We investigate the role played by membrane composition on the interaction and self-assembly of beta-amyloid peptide (AbetaP1-40) during pore formation in planar lipid membranes (PLMs). Incorporation studies showed that AbetaP does not interact with zwitterionic membranes made up of phosphatidylcholine, whereas the addition of cholesterol or ergosterol to the membranes leads to channel formation. Among the PLMs used, a higher propensity of AbetaP to form channels at low applied potential (+/-20 mV) was observed in 7-dehydrocholesterol and in oxidized cholesterol PLMs. These channels present long lifetimes, high-occurrence frequencies, and are voltage dependent. In particular, the AbetaP channel in oxidized cholesterol showed anion selectivity. Thus cholesterol (and sterols in general) could be considered as targets for AbetaP, which prevents the fibrillation process by increasing incorporation into membranes. Furthermore, by switching the channel selectivity versus anions, cholesterol helps to reduce the imbalance of the cellular ions, calcium included, induced by membrane depolarization, which could be one of the factors responsible for cytotoxicity in Alzheimer's disease.

Kissper is a 39-residue peptide isolated from kiwi fruit (Actinidia deliciosa). Its primary structure, elucidated by direct protein sequencing, is identical to the N-terminal region of kiwellin, a recently reported kiwi fruit allergenic protein, suggesting that kissper derives from the in vivo processing of kiwellin. The peptide does not show high sequence identity with any other polypeptide of known function. However, it displays a pattern of cysteines similar, but not identical, to those observed in some plant and animal proteins, including toxins involved in defence mechanisms. A number of these proteins are also active on mammalian cells. Functional characterization of kissper showed pH-dependent and voltage-gated pore-forming activity, together with anion selectivity and channeling in model synthetic PLMs, made up of POPC and of DOPS:DOPE:POPC. A 2DNMR analysis indicates that in aqueous solution kissper has only short regions of regular secondary structure, without any evident similarity with other bioactive peptides. Comparative analysis of the structural and functional features suggests that kissper is a member of a new class of pore-forming peptides with potential effects on human health.

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Bone metabolism and density have been shown to be abnormal in adult asthmatic patients treated with inhaled corticosteroids. Because the largest increases in bone growth and mineral deposition occur during childhood and adolescence, we performed a cross-sectional evaluation of cortical and trabecular bone mass by dual-photon absorptiometry at the proximal one third of the radius (cortical bone) and by dual-energy X-ray absorptiometry at the L2-L4 lumbar spine (trabecular bone) in 64 prepubertal asthmatic children receiving beclomethasone dipropionate (BDP) or cromolyn sodium (CS). Dual-energy X-ray absorptiometry was performed by anteroposterior scan and also by lateral vertebral scan in order to exclude the posterior elements of the vertebrae, which are composed mainly of cortical bone and which are less sensitive to the negative effect of steroids. Furthermore, we calculated "volumetric" bone density, dividing lateral mineral content by the vertebral volume. Bone mineral areal density and volume bone density did not differ in children receiving BDP for 6.7 +/- 1.3 mo at a mean dose of 319.3 +/- 130 micrograms/d compared with those in children treated with CS. Furthermore, anteroposterior bone density in our study population was in agreement with published normative data and with that of normal age-related healthy nonasthmatic children living in the same area and with the same dietary intake of calcium. No normal values are available for lateral and calculated-volume bone density. In conclusion, treatment with BDP does not appear to have an adverse effect on bone mass in prepubertal children with mild moderate asthma. Longitudinal studies should be performed in order to evaluate the effect of early introduction of inhaled corticosteroids in children with mild asthma.

In this study we investigated the interaction of salmon and human calcitonin (Ct) with artificial lipid bilayer membranes. Both peptides were able to form either transient or permanent channels in the model membranes. The channels formed by salmon Ct at concentration (125 nM) had, on average, a single-channel conductance of 0.58 +/- 0.04 nS in 1M KCl (+10 mV), which is voltage-dependent at lower voltages. Human Ct forms at the same concentration channels with a much lower probability, and high voltages of up to +150 mV were needed to initiate channel formation. The estimated single-channel conductance formed under these conditions was approximately 0.0119 +/- 0.0003 nS in 1 M KCl. Both salmon and human Ct channels were found to be permeable to calcium ions. The possibility is discussed that the superior therapeutic effect of salmon Ct as a tool to treat bone disorders, including Paget disease, osteoporosis, and hypercalcemia of malignancy, rather than human Ct is related to the lack of the fibrillating property of salmon Ct. Preliminary data indicate that also eel and porcine Ct and carbocalcitonin form channels in model membranes.