Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: insight with genomics

Most clinical trials with vitamin E could not lower cholesterol and thus, have been deemed unsuccessful. Recently, tocotrienols, isomers of vitamin E have been found to lower LDL levels. To explore if tocotrienols could be the drug target for vitamin E, rabbits were kept on cholesterol diet for 60 days supplemented with tocotrienol-α, tocotrienol-δ, and tocotrienol-γ for the last 30 days. The serum cholesterol levels (in mmol/l) were 24.4 (tocotrienol-α), 34.9 (tocotrienol-δ), 19.8 (tocotrienol-γ) vs. 39.7 (control). Left ventricular function including aortic flow and developed pressure exhibited significantly improved recovery with tocotrienol-γ and -α, but not with tocotrienol-δ. The myocardial infarct size showed a similar pattern: 33% (tocotrienol-α), 23% (tocotrienol-γ), and 47% (tocotrienol-δ). To examine the molecular mechanisms of cardioprotective effects, gene expression profile was determined using Atlas 1.2/1.2II followed by determination of gene profiles using PedQuest 8.3 software. Based on genomic profiles, the following cholesterol-related proteins were examined: FABP, TGF-β (cholesterol suppresses TGF-β), ET-1 (increased by hypercholesterolemia), SPOT 14 (linked with hypercholesterolemia), and matrix metalloproteinase (MMP) 2 and MMP9 (cholesterol regulates MMP2 and MMP9 expression) in the heart. Consistent with the cardioprotective effects of tocotrienol-α and -γ, these two isomers reduced ET-1, decreased MMP2 and MM9, increased TGF-β and reduced SPOT 14, while tocotrienol-δ had no effects. The results of the present study demonstrate that the two isomers of tocotrienols, α and γ, render the hypercholesterolemic hearts resistant to ischemic reperfusion injury by lowering several hypercholesterolemic proteins including MMP2, MMP9, ET-1, and SPOT 14 and upregulating TGF-β.     

Development of a 3D finite element model of lens microcirculation

Background

It has been proposed that in the absence of a blood supply, the ocular lens operates an internal microcirculation system. This system delivers nutrients, removes waste products and maintains ionic homeostasis in the lens. The microcirculation is generated by spatial differences in membrane transport properties; and previously has been modelled by an equivalent electrical circuit and solved analytically. While effective, this approach did not fully account for all the anatomical and functional complexities of the lens. To encapsulate these complexities we have created a 3D finite element computer model of the lens.

Methods

Initially, we created an anatomically-correct representative mesh of the lens. We then implemented the Stokes and advective Nernst-Plank equations, in order to model the water and ion fluxes respectively. Next we complemented the model with experimentally-measured surface ionic concentrations as boundary conditions and solved it.

Results

Our model calculated the standing ionic concentrations and electrical potential gradients in the lens. Furthermore, it generated vector maps of intra- and extracellular space ion and water fluxes that are proposed to circulate throughout the lens. These fields have only been measured on the surface of the lens and our calculations are the first 3D representation of their direction and magnitude in the lens.

Conclusion

Values for steady state standing fields for concentration and electrical potential plus ionic and fluid fluxes calculated by our model exhibited broad agreement with observed experimental values. Our model of lens function represents a platform to integrate new experimental data as they emerge and assist us to understand how the integrated structure and function of the lens contributes to the maintenance of its transparency.     

Fate of leucine in the biosynthesis of bakuchiol, a meroterpene from Psoralea corylifolia

Significant incorporations of labelled leucine, valine and isovaleric acid into the meroterpene, bakuchiol (1) isolated from the medicinal plant, Psoralea corylifolia have been observed. Degradation experiments show that labels from these substrates find their way into both phenylpropane derived as well as terpenic part of 1 thereby indicating that none of the known pathways is operative in the case of 1. It is suggested that these substrates are metabolised to CO2 which is then incorporated into 1.     

Observations on natural breeding and larval development of the common mud-eel Amphipnous cuchia (Ham.)

Amphipnous cuchia is a rare fish in India with a spawning period confined down to peak summer. The fish lays its eggs in especially prepared nest-holes and keeps a guard on the developing young ones. The yolk reserve persists till about 22 to 24 days of development. Larvae respond to direct feeding even before yolk-absorption. The young ones feed actively on chironomus larvae. Surface breaking habit for aerial respiration apparently commences around 15th–16th day of larval life. Adult characters are almost attained in about a month's time.     

An immunologically active arabinogalactan from Tinospora cordifolia

An arabinogalactan of mean M(r) 2.2 x 10(6) has been isolated from the dried stems of Tinospora cordifolia and examined by methylation analysis, partial hydrolysis and carboxyl reduction. Purified polysaccharide showed polyclonal mitogenic activity against B-cells, their proliferation did not require macrophages.     

Post-eocene biofacies,palaeoenvironments and palaeogeography of the Bengal Basin,India

The Bengal Basin is known for the extensive development of a thick Cretaceous— Tertiary sedimentary sequence in the eastern part of India. The basin has undergone several phases of transgressions, regressions, periodic uplifts and localised negative movements throughout the period of its evolution. The sedimentation up to the end of the Eocene was largely under the influence of a major transgressive phase which was later replaced by a regressive phase on account of the uplift and resulting marine retreat. in this paper, an analysis of the microfaunal distribution, biofacies and sedimentary and tectonic history is made for reconstruction of the palaeoenvironmental conditions and palaeogeography of the Bengal Basin relating to the post-Eocene regressive phase of evolution.During the Oligocene—Early Miocene, the open marine conditions existing since the Eocene were progressively modified on account of the regression into more brackish, lagoonal and estuarine types. A typical prograding delta started to spread over a large part of the marginal area of the basin. The rocks of the Barail Group, formed under the transitional environments of the delta, are found to occur in almost all the major geo-provinces of the basin. The sedimentary environments and characteristics of the rocks were ultimately controlled by the configurations of the respective geo-provinces. The negative movements in the Miocene along certain marginal areas were associated with the marine transgressive phase giving rise to the Surma Group. This transgressive phase was, however, short lived and its impact was not equally felt in all areas. The northeastern region was still uplifted which favoured an almost continuous existence of the deltaic phase.By the end of Miocene a greater part of the basin underwent a strong tectonic upheaval which was possibly the precursor of the main Himalayan orogeny. The intermontane depressions formed in the uplifted areas were the depositional sites for the Tipam Group and younger beds in Plio-Pleistocene times. The rapidly eroded debris from the highlands spread over a wide area towards the south under the influence of the river system of the Ganga and Brahmaputra which has transformed the original basinal areas into a large modern delta complex.     

Structural and synthetic studies on the retrofractamides—amide constituents of Piper retrofractum

Two new unsaturated amides, retrofractamides A and C, were isolated from the total above-ground parts of Piper retrofractum. Retrofractamide A was shown to be N-isobutyl-9(3′,4′-methylenedioxyphenyl)2E,4E,8E-nonatrienamide from spectroscopic and chemical investigations. The structure 6 for retrofractamide C was suggested from spectroscopic and chemical studies and was confirmed by a total stereoselective synthesis. The presence of sesamin and 3,4,5-trimethoxydihydrocinnamic acid as well as two higher homologues of retrofractamide A, viz. pipericide (retrofractamide B) and retrofractamide D was demonstrated. The synthesis of pipericide was also achieved.     

Aurantiamides: A new class of modified dipeptides from Piper aurantiacum

Two new amides, aurantiamide and aurantiamide acetate, were isolated from Piper aurantiacum. Their structures were determined as N-(N′-benzoyl-S-phenylalaninyl)-S-phenylalaninol and its acetate, respectively, from chemical and spectroscopic studies. The structures and stereochemistry were confirmed by synthesis. The corresponding diastereoisomers were also synthesized and their spectroscopic properties compared with those of the natural compounds.