Efficacy of an emollient dermoprotective cream in the treatment of elderly skin affected by xerosis.

AIM: Xerosis cutis is a frequent condition in the elderly and the topical treatments are aimed to maintain a balance between the physiological components of the epidermis and an optimal moisturization. The aim was to evaluate the efficacy of a dermoprotective cream, glycerol and paraffin-based, in the treatment of individuals affected by senile xerosis. METHODS: The patients were recruited at the Professional Dermatology and Allergology Outpatient Clinic of the San Gallicano Dermatological Institute of Rome, between 1st January 2013 and 30th September 2014. To assess the efficacy of the cream, two different areas of treatment were identified in each patient upper the limbs. All patients were staged at baseline (T0) and evaluated after 14 days (T1) and 28 days (T2) of topical treatment, using five clinical parameters: scaling, sensation of skin tightness, presence of fissuring and excoriations from scratching and erythema. The itching degree was also evaluated using a 10-steps analogical scale. RESULTS: Fifty patients with xerosis, 25 with a severe and 25 with a moderate form, over 60 were recruited and evaluated. Median age was 65 years (IQR=61-70). After 28 day of topical administration of the cream, the 54.0% of patients showed the absence of signs of xerosis, the 44.0% a mild form and the 2.0% (one patient) a moderate form. Consistently, a progressive and significative reduction of itching and transepidermal water loss (TEWL), and an improvement in skin hydration was also measured. A good profile of tolerability and no episodes of undesirable side effects, was also observed. CONCLUSION: The topical daily use of a cream glycerol and paraffin-based, seem to able to control the xerosis in elderly patients, with a significant reduction of all associated signs and symptoms. Further additional data should be collected to better confirm the role of the topical treatment in the control of disease.

166Ho and 90Y labeled 6D2 monoclonal antibody for targeted radiotherapy of melanoma: comparison with 188Re radiolabel.

INTRODUCTION: An approach to radioimmunotherapy (RIT) of metastatic melanoma is the targeting of melanin pigment with monoclonal antibodies (mAbs) to melanin radiolabeled with therapeutic radionuclides. The proof of principle experiments were performed using a melanin-binding antibody 6D2 of IgM isotype radiolabeled with a ß emitter (188)Re and demonstrated the inhibition of tumor growth. In this study we investigated the efficacy of 6D2 antibody radiolabeled with two other longer lived ß emitters (90)Y and (166)Ho in treatment of experimental melanoma, with the objective to find a possible correlation between the efficacy and half-life of the radioisotopes which possess high energy ß (E(max)>1.5 MeV) emission properties. METHODS: 6D2 was radiolabeled with longer lived ß emitters (90)Y and (166)Ho in treatment of experimental melanoma in A2058 melanoma tumor-bearing nude mice. The immunoreactivity of the radiolabeled 6D2 mAb, its in vitro binding to the MNT1 human melanoma cells, the biodistribution and therapy in A2058 human melanoma bearing nude mice as well as dosimetry calculations were performed. RESULTS: When labeled with the longer lived (90)Y radionuclide, the 6D2 mAb did not produce any therapeutic effect in tumor bearing mice while the reduction of the tumor growth by (166)Ho-6D2 was very similar to the previously reported therapy results for (188)Re-6D2. In addition, (166)Ho-labeled mAb produced the therapeutic effect on the tumor without any toxic effects while the administration of the (90)Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. CONCLUSIONS: (166)Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the (90)Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. We concluded that the serum half-life of the 6D2 carrier antibody matched well the physical half-life of (166)Ho to deliver the tumoricidal absorbed dose to the tumor. Further investigation of this radionuclide for RIT of melanoma is warranted.

Increased annexin-V and decreased TNF-α serum levels in chronic-medicated patients with schizophrenia.

Schizophrenia (SZ) is a chronic severe mental disorder. Increased inflammatory processes have been shown in acute and chronic SZ. Apoptotic processes may alter the neuronal network and are involved in the pathogenesis of several neurodegenerative diseases, such as SZ. Annexin-V seems to have a role on inhibition of pro-inflammatory activities during apoptosis. Tumor necrosis factor (TNF-alpha) is a cytokine involved in systemic inflammation and is a member of a group of cytokines which stimulate acute phase reactions. A chronic immune activation in SZ has been shown. The aim of this study was to compare annexin-V and TNF-alpha serum levels in chronic medicated patients with SZ and healthy controls. Thirty-eight outpatients from the HCPA Schizophrenia Program and 38 healthy controls were enrolled to this study protocol. Annexin-V and TNF-alpha serum levels were measured with ELISA. Serum annexin-V levels were significantly higher in patients with SZ than in controls (p<0.001) and TNF-alpha significantly lower (p<0.001). The present result of increased annexin-V and decreased serum levels of TNF-alpha compared to controls may be a result of the stabilization phase of psychosis and a reduction in metabolic brain aggression. In this complex picture, increased levels of annexin-V and decreased levels of TNF-alpha in our sample would be explained by illness stability and chronic treatment. Our findings support the hypothesis of a state dependant process of inflammation in SZ. Further prospective studies to clarify the findings described in this paper are needed.

2-(2-Piperidyl)- and 2-(2-pyrrolidyl)chromans as nicotine agonists: synthesis and preliminary pharmacological characterization.

As part of an effort to develop a new class of subtype selective nicotine agonists, we have synthesized and tested a group of 12 hydroxylated 2-(2-piperidyl)- and 2-(2-pyrrolidyl)chromans. In rat brain membranes, all 12 compounds displayed poor affinity for [(125)I]-alpha-bunagarotoxin binding sites. In contrast, three compounds, 17c, 24, and 26, displayed moderate to high affinity for [(3)H]cytisine binding sites, while three (17b, 18b,c) and six (17a,d,e and 18a,d,e) compounds showed weak and poor affinity, respectively, for these same sites. In subsequent studies, compounds 17a and 17c were found to stimulate the efflux of (86)Rb(+) from rat cortical synaptosomes, an indication of agonist activity. Further, both 17c and 26 displayed high intrinsic activity in stimulating the release of [(3)H]dopamine from striatal synaptosomes; however, only 17c was effective at stimulating the release of [(3)H]acetylcholine from cortical synaptosomes, suggesting differential selectivity. In cloned human nicotinic acetylcholine receptors (nAChR) expressed in Xenopus oocytes, both 17c and 26 activated alpha7 and alpha3beta2 receptor subtypes in a dose-dependent manner, but 26 was clearly the more potent agonist. Last, neither compound displayed dose-dependent activation of alpha4beta2 nAChRs. We conclude that 2-(2-azacyclic)chromans appear to be a promising new class of nicotine agonists.

Coordination of rare-earth elements in complexes with monovacant Wells-Dawson polyoxoanions.

The alpha-1 and alpha-2 isomers of the monovacant Wells-Dawson heteropolyoxoanion [P(2)W(17)O(61)](10-) are complexants of trivalent rare-earth (RE) ions and serve to stabilize otherwise reactive tetravalent lanthanide (Ln) and actinide (An) ions in aqueous solution. Aspects of the bonding of Ln ions with alpha-1-[P(2)W(17)O(61)](10-) and alpha-2-[P(2)W(17)O(61)](10-) were investigated to address issues of complex formation and stability. We present structural insights about the Ln(III) coordination environment and hydration in two types of stoichiometric complexes, [Ln(alpha-1-P(2)W(17)O(61))](7-) and [Ln(alpha-2-X(2)W(17)O(61))(2)](17-) (for Ln identical with Sm, Eu, Lu; X identical with P, As). The crystal and molecular structures of [(H(2)O)(4)Lu(alpha-1-P(2)W(17)O(61))](7-) (1) and [Lu(alpha-2-P(2)W(17)O(61))(2)](17-) (2) were solved and refined through use of single-crystal X-ray diffraction. The crystallographic results are supported with corresponding insights from XAFS (X-ray absorption fine structure) for a series of nine solid-state complexes as well as from optical luminescence spectroscopy of the Eu(III) analogues in aqueous solution. All the Ln ions are eight-coordinate with oxygen atoms in a square antiprism arrangement. For the 1:1 stoichiometric Ln/alpha-1-[P(2)W(17)O(61)](10-) complexes, the Ln ions are bound to four O atoms of the lacunary polyoxometalate framework in addition to four O atoms from solvent (water) molecules as [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7-). This structure (1) is the first of its kind for any metal complex of alpha-1-[P(2)W(17)O(61)](10-), and the data indicate that the general stoichiometry [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7-) is maintained throughout the lanthanide series. For the 1:2 stoichiometric Ln/alpha-2-[X(2)W(17)O(61)](10-) complexes, no water molecules are in the Ln-O(8) coordination sphere. The Ln ions are bound to eight O atoms-four from each of two heteropolyanions-as [Ln(alpha-2-X(2)W(17)O(61))(2)](17-). The average Ln-O interatomic distances decrease across the lanthanide series, consistent with the decreasing Ln ionic radius.

Technetium-99m N,N'-bis(2-mercapto-2-methylpropyl)-2-aminobenzylamine: technetium-99m complexes of a novel bis(aminoethanethiol) ligand.

A new N2S2 ligand system, N,N'-bis(2-mercapto-2-methylpropyl)-2- aminobenzylamine, U-BAT, 1, containing uneven amine groups (two amine groups with different pKa values) for complexing [TcVO]3+, was prepared. The reaction of this novel ligand with [99mTc]pertechnetate, in the presence of stannous tartrate as the reducing agent, produces the neutral and lipid-soluble [99mTc]TcVO(U-BAT), TcS2C15H23N2O, 2. However, when the same reaction was carried out at a higher pH, 9-10, and with 30 min of heating (100 degrees C), a second neutral but more lipid-soluble complex, [99mTc]TcVO(OU-BAT), TcS2C15H21N2O, 3, was isolated. The X-ray crystallography data of the 99Tc complexes show square pyramidal coordination with N2S2 as the base and the Tc = O in the apical position. Compound 3 can be derived from 2 by an oxidation of the ligand to form an imine. After iv injection into rats, the neutral and lipid-soluble technetium-99m complexes showed significant brain uptake, 1.54 and 1.07% dose/organ at 2 min for [99mTc]TcVO(U-BAT) and TcVO(OU-BAT), respectively. The novel Tc chemistry of this new ligand system may provide a useful foundation for designing Tc complexes with a built-in redox mechanism.

Dicarboxylate diamide dimercaptide (N2S2) technetium-99m complexes: synthesis and biological evaluation as potential renal radiopharmaceuticals.

Novel diamide dimercaptide (N2S2) ligands 4, 5, and 8 have been synthesized and evaluated as potential renal radiopharmaceuticals. The target compounds were prepared in modest overall yields of 22%, 19%, and 20%, respectively, using readily available starting materials. Following in situ deprotection, 99mTc complexes of high radiochemical purity were obtained in excellent yield and were found to be stable for up to 6 h. The 99Tc complex of ligand 8 was isolated as the AsPh4 salt. The X-ray crystallographic data for [99TcO(8)]AsPh4 (space group P2(1)/n: Z = 4, a = 9.342(3) A; b = 18.594(5) A; c = 18.417(7) A; beta, deg = 90.61(3); V, A3 = 3199.1(20)) show that the Tc is bound to both thiolate sulfur atoms and to two deprotonated amide nitrogen atoms. The coordination geometry about the Tc is square-pyramidal with an -yl oxygen atom in the apical position. The Tc-N bond distances (2.002(12) and 1.984(12) A), the Tc-S bond distances (2.300(5) and 2.286(5) A), and the Tc-O bond distance (1.667(11) A) are in good agreement with bond lengths reported for similar complexes. The carboxylate groups are not bonded to the Tc atom in the solid state, nor in CDCl3 solution, as evidenced by X-ray crystal data and solution NMR data, respectively. In the solid state, [99TcO(8)]AsPh4 is monoanionic, therefore, at physiological pH, [99mTcO(8)] is presumably trianionic. Biodistribution studies performed in rats with the 99mTc complexes revealed slow blood clearance and high muscle uptake for these agents. Modest hepatobiliary excretion was observed, and low quantities of the complexes were found in the heart, lungs, and spleen after 1 h. The urinary excretion of the 99mTc complexes of ligands 4, 5, and 8 was found to be slow when compared to the excretion of [131I]OIH in rats (22%, 22%, and 32% vs 85-86%, respectively). Protein binding of 99mTc complexes of ligands 4, 5, and 8 in both rat and monkey plasma was found to be similar to MAG3. While the synthetic schemes reported here supply facile routes to novel N2S2 ligands, biodistribution studies of the 99mTc complexes performed on rats revealed slow renal excretion rates, accompanied by slow blood clearance and high uptake in muscle tissue. Preliminary planar imaging studies in monkeys also revealed slow renal excretion for these agents. The 99mTc complexes evaluated here are poor candidates as renal radiopharmaceuticals.

New conformationally restricted 99mTc N2S2 complexes as myocardial perfusion imaging agents.

In developing 99mTc complexes as potential myocardial imaging agents, a new series of ligands based on a conformationally restricted N2S2 system were investigated. Using piperazine or homopiperazine as the starting material, two N2S2 ligands (4a and 4b) with additional conformation restriction between the two nitrogen donor atoms were synthesized. The 99mTc complexes were prepared by a direct labeling method with tin(II) tartrate as the reducing agent for [99mTc]pertechnetate. The resulting 99mTc complexes were purified through a sulfonpropyl Sephadex column and further purified by HPLC with a reverse-phase column eluting with a solvent system of acetonitrile/buffer. Biodistribution studies in rats showed initial uptake in the heart (0.21%, 0.42% dose/order for [99mTc]4a and 4b at 2 min postinjection). Carrier-added preparation of [99mTc]4b was successful. NMR, IR, UV, crystallographic, and elemental analysis of the [99Tc]4b complex suggest that it contains a TcVO3+ center core and is 1+ charged. The results suggest that this series of 1+ charged 99mTc complexes may have potential as myocardial imaging agents, and further study of the complexes is warranted.

A new myocardial imaging agent: synthesis, characterization, and biodistribution of gallium-68-BAT-TECH.

In order to develop a new myocardial perfusion agent for positron emission tomography (PET), a new lipid-soluble gallium complex was evaluated. Synthesis, radiolabeling, characterization, and biodistribution of a unique gallium complex, [67Ga]BAT-TECH (bis-aminoethanethiol-tetraethyl-cyclohexyl), are described. The complex formation between Ga+3 and BAT-TECH ligand is simple, rapid, and of high yield (greater than or equal to 95%). This process is amenable to kit formulation. The complex has a net charge of +1 and a Ga/ligand ratio of 1:1. Biodistribution in rats shows high uptake in the heart as well as in the liver. When [68Ga] BAT-TECH was injected into a monkey, the heart and liver are clearly delineated by PET imaging, suggesting that this complex may be a possible tracer for myocardial perfusion imaging.

[A retrospective clinico-endoscopic study of colorectal cancer. Personal case histories]. / Studio retrospettivo, clinico-endoscopico, sul cancro colorettale. Casistica personale.

Over a decade (1978-88), 180 cases of colorectal carcinoma were diagnosed. Twenty of the patients had shown no "precancerous" colonic conditions whereas screening had revealed various pathologies indicating risk in the remaining 160. The percentage distribution of the tumour in the large bowel was as follows: sigmoid colon 38%, rectum 25%, descending colon 21%, caecum 12%, transverse colon 4%. Dukes-type surgical staging of the screened patients revealed 42% in stage A, 48% stage B and 10% stage C. The sensitivity and specificity of the haemoccult test was 86% and 98% respectively while the diagnostic accuracy of double-contrast opaque enema was 79% compared to 84% for coloscopy alone and 98% for combined coloscopy and biopsy.

[Evaluation of immune status in rubella infection in the pregnant population of the U.S.L. 3 of Pesaro 1981-1985]. / Valutazione dello stato immunitario nei confronti dell'infezione rubeolica nella popolazione gravida del comprensorio dell'U.S.L. 3 di Pesaro negli anni 1981-1985.

The object of this study is an evaluation of the epidemic situation concerning the rubella in the pregnant population of age included between 18 and 40 years of the U.S.L. 3 of Pesaro, in the period 1981-1985. The percentage of seropositivity in an average is around 93.8%; nevertheless such a percentage of seronegativity persists as to justify an intervention of prophylaxis by means of vaccination above all in the age from 18 to 25 years, that represents the 43.8% of the examined sample. It must be pointed out the evolution of the immunity situation from the 36 to the 40 years.