A review of palaeoclimates and palaeoenvironments in the Levant and Eastern Mediterranean from 25,000 to 5000 years BP: setting the environmental background for the evolution of human civilisation

The southern Levant has a long history of human habitation and it has been previously suggested that climatic changes during the Late Pleistocene-Holocene stimulated changes in human behaviour and society. In order to evaluate such linkages, it is necessary to have a detailed understanding of the climate record. We have conducted an extensive and up-to-date review of terrestrial and marine climatic conditions in the Levant and Eastern Mediterranean during the last 25,000 years. We firstly present data from general circulation models (GCMs) simulating the climate for the last glacial maximum (LGM), and evaluate the output of the model by reference to geological climate proxy data. We consider the types of climate data available from different environments and proxies and then present the spatial climatic "picture" for key climatic events. This exercise suggests that the major Northern Hemisphere climatic fluctuations of the last 25,000 years are recorded in the Eastern Mediterranean and Levantine region. However, this review also highlights problems and inadequacies with the existing data. (c) 2006 Elsevier Ltd. All rights reserved.

Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action.

Apolipoprotein E genotype and alpha-tocopherol modulate amyloid precursor protein metabolism and cell cycle regulation

Apolipoprotein E4 (apoE4) genotype is associated with an increased risk for Alzheimer's disease (AD). This is thought to be in part attributable to an impact of apoE genotype on the processing of the transmembrane amyloid precursor protein (APP) thereby contributing to amyloid beta peptide formation in apoE4 carriers, which is a primary patho-physiological feature of AD. As apoE and alphato-copherol (alpha-toc) have been shown to modulate membrane bilayer properties and hippocampal gene expression, we studied the effect of apoE genotype on APP metabolism and cell cycle regulation in response to dietary a-toc. ApoE3 and apoE4 transgenic mice were fed a diet low (VE) or high (+VE) in vitamin E (3 and 235 mg alpha-toe/kg diet, respectively) for 12 weeks. Cholesterol levels and membrane fluidity were not different in synaptosomal plasma membranes isolated from brains of apoE3 and apoE4 mice (-VE and +VE). Non-amyloidogenic alpha-secretase mRNA concentration and activity were significantly higher in brains of apoE3 relative to apoE4 mice irrespective of the dietary a-toe supply, while amyloidogenic beta-secretase and gamma-secretase remained unchanged. Relative mRNA concentration of cell cycle related proteins were modulated differentially by dietary a-toc supplementation in apoE3 and apoE4 mice, suggesting genotype-dependent signalling effects on cell cycle regulation.

Interactions between herbal and conventional medicines

Herb-drug interactions are subject to much interest at present, but for various reasons reports may be unreliable or unsubstantiated. Herbal medicines are variable in composition and quality, which may affect their interaction profile as well as the reliability of reports concerning them. In this review, clinical and experimental reports have been collated, evaluated and summarised, and the theoretical and clinical evidence presented. There is an explanation of the particular issues involved with herbal medicines as compared with conventional drugs, and reasons why comparisons may or may not be valid, which is intended for those without specialist experience in herbal products. It has become apparent that only a few herbal drugs have so far been cited in interaction reports, for example St John's Wort, Ginkgo biloba, Dan Shen, liquorice, Ma huang and garlic, and that the main drugs involved are those which are already susceptible to interactions with many other conventional drugs, such as warfarin, protease inhibitors and anti-cancer drugs. An attempt has been made to put the matter into perspective and recommendations have been given for health professionals to advise or develop strategies to safeguard patients, without resorting to speculation or scaremongering.

Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study

Background: Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. OBJECTIVE: Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. DESIGN: In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. RESULTS: Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). CONCLUSIONS: Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features.