Inflammatory mediators as biomarkers in brain disorders.

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules involved in this process could be a strategy for finding new biomarkers. The ideal inflammatory biomarker needs to be easily measurable, must be reproducible, not subject to wide variation in the population, and unaffected by external factors. Our review summarizes the most important inflammation biomarkers currently available, whose specificity could be utilized for identifying and monitoring distinctive phases of different neurodegenerative diseases

Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect

Clinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformin's effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression

The CMS RPC gas gain monitoring system: an overview and preliminary results

The status of the CMS RPC Gas Gain Monitoring (GGM) system developed at the Frascati Laboratory of INFN (Istituto Nazionale di Fisica Nucleare) is reported on. The GGM system is a cosmic ray telescope based on small RPC detectors operated with the same gas mixture used by the CMS RPC system. The GGM gain and efficiency are continuously monitored on-line, thus providing a fast and accurate determination of any shift in working point conditions. The construction details and the first result of GGM commissioning are described.Comment: 8 pages, 9 figures, uses lnfprepCMS.sty, presented by L. Benussi at RPC07, Mumbai, INDIA 200

Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: evidence from the Italian Psocare Registry.

Objective To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees.Design Prospective cohort study.Setting Italian public referral centres for psoriasis treatment.Patients First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks.Main outcome measure Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinicallymeaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartateamino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of newdiagnoses of diabetes mellitus and arterial hypertension.Results Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin orcyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Meantransaminase values increased in methotrexate-treated patients, and mean aspartate amino transferase levelsincreased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treatedpatients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34)and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated withrisk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanineamino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension anddiabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88).Conclusion Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed.Received: 1 September 2011; Accepted: 12 January 201

Notulae to the Italian flora of algae, bryophytes, fungi and lichens: 5

In this contribution, new data concerning bryophytes, fungi, and lichens of the Italian flora are presented. It includes new records and confirmations for the bryophyte genera Diplophyllum and Ptychostomum, the fungal genera Arrhenia, Gymnosporangium, and Sporidesmium and the lichen genera Arthonia, Coenogonium, Flavoplaca, Gyalolechia, Parmotrema, Peltigera, Pterygiopsis, Squamarina, Tornabea, and Waynea

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO