The role of integrative and complementary medicine in the management of breast cancer patients on behalf of the Integrative Medicine Research Group (IMRG).

The aim of this conference was to explain the role of integrative and complementary medicine in breast cancer patients. The topics covered are numerous and their peculiarities are the multidisciplinary characteristics of the researchers involved. The Integrative Medicine Research Group (IMRG) believes in the complementary and integrative approach in cancer patients to improve the quality of life in this particular setting.

[Menstruation, inflammation and comorbidities: implications for woman health]. / Mestruazione, inflammazione e comorbilità: implicazioni per la salute della donna.

Menstruation is the genital sign of systemic endocrine events. Heterogeneity of perimenstrual symptoms is associated with levels of inflammation, triggered by the fall of estrogens at genital and systemic level. Aim of the review is to concisely analyze the evidence on: 1) genital and systemic endocrine and inflammatory events associated with periods and perimenstrual symptoms; 2) rationale of intervention to reduce their intensity and impact on women's lives. This review of the literature, selected with a clinical perspective, supports the inflammatory basis of the menstrual event, triggered by the estrogens' and progesterone' fall. Moreover, the review analyzes the endocrine and inflammatory basis of perimenstrual pelvic and extrapelvic symptoms such as: menstrual pain, menstrual irregularities, premenstrual syndrome, gastrointestinal symptoms, catamenial headache, depression, perimenstrual myalgia, joint pain, allergies and asthma, heavy menstrual bleeding, associated ironless anemia, brain and behavioral consequences. Inflammation, with increase of cytokines and other markers, is modulated by the degranulation of mast cells at the basal level of the endometrium, in the blood, in all the organs where mast-cell are already activated from local pathologies and within the brain. The shift of inflammation from physiological to a pathologic intensity increases the severity of perimenstrual symptoms. Symptoms persist, moderately attenuated, also during the hormone free interval (HFI) in contraception. The HFI reduction from seven to two days significantly reduces menstrual inflammation and associated symptoms.

[Recurrent cystitis and vaginitis: role of biofilms and persister cells. From pathophysiology to new therapeutic strategies]. / Cristiti e vaginitis recidivanti: ruolo dei biofilm e delle persister cells. Dalla fisiopatologia a nuove strategie terapeutiche.

Recurrent vaginitis and cystitis are a daily challenge for the woman and the physician. The recurrence worsens the symptoms' severity, increases comorbidities, both pelvic (provoked vestibulodynia, bladder pain syndrome, levator ani hyperactivity, introital dyspareunia, obstructive constipation, chronic pelvic pain) and cerebral (neuroinflammation and depression), increases health costs, worsens the quality of life. Antibiotics increase the risk of bacterial resistences and devastate the ecosystems: intestinal, vaginal and mucocutaneous. Pathogenic biofilms are the (still) neglected etiology of recurrences. Biofilms are structured communities of bacteria and yeasts, protected by a self-produced polymeric matrix adherent to a living or inert structures, such as medical devices. Biofims can be intra or extracellular. Pathogens live in a resting state in the deep biofilm layers as "persister cells", resistant to antibiotics and host defences and ready to re-attack the host. The paper updates the evidence on biofilms and introduces new non-antibiotic strategies of preventing and modulating recurrent vaginitis and cystitis.

A prospective study to evaluate the efficacy of Cistiquer in improving lower urinary tract symptoms in females with urethral syndrome.

AIM: The aim of the study was to compare Cistiquer, a new phytotherapeutic product developed for chronic bladder inflammatory diseases, and intra-vesical administration of gentamicin plus betametasone, in females with urethral syndrome. METHODS: Between september 2013 and may 2014, 60 women with urethral syndrome and trigonitis were incuded in this study. Patients were randomly assigned to treatment with intra-vesical administration of betametasone 8 mg plus gentamicin 80 mg (group A), and oral administration of Cistiquer (group B) for 7 weeks. Before and after the therapeutic protocol, symptoms were assessed by three days voiding diary, the overactive bladder questionnaire short form and a ten points visual analogic scale adopted to assess the micturition discomfort. Histologic findings were assessed by the examination of specimens obtained by cold bladder biopsies of the bladder trigone at baseline in all the subjects. RESULTS: The two groups had significant and comparable symptoms improvement. However, the score obtained from the visual analogic scale decreased significantly only in the group submitted to oral therapy. Furthermore, in the group treated with endovesical approach, higher drop out rate and higher incidence of urinary infection were observed. CONCLUSION: Patients with urethral syndrome and trigonitis improved symptoms either with oral therapy with Cistiquer and with intra-vesical administration of gentamicin plus betametasone. However, treatment adherence resulted higher for patients treated by oral therapy and rate of adverse events resulted higher for those submitted to endovesical treatment.

Airway barrier dysfunction induced by exposure to carbon nanotubes in vitro: which role for fiber length?

Although carbon nanotubes (CNTs) are increasingly used, their biological effects are only incompletely characterized. However, experimental evidence suggests that the intratracheal instillation of CNTs causes the formation of interstitial granulomas and progressive pulmonary fibrosis in rodents. Using human epithelial Calu-3 cells as a model of airway epithelium in vitro, we have recently reported that the exposure to commercial multi-walled CNTs (MWCNTs) causes a progressive decrease of the transepithelial electrical resistance (TEER), pointing to a CNT-dependent impairment of the epithelial barrier function. To characterize better this behavior, we compared the effects of two types of MWCNTs and single-walled CNTs (SWCNTs) of different lengths on the TEER of Calu-3 monolayers. All the materials were used at a dose of 100 microg/mL corresponding to an exposure of 73 microg/cm(2) of cell monolayer. Only the longer MWCNTs and SWCNTs cause a significant decrease in TEER. To elucidate the mechanism underlying the changes in barrier function, the expression of the junction proteins occludin and ZO-1 has been also assessed. No significant decrease in the mRNA for either protein is detectable after the exposure to any type of CNTs. It is concluded that the impairment of barrier function in Calu-3 monolayers is a peculiar effect of CNTs endowed with clear cut fiber properties and is not referable to marked changes in the expression of junction proteins.

Calcified cysticercotic lesions and intractable epilepsy: a cross sectional study of 512 patients.

BACKGROUND: Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy. METHODS: A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non-contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non-neurocysticercosis groups according to previous diagnostic criteria. RESULTS: The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p<0.001). Isolated neurocysticercosis was found in only eight patients (1.56%). CONCLUSIONS: These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause-effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co-vary with a missing variable, such as socio-economic status.

Electronic communication in oligometallic complexes with ferrocene-based tris(1-pyrazolyl)borate ligands.

Ferrocene-based tris(1-pyrazolyl)borate ligands 1R-Li and 1R-Tl have been synthesized and used to generate a variety of heterotrinuclear transition metal complexes, 3R-M [R = H, SiMe(3), cyclohexyl, (cyclohexyl)methyl, phenyl; M(II) = Mn, Fe, Co, Ni, Cu, Zn]. The poor solubility of 3H-M is greatly enhanced by the introduction of large organic substituents into the 4-positions of all pyrazolyl rings. The unsubstituted ligand 1H-Li and the trinuclear complex 3Cym-Cu [Cym = (cyclohexyl)methyl] have been investigated by X-ray crystallography. 1H-Li, which represents the first example of a structurally characterized lithium tris(1-pyrazolyl)borate, forms centrosymmetric dimers in the solid state. A severe Jahn-Teller distortion was observed for the (Bpz(3))(2)Cu fragment in 3Cym-Cu. Compared to the parent compounds [(HBpz(3))(2)M], the presence of uncharged ferrocenyl substituents in 3R-M tends to shift the M(2+)/M(3+) redox potential to significantly more cathodic values. The opposite is true if the ferrocenyl fragments are in their cationic state, which results in an anodic shift of the M(2+)/M(3+) transition. Most interestingly, the two ferrocenyl fragments in 3R-Cu appear to be electronically communicating.

Synthesis and X-ray characterization of the phosphido-carbonyl cluster anions.

The [Co(9)P(CO)(21)](2)(-) anion has been isolated from the products of the reaction between Na[Co(CO)(4)] and PCl(5) in tetrahydrofuran at reflux. The structure of the cluster anion [Co(9)P(CO)(21)](2)(-) in its tetraphenylphosphonium salt has been elucidated by X-ray analysis. The crystals are monoclinic, space group P2(1)/n, a = 12.528(3), b = 14.711(5), c = 19.312(6) A, beta = 93.68(2) degrees, Z = 2. Final R = 0.065 for 2300 unique reflections having I > 3sigma(I). The anion, which is disordered about an inversion center, consists of a monocapped square antiprismatic cluster containing an interstitial phosphide and surrounded by 13 terminal and 8 edge-bridging carbonyl ligands. Average values are: Co-Co 2.685 A, and Co-P 2.256 A. The [Co(10)P(CO)(22)](3)(-) anion has been obtained by condensation of the [Co(9)P(CO)(21)](2)(-) anion with [Co(CO)(4)](-) in tetrahydrofuran at reflux. While the [Co(9)P(CO)(21)](2)(-) anion is stable under CO, the [Co(10)P(CO)(22)](3)(-) anion is decomposed to [Co(9)P(CO)(21)](2)(-) and [Co(CO)(4)](-). The benzyltrimethylammonium salt of the [Co(10)P(CO)(22)](3)(-) anion has been studied by X-ray analysis. It gives triclinic crystals, space group P_1, a = 11.452(3), b = 23.510(6), c = 25.606(4) A, alpha = 112.46(1), beta = 95.79(1), gamma = 73.548(2) degrees, Z = 4. Final R = 0.041 for 8600 unique reflections having I > 3sigma(I). There are two independent trianions in the asymmetric unit, both showing similar geometries, consisting of bicapped square antiprismatic clusters with a central P atom, each bearing 10 terminal and 12 edge-bridging carbonyl ligands, 8 of which, bound to the capping metals, are markedly asymmetric. Average values are: Co-Co 2.678 A, and Co-P 2.262 A. Electrochemistry shows that [Co(9)P(CO)(21)](2)(-) and [Co(10)P(CO)(22)](3)(-) in acetonitrile solution undergo either a one-electron oxidation or a two-electron reduction. This latter process appears as a single step in the case of the dianion and as two separated one-electron steps in the case of the trianion. All the processes are accompanied by slow chemical complications, thus testifying that no stable redox congeners exist for these phosphide clusters.

Mono-, di-, and trimetallic complexes of the nonalternating polycondensed pi-perimeter decacyclene, C36H18: synthesis, structure, and spectroelectrochemistry of

Reaction of the half-sandwich complexes [(eta5-Me4RC5)M(eta2:O-acac)] (M = Co, Ni; R = Me or Et) with di- and trianions of the polycondensed pi-hydrocarbon decacyclene results in formation of the first Co and Ni triple-decker complexes of this hydrocarbon. For the title compound NMR spectra as well as a crystal structure analysis reveal an antarafacial coordination of two (eta5-Me4EtC5)Co fragments at the central six-membered ring and one of the neighboring five-membered rings of decacyclene. The bridging pi-perimeter decacyclene displays a bowl-shaped topology. In the case of Ni, coordination of two (eta5-Me5C5)Ni fragments at the central six-membered ring of decacyclene is observed, based on the results of 1H and 13C NMR studies. This coordination mode is without precedent for nickel organometallic compounds reported so far. The cobalt complex shows a rich spectroelectrochemistry. Results of cyclic voltammetry and coupled ESR experiments reveal a strong interaction of both metal centers in the mixed-valent monocation of [(eta5-Me4EtC5)Co2(mu-eta5:eta4-C36H18)]. This categorizes the title compound into Robin Day class III.

Gold(III) complexes as potential antitumor agents: solution chemistry and cytotoxic properties of some selected gold(III) compounds.

Gold(III) complexes generally exhibit interesting cytotoxic and antitumor properties, but until now, their development has been heavily hampered by their poor stability under physiological conditions. To enhance the stability of the gold(III) center, we prepared a number of gold(III) complexes with multidentate ligands - namely [Au(en)(2)]Cl(3), [Au(dien)Cl]Cl(2), [Au(cyclam)](ClO(4))(2)Cl, [Au(terpy)Cl]Cl(2), and [Au(phen)Cl(2)]Cl - and analyzed their behavior in solution. The solution properties of these complexes were monitored by visible absorption spectroscopy, mass spectrometry, and chloride-selective potentiometric measurements; the electrochemical properties were also studied by cyclic voltammetry and coulometry. Since all the investigated compounds exhibited sufficient stability under physiological conditions, their cytotoxic properties were tested in vitro, via the sulforhodamine B assay, on the representative human ovarian tumor cell line A2780, either sensitive or resistant to cisplatin. In most cases the investigated compounds showed relevant cell-killing properties with IC(50) values falling in the 0.2-10 microM range; noticeably most investigated gold(III) complexes were able to overcome, to a large extent, resistance to cisplatin when tested on the corresponding cisplatin-resistant cell line. The cytotoxic properties of the free ligands were also determined under the same solution conditions. Ethylenediamine, diethylenetriamine, and cyclam were virtually nontoxic (IC(50) values > 100 microM) so that the relevant cytotoxic effects observed for [Au(en)(2)]Cl(3) and [Au(dien)Cl]Cl(2) could be quite unambiguously ascribed to the presence of the gold(III) center. In contrast the phenanthroline and terpyridine ligands turned out to be even more cytotoxic than the corresponding gold(III) complexes rendering the interpretation of the cytotoxicity profiles of the latter complexes less straightforward. The implications of the present findings for the development of novel gold(III) complexes as possible cytotoxic and antitumor drugs are discussed.

Binding of nitrite and its reductive activation to nitric oxide at biomimetic copper centers.

The reactivity of nitrite towards the copper(II) and copper(I) centers of a series of complexes with tridentate nitrogen donor ligands has been investigated. The ligands are bis[(1-methylbenzimidazol-2-yl)methyl]amine (1-bb), bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-bb), and bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (ddah) and carry two terminal benzimidazole (1-bb, 2-bb) or pyrazole (ddah) rings and a central amine donor residue. While 2-bb and ddah form two adjacent six-membered chelate rings on metal coordination, 1-bb forms two smaller rings of five members. The binding affinity of nitrite and azide to the Cu(II) complexes (ClO4- as counterion) has been determined in solution. The association constants for the two ligands are similar, but nitrite is a slightly stronger ligand than azide when it binds as a bidentate donor. The X-ray crystal structure of the nitrite complex [Cu(ddah)(NO2)]ClO4 (final R=0.056) has been determined: triclinic P1space group, a=8.200(2) A, b=9.582(3) A, c=15.541(4) A. It may be described as a perchlorate salt of a "supramolecular" species resulting from the assembly of two complex cations and one sodium perchlorate unit. The copper stereochemistry in the complex is intermediate between SPY and TBP, and nitrite binds to Cu(II) asymmetrically, with Cu-O distances of 2.037(2) and 2.390(3) A and a nearly planar CuO2N cycle. On standing, solutions of [Cu(ddah)(NO2)]ClO4 in methanol produce the dinuclear complex [Cu(ddah)(OMe)]2(ClO4)2, containing dibridging methoxy groups. In fact the crystal structure analysis (final R=0.083) showed that the crystals are built up by dinuclear cations, arranged on a crystallographic symmetry center, and perchlorate anions. Electrochemical analysis shows that binding of nitrite to the Cu(II) complexes of 2-bb and ddah shifts the reduction potential of the Cu(II)/Cu(I) couple towards negative values by about 0.3 V. The thermodynamic parameters of the Cu(II)/Cu(I) electron transfer have also been analyzed. The mechanism of reductive activation of nitrite to nitric oxide by the Cu(I) complexes of 1-bb, 2-bb, and ddah has been studied. The reaction requires two protons per molecule of nitrite and Cu(I). Kinetic experiments show that the reaction is first order in [Cu(I)] and [H+] and exhibits saturation behavior with respect to nitrite concentration. The kinetic data show that [Cu(2-bb)]+ is more efficient than [Cu(1-bb)]+ and [Cu(ddah)]+ in reducing nitrite.

Photophysical and electrochemical characterisation of the interactions between components in neutral pi-associated

The electrochemical and photophysical properties of a variety of neutral pi-associated [2]catenanes have been explored by using cyclic voltammetry, absorption and luminescence spectrophotometry and the measurement of exited-state lifetimes. Several trends that could be correlated with interactions between the mechanically linked components of the structures were revealed from comparative study of catenane precursors, model compounds and the [2]catenanes themselves. Throughout, emphasis is placed on pair-wise comparisons between systems which differ in a single structural feature. Substitution in a catenane of a pyromellitic diimide unit by a naphthalene diimide yields more readily reduced derivatives, whose absorption spectra reveal charge transfer within the catenane to be a lower energy process of reduced intensity. Conversion of the butadiyne links within the diimide macrocycle of the catenanes to saturated chains results in an increase in both the energy and intensity of their charge-transfer bands; electrochemically these derivatives are all harder to reduce than the parent systems. Replacement of one of the electron-donating components of the catenanes with a less effective aromatic donor bearing a carboxy group also decreases the energy and intensity of the charge-transfer feature and is accompanied by a slightly more ready reduction. A sequence of reduction and translational events is proposed to explain the intriguing electrochemical behaviour of a catenane that contains one pyromellitic and one naphthalene diimide. For some systems the photophysical and electrochemical techniques, whilst exploring distinct physical phenomena, are shown to be in good agreement by comparison of shifts of electrochemical reduction waves with those of charge-transfer absorption features.

Synthesis, structure, and spectroelectrochemical investigation of novel ternary Co/S(Se)/Sn clusters derived from binary cobalt stannanediyl complexes.

The synthesis and structure of heterobimetallic Co/Sn complexes [(eta5-CpR)Co-Sn[CH(SiMe3)2]2] (CpR = C5Me5 2; C5EtMe4 3) are described. Insertion reactions of sulfur and selenium into the unbridged heteronuclear Co-Sn bonds of 1, 2, and 3 (R= H5 1, Me5 2, EtMe4 3) have been studied. Depending on the stoichiometry of the chalcogen element used, novel ternary Sn-chalcogen-Co clusters (8, 9, 15, and 16) can be synthesized, and their molecular structures, which represent rare examples of crystallographically characterized cases of ternary transition metal/chalcogen/tin complexes, have been determined. Electrochemistry shows that complexes 8 and 9 are able to support reversibly either the removal or addition of one electron. Insertion of a further (Cp)Co-E (E = chalcogen) fragment significantly affects the electron distribution and causes complexes 9 and 16 to undergo two consecutive one-electron oxidations. The EPR spectra of the respective monocations have been recorded. In all cases, the unpaired electron strongly interacts with the cobalt nucleus(i), thus testifying that the main contribution to the relevant HOMO orbitals comes from the cobalt atom(s).

Electroanalytical investigation on the interaction between 6-mercaptopurine and zinc(II), lead(II), and cadmium(II) ions in nonaqueous solvents.

Different electroanalytical techniques have been employed in the study of the interaction between 6-mercaptopurine and zinc(II), lead(II), and cadmium(II) ions in ethanol, dimethylformamide, and dimethylsulfoxide. The stoichiometry of the formed complexes was determined as well as their instability constants. The kinetic parameters of the electrode processes have been also evaluated.

Electroreduction of molybdenum(VI) at a prehydrogenated platinum electrode.

The use of hydrogenated platinum electrodes allows observation of the electroreduction of some oxygenated ions, which is otherwise masked by the reduction of the hydrogen ion. The present paper deals with the reduction of molybdenum(VI) at a prehydrogenated platinum electrode in acid solutions. The experimental conditions for the electrode hydrogenation process are the following: 90 min at a cathodic current density of about 7 A/cm(2) for microelectrodes with an area of 0.02-0.03 cm(2); about 120 min at a current density of 1.5-2 A/cm(2) for microelectrodes with an area of 0.25-0.35 cm(2). The reduction of molybdenum(VI) in 0.8-1.6M H(2)SO(4) occurs in two consecutive steps: the more cathodic wave [Mo(V) to Mo(III)] is for the most part masked by the reduction of the solvent; the less cathodic wave [Mo(VI) to Mo(V)] takes place at E(1 2 ) values of about +0.07 V, is well shaped, diffusion-controlled and usable for the determination of molybdenum down to 4 x 10(-5)M or 6 x 10(-5)M if a rotating disk electrode is used. Interferences from diverse ions have been studied. A generalization of the effect of electrode hydrogenation on the reduction of those oxygenated ions so far studied [i.e., vanadium(IV), uranium(VI) and molybdenum(VI)] is presented.

Electroreduction of uranium (VI) at a platinum electrode and its analytical applications.

Under normal conditions, the reduction of uranium(VI) at a platinum electrode, in acid solutions, is masked by the reduction of the hydrogen ion. If the working electrode is subjected to hydrogen evolution (at a current density of about 7 A cm (2) for 90-120 min) the H(ads) on the platinum surface, acting as a bridge in the electron transfer, shifts the reduction wave of uranium(VI), in 1M sulphuric acid solutions, to potentials (E(1 2 ) congruent with - 0.03 V) less negative than that of the hydrogen discharge (about -0.25 V). The wave corresponding to the reduction of uranium(VI) to uranium(IV) is well shaped, diffusion-controlled, and can be used for the determination of uranium down to 2 x 10(-5)M or 3 x 10(-6)M if a rotating electrode is used. Interferences arise from those ions with similar E(1 2 ) [i.e., Cu(II) and Bi(III)], or from those such as permanganate and dichromate, which oxidize the H(ads) on the platinum electrode. Because of the time required for the electrode pretreatment, the determination is time-consuming but in some respects it appears a useful improvement over the DME.