), oxidized low-density lipoprotein (oxLDL), and a mixture of proinflammatory cytokines. Trichostatin A, a sirtuin inhibitor, was used to induce keratinocyte inflammatory senescence. ECC55 (1050 μg/mL) protected PHK from solar UV-driven damage, by enhancing early intracellular levels of nitric oxide, although not affecting UV-induced expression of inflammatory genes. Comparison of the dose-dependent inhibition of chemokine (IL-8, IP-10, MCP-1) and growth factor (GM-CSF) release from PHK activated by TNFα + IFNγ showed that leontopodic acid was mainly responsible for the inhibitory effects of ECC55. Sirtuin-inhibited cell cycle, proliferation, and apoptosis markers were restored by ECC55. The extract inhibited LPS-induced IL-6 and VCAM1 genes in HUVEC, as well as oxLDL-induced selective VCAM1 overexpression. Conclusion. Edelweiss cell cultures could be a valuable source of anti-inflammatory substances potentially applicable for chronic inflammatory skin diseases and bacterial and atherogenic inflammation. © 2012 Lulli Daniela et al.


Caccamo D.,Messina University | Cesareo E.,Dermatology Institute IDI IRCCS | Mariani S.,Dermatology Institute IDI IRCCS | Raskovic D.,Dermatology Institute IDI IRCCS | And 4 more authors.
Oxidative Medicine and Cellular Longevity | Year: 2013

In the environmental sensitivity-related illnesses (SRIs), multiple chemical sensitivity (MCS), chronic fatigue syndrome (FCS), and fibromyalgia (FM), the search for genetic polymorphisms of phase I/II xenobiotic-metabolizing enzymes as suitable diagnostic biomarkers produced so far inconclusive results, due to patient heterogeneity, geographic/ethnic differences in genetic backgrounds, and different methodological approaches. Here, we compared the frequency of gene polymorphisms of selected cytochrome P450 (CYP) metabolizing enzymes and, for the first time, the frequency of the xenobiotic sensor Aryl hydrocarbon receptor (AHR) in the three cohorts of 156 diagnosed MCS, 94 suspected MCS, and 80 FM/FCS patients versus 113 healthy controls. We found significantly higher frequency of polymorphisms CYP2C9.2, CYP2C93, CYP2C19ast;2, CYP2D6ast;4 and CYP2D6ast;41 in patients compared with controls. This confirms that these genetic variants represent a genetic risk factor for SRI. Moreover, the compound heterozygosity for CYP2C92 and 3 variants was useful to discriminate between either MCS or FM/CFS versus SMCS, while the PM 41/41 genotype discriminated between MCS and either SMCS or FM/CFS. The compound heterozygosity for CYP2C9 1/3 and CYP2D6 1/4 differentiated MCS and SMCS cases from FM/CFS ones. Interestingly, despite the distribution of the AHR Arg554Lys variant did not result significantly different between SRI cases and controls, it resulted useful for the discrimination between MCS and SMCS cases when considered within haplotypes in combination with CYP2C19 1/2 and CYP2D6 1/4. Results allowed us to propose the genotyping for these specific CYP variants, together with the AHR Arg554Lys variant, as reliable, cost-effective genetic parameters to be included in the still undefined biomarkers' panel for laboratory diagnosis of the main types of environmental-borne SRI. © 2013 Daniela Caccamo et al.


Korkina L.,Dermatology Institute IDI IRCCS | De Luca C.,Dermatology Institute IDI IRCCS | Pastore S.,Dermatology Institute IDI IRCCS
Annals of the New York Academy of Sciences | Year: 2012

In response to abiotic and biotic stressors, numerous polyphenols (PPs) are synthesized from phenylalanine by higher plants, amid many other plants that are poisonous for insects, birds, animals, and humans. PPs are also widely recognized by botanical dermatology as major plant constituents inducing allergic reactions, contact dermatitis, phytodermatoses, and photophytodermatoses. Notwithstanding these clinical observations, thousands of cosmetic/dermatological preparations based on PP-containing plant extracts or pure PPs emerge yearly with the claims of photoprotection, chemoprevention of skin tumors, anti-aging, wound healing, etc. However, because of their peculiar physical, chemical, and biological properties, PPs could be a double-edged sword for human skin, exerting both protective and damaging actions. Here, we distinguish direct and indirect anti- and pro-oxidant properties of PPs, their interactions with major xenobiotic metabolic systems and sensors/receptors of environmental hazards, anti- and proinflammatory potential, and photoprotection versus photosensitization. © 2012 New York Academy of Sciences.


PubMed | Dermatology Institute IDI IRCCS
Type: | Journal: Annals of the New York Academy of Sciences | Year: 2012

In response to abiotic and biotic stressors, numerous polyphenols (PPs) are synthesized from phenylalanine by higher plants, amid many other plants that are poisonous for insects, birds, animals, and humans. PPs are also widely recognized by botanical dermatology as major plant constituents inducing allergic reactions, contact dermatitis, phytodermatoses, and photophytodermatoses. Notwithstanding these clinical observations, thousands of cosmetic/dermatological preparations based on PP-containing plant extracts or pure PPs emerge yearly with the claims of photoprotection, chemoprevention of skin tumors, anti-aging, wound healing, etc. However, because of their peculiar physical, chemical, and biological properties, PPs could be a double-edged sword for human skin, exerting both protective and damaging actions. Here, we distinguish direct and indirect anti- and pro-oxidant properties of PPs, their interactions with major xenobiotic metabolic systems and sensors/receptors of environmental hazards, anti- and proinflammatory potential, and photoprotection versus photosensitization.

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