Development and validation of a Structured Telephone Interview for Dementia Assessment (STIDA): the NIMH Genetics Initiative

Eating disorders are an increasing problem for society and the medical professions. The dental practitioner has an important role both in identifying the illnesses and in minimising its affects on the dentition. This paper highlights the features of the most common eating disorders and discusses the possible role of the dental profession in the long-term care of patients suffering from the problem.     

Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: the Strong Heart Study

Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (> or = 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA1c, study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin.     

Unique CT imaging advantages. Hemorrhage and calcification

Computed tomography remains the imaging modality of choice in the detection of two processes: acute intracranial hemorrhage and calcification; however, in the subacute and chronic stages of hemorrhage, MR imaging is more sensitive in aging and staging hemorrhage. FLAIR imaging increases the sensitivity of MR imaging in the detection of subarachnoid hemorrhage. The signal characteristics of calcification on MR imaging is variable, especially on T1-weighted images decreasing its detectability. CT is superior to MR imaging in the detection of calcification. A number of factors including slice thickness, as well as window width and level may affect the detectability of calcification on CT.     

Thermodynamics of partitioning of the antimalarial drug mefloquine in phospholipid bilayers and bulk solvents

The antimalarial drug mefloquine binds avidly to phospholipids in biomembranes. The thermodynamics of the partitioning process in dimyristoylphosphatidylcholine (DMPC) bilayers was investigated to give some insight into the drug-phospholipid interaction. Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium partition coefficients measured as a function of temperature. Negative values of delta H and delta S were obtained for the transfer of mefloquine from the aqueous to the gel phase of the phospholipid. The partitioning is enthalpy controlled which suggests that mefloquine interacts strongly with the phospholipid phase. In contrast, the partitioning of mefloquine into the liquid crystalline phase of DMPC is entropy controlled which is typical of a hydrophobic interaction between mefloquine and the aqueous phase. The partitioning of mefloquine into the bulk solvents octanol and hexane were found to be enthalpy and entropy controlled, respectively. The enthalpy dominated partitioning of mefloquine into gel phase DMPC and octanol is attributed to the occurrence of hydrogen bonding and van der Waals interactions between solute and solvent. The flat shape of mefloquine may further aid its interaction with the orderly domains of the lipidic/organic phase. This is apparent from a comparison of the partitioning characteristics of another structurally related but conformationally different molecule, quinine into DMPC and octanol.     

Membrane fusion induced by the HIV type 1 fusion peptide: modulation by factors affecting glycoprotein 41 activity and potential anti-HIV compounds

Peptides representing a sequence of 23 amino acid residues at the N terminus of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 bind and subsequently induce fusion of large unilamellar vesicles (LUV), an activity presumably related to gp41 function in viral infection. These in vitro effects can be modulated by several factors that are known to affect HIV-1 infectivity and gp41-mediated virus-cell fusion. Peptide-induced membrane fusion but not peptide binding can be inhibited by two factors known to block gp41 activity: a polar amino acid substitution V --> E in position 2 and the presence of the N-terminal hexapeptide of gp41 in addition to the parent sequence. Whereas inclusion of the alternative gp120 receptor galactosylceramide in membranes has virtually no effect, membrane cholesterol stimulates fusion activity. In view of its putative physiological relevance, we have used the fusion activity of the peptides as a tool to evaluate the inhibitory effect of antivirals that might target this sequence. We describe three dissimilar effects: Amphotericin B inhibits in a cholesterol-independent way peptide-induced fusion but not binding, human serum albumin inhibits binding and consequently fusion, and dextran sulfate (M(r) 5000) does not affect either binding or fusion.     

Mechanical properties of a modified acrylic bone cement with etoxytriethyleneglycol monomethacrylate

With the aim of improving some of the disadvantages of the acrylic bone cements, an acrylic bone cement based on polymethyl methacrylate has been modified by substituting different quantities, up to 20%, of the monomer methyl methacrylate (MMA) with the same amount of ethoxytriethyleneglycol monomethacrylate (TEG). The addition of this new monomer decreased noticeably the maximum temperature and increased both setting and working times. Mechanical testing revealed that the introduction of TEG gave rise to a less fragile bone cement by increasing slightly the total deformation without any change in the rest of the tensile parameters.     

Phosphatidylinositol-dependent membrane fusion induced by a putative fusogenic sequence of Ebola virus

The membrane-interacting abilities of three sequences representing the putative fusogenic subdomain of the Ebola virus transmembrane protein have been investigated. In the presence of calcium, the sequence EBO(GE) (GAAIGLAWIPYFGPAAE) efficiently fused unilamellar vesicles composed of phosphatidylcholine, phosphatidylethanolamine, cholesterol, and phosphatidylinositol (molar ratio, 2:1:1:0.5), a mixture that roughly resembles the lipid composition of the hepatocyte plasma membrane. Analysis of the lipid dependence of the process demonstrated that the fusion activity of EBO(GE) was promoted by phosphatidylinositol but not by other acidic phospholipids. In comparison, EBO(EA) (EGAAIGLAWIPYFGPAA) and EBO(EE) (EGAAIGLAWIPYFGPAAE) sequences, which are similar to EBO(GE) except that they bear the negatively charged glutamate residue at the N terminus and at both the N and C termini, respectively, induced fusion to a lesser extent. As revealed by binding experiments, the glutamate residue at the N terminus severely impaired peptide-vesicle interaction. In addition, the fusion-competent EBO(GE) sequence did not associate significantly with vesicles lacking phosphatidylinositol. Tryptophan fluorescence quenching by vesicles containing brominated phospholipids indicated that the EBO(GE) peptide penetrated to the acyl chain level only when the membranes contained phosphatidylinositol. We conclude that binding and further penetration of the Ebola virus putative fusion peptide into membranes might be governed by the nature of the N-terminal residue and by the presence of phosphatidylinositol in the target membrane. Moreover, since insertion of such a peptide leads to membrane destabilization and fusion, the present data would be compatible with the involvement of this sequence in Ebola virus fusion.