Molecular Simplification in Bioactive Molecules: Formal Synthesis of (+)-Muconin

7 páginas, 1 figura, 7 esquemas, 1 tabla.-- El PDF es la versión post-print.The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel approach that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor is described. An additional advantage of the method is complete stereochemical control and the decrease in the number of chemical steps required, thus providing an enhancement of the overall yield. Antiproliferative studies against the human solid tumor cell lines showed that the aliphatic chain-THF/THP fragment of (+)-muconin has modest cytotoxic activity. The strategy opens the way to preparing novel bioactive acetogenin analogues by shorter synthetic routes.The authors thank the MYCT (PPQ2002- 04361-C04-02) of Spain and the Canary Islands Government for supporting this research. F.R.P.C. thanks CajaCanarias for a FPI fellowship. R.C. thanks the Spanish MEC for a FPU fellowship. J.M.P. thanks ICIC for a postdoctoral fellowship.Peer reviewe

Microfluidic pneumatic cages : A novel approach for in-chip crystal trapping, manipulation and controlled chemical treatment

The precise localization and controlled chemical treatment of structures on a surface are significant challenges for common laboratory technologies. Herein, we introduce a microfluidic-based technology, employing a double-layer microfluidic device, which can trap and localize in situ and ex situ synthesized structures on microfluidic channel surfaces. Crucially, we show how such a device can be used to conduct controlled chemical reactions onto on-chip trapped structures and we demonstrate how the synthetic pathway of a crystalline molecular material and its positioning inside a microfluidic channel can be precisely modified with this technology. This approach provides new opportunities for the controlled assembly of structures on surface and for their subsequent treatment

Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis

Atherosclerosis is nowadays generally accepted as an inflammatory disease but the mechanism of its origin and development have not yet been fully clarified. The present review focuses on the role of the local immune system as one of the key players in the pathogenesis of the complex process. Its part represented by vascular-associated lymphoid tissue (VALT) within the arterial wall participates directly in the vascular wall's homeostatis. Its inordinate activation during ontogenic development of an individual, this formerly defensive and physiologic mechanism transform into a pathological process resulting in an impairing inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious candidates for triggering these pathological changes. The principal role is played by anti-Hsp60 antibodies and by shear stress originating on the surface of endothelium due to blood flow. The experimental and clinical data supporting this immunological hypothesis of atherosclerosis are discussed

Planck intermediate results V : Pressure profiles of galaxy clusters from the Sunyaev-Zeldovich effect

This article has an erratum: http://dx.doi.org/10.1051/0004-6361/201220040ePeer reviewe

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

COMMERCIAL FOOD FISHES AND THEIR HELMINTH PARASITES DIVERSITY OF PUMLEN LAKE, TOKPACHING, MANIPUR

The present research paper which communicates with the objective to high light the diversity of fish as well as helminth parasite infection rate of the commercial food fishes of Pumlen Lake locally known as Pumlen Pat (- a Lake in Manipur) is the second largest freshwater wetland located in the Southern part of the Manipur valley. During the study period we come across 40 different species of fishes belonging to 27 genera, under 14 families and 7 orders. Of these, the most abundant is Trichogaster labiosa (6.37%), followed by Amblypharyngodon mola (5.84%) and Monopterus albus was least abundant (0.33%). And parasite infection is very common in the fishes like Clarias magur, Channa punctata, Channa striata, Channa orientalis Trichogaster fasciata, Trichogaster labiosa, Glossogobius giuris, Lepidocephalus guntea, Heteropneustes fossilis and Anabas testudineus. The study was conducted between January 2015 to December 2015 and found four groups of parasites in 280 fishes. The total parasitic infestation rate is 28.22%. The fishes belong to 5 different orders and 14 families. Among the fishes, 280 are found infected with helminth parasites belonging to four different groups in which 40 parasites belong to class acanthocephala, 25 parasites belong to class.Cestoda, 66 parasites belong to class Trematoda and l l parasites belongs to class Nematoda

ROLE OF CERTAIN PHYSICO-CHEMICAL PROPERTIES OF WATER ON ABUNDANCE OF TREMATO DE PARASITES OF CHANNA PUNCTATA (BLOCH) IN SONE BEEL, ASSAM INDIA

Helminth parasite infection in fishes by trematode (Liver fluke : Parasitic flatworms having external suckers for attaching to a host) parasites can lead to severe change in nutrient content and may result in host mortalities and character of a water body may influence the parasitic fauna. Hence a study was carried out from January 2014 to December 2014 to find out the effect of physico-chemical characteristics of water on the abundance of trematode parasites of Channa punctata (Bloch) in Sone Beel, Assam, India. During the present investigation two species of trematodes were recorded. In the present study We had come across concurrent infections by two parasite species. Percentage abundance infection is positively correlated to pH (r = 0.688, p-0.05), Dissolved oxygen (DO mg/L) (r. = 0.847, p&lt;0.01) and Water Temperature (WT) (r. = 0.720, p&lt;0.01) but negatively correlated with Total Alkalinity (TA), Dissolved oxygen (DO mg/L) is positively correlated with pH (r= 0.668, p&lt;0.05), Free carbon dioxide (FCO) is also positively correlated with pH ( r = 0.763, p&lt;0.001), &amp; Dissolved oxygen (DO mg/L) at r = 0.615, p&lt;0.01, TA mg/L is negatively correlated with free carbon dioxide and water temperature strongly correlated with percentage abundance (r = 0.720, p&lt;0.01), pH (r = 0.863, p&lt;0.01), DO (0.808, p:0.15), FCO (r = 0.669, p&lt;0.05) and negatively correlated with TA. The mean Abundance, Water temperature (WT), pH, dissolved oxygen (DO mg/L), free carbon dioxide (FCO2 mg/L) and Total alkalinity (TA mg/L) respectively 60.15%, 27.3°C, 6,7, 5.3 mg/L. 12.2 mg/L and 44.43 mg/L. Seasonal variation in the occurrence of these parasites are also effected by certain ecological conditions, particularly distribution of intermediate hosts and also the age of the host and the life cycle of the parasite species