Search

Background. Antipsychotic medications (APM) are the first line pharmacological treatment for psychotic disorders and other behavioral disorders. Nevertheless, their use causes a number of side effects, including extrapyramidal symptoms (EPS). EPS decrease the efficacy of the antipsychotic treatments by causing poorer compliance to the treatment, stigma and a poorer quality of life for patients. Genetic studies hold the potential to unravel the molecular underpinnings of the EPS induced by APM but results are not conclusive and are far to be used in clinical practice despite decades of research. A more sophisticated selection of the list of genetic mutations explaining the genetic variance of EPS induced by APM could help in the definition of a personalized treatments for patients. Moreover, it would increase the quality of the current treatments with APM. Methods: We reviewed the literature searching for the genetic association studies focused on dystonia, parkinsonism, akathisia and tardive dyskinesia. Moreover, we reviewed the current biological knowledge of the APM induced side effects. Finally, we provide a reasoned list of candidate genes and their genetic variations, with the aim of identifying a list of candidates for APM induced EPS genetic investigations. Results: Variations located within PIK3CA (phosphoinositide-3- kinase, catalytic, alpha polypeptide), PLA2G4A (phospholipase A2, group IVA, cytosolic, calcium-dependent), PRKCA (protein kinase C, alpha), PRKACG (Phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma), ERK-1 (extracellular signalregulated kinase 1 (MAPK3)), ERK-2 (extracellular signal-regulated kinase 2 (MAPK1)), GNAS (guanine nucleotide binding protein (G protein), alpha stimulating activity polypeptide 1), PLCB1 (phospholipase C, beta 1 (phosphoinositide-specific)) and ITPR1 (inositol 1,4,5-triphosphate receptor type 1) were found to be relevant for APM induced EPS. Some of the genes are classical candidates for this kind of research, others were never investigated. For each of these genes we provide a list of variations that balances the limitations of multitesting with the advantages of the tagging approach. Conclusions: We undertook a review of the literature about the APM induced EPM to provide some rational genetic candidates to be tested in further genetic investigations.

The aim of the present study is to evaluate the contribution of mitogen-activated protein kinase 1–3 (MAPK3/MAPK1) in a model of acute lung inflammation in mice. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent adhesion molecule expression (I-CAM and P-selectin), lipid peroxidation, and increased production of tumour necrosis factor-α, (TNF-α) and interleukin-1β (IL-1β). Furthermore, carrageenan induced lung apoptosis (Bax and Bcl-2 expression) as well as nitrotyrosine formation, NF-κB activation, and pJNK expression, as determined by immunohistochemical analysis of lung tissues and the degree of lung inflammation and tissue injury (histological score). Administration of PD98059, an inhibitor of MAPK3/MAPK1 (10 mg/kg) 1 h after carrageenan caused a reduction in all the parameters of inflammation measured. Thus, based on these findings we propose that inhibitors of the MAPK3/MAPK1 signaling pathways, such as PD98059, may be useful in the treatment of various inflammatory diseases.

This paper reports the effect of noble metal addition (Ru, Pd) to supported Ni catalysts towards the reaction of CO2reforming of methane. On the basis of FT-IR spectra of adsorbed CO, H2chemisorption and TPR measurements it has been proposed that the different behaviour of the Ni-based bimetallic catalysts can be related to different metal–metal interactions occurring on the catalysts. In particular, the strong improvement in the activity and stability observed in the case of ex-nitrate Ni–Ru catalysts has been attributed to an enrichment of the catalyst surface in nickel due to the formation of Ni–Ru clusters with the surface mainly covered by Ni. This leads to an increase in the metallic dispersion of Ni and favours the formation of more reactive intermediate carbonaceous species.

Coprecipitated Au/Fe2O3catalysts used for low-temperature catalytic oxidation of carbon monoxide have been studied by FT-IR spectroscopy of adsorbed CO. The FT-IR results have shown that after preparation and exposure to a CO/O2mixture gold is present on the surface mainly as Au1+and Au0species. It has been found that in the CO oxidation Au1+is more active and less stable than Au0.

Addition of Sn modifies the catalytic performance of Pt/ZSM-5. Total conversions decrease with increasing Sn/Pt ratio. Selectivity to aromatics is higher on the Pt−Sn samples. A Pt−Sn interaction has been confirmed by H2 chemisorption and TPR experiments.

Bimetallic Ru-Cu catalysts supported on SiO2, a-Al2O3, ?-Al2O3 have been prepared using precursors which do not contain chlorine and characterized by CO chemisorption and TPR. Catalytic activity has been tested in the propane hydrogenolysis. It has been observed that the degree of formation of bimetallic Ru-Cu aggregates depends on the support used. It is suggested that the degree of interaction between Ru and Cu is strongly influenced by the strength of the metal-support interaction.

Ru/MgO, Cu/MgO, and Ru-Cu/MgO systems were characterized by FT-IR spectroscopy of adsorbed CO. The systems studied contained a total amount of metal of about 2 wt%: RCM100, RCM083, RCM070, RCM046, RCM034, and RCM000, with Ru/(Cu + Ru) atomic ratios 1, 0.83, 0.70, 0.46, 0.34, and 0.00, respectively. A comparison was made between the spectroscopic results and the catalytic properties in propane hydrogenolysis. On the Ru/MgO (RCM100) system CO originated an asymmetric band centered at 2038cm−1 , shifting to lower frequency upon evacuation, in the spectral range of CO linearly adsorbed on (0001) faces. On Cu/MgO (RCM000) CO revealed the presence of two sites on which CO is adsorbed linearly giving bands at 2078 and 2060 cm−1. On RCM083 catalyst large islands of uncovered Ru coexisted with areas of Ru heavily decorated by Cu, as revealed by the presence, upon CO adsorption, of a band at ≈2040 cm−1 and of a very broad band at ν < 2000 cm−1. On RCM070 catalyst only areas of Ru heavily decorated by Cu were present, while on RCM046 and RCM034 samples large islands of uncovered Ru coexisted with areas of Ru heavily decorated by Cu, despite the increase in the Cu content. On the four bimetallic catalysts a variety of Cu(0) sites were revealed, bonding CO linearly (sharp CO stretching bands in the 2140-2098 cm−1 region), belonging to different Cu aggregates adsorbed on Ru microcrystals. These results are consistent with those obtained by catalytic measurements: the minimum catalytic activity and the maximum selectivity in ethane formation are found for the RCM070 sample, which shows only surface Ru(0) heavily decorated by Cu, as expected.Copyright 1993, 1999 Academic Press

Bimetallic Ru-Cu samples supported on SiO2, Al2O3 and MgO were studied by the temperature-programmed reduction (TPR) technique. Experiments were carried out both on unreduced impregnated salts and after oxidation of already reduced samples.

Ru and Cu samples supported on SiO2, Al2O3 and MgO were studied by the temperature-programmed reduction (TPR) technique. Experiments were carried out both on unreduced impregnated salts and after oxidation of already reduced samples.

Monolithic supported nickel catalysts were investigated in benzene hydrogenation between 100 and 280 °C. The conversion of benzene to cyclohexane reaches a maximum around 210 °C with a maximum yield at a ratio poH2/poBz=3. The experimental results and some kinetic aspects are discussed.

Monolithic supported platinum catalysts were investigated with respect to their hydrogenation and dehydrogenation activity towards benzene and cyclohexane, respectively, between 250° and 350°C. Conversion of benzene to cyclohexane is optimal for the volume ratio H2/Bz=5 at lower temperatures. In the cyclohexane dehydrogenation reaction, high temperatures, associated with lower N2/Cy ratios, are beneficial. No byproducts were observed in the two reactions.

Bimetallic Ru−Cu catalysts supported on ZSM5 have been prepared using RuCl3 or Ru(NO) (NO3)3 as precursors. Co chemisorption, TPR measurements and catalytic activity in propane hydrogenolysis have shown that the degree of Ru−Cu interaction depends on the Ru precursor used.

Propane aromatization has been investigated over Pt/ZSM-5 in the temperature range of 400–500°C. Hydrogenolysis of propane to methane occurs mainly on the platinum sites and becomes an important route in propane transformation when reactions leading to aromatics tend to reach thermodynamic equilibrium.

Aromatization of propane has been investigated over Pt-Pb/ZSM5. Addition of Pb decreases propane conversion with a corresponding increase in the aromatic selectivity. Hydrogenolysis reactions are inhibited by the presence of lead.

The hydrogenation of CO2to methane has been investigated over Ru catalysts supported on zeolite (H-ZSM-5) and on silica. Supported Ru catalysts were very active for the hydrogenation of CO2. Ru/ZSM-5 was more selective to methane than Ru/SiO2. On the basis of FT-IR spectra of CO and CO2adsorbed on the catalysts, it has been suggested that this behaviour can be related to a higher positive polarization of ruthenium on the zeolite. This leads to a weaker Ru–CO bond on the H-ZSM-5-supported sample with a corresponding increase of the hydrogen surface coverage that favours the transformation of the intermediate CO to methane.