Dietary tannins are polyphenols that are effectively precipitated by salivary histatins (Hsts), a novel family of tannin binding proteins. Epigallocatechin gallate (EGCG), a flavan-3-ol ester related to condensed tannins (polymerized products of flavan-3-ols), and pentagalloyl glucose (PGG), a hydrolyzable tannin, were used to evaluate the molecular nature of Hst-polyphenol interaction. NMR demonstrated that Hst5, a representative Hst, bound to EGCG in a hydrophobic manner via basic and aromatic residues. In contrast, proline plays a dominant role in polyphenol binding to other tannin precipitating proteins. The role of basic and aromatic amino acids in EGCG binding was investigated using a series of modified Hsts in each of which one type of amino acid was substituted by Ala. EGCG bound to all modified Hsts, but the binding was diminished. Optimal EGCG binding also depended on the primary structure, as a polypeptide with randomised Hst5 sequence showed significantly diminished interaction with EGCG. Soluble EGCG/Hst5 complexes containing up to seven molecules of EGCG per mol of Hst5 had a 1-mM dissociation constant. In contrast to EGCG, PGG formed small soluble complexes with Hst5 consisting of only one molecule each of PGG and Hst5, as demonstrated by analytical ultracentrifugation. These complexes became insoluble upon binding of additional molecules of PGG. Diminished PGG binding was seen to a peptide with a Hst5 randomized sequence showing the importance of the primary structure. Hsts may serve to form insoluble complexes with tannins thereby preventing their absorption from the intestines and potentially harmful biological effects. In contrast the much weaker interaction with EGCG may allow its uptake into the organism and exploitation of its antioxidant effect.Keywords: histatin; tannin; saliva; epigallocatechin gallate; pentagalloyl glucose.Tannins are plant derived polyphenolic compounds that are commonly found in foods such as grains, legumes, fruits and beverages [1,2]. Based on their chemical structure, tannins are divided into hydrolyzable and condensed tannins [3]. Hydrolyzable tannins, also known as tannic acids, consist of a polyhydric alcohol such as glucose to which molecules of gallic or hexahydroxydiphenic acid are linked by ester bonds [3]. Condensed tannins are structurally more complex, being polymers of the flavonoids flavan-3-ols [3]. A characteristic property of tannins is their ability to precipitate proteins from aqueous solution. Many studies have demonstrated the detrimental effects of tannins in animals including decreased digestibility of dietary protein and decreased utilization of mineral in food [4,5]. Condensed tannin is also considered to be a causative agent of acute pulmonary inflammation in cotton-mill and grainelevator workers [6,7]. In addition, tannic acid has been shown to be hepatotoxic [8], and several fatalities in humans have been shown to result from the absorption of tannic acid incorporated in barium enemas used in colonic radiological examinations [9]. On the o...

The ability of all major human salivary histatins to precipitate condensed tannin was demonstrated, and it was found that histatins 3 and 5 share the same condensed tannin-binding region but less tannin bound to histatin 1. The condensed tannin-binding region of histatin 5 includes both the N- and the C-terminal parts, although more tannin binding occurs in the C-terminal region. Epigallocatechin gallate (EGCG) showed similar binding characteristics as condensed tannin, but much less EGCG was precipitated. Pentagalloyl glucose (PGG) was precipitated equally well by histatins 1, 3, and 5 and bound equally well to the N- and C-terminal regions of histatin 5. In contrast to condensed tannin, cleaving histatin 5 into N- and C-terminal fragments increased their ability to precipitate PGG. Together, these results show a number of differences in the nature of interaction of histatins with condensed tannin, EGCG, and PGG. Most of the condensed tannin-protein complexes remained insoluble under conditions similar to those in the stomach and the small intestine, suggesting that histatins may act as a defense against dietary tannin in humans.

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4Head injuries represent a significant burden of illness. In the United States, where the incidence is approximately 200 per 100,000 population, head trauma accounts for 12% of all hospital admissions, and is associated with a mortality rate of 25 per 100,000. 1 However, with advances in the management of head traumas, there are more individuals who are either in, or emerging from, a state of decreased level of consciousness (LOC). 2 Moreover, there is a growing body of evidence that suggests that medical or pharmacological interventions can alleviate two important consequences of brain injury: postinjury neurological impairments and decreased LOC.Neurological symptoms related to the dysfunction of higher ABSTRACT: Brain injuries are a serious burden of illness to Canada and the US. Advances in managing head trauma have allowed more patients to emerge from decreased levels of consciousness and helped them cope with neurocognitive, neurobehavioural, and neuropsychiatric deficits. In this article, we review the current (1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) evidence surrounding the pharmacological management of arousal states and the aforementioned neurological sequelae of head injury in either acute or chronic conditions. This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury. The review did not include all anticonvulsants, neuroleptics, beta-blockers, benzodiazepines, azospirones or cognitive enhancers. Unfortunately, the quality of the evidence is generally poor, and sometimes conflicting, which in turn results in indecisive guidelines for treating patients. Accepting the inherent flaws in the evidence we feel that this paper may serve as a stepping-stone for future researchers to improve data gathering that targets neurocognitive, neurobehavioural and neuropsychiatric symptoms following a head injury. Nous n'avons pas inclus l'utilisation de tous les anticonvulsivants, de tous les neuroleptiques, bêtabloquants, benzodiazépines, azospirones ou facilitateurs cognitifs. Malheureusement, la qualité des données est généralement médiocre et parfois elles sont contradictoires, ce qui donne lieu à des lignes directrices ambiguës quant au traitement de ces patients. Le fait de reconnaître les lacunes de ces données peut servir de prémices à une amélioration dans la collecte des données sur les symptômes neurocognitifs, neurocomportementaux et neuropsychiatriques chez les traumatisés crâniens.

Correct identification and effective visualization of interactions in biomolecular structures facilitate understanding of their functions and molecular design. In response to the practical needs of structure-based analysis, we have created a Mapiya web server. The Mapiya integrates four main functionalities: (i) generation of contact maps – intramolecular and intermolecular—for proteins, nucleic acids, and their complexes; (ii) characterization of the interactions physicochemical nature, (iii) interactive visualization of biomolecular conformations with automatic zoom on selected contacts using Molstar and (iv) additional sequence- and structure-based analyses performed with third-party software and in-house algorithms combined into an easy-to-use interface. Thus, Mapiya offers a highly customized analysis of the molecular interactions' in various biological systems. The web server is available at: http://mapiya.lcbio.pl/