Human Health Effects of Lactose Consumption as a Food and Drug Ingredient.

Lactose is a reducing sugar consisting of galactose and glucose, linked by a ß (1→4) glycosidic bond, considered as an antioxidant due to its α-hydroxycarbonyl group. Lactose is widely ingested through the milk and other unfermented dairy products and is considered to be one of the primary foods. On the other hand, lactose is also considered as one of the most widely used excipients for the development of pharmaceutical formulations. In this sense, lactose has been related to numerous drug-excipient or drug-food pharmacokinetic interactions. Intolerance, maldigestion and malabsorption of carbohydrates are common disorders in clinical practice, with lactose-intolerance being the most frequently diagnosed, afflicting 10% of the world's population. Four clinical subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital lactase deficiency, adult-type hypolactasia and secondary lactase intolerance. An overview of the main uses of lactose in human nutrition and in the pharmaceutical industry and the problems derived from this circumstance are described in this review.

Transient occurrence of an ebulin-related D-galactose-lectin in shoots of Sambucus ebulus L.

Young shoots of Sambucus ebulus L. contain a monomeric d-galactose binding lectin (SELlm), which disappears upon shoot development, and was previously undetected since it co-purifies with the non-toxic type 2 ribosome-inactivating protein ebulin l and the dimeric lectin SELld. Molecular cloning of cDNA coding for SELlm and mass spectrometry analysis revealed a protein with a molecular mass of 34,239 Da, which displays 80%, 77% and 45% of amino acid sequence identity with the ebulin l-B chain, SELld and ricin-B chain, respectively. Furthermore, the cloned precursor, with respect to the ebulin l precursor is truncated and contains the signal peptide, a piece of the A chain, a piece of the connecting peptide and the B chain. Further processing yields the lectin protein, which contains only the B chain. Despite the fact that SELlm displays the same d-galactose-binding sites than ricin, it was found that the lectin has different binding properties to D-galactose-containing matrix than ricin. Notably, and unlike ricin, the binding of SELlm and other Sambucus lectins to such matrix was maximum in range of 0-10 degrees C and abolished at 20 degrees C.

Targeting a marker of the tumour neovasculature using a novel anti-human CD105-immunotoxin containing the non-toxic type 2 ribosome-inactivating protein nigrin b.

Targeting tumour neovasculature using antibodies to the endothelial receptor CD105 (endoglin), is a potentially useful approach for anti-tumour therapy. We report on the preparation and the cytotoxicity of a novel immunotoxin consisting in the non-toxic type 2 ribosome-inactivating protein (RIP) nigrin b linked to the monoclonal anti-human CD105 (hCD105) antibody 44G4. The immunotoxin kills specifically mouse fibroblasts expressing the biomarker CD105 (L929-hCD105+ cells) with an IC(50) value of 6x10(-10)M while nigrin b does it at 2.4x10(-7)M. Immunofluorescence analysis indicated that the immunotoxin accumulates in a perinuclear region. In contrast, 44G4 showed a specific localization on the cell surface.

Elderberry bark lectins evolved to recognize Neu5Ac alpha2,6Gal/GalNAc sequence from a Gal/GalNAc binding lectin through the substitution of amino-acid residues critical for the binding to sialic acid.

Bark lectins from the elderberry plants belonging to the genus Sambucus specifically bind to Neu5Acalpha2,6Gal/GalNAc sequence and have long been used for the analysis of sialoglycoconjugates that play important roles in many biological phenomena. However, molecular basis of such a unique carbohydrate binding specificity has not been understood. To answer these questions, we tried to identify the amino-acid residues in the Japanese elderberry bark lectin, Sambucus sieboldiana agglutinin that enabled the lectin to recognize sialic acid by using in silico docking simulation and site-directed mutagenesis. These studies showed that three amino-acid residues, S(197), A(233) and Q(234), in the C-terminal subdomain of SSA-B chain are critical for the binding to the sialic acid in Neu5Acalpha2,6Gal/GalNAc sequence. Replacement of one of these residues to the one in the corresponding position of ricin B-chain completely abolished the binding to a sialoglycoprotein, fetuin. Conserved presence of these amino acid residues in the corresponding sequences of two other elderberry lectins with similar binding specificity further supported the conclusion. These findings indicated that the replacement of the corresponding amino-acid residues in a putative Gal/GalNAc-specific ancestral lectin to these amino-acid residues generated the unique Neu5Acalpha2,6Gal/GalNAc-specific elderberry lectins in the course of molecular evolution.