Carbohydrate toxins

In addition, carbohydrate conjugates can be utilized to develop carbohydrate-based vaccines for treatment of diseases in which carbohydrate toxins or antigens, respectively, are involved. Thus, fully synthetic glycoconjugates might be developed into vaccines for malaria, and other parasites such as different bacteria, tuberculosis, tropical diseases, leishmaniasis and the Influenzae virus. 

Coelenterates and Echinoderms. Coelenterate and echinoderm toxins range from small molecular weight amines, to sterols, to large complex carbohydrate chains, to proteins of over 100,000 daltons. Molecular size sometimes reflects taxonomy, e.g., sea anemones (Actiniaria) all possess toxic polypeptides varying in size from 3,000 to 10,000 daltons while jellyfish contain toxic proteins (ca. 100,000 daltons). Carotenoids have been isolated from Asterias species (starfish), Echinoidea (sea urchins), and Anthozoans such as Actiniaria (sea anemones) and the corals. These are sometimes complexed with sterols (J5). 

Glycophorin A appears to serve a variety of functions on the red-cell membrane, and has been implicated in several red-cell disorders. Because it extends from the external environment of the cell into the cell cytoplasm, it is considered to constitute a receptor for malarial parasites,"" influenza viruses, lectins, and Portuguese man-of-war toxin. Many of these receptor functions are attributable to the carbohydrate composition of these... 

Crude chloroform-methanol-water (30 60 8, v/v) extracts of immunostainedTLC bands were analyzed without further purification by nanoelectrospray low-energy mass spectrometry. The authors showed that this effective PLC/MS-joined procedure offers a wide range of applications for any carbohydrate-binding agents such as bacterial toxins, plant lectins, and others. Phenyl-boronic acid (PBA) immobilized on stationary support phases can be put to similar applications. This technology, named boronate affinity chromatography (BAC), consists of a chemical reaction of 1,2- and 1,3-diols with the bonded-phase PBA to form a stable... 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

P. I. Kitov, J. M. Sadowska, G. Mulvey, G. D. Armstrong, H. Ling, N. Pannu, R. J. Read, and D. R. Bundle, Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands, Nature, 403 (2000) 669-672. 

G. D. Armstrong, Assessment in mice of the therapeutic potential of tailored, multivalent Shiga Toxin carbohydrate ligands, J. Infect. Dis., 187 (2003) 640-649. 

K. Nishikawa, K. Matsuoka, E. Kita, N. Okabe, M. Mizugushi, K. Hino, S. Miyazawa, C. Yamasaki, J. Aoki, S. Takashima, Y. Yamakawa, M. Nishijima, et al., A therapeutic agent with oriented carbohydrates for treatment of infections by Shiga toxin-producing Escherichia coli 0157 H7, Proc. Natl. Acad. Sci. (USA), 99 (2002) 7669-7674. 

K. Nishikawa, K. Matsuoka, M. Watanabe, K. Igai, K. Hino, K. Hatano, A. Yamada, N. Abe, D. Terunuma, H. Kuzuhara, and Y. Natori, Identification of the optimal structure required for a Shiga Toxin neutralizer with oriented carbohydrates to function in the circulation, J. Infect. Dis., 191 (2005) 2097-2106. 

The use of BRMs to treat human disease has its origins in the use of bacterial toxins to treat cancer by William B. Coley.73 These early studies resulted in the use of microbi-ally-derived substances such as BCG, Picibanil, carbohydrates from plants or fungi such as Krestin and Lentinan, other products such as Biostim and Broncho-Vaxom, as well as thymic extracts (Table 9.4). However, the lot-to-lot variation in the manufacture of these drugs has dampened enthusiasm. Equally, the focus on MOAs in drug development strategies has also dampened developmental efforts. The particulate nature of some BRMs can also result in pulmonary thrombosis and respiratory distress following i.v. injection. However, BRMs are commonly used to treat bladder cancer and derivatives of natural products are routinely used clinically. 

Large, generalist marine grazers such as fishes and urchins attempt to choose foods that maximize nutritional input (e.g., protein, lipids, and carbohydrate) (Mattson 1980 Choat and Clements 1998) and minimize intake of secondary metabolites (Hay 1991). The untested assumption underlying these optimal foraging decisions is that detoxification and excretion rates are a constraint on toxin intake and thus drive feeding choice (Freeland and Janzen 1974). However, we have virtually no information on such constraints in marine herbivores, because it requires an understanding of the metabolic fate of secondary metabolites. 

Some plants regularly eaten by humans contain neurotoxins that pose serious health problems. On Guam, for example, the seeds of Cycas circinalis used to be an important source of carbohydrates. Seeds of Cycas rumphii were ground into flour for tortillas. However, the seeds contain jS-N-methylamino-i-alanine, a suspected excitotoxin that overstimulates and destroys nerve cells. This compound causes a parkinsonism-like disease in macaques (Spencer et al, 1987). Other toxins have been proposed to be responsible for the disease, among them cycasin, another cycad toxin (Stone, 1993). 

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