Coumarin-Rasagiline Hybrids as Potent and Selective hMAO-B Inhibitors,Antioxidants, and Neuroprotective Agents

The frequency, complexity and morbidity of neurodegenerative diseases make them a great challenge for nowadays medicine. Most of the treatments currently used for Parkinson's disease – the second most prevalent – are only symptomatic. Therefore, it is urgent to develop drugs that are able to act simultaneously on different targets, being able to stop neuronal death and promote the recovery of neuronal populations already affected. In this work, we studied the activity of a series of hybrid molecules, which combine the structure of both coumarin and an alkynylamine group inspired on rasagiline, as MAO inhibitors, antioxidants and neuroprotective agents. Half of the studied hybrids turned out to be selective monoamine oxidase B (hMAO-B) inhibitors in the low micro/nanomolar range, demonstrating that positions 3 (compounds 1–3 ) and 7 (compounds 8 and 10 ) of the coumarin scaffold are the most suitable for the incorporation of the alkynylamine chain. All the studied compounds proved to be capable of neutralizing free radicals (DPPH). Finally, the 4-(but-2-yn-1-ylamino)coumarin ( 5 ) showed neuroprotective effects on glial cells and the 4-methyl-7-(pent-2-yn-1-ylamino)coumarin ( 8 ) inhibited intraneuronal ROS production as well.     

Production of luteolin extracts from Reseda luteola and assessment of their dyeing properties

In this work, several experiments were performed sequentially in 50 cm³ shaken tubes and a 1 dm³ stirred extractor, thus allowing methanol to be selected as the most appropriate leaching solvent for luteolin from leaves, stems and flowers of weld (Reseda luteola). The extraction capability of methanol at 25 °C was found to be about 7 times greater than that of boiling water at pH 10. A composite design experiment allowed the effects of particle size and liquid/solid ratio to be determined, thus resulting in an optimal luteolin extraction yield of 8.6 ± 0.2 g kg^?1 dried weld material when leaching plant particles sieved through 0.5 mm openings with 40 dm³ methanol kg^?1. Preliminary dyeing tests on pre‐mordanted raw cotton and wool standard specimens gave rise to dyed specimens with the same greenish‐yellow hue but greater or smaller values of lightness and chroma respectively. Despite all dyed specimens exhibiting a minimum resistance to a simulated acid perspiration solution, the resistance to fading of dyed wool specimens was generally greater than that of cotton ones. © 2002 Society of Chemical Industry     

Assessment of the dyeing properties of pigments from Monascus purpureus

Monascus purpureus C322 was cultivated on well‐established production media to yield prevailingly red or orange pigment‐rich ethanolic extracts. Once these extracts had been diluted by an overall factor of 50, they were used as such to dye raw wool standard specimens differently premordanted using alum or stannic chloride. Independently of the mordant used, the specimens dyed with the red pigment‐rich extracts showed a pale red colour tending to pink, whereas the specimens dyed with the orange pigment‐rich extracts exhibited a more definite orange colour. By carrying out a few colourfastness standard tests (manual washing at 40 °C, acid and basic perspiration and hot pressing), stannic chloride‐premordanted wool specimens dyed with the red pigment‐rich extracts were found to be less resistant to acid and basic perspiration than their orange counterparts. Since the production of the orange pigment‐rich ethanolic extracts appeared to be more cost‐effective than that of their red counterparts, the former might support the present demand for colorants of natural origin in the textile sector. Copyright © 2005 Society of Chemical Industry     

Multiple colon tumors. Diagnosis and follow-up of 450 patients with colorectal carcinoma

OBJECTIVE: Failure to diagnose synchronous tumors leads to errors in patient treatment and prognosis. The existence of metachronous tumors requires strict patient follow-up to ensure early identification of the second tumor. The present study evaluates the results obtained in the application of a structured procedure for the diagnosis and follow-up of multiple colorectal carcinoma. MATERIALS AND METHODS: A structured procedure was used to follow for 5 years a group of 12 patients with multiple colorectal tumors (7 synchronous and 5 metachronous) of a series of 450 colorectal neoplasms. RESULTS: Six synchronous tumors were diagnosed preoperatively and one intraoperative. Of the 5 metachronous neoplasms, 4 strictly adhered to the follow-up protocol, as a result of which the second tumor was detected at an early stage. The remaining case involved no follow-up, and the second tumor was diagnosed in an advanced stage as a result of bowel occlusion. The left colon was predominantly involved; polyps were detected in 9 cases, while two patients had 3 malignancies detected by histopathological study. COMMENTS: We emphasize the need for a full evaluation of the colon in all patients with colorectal carcinoma. In the case of incomplete preoperative evaluation, intraoperative colonoscopy is to be considered; if this is not feasible it should be performed one month after surgery. A structured follow-up procedure permits the early detection of these tumors, there by improving patient prognosis.     

Evolution of cardiac rhabdomyoma in tuberous sclerosis complex

The objective of the study was to define the longitudinal evolution of cardiac rhabdomyomas (CR) in patients with tuberous sclerosis complex (TSC). A cohort of patients with TSC who had undergone videotaped echocardiographic (ECHO) examination during the 10-year interval (1984-1994) were retrospectively studied by reviewing and quantifying the CR appearance and associated cardiac abnormalities in sequentially obtained ECHO examinations. Sixteen patients with TSC (8 males) underwent a total of 35 recorded studies. Ten of the 16 (62.5%) had CR identified at initial study; none were found in the atria. Localization was the ventricular walls as compared with the ventricular septum by a ratio of 2:1. The number of CRs sequentially studied declined as follows; initial study: 23 lesions in 10 patients; second study: 16 lesions in 8 patients; third study: 12 lesions in 5 patients; and fourth study: 4 lesions in 2 patients. Total CR size index declined at each study as follows: initial index of 2,684; second index of 1,746 (-35% from initial); third index 1,141 (-57% from initial); and fourth index 705 (-74% from initial). Complete spontaneous regression of CR was seen by age 6 years with prolonged gradual resolution thereafter. Two patients had bicuspid aortic valves and two had conduction defects. Patients with TSC who have CR can be expected to experience a decline in both the number and size of CR over time; early complete regression on ECHO occurs before age 6 years.     

Powder Metallurgy Overcomes Economic Difficulties

The state of the production of metallic and ceramic powders (including nano-dimensional powders) and of articles fabricated from these powders in North America is discussed. New technologies that produce an increase in the density and improvement in the mechanical properties of powder-based articles are considered. Technological developments and articles for which prizes were awarded by the North American Metal Powders Industry Federation in 2003 are adduced.__________Translated from Poroshkaya Metallurgiya, Nos. 1–2(441), pp. 117–125, January–February, 2005.     

The G Protein-Coupled Receptor Heterodimer Network (GPCR-HetNet) and Its Hub Components

G protein-coupled receptors (GPCRs) oligomerization has emerged as a vital characteristic of receptor structure. Substantial experimental evidence supports the existence of GPCR-GPCR interactions in a coordinated and cooperative manner. However, despite the current development of experimental techniques for large-scale detection of GPCR heteromers, in order to understand their connectivity it is necessary to develop novel tools to study the global heteroreceptor networks. To provide insight into the overall topology of the GPCR heteromers and identify key players, a collective interaction network was constructed. Experimental interaction data for each of the individual human GPCR protomers was obtained manually from the STRING and SCOPUS databases. The interaction data were used to build and analyze the network using Cytoscape software. The network was treated as undirected throughout the study. It is comprised of 156 nodes, 260 edges and has a scale-free topology. Connectivity analysis reveals a significant dominance of intrafamily versus interfamily connections. Most of the receptors within the network are linked to each other by a small number of edges. DRD2, OPRM, ADRB2, AA2AR, AA1R, OPRK, OPRD and GHSR are identified as hubs. In a network representation 10 modules/clusters also appear as a highly interconnected group of nodes. Information on this GPCR network can improve our understanding of molecular integration. GPCR-HetNet has been implemented in Java and is freely available at http://www.iiia.csic.es/~ismel/GPCR-Nets/index.html.