Reviewing the biological activity of chitosan in the mucosa: Focus on intestinal immunity.

Chitosan is a polymer derived from the partial deacetylation of chitin with particular characteristics, such as mucoadhesiveness, tolerability, biocompatibility and biodegradability. Biomedical uses of chitosan cover a wide spectrum of applications as dietary fiber, immunoadjuvant and regulator of the intestinal microbiota or delivery agent. Chemical modification of chitosan is feasible because its reactive amino and hydroxyl groups can be modified by a diverse array of ligands, functional groups and molecules. This gives rise to numerous derivatives that allow different formulation types influencing their activity. Considering the multiple events resulting from the interaction with mucosal tissues, chitosan is a singular candidate for strategies targeting immune stimulation (i.e., tolerance induction, vaccination). Its role as a prebiotic and probiotic carrier represents an effective option to manage intestinal dysbiosis. In the intestinal scenario where the exposure of the immune system to a wide variety of antigens is permanent, chitosan increases IgA levels and favors a tolerogenic environment, thus becoming a key ally for host homeostasis.

Animal health and price transmission along livestock supply chains.

Animal health diseases can severely affect the food supply chain by causing variations in prices and market demand. Price transmission analysis reveals in what ways price variations are transmitted along the supply chain, and how supply chains of substitute products and different regional markets are also affected. In perfect markets, a price variation would be completely and instantaneously transmitted across the different levels of the supply chain: producers, the processing industry, retailers and consumers. However, empirical studies show that food markets are often imperfect, with anomalies or asymmetries in price transmission and distortions in the distribution of market benefits. This means, for instance, that a price increase at the consumer level may not be transmitted from retailers to processors and producers; yet, on the other hand, price falls may rapidly affect the upstream supply chain. Market concentration and the consequent exertion of market power in key segments of the supply chain can explain price transmission asymmetries and their distributional effects, but other factors may also be involved, such as transaction costs, scale economies, and imperfect information. During the bovine spongiform encephalopathy (BSE) crisis, asymmetric price transmission in the beef supply chain and related meat markets determined distributional effects among sectors. After the spread of the BSE food scare, the fall in demand marginally affected the price paid to retailers, but producers and wholesalers suffered much more, in both price reductions and the time needed to recover to precrisis demand. Price transmission analysis investigates how animal health crises create different economic burdens for various types of stakeholder, and provides useful socioeconomic insights when used with other tools.

Les maladies animales peuvent avoir de graves répercussions sur la filière agroalimentaire en occasionnant une instabilité des prix et de la demande. L'analyse de la transmission des prix met en lumière la manière dont les variations de prix se transmettent tout au long de la chaîne d'approvisionnement et leurs conséquences sur les productions de substitution et sur les différents marchés régionaux. Dans un marché parfait, toute variation de prix se répercute de manière intégrale et instantanée à chaque niveau de la chaîne d'approvisionnement : producteurs, transformateurs, détaillants et consommateurs. Des études empiriques ont toutefois montré que les marchés de l'agroalimentaire sont souvent imparfaits, avec des anomalies ou des asymétries dans la transmission des prix ainsi que des distorsions dans la répartition des bénéfices commerciaux. Ainsi, par exemple, une hausse du prix payé par le consommateur ne se transmet pas nécessairement du détaillant aux transformateurs et aux producteurs, tandis qu'une baisse des prix affecte très rapidement la filière en amont. Si les asymétries de la transmission des prix et leur impact distributif peuvent s'expliquer par la concentration des marchés et par la puissance commerciale exercée par des segments clés de la chaîne d'approvisionnement, d'autres facteurs entrent également en jeu, tels les coûts de transaction, les économies d'échelle et les failles de l'information. Lors de la crise due à l'encéphalopathie spongiforme bovine (ESB), l'asymétrie de la transmission des prix au sein de la filière viande bovine et des marchés connexes de la viande a eu pour conséquence un impact distributif parmi les secteurs concernés. Suite à la panique causée par l'ESB, la chute de la demande a eu des répercussions marginales sur le prix payé aux détaillants, tandis que les producteurs et les grossistes ont été beaucoup plus affectés, non seulement par la chute des prix mais aussi par le temps qu'il leur a fallu attendre avant que la demande retrouve son niveau d'avant la crise. L'analyse de la transmission des prix permet de comprendre la diversité des répercussions économiques d'une crise de santé animale en fonction des parties prenantes concernées et fournit un éclairage socio-économique précieux lorsqu'elle est utilisée parallèlement à d'autres outils.

Las enfermedades de los animales pueden resultar muy perjudiciales para la cadena de suministro alimentario por las oscilaciones que provocan en los precios y la demanda del mercado. El análisis de la transmisión de precios revela de qué manera las variaciones de precios se transmiten a lo largo de la cadena de suministro y cómo afectan también a las cadenas de suministro de productos sustitutorios y a mercados regionales diferentes. En un mercado perfecto, la variación de un precio se transmitiría de forma completa e instantánea a los distintos eslabones de la cadena de suministro: productores, industria transformadora, minoristas y consumidores. Sin embargo, los estudios empíricos demuestran que los mercados agroalimentarios suelen ser imperfectos y presentar anomalías o asimetrías en la transmisión de los precios, así como distorsiones en la distribución de los beneficios comerciales. Ello significa, por ejemplo, que un aumento de precio a nivel del consumidor puede no transmitirse de los minoristas a los transformadores y productores. Por otro lado, en cambio, las caídas de precios pueden afectar rápidamente a los primeros eslabones de la cadena de suministro. La concentración del mercado y el consiguiente ejercicio del poder de mercado en segmentos clave de la cadena de suministro pueden explicar las asimetrías de la transmisión de precios y sus efectos en la distribución, aunque también es posible que intervengan otros factores, como los costos de transacción, las economías de escala o las imperfecciones de la información. Durante la crisis causada por la encefalopatía espongiforme bovina (EEB), la transmisión asimétrica de los precios en la cadena de suministro de carne vacuna y en los mercados cárnicos conexos trajo consigo una serie de efectos distributivos entre los sectores. Cuando cundió la alarma causada por la EEB, la caída de la demanda afectó solo de manera marginal al precio pagado a los minoristas, pero en cambio productores y mayoristas sufrieron mucho más, tanto por la caída de precios como por el tiempo necesario para que la demanda recuperara los niveles previos a la crisis. El análisis de la transmisión de precios estudia cómo las crisis zoosanitarias imponen una carga económica variable a las distintas partes interesadas y proporciona información socioeconómica de utilidad cuando se emplea en combinación con otras herramientas.

Chitosan enhances transcellular permeability in human and rat intestine epithelium.

The intestinal epithelium regulates the transit of molecules from and into the organism. Several agents act as absorption enhancers inducing changes in both transcellular and paracellular routes. Chitosan is a non-toxic biocompatible polysaccharide widely used as dietary supplement and mucosal delivery. Chitosan triggers both the activation of intestinal epithelial cells and the release of regulatory factors relevant for its immunomodulatory activity. Yet, the interaction of chitosan with intestinal epithelial cells is poorly characterized. We studied the uptake of this polysaccharide, and we evaluated its effects in both the net water and ion movements across human and rat colon samples and the epithelial permeability. Herein, we demonstrate that chitosan increases the transcellular permeability to ions, water and protein markers in human and rat intestinal mucosa and decreases the water permeability across the paracellular pathway. These findings are relevant to understand the activity of the polysaccharide in the mucosal environment.

Signals elicited at the intestinal epithelium upon chitosan feeding contribute to immunomodulatory activity and biocompatibility of the polysaccharide.

Chitosan is a copolymer of N-acetylglucosamine and glucosamine derived from chitin with several applications in pharmaceutical and medical fields. This polysaccharide exhibits adjuvant properties in mucosal immune responses of humans, rats and mice. Characterization of signals elicited by chitosan at the intestinal epithelium could explain its immunomodulatory activity and biocompatibility. We fed normal rats with single doses of chitosan and 16h later, we purified intestinal epithelial cells (IECs) to assess immune and biochemical parameters. Following chitosan administration, mRNA expression and release of several cytokines and chemokines increased, injury markers maintained constitutive levels and MHC type II molecule expression was augmented. IEC supernatants showed higher levels of IL-10, IL-6 and TGF-beta. Arginase activity of IECs increased upon chitosan interaction in vivo and in vitro. Together, after chitosan feeding, mild activation of IECs occurs in vivo, with production of regulatory factors that could be relevant for its biocompatibility and immunomodulatory effects.

Ability of the polysaccharide chitosan to inhibit proliferation of CD4+ lymphocytes from mucosal inductive sites, in vitro and in vivo.

OBJECTIVE: After oral administration of chitosan (a copolymer of glucosamine and N-acetylglucosamine), mesenteric lymph node (MLN) lymphocytes exhibited traits of anergy, a process coupled with inability of mature T cells to proliferate. We wondered whether biological activity of chitosan could be affecting division of lymphocytes at the mucosal inductive sites. MATERIALS AND METHODS: We studied the effect of chitosan on proliferation of carboxyfluorescein diacetate-labelled MLN lymphocytes stimulated with concanavalin A in vitro. We assessed expression of CD25 and CD71 activation markers and pro-apoptotic molecule CD95L. Moreover, we studied the effect of chitosan ex vivo, in carboxyfluorescein diacetate-labelled MLN cells isolated after feeding single or repetitive doses of the polysaccharide, and we evaluated cell cycle parameters. RESULTS: Chitosan suppressed cell proliferation and down-modulated expression of CD25 in these MLN CD4+ cells isolated from normal rats. After in vivo contact, chitosan inhibited proliferation of MLN cells and reduced secretion of interferon-gamma. Furthermore, sustained feeding produced reduction in percentage of CD4+ cells in S phase of the cell cycle. CONCLUSION: Here we demonstrate the ability of chitosan to suppress proliferation of CD4+ lymphocytes from mucosal inductive sites in vivo and in vitro This effect could be relevant in modulatory activity of chitosan in the intestinal microenvironment.

The biocompatible polysaccharide chitosan enhances the oral tolerance to type II collagen.

Chitosan is a mucoadhesive polysaccharide that promotes the transmucosal absorption of peptides and proteins. At mucosal sites chitosan exhibits immunomodulatory activities and stimulates the release of regulatory cytokines. Herein we evaluated the effect of the co-administration of chitosan in the tolerance to type II collagen (CII) using an experimental model of arthritis. Rats were fed diluent (acetic acid), 1 mg CII, 1 mg chitosan or 1 mg CII + 1 mg chitosan during 5 days before immunization with CII in Freund's complete adjuvant. Systemic effects were evaluated in draining lymph nodes after antigenic challenge or during the clinical evolution of arthritis. Specific antibodies, proliferation against CII and the production of interferon (IFN)-gamma and interleukin-10 were assessed. Clinical signs were observed 13-15 days after primary immunization. The CII : chitosan group presented the lowest incidence and developed moderate arthritis, with reduced levels of immunoglobulin (Ig)G2a anti-CII, a limited proliferation in draining lymph nodes and a lower release of IFN-gamma after restimulation with CII. Our results demonstrate that chitosan enhances the tolerance to an articular antigen with a decrease in the inflammatory responses and, as a consequence, an improvement in clinical signs.

Low sodium cotransport in red cells with physiological internal sodium concentration in essential hypertension.

Ouabain-resistant Na and Li effluxes in erythrocytes from 18 normal subjects and 19 hypertensive subjects were studied in fresh cells that contained about 9 mmol Li and 2.5 or 6.5 mmol Na per liter of erythrocytes after intact cells had been incubated for 5 hours in 110 mM Li, 40 mM Na medium, with or without ouabain 10(-4) M. Outward Na cotransport was estimated at both internal Na concentrations as the furosemide-sensitive unidirectional 22Na efflux from erythrocytes into a Na free-medium containing 75 mM MgCl2. The changes in furosemide-sensitive outward Na transport between the two levels of internal Na were considered as a measure of the response of Na cotransport to the changes in internal Na within its physiological range. At both levels of internal Na, outward Na cotransport was reduced in the majority but not in all of the patients with essential hypertension (p less than 0.05 at 2.5 mmol; p less than 0.001 at 6.5 mmol). The ratio of the changes in Na cotransport to those in internal Na was lower in the hypertensive patients than in the control subjects (17.2 mumol/liter red blood cells/hr/1 mmol in internal Na increase vs 42.2, p less than 0.001). The Li-Na countertransport was increased in a few patients with essential hypertension, with no relationship to cotransport. We conclude that, in essential hypertension, the outward Na + K cotransport is impaired in fresh erythrocytes not treated with PCMBS (2,5 p-chloromercuribenzene sulfonate) or nystatin, even when internal Na is around its physiological range.

Skeletal muscle cell abnormalities in acute hypophosphatemia during total parenteral nutrition.

Muscle tissue H2O, Na, K, Mg, Cl and total P were studied in 23 patients with acute hypophosphatemia during P-deficient total parenteral nutrition. Increased muscle extracellular water and low intracellular K and Mg with high intracellular Na were found. These abnormalities were detected either in previously underfed patients with low muscle P or in well-nourished, acutely ill subjects with muscle P near to normal. These findings show that acute depletion of extracellular inorganic P is associated with changes of muscle cell composition independently of muscle cell P content.

Erythrocyte sodium transport in acute hypophosphatemia in man.

In 21 patients with acute hypophosphatemia (AHPP), we measured red cell intracellular Na concentration (Nai) and either total (T), ouabain-sensitive (OS) or ouabain-resistant (OR) efflux rate constant of Na (0K Na) in a 'physiological' Na medium. High Nai, normal 0K Na T, reduced 0K Na OS and normal 0K Na OR were found. Total OS and OR unidirectional Na effluxes were increased, normal and increased, respectively. The findings suggest that high Nai in AHPP is due to an impairment of active (OS) red cell Na transport; the increase of total Na efflux is only supported by the OR Na efflux, which, under physiological conditions, is mediated mostly by the 1 Na:1 Na exchange diffusion.

Increased erythrocyte lithium--sodium countertransport in essential hypertension: its relationship to family history of hypertension.

1. Erythrocyte lithium--sodium countertransport was measured in 46 normotensive healthy controls without family history of hypertension, 15 subjects with essential hypertension, but without evidence of family history of high blood pressure, and 43 subjects with essential hypertension and at least one hypertensive first-degree relative. 2. Mean values (mmol h-1 l-1 of erythrocytes) were 0.248 +/- 0.092 in controls, 0.258 +/- 0.087 in hypertensive subjects without family history (not significant vs controls), 0.360 +/- 0.115 in hypertensive subjects with family history of hypertension (P less than 0.001 vs controls), 0.334 +/- 0.117 in all hypertensive subjects, both with and without family history (P less than 0.001 vs controls). 3. Our data confirm the finding of an increased erythrocyte lithium--sodium countertransport, but with a significant overlap between essential hypertension and control values. Lithium--sodium countertransport is higher only in hypertensive subjects with at least one hypertensive first-degree relative. 4. We suggest that the increase of lithium--sodium countertransport in erythrocytes is not a consistent marker of essential hypertension. It seems to be associated with the family prevalence and/or the hereditability of hypertension, rather than with high blood pressure per se.

The influence of renal function on the elimination kinetics of sulbenicillin in man.

Serum concentration and urinary excretion following a single i.v. dose of 1 g Sulbenicillin (SB) have been studied in 13 subjects with different degrees of renal insufficiency and 4 control subjects. With normal GFR, serum half-life averages 27 min, with GFR between 45 and 14 ml/min, 1,5 hours, with GFR below 8-10 ml/min, 4,6 hours (maximum 7 hours). The usually recommended dosage schedule is 1 g every 6 hours. Only when GFR falls below 8-10 ml/min, the interval between doses must be changed; 1 g every 8-12 hours should be given under these conditions. However, in cases of severe extrarenal or urinary tract infections due to antibiotic-resistant strains of E. coli, Ps. aeruginosa, Pr. morganii, a first dose of 2-4 g SB should be given, followed by maintenance half-doses (1-2 g SB) every half-life.

[Na/K transport in red blood cells from normal subjects: methodological problems (author's transl)]. / Transporto Na/K nei globuli rossi di soggetti sani: problemi metodologici.

In this work we present a method which evaluates the facility of applying and reproducing ion fluxes in human cells using radioactive 22Na as a tracer. Intracellular sodium concentration, rate constants for total (oKNa TOT), ouabain-sensitive (oKNa OUABs) and ouabain-insensitive (oKNa OUABins), sodium efflux and relative effluxes obtained by multiplying the rate constant by the sodium concentration were measured in the red cells of 20 normal subjects. Our results have been shown to be comparable with those obtained in other reports and show a statistically significant relationship between intracellular sodium concentration and the rate constant for active sodium efflux: one would conclude that the intracellular sodium constant probably depends on the activity of the sodium pump genetically determined in each individual. Since such a method is precise can be exactly reproduced, it can be applied to the study of cellular metabolism of different clinical disorders characterized by significant fluid and electrolyte imbalances.

[Na/K transport in red blood cells from severely burned patients (author's transl)]. / Transporto Na/K nei globuli rossi di soggetti con gravi ustioni.

The working of the Na/K pump in the red cells of 6 patients with extensive burns was analyzed using radioactive substances with the aim of comparing their red cells with those of 20 normal subjects. In the red cells of patients with extensive burns was found that the intracellular sodium concentration was clearly increased, that the rate constant of ouabain-sensitive efflux diminished, and that the total sodium efflux was augmented by the increase of the ouabain-insensitive part. It is likely that the intra and extra-cellular transportation defects produce an accumulation of sodium inside the cell which succeeds in stimulating the activity of the pump. Although this pump is impaired, the high sodium concentration obtains a new steady state characterized by apparently normal ouabain-sensitive sodium efflux and by an increased ouabain insensitive efflux. The pathogenesis of these defects of cellular homeostasis which are linked to the presence of various complex mechanisms (shock, calorie balance, fluid and electrolyte imbalances, the circulation of "toxic substances" etc), in cases of extensive burns, has not been completely elucidated.