New olfactometric findings in Parkinson's disease.

Objectives: To investigate in Parkinson's disease-affected patients a correlation between hyposmia and gastrointestinal dysfunction and their possible identical etiopathogenesis.

Design: Retrospective cohort study.

Setting: ENT and neurology departments (Gemelli Hospital, Rome, Italy).

Discovery of the Aryl-phospho-indole IDX899, a Highly Potent Anti-HIV Non-nucleoside Reverse Transcriptase Inhibitor.

Here, we describe the design, synthesis, biological evaluation, and identification of a clinical candidate non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a novel aryl-phospho-indole (APhI) scaffold. NNRTIs are recommended components of highly active antiretroviral therapy (HAART) for the treatment of HIV-1. Since a major problem associated with NNRTI treatment is the emergence of drug resistant virus, this work focused on optimization of the APhI against clinically relevant HIV-1 Y181C and K103N mutants and the Y181C/K103N double mutant.

Classification and characterization of human endogenous retroviruses; mosaic forms are common.

Background: Human endogenous retroviruses (HERVs) represent the inheritance of ancient germ-line cell infections by exogenous retroviruses and the subsequent transmission of the integrated proviruses to the descendants. ERVs have the same internal structure as exogenous retroviruses. While no replication-competent HERVs have been recognized, some retain up to three of four intact ORFs.

QTREDS: a Ruby on Rails-based platform for omics laboratories.

Background: In recent years, the experimental aspects of the laboratory activities have been growing in complexity in terms of amount and diversity of data produced, equipment used, of computer-based workflows needed to process and analyze the raw data generated. To enhance the level of quality control over the laboratory activities and efficiently handle the large amounts of data produced, a Laboratory Management Information System (LIMS) is highly-recommended. A LIMS is a complex software platform that helps researchers to have a complete knowledge of the laboratory activities at each step encouraging them to adopt good laboratory practices.

Synthesis and antiviral evaluation of thieno[3,4-d]pyrimidine C-nucleoside analogues of 2',3'-dideoxy- and 2',3'-dideoxy-2',3'-didehydro-adenosine and -inosine.

Several thieno[3,4-d]pyrimidine derivatives, including four hitherto unknown 2',3'-dideoxy- and 2',3'-dideoxy-2',3'-didehydro-C-nucleoside analogues of adenosine and inosine have been synthesized. When evaluated in cell culture experiments against human immunodeficiency virus, none of the tested compounds exhibited any significant antiviral effect, while two of them showed some cytotoxicity.

Generation of PCDD/F in fly ash from municipal solid waste incinerators.

Fly ash from municipal solid waste incinerators (MSWIs) has been characterized in terms of polychlorinated dibenzyl-p-dioxin and polychlorinated dibenzofuran (PCDD/F) content. Increasing values of PCDD/Fs have been found to correlate with decreasing temperatures of sampling points in flue gas treatment lines of the plants, confirming other researchers' findings about temperature as the major controlling parameter for the PCDD/F formation. Measured PCDD/F ratios show that de novo synthesis is the dominant formation mechanism.

Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: synthesis and SAR studies.

The potent anti-HIV-1 activities of L-737,126 (2) and PAS sulfones prompted us to design and test against HIV-1 in acutely infected MT-4 cells a number of novel 1- and 3-benzenesulfonylindoles. Indoles belonging to the 1-benzenesulfonyl series were found poorly or totally inactive. On the contrary, some of the 3-benzenesulfonyl derivatives turned out to be as potent as 2, being endowed with potencies in the low nanomolar concentration range.

Design, synthesis, SAR, and molecular modeling studies of acylthiocarbamates: a novel series of potent non-nucleoside HIV-1 reverse transcriptase inhibitors structurally related to phenethylthiazolylthiourea derivatives.

A novel series of potent, selective HIV-1 N-acylthiocarbamate (ATC) nonnucleoside reverse transcriptase inhibitors (NNRTIs) is described. The title compounds were synthesized through a highly convergent, one-pot procedure. In cell-based assays, the lead compound (17c) prevented the HIV-1 multiplication with an EC(50) of 8 microM.

Synthesis and antiproliferative activity of 3-aryl-2-(1H-benzotriazol-1-yl)acrylonitriles. Part III.

A new series of 30 3-aryl-2-(1H-benzotriazol-1-yl)acrylonitriles were synthesized and tested for biological activity as part of our research in the antimicrobial and antitumor fields. In particular, title compounds were evaluated in vitro against representative strains of Gram-positive and Gram-negative bacteria (S. aureus, Salmonella spp), mycobacteria (M.

1,5-Benzodiazepines. Part XII. Synthesis and biological evaluation of tricyclic and tetracyclic 1,5-benzodiazepine derivatives as nevirapine analogues.

A number of properly substituted 5H-pyrimido[4,5-b][1,5]benzodiazepines (2) and pyrazolo[3,4-b][1,5]benzodiazepines (3 and 4), as well as compounds 5-7, which are derivatives of new tetracyclic systems, were prepared as nevirapine analogues through multistep synthetic routes. The cytotoxic and anti-HIV-1 properties of compounds 2-7 were evaluated in cell-based assays, together with their inhibitory activity against the HIV-1 recombinant reverse transcriptase (rRT) in enzyme assays. The modifications introduced into nevirapine heterocyclic skeleton proved to have a negative effect for the anti-HIV-1 activity.

Synthesis and anti-HIV-1 activity of new delavirdine analogues carrying arylpyrrole moieties.

In our search for novel anti-human immunodeficiency virus (HIV)-1 agents, 14 delavirdine analogues were synthesized and evaluated as potential anti-HIV-1 agents in cell-based assays. Compound 1Aa exhibited potent and selective anti-HIV-1 activity in acutely infected MT4 cells, with effective concentration (EC50) values in the submicromolar range.

MDR1, cholesterol certification and cell growth: a comparative study in normal and multidrug-resistant KB cell lines.

The product of the gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification. In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth and that the gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this matter, the rate of cell growth, cholesterol metabolism, expression of the gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive phenotype versus MDR phenotype).

Pyrazole related nucleosides 5. Synthesis and biological activity of 2'-deoxy-2',3'-dideoxy- and acyclo-analogues of 4-iodo-1-beta-D-ribofuranosyl-3-carboxymethyl pyrazole (IPCAR).

Continuing our studies on the structure-activity relationships (SAR) of 4-iodo-1-beta-D-ribofuranosyl-3-carboxymethyl pyrazole (IPCAR), the ribofuranosyl moiety has been substituted with acyclic chains, namely 1-[(2-hydroxyethoxy)methyl]- and 1-[(1,3-dihydroxy-2-propoxy)methyl]-pyrazole derivatives (4, 5 and 8, 9 respectively), with the 2'-deoxy-beta-D-ribofuranosyl group (12 and 13) and finally with the 2',3'-dideoxy-D-glycero-pentofuranosyl-moiety (16 and 17). None of the new compounds display any interesting biological activity.

Disoxaril-related 3-(diethylamino)-5-phenylisoxazoles.

Previous research has shown that 3-(dialkylamino)-5-phenylisoxazoles possessing a compact structure were active against HRV-2 and, consequently, presented a type B activity. In this paper, 3-(diethylamino)-5-phenylisoxazoles, which are structurally more elongated and related to Disoxaril, were synthesized in view to attempt type A activity against HRV-14. Unfortunately, all tested compounds were devoid of activity against HRV-14 (and HIV-1) or exhibited great toxicity.

d(CH2)5Tyr(Me)-[Orn8]vasotocin, a potent oxytocin antagonist, antagonizes penile erection and yawning induced by oxytocin and apomorphine, but not by ACTH-(1-24).

Intraventricular (i.c.v.

Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area.

In unanesthetized rats the intravenous administration of low doses of ethanol (0.125-0.5 g/kg) produced a dose-dependent increase (30-80%) in the firing rate of dopaminergic (DA) neurons in the Ventral Tegmental Area (VTA).

Stimulation of "regulatory" dopamine receptors by bromocriptine (CB-154).

Bromocriptine produces long-lasting hypomotility and decreases brain dihydroxyphenylacetic acid (DOPAC) in mice. These effects are obtained with doses much lower than those which produce hypermotility. The decrease of brain DOPAC is correlated to the hypomotility both on a dose and on a time basis.

Evidence for selective and long-lasting stimulation of "regulatory" dopamine-receptors by bromocriptine (CB 154).

Bromocriptine, an ergot-derivate with DA-receptor stimulating properties in vivo, produces long-lasting hypomotility in mice not accustomed to the motility cage and decreases brain DOPAC and HVA without affecting brain DA. These effects are obtained with doses 25 times lower than those which produce hypermotility. The decrease of brain DOPAC is correlated to the hypomotility both on a dose- and on a time-basis.