Balneotherapy using thermal mineral water baths and dermatological diseases: a systematic review.

Balneotherapy includes practices and methods using medically and legally recognized mineral-medicinal waters, muds and natural gases from natural springs for therapeutic purposes. One of the most widely used method in balneotherapy is bathing with thermal mineral water. In the course of the years, scientific community has produced an increasing number of evidences that this practice is an effective method for treating signs and symptoms of several pathologies such as rheumatic, cardiovascular and dermatological diseases. This systematic review is aimed at evaluating the effect of balneotherapy with thermal water baths as a treatment to manage signs and symptoms of patients affected by all types of dermatological diseases. The systematic review was conducted according to the PRISMA Statement, and its protocol was registered on PROSPERO platform (CRD42022295913). The research was performed on the databases Pubmed, Scopus, Web of Science and Cochrane. We included clinical trials evaluating the effects of balneotherapy using thermal mineral water baths for managing dermatological diseases in humans, published in English and Italian language. Eight studies were included, seven of them enrolled adults affected by psoriasis and one studied atopic dermatitis patients. The common result of all the articles included was a clear improvement of signs and symptoms of psoriasis and eczematous diseases after use of thermal mineral water baths. These effects seem to be strictly related to physical and chemical properties of thermal water used for balneotherapy. However, studies in this field are still limited to support robust evidence of the effectiveness of balneotherapy using thermal mineral water baths and often their quality is low. Thus, new clinical studies need to be carried out, using more correct methods for conducting the studies and for processing statistical data.

Balneotherapy for osteoarthritis: a systematic review.

This systematic review is aimed to evaluate the effects of balneotherapy with thermal mineral water for managing the symptoms and signs of osteoarthritis located at any anatomical site. The systematic review was conducted according to the PRISMA Statement. The following databases were consulted: PubMed, Scopus, Web of Science, Cochrane Library, DOAJ and PEDro. We included clinical trials evaluating the effects of balneotherapy as a treatment for patients with osteoarthritis, published in English and Italian language, led on human subjects. The protocol was registered in PROSPERO. Overall, 17 studies have been included in the review. All of these studies were performed on adults or elderly patients suffering from osteoarthritis localized to knees, hips, hands or lumbar spine. The treatment assessed was always the balneotherapy with thermal mineral water. The outcomes evaluated were pain, palpation/pressure sensibility, articular tenderness, functional ability, quality of life, mobility, deambulation, ability to climb stairs, medical objective and patients' subjective evaluation, superoxide dismutase enzyme activity, serum levels of interleukin-2 receptors. The results of all the included studies agree and demonstrated an improvement of all the symptoms and signs investigated. In particular, pain and quality of life were the main symptoms evaluated and both improved after the treatment with thermal water in all the studies included in the review. These effects can be attributed to physical and chemical-physical properties of thermal mineral water used. However, the quality of many studies resulted not so high due and, consequently, it is necessary to perform new clinical trial in this field using more correct methods for conducting the study and for processing statistical data.

Effect of Natural Deep Eutectic Solvents on trans-Resveratrol Photo-Chemical Induced Isomerization and 2,4,6-Trihydroxyphenanthrene Electro-Cyclic Formation.

trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations.

Pharmacokinetic properties of a novel formulation of S-adenosyl-L-methionine phytate.

S-adenosyl-L-methionine (SAM), the main endogenous methyl donor, is the adenosyl derivative of the amino acid methionine, which displays many important roles in cellular metabolism. It is widely used as a food supplement and in some countries is also marketed as a drug. Its interesting nutraceutical and pharmacological properties prompted us to evaluate the pharmacokinetics of a new form of SAM, the phytate salt. The product was administered orally to rats and pharmacokinetic parameters were evaluated by comparing the results with that obtained by administering the SAM tosylated form (SAM PTS). It was found that phytate anion protects SAM from degradation, probably because of steric hindrance exerted by the counterion, and that the SAM phytate displayed significant better pharmacokinetic parameters compared to SAM PTS. These results open to the perspective of the use of new salts of SAM endowed with better pharmacokinetic properties.

Pheomelanin Effect on UVB Radiation-Induced Oxidation/Nitration of l-Tyrosine.

Pheomelanin is a natural yellow-reddish sulfur-containing pigment derived from tyrosinase-catalyzed oxidation of tyrosine in presence of cysteine. Generally, the formation of melanin pigments is a protective response against the damaging effects of UV radiation in skin. However, pheomelanin, like other photosensitizing substances, can trigger, following exposure to UV radiation, photochemical reactions capable of modifying and damaging cellular components. The photoproperties of this natural pigment have been studied by analyzing pheomelanin effect on oxidation/nitration of tyrosine induced by UVB radiation at different pH values and in presence of iron ions. Photoproperties of pheomelanin can be modulated by various experimental conditions, ranging from the photoprotection to the triggering of potentially damaging photochemical reactions. The study of the photomodification of l-Tyrosine in the presence of the natural pigment pheomelanin has a special relevance, since this tyrosine oxidation/nitration pathway can potentially occur in vivo in tissues exposed to sunlight and play a role in the mechanisms of tissue damage induced by UV radiation.

Valorization of calcium phosphite waste as phosphorus fertilizer: Effects on green manure productivity and soil properties.

The potential to use calcium phosphite (Ca-Phi) as phosphorus (P) fertilizer may represent an effective recycling of P-containing by-products. A greenhouse experiment was conducted to investigate the effect of Ca-Phi (38 kg P ha-1) on soil properties and the growth parameters of four green manure species in clay and sandy soils using Ca-Phi, TSP (triple superphosphate) and control (no fertilization) as treatments. Eight weeks after sowing, we measured aboveground biomass yield, phosphite (Phi) concentration in plant biomass, different soil P pools as well as microbial biomass nutrients. Compared to control, the addition of Ca-Phi did not negatively affect green manure yield, except for lupine (Lupinus albus L.) in clay soil. The Phi concentration in plant biomass varied across species and soil type with a maximum concentration of about 400 mg Phi kg-1 for mustard (Brassica juncea L.) in clay soil. Compared to control, TSP and Ca-Phi fertilization had a similar effect on different P pools and microbial biomass nutrients (C, N and P) although the response was soil-type dependent. In the sandy soil, after Ca-Phi addition the amount of available P (PNHCO3) increased to the same extent as in the TSP treatment (i.e. around 6 mg P kg-1) suggesting that Ca-Phi was, at least partly, oxidized. In the clay soil with high P fixing capacity, Ca-Phi promoted higher PNaHCO3 than TSP likely due to different solubility of chemical P forms. Additional studies are however required to better understand soil microbial responses and to quantify the P agronomical efficiency for the following crop under Ca-Phi fertilization.

Legacy effect of green manure crops fertilized with calcium phosphite on maize production and soil properties.

Recycling phosphorus (P) is crucial to meet future P demand for crop production. We investigated the possibility to use calcium phosphite (Ca-Phi) waste, an industrial by-product, as P fertilizer following the oxidation of phosphite (Phi) to phosphate (Pi) during green manure (GM) cropping in order to target P nutrition of subsequent maize crop. In a greenhouse experiment, four GM crops were fertilized (38 kg P ha-1) with Ca-Phi, triple super phosphate (TSP) or without P (Control) in sandy and clay soils. The harvested GM biomass (containing Phi after Ca-Phi fertilization) was incorporated into the soil before maize sowing. Incorporation of GM residues containing Phi slowed down organic carbon mineralization in clay soil and mass loss of GM residues in sandy soil. Microbial enzymatic activities were affected by Ca-Phi and TSP fertilization at the end of maize crop whereas microbial biomass was similarly influenced by TSP and Ca-Phi in both soils. Compared to Control, Ca-Phi and TSP increased similarly the available P (up to 5 mg P kg-1) in sandy soil, whereas in clay soil available P increased only with Ca-Phi (up to 6 mg P kg-1), indicating that Phi oxidation occurred during GM crops. Accordingly, no Phi was found in maize biomass. However, P fertilization did not enhance aboveground maize productivity and P export, likely because soil available P was not limiting. Overall, our results indicate that Ca-Phi might be used as P source for a subsequent crop since Phi undergoes oxidation during the preliminary GM growth.

Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity.

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes' size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02-1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76-1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.

Green Route for the Isolation and Purification of Hyrdoxytyrosol, Tyrosol, Oleacein and Oleocanthal from Extra Virgin Olive Oil.

Extra virgin olive oil (EVOO) phenols represent a significant part of the intake of antioxidants and bioactive compounds in the Mediterranean diet. In particular, hydroxytyrosol (HTyr), tyrosol (Tyr), and the secoiridoids oleacein and oleocanthal play central roles as anti-inflammatory, neuro-protective and anti-cancer agents. These compounds cannot be easily obtained via chemical synthesis, and their isolation and purification from EVOO is cumbersome. Indeed, both processes involve the use of large volumes of organic solvents, hazardous reagents and several chromatographic steps. In this work we propose a novel optimized procedure for the green extraction, isolation and purification of HTyr, Tyr, oleacein and oleocanthal directly from EVOO, by using a Natural Deep Eutectic Solvent (NaDES) as an extracting phase, coupled with preparative high-performance liquid chromatography. This purification method allows the total recovery of the four components as single pure compounds directly from EVOO, in a rapid, economic and ecologically sustainable way, which utilizes biocompatible reagents and strongly limits the use or generation of hazardous substances.

One- and Two-Electron Oxidations of ß-Amyloid25-35 by Carbonate Radical Anion (CO3•-) and Peroxymonocarbonate (HCO4-): Role of Sulfur in Radical Reactions and Peptide Aggregation.

The ß-amyloid (Aß) peptide plays a key role in the pathogenesis of Alzheimer's disease. The methionine (Met) residue at position 35 in Aß C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aß most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aß25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4-, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•-). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aß to aggregate. Conversely, CO3•- causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS•+). The formation of this transient reactive intermediate during Aß oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation.

Thiotaurine: From Chemical and Biological Properties to Role in H2S Signaling.

In the last decade thiotaurine, 2-aminoethane thiosulfonate, has been investigated as an inflammatory modulating agent as a result of its ability to release hydrogen sulfide (H2S) known to play regulatory roles in inflammation. Thiotaurine can be included in the "taurine family" due to structural similarity to taurine and hypotaurine, and is characterized by the presence of a sulfane sulfur moiety. Thiotaurine can be produced by different pathways, such as the spontaneous transsulfuration between thiocysteine - a persulfide analogue of cysteine - and hypotaurine as well as in vivo from cystine. Moreover, the enzymatic oxidation of cysteamine to hypotaurine and thiotaurine in the presence of inorganic sulfur can occur in animal tissues and last but not least thiotaurine can be generated by the transfer of sulfur from mercaptopyruvate to hypotaurine catalyzed by a sulfurtransferase. Thiotaurine is an effective antioxidant agent as demonstrated by its ability to counteract the damage caused by pro-oxidants in the rat. Recently, we observed the influence of thiotaurine on human neutrophils functional responses. In particular, thiotaurine has been found to prevent human neutrophil spontaneous apoptosis suggesting an alternative or additional role to its antioxidant activity. It is likely that the sulfane sulfur of thiotaurine may modulate neutrophil activation via persulfidation of target proteins. In conclusion, thiotaurine can represent a biologically relevant sulfur donor acting as a biological intermediate in the transport, storage and release of sulfide.

The Interaction of Hypotaurine and Other Sulfinates with Reactive Oxygen and Nitrogen Species: A Survey of Reaction Mechanisms.

Considerable strides have been made in understanding the oxidative mechanisms involved in the final steps of the cysteine pathway leading to taurine. The oxidation of sulfinates, hypotaurine and cysteine sulfinic acid, to the respective sulfonates, taurine and cysteic acid, has never been associated with any specific enzyme. Conversely, there is strong evidence that in vivo formation of taurine and cysteic acid is the result of sulfinate interaction with a variety of biologically relevant oxidants. In the last decade, many experiments have been performed to understand whether peroxynitrite, nitrogen dioxide and carbonate radical anion could be included in the biologically relevant reactive species capable of oxidizing sulfinates. Thanks to this work, it has been possible to highlight two possible reaction mechanisms (direct and indirect reaction) of sulfinates with reactive oxygen and nitrogen species.The sulfinates oxidation, mediated by peroxynitrite, is an example of both reaction mechanisms: through a two-electron-direct-reaction with peroxynitrite or through a one-electron-indirect-transfer reaction. In the indirect mechanism, the peroxynitrite homolysis releases hydroxyl and nitrogen dioxide radical and in addition the degradation of short-lived adduct formed by peroxynitrite and CO2 can generate carbonate radical anion. The reaction of hypotaurine and cysteine sulfinic acid with peroxynitrite-derived radicals is accompanied by extensive oxygen uptake with the generation of transient intermediates, which can begin a reaction by an oxygen-dependent mechanism with the sulfonates, taurine, and cysteic acid as final products. Due to pulse radiolysis studies, it has been shown that transient sulfonyl radicals (RSO2•) have been produced during the oxidation of both sulfinates by one-electron transfer reaction.The purpose is to analyze all the aspects of the reactive mechanism in the sulfinic group oxidation of hypotaurine and cysteine sulfinic acid through the results obtained from our laboratory in recent years.

Carbonate Anion Radical Generated by the Peroxidase Activity of Copper-Zinc Superoxide Dismutase: Scavenging of Radical and Protection of Enzyme by Hypotaurine and Cysteine Sulfinic Acid.

Copper-zinc superoxide dismutase (SOD) is considered one of the most important mammalian antioxidant defenses and plays a relevant role due to its main function in catalyzing the dismutation of superoxide anion to oxygen and hydrogen peroxide. However, interaction between SOD and H2O2 produced a strong copper-bound oxidant (Cu(II)•OH) that seems able to contrast the self-inactivation of the enzyme or oxidize other molecules through its peroxidase activity. The bicarbonate presence enhances the peroxidase activity and produces the carbonate anion radical (CO3•-). CO3•- is a freely diffusible reactive species capable of oxidizing several molecules that are unwieldy to access into the reactive site of the enzyme. Cu(II)•OH oxidizes bicarbonate to the CO3•-, which spreads out of the binding site and oxidizes hypotaurine and cysteine sulfinic acid to the respective sulfonates through an efficient reaction. These findings suggest a defense role for sulfinates against the damage caused by CO3•- . The effect of hypotaurine and cysteine sulfinic acid on the CO3•--mediated oxidation of the peroxidase probe ABTS to ABTS cation radical (ABTS•+) has been studied. Both sulfinates are able to inhibit the oxidation of ABTS mediated by CO3•-. The effect of hypotaurine and cysteine sulfinic acid against SOD inactivation by H2O2 (~42% protection of enzyme activity) has also been investigated. Interestingly, hypotaurine and cysteine sulfinic acid partially avoid the H2O2-mediated SOD inactivation, suggesting that the two sulfinates may have access to the SOD reactive site and preserve it by reacting with the copper-bound oxidant. In this way hypotaurine and cysteine sulfinic acid not only intercept CO3•- which could move out from the reactive site and cause oxidative damage, but also prevents the inactivation of SOD.

A Proteomic Approach to Study the Effect of Thiotaurine on Human Neutrophil Activation.

Thiotaurine, a thiosulfonate related to taurine and hypotaurine, is formed by a metabolic process from cystine and generated by a transulfuration reaction between hypotaurine and thiocysteine. Thiotaurine can produce hydrogen sulfide (H2S) from its sulfane sulfur moiety. H2S is a gaseous signaling molecule which can have regulatory roles in inflammatory process. In addition, sulfane sulfur displays the capacity to reversibly bind to other sulfur atoms. Thiotaurine inhibits PMA-induced activation of human neutrophils, and hinders neutrophil spontaneous apoptosis. Here, we present the results of a proteomic approach to study the possible effects of thiotaurine at protein expression level. Proteome analysis of human neutrophils has been performed comparing protein extracts of resting or PMA-activated neutrophils in presence or in absence of thiotaurine. In particular, PMA-stimulated neutrophils showed high level of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression compared to the level of the same glycolytic enzyme in the resting neutrophils. Conversely, decreased expression of GAPDH has been observed when human neutrophils were incubated with 1 mM thiotaurine before activation with PMA. This result, confirmed by Western blot analysis, suggests again that thiotaurine shows a bioactive role in the mechanisms underlying the inflammatory process, influencing the energy metabolism of activated leukocytes and raises the possibility that thiotaurine, acting as a sulfur donor, could modulate neutrophil activation via persulfidation of target proteins, such as GAPDH.

HPLC Determination of Bioactive Sulfur Compounds, Amino Acids and Biogenic Amines in Biological Specimens.

There is an increasing interest for analytical methods aimed to detect biological sulfur-containing amines, because of their involvement in human diseases and metabolic disorders. This work describes an improved HPLC method for the determination of sulfur containing amino acids and amines from different biological matrices. We optimized a pre-column derivatization procedure using dabsyl chloride, in which dabsylated products can be monitored spectrophotometrically at 460 nm. This method allows the simultaneous analysis of biogenic amines, amino acids and sulfo-amino compounds including carnosine, dopamine, epinephrine, glutathione, cysteine, taurine, lanthionine, and cystathionine in brain specimens, urines, plasma, and cell lysates. Moreover, the method is suitable for the study of physiological and non-physiological derivatives of taurine and glutathione such as hypotaurine, homotaurine, homocysteic acid and S-acetylglutathione. The present method displays good efficiency of derivatization, having the advantage to give rise to stable products compared to other derivatizing agents such as o-phthalaldehyde and dansyl chloride.With this method, we provide a tool to study sulfur cycle from a metabolic point of view in relation to the pattern of biological amino-compounds, allowing researchers to get a complete scenario of organic sulfur and amino metabolism in tissues and cells.

Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and lipoprotein metabolism.

The consequences of angiopoietin-like protein 3 (ANGPTL3) deficiency on postprandial lipid and lipoprotein metabolism has not been investigated in humans. We studied 7 homozygous (undetectable circulating ANGPTL3 levels) and 31 heterozygous (50% of circulating ANGPTL3 levels) subjects with familial combined hypolipidemia (FHBL2) due to inactivating ANGPTL3 mutations in comparison with 35 controls. All subjects were evaluated at fasting and during 6 h after a high fat meal. Postprandial lipid and lipoprotein changes were quantified by calculating the areas under the curve (AUCs) using the 6 h concentration data. Plasma changes of ß-hydroxybutyric acid (ß-HBA) were measured as marker of hepatic oxidation of fatty acids. Compared with controls, homozygotes showed lower incremental AUCs (iAUCs) of total TG (-69%, P < 0.001), TG-rich lipoproteins (-90%, P < 0.001), apoB-48 (-78%, P = 0.032), and larger absolute increase of FFA (128%, P < 00.1). Also, heterozygotes displayed attenuated postprandial lipemia, but the difference was significant only for the iAUC of apoB-48 (-28%; P < 0.05). During the postprandial period, homozygotes, but not heterozygotes, showed a lower increase of ß-HBA. Our findings demonstrate that complete ANGPTL3 deficiency associates with highly reduced postprandial lipemia probably due to faster catabolism of intestinally derived lipoproteins, larger expansion of the postprandial FFA pool, and decreased influx of dietary-derived fatty acids into the liver. These results add information on mechanisms underlying hypolipidemia in FHBL2.

5-S-cysteinyldopamine neurotoxicity: Influence on the expression of α-synuclein and ERp57 in cellular and animal models of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is still unclear in spite of extensive investigations. It has been hypothesized that 5-S-cysteinyldopamine (CysDA), a catechol-thioether metabolite of dopamine (DA), could be an endogenous parkinsonian neurotoxin. To gain further insight into its role in the neurodegenerative process, both CD1 mice and SH-SY5Y neuroblastoma cells were treated with CysDA, and the data were compared with those obtained by the use of 6-hydroxydopamine, a well-known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long-lasting depletion of DA, providing evidence of in vivo neurotoxicity of CysDA. Both in mice and in SH-SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and glutathione depletion, and affected the expression of two proteins, α-synuclein (α-Syn) and ERp57, whose levels are modulated by oxidative insult. Real-time PCR experiments support these findings, indicating an upregulation of both ERp57 and α-Syn expression. α-Syn aggregation was also found to be modulated by CysDA treatment. The present work provides a solid background sustaining the hypothesis that CysDA is involved in parkinsonian neurodegeneration by inducing extensive oxidative stress and protein aggregation.

Thiotaurine prevents apoptosis of human neutrophils: a putative role in inflammation.

Thiotaurine, a metabolic product of cystine, contains a sulfane sulfur atom that can be released as H(2)S, a gaseous molecule with a regulatory activity on inflammatory responses. The influence of thiotaurine on human leukocyte spontaneous apoptosis has been evaluated by measuring caspase-3 activity in human neutrophils. Addition of 100 µM thiotaurine induced a 55% inhibition of caspase-3 activity similar to that exerted by 100 µM H(2)S. Interestingly, in the presence of 1 mM GSH, an increase of the inhibition of apoptosis by thiotaurine has been observed. These results indicate that the bioactivity of thiotaurine can be modulated by GSH, which promotes the reductive breakdown of the thiosulfonate generating H(2)S and hypotaurine. As thiotaurine is able to incorporate reversibly reduced sulfur, it is suggested that the biosynthesis of this thiosulfonate could be a means to transport and store H(2)S.

Natural Mineral Water and Diuresis: A Systematic Review.

The present systematic review is aimed at evaluating the diuretic effects determined according to the natural mineral water consumption on healthy individuals. This systematic review has been performed following the guidelines of the PRISMA (preferred reporting items for systematic reviews and meta-analyses) Statement, investigating PubMed, Scopus, Web of Science and Cochrane Library from inception to November 2022. Studies performed both on animals and on humans were considered. After screening, a total of 12 studies have been identified. Of these, 11 studies were performed in Italy and 1 in Bulgaria. The time range of publication is very wide, ranging from 1962 to 2019 for human studies and from 1967 to 2001 for animal studies. All the included studies found an increase in diuresis determined according to the consumption of natural mineral water, in some cases after just one administration of the tested water. However, the quality of the studies is not so high, especially for the research conducted many years ago. Thus, it would be desirable to carry out new clinical studies using more appropriate methodological approaches and more refined methods of statistical data processing.

Formation of 3-nitrotyrosine by riboflavin photosensitized oxidation of tyrosine in the presence of nitrite.

The results of the present investigation show the susceptibility of tyrosine to undergo visible light-induced photomodification to 3-nitrotyrosine in the presence of nitrite and riboflavin, as sensitizer. By changing H2O by D2O, it could be established that singlet oxygen has a minor role in the reaction. The finding that nitration of tyrosine still occurred to a large extent under anaerobic conditions indicates that the process proceeds mainly through a type I mechanism, which involves the direct interaction of the excited state of riboflavin with tyrosine and nitrite to give tyrosyl radical and nitrogen dioxide radical, respectively. The tyrosyl radicals can either dimerize to yield 3,3'-dityrosine or combine with nitrogen dioxide radical to form 3-nitrotyrosine. The formation of 3-nitrotyrosine was found to increase with the concentration of nitrite added and was accompanied by a decrease in the recovery of 3,3'-dityrosine, suggesting that tyrosine nitration competes with dimerization reaction. The riboflavin photosensitizing reaction in the presence of nitrite was also able to induce nitration of tyrosine residues in proteins as revealed by the spectral changes at 430 nm, a characteristic absorbance of 3-nitrotyrosine, and by immunoreactivity using 3-nitrotyrosine antibodies. Since riboflavin and nitrite are both present endogenously in living organism, it is suggested that this pathway of tyrosine nitration may potentially occur in tissues and organs exposed to sunlight such as skin and eye.