Pathophysiology of cestode infections: Effect of Hymenolepis diminuta on oxygen tensions,pH and gastrointestinal function

Studies on the normal and parasitized rat intestine were used to investigate the effect of the tapeworm, Hymenolepis diminuta, on in vivo intestinal lumenal oxygen tensions, acid-base balance and mucosal absorption and accumulation of fluid and glucose.The lumenal bulk aqueous phase is considerable, well mixed and aerobic with an oxygen tension of 40–50 mm Hg. Neither the unstirred layers adjacent to the brush border membrane nor the area adjacent to the mucosa (“paramucosal lumen”) are significant barriers to the diffusion of oxygen from the blood to the intestinal lumen. In the uninfected distal ileum and colon anoxic conditions may occur in the central lumen, but, in the parasitized intestine fluid absorption is reduced and anoxic conditions do not occur. Increased H⁺ ion concentration in the parasitized intestine plays a role in increasing the availability of oxygen to intestinal helminths. Concomitant with the lower pH, the pCO₂ in the lumen of the parasitized intestine was twice as high as that found in normal animals. The total CO₂ in the parasitized intestine steadily decreased over a 3-h perfusion period, while in the normal intestine the total CO₂ content increased after an initial fall during the first 30 min of perfusion. When the worms were removed, the ability of the intestine to restore normal acid-base balance was restored. Glucose and fluid absorption in both the infected and uninfected intestine were reduced by an increase in H⁺ ion concentration; both parameters were lower in the parasitized intestine than in the normal animals. Low pH increased fluid and glucose transport by H. diminuta.While the dry weights of both the parasitized and uninfected total small intestine and of the intestinal mucosa were the same, the wet weights were considerably different, indicating defective fluid balance in the infected intestine. Accumulation of glucose by the parasitized mucosa was greater than in control animals and decreased with an increase in H⁺ ion concentration. The glucose transport system in the parasitized gut was therefore affected at two levels, one at the brush border, where transport into the mucosa was decreased by lowering the pH, and secondly at the level of the basal and lateral membranes, where transport out of the mucosal tissue into the circulatory system was also reduced.The above results are discussed in terms of current widely accepted but erroneous concepts relating to the intestinal ‘microcosm’.     

Proximal-distal absorptive gradients in the in vivo intestine of normal and infected (Hymenolepis diminuta: Cestoda) rats.

Using a single-pass perfusion technique, H2O, Na+, Cl-, HCO3-, and glucose absorption were studied in the jejunum and proximal and distal ileum of rats either uninfected or infected with a tapeworm parasite (Hymenolepis diminuta). The effect of parasitization, region of the intestine, type of buffer, and concentration of glucose in the perfusion fluids on the transport data were analyzed by univariate and multivariate techniques. Proximal-distal flux gradients were observed for water and all the solute species studied, as well as for glucose- and bicarbonate-stimulated salt and water transport; there was a decreasing sensitivity to low pH proceeding distally. The major regional differences occurred between the proximal and distal ileum, with the fluxes in the jejunum being similar to those in the proximal ileum. Na+, H2O, and glucose transport decreased, while Cl- absorption increased, proceeding distally. The parasites diminished the rates of absorption of glucose, salt, and water, and altered the flux gradients, particularly the Na+ and HCO3- transport gradients. The differences in the gradients between control and infected animals were related to differential sensitivity of the different transport systems in the various regions of the gut to parasitism.     

Local and systemic effects on inflammation during Eimeria nieschulzi infection

Rats infected with Eimeria nieschulzi, a coccidium that inhabits intestinal epithelium, have a lower basal inflammatory state in their intestinal mucosa eight days postinoculation as reflected by a drop in mucosal peroxidase activity and a decrease in the number of granulocytes in the lamina propria. The reduction of systemic inflammation in infected rats was assessed from a reduction in the formation of granulation tissue around a sterile cotton string implanted under the abdominal skin of the hosts. This reduced inflammatory response, both locally and systemically, occurs during the development of gamonts by the parasite and the release of oocysts from the host. These results plus the presence of normal or slightly elevated numbers of granulocytes in peripheral blood lead to the conclusion that the parasite does not affect hematopoiesis but interferes with some phase in the directed migration of leukocytes to specific sites.     

Certain aspects of the mechanism of intestinal transport of sodium, potassium, calcium and magnesium in rats

Intestinal absorption of sodium, potassium, calcium and magnesium was studied in rats by the method of intestinal perfusion using ouabain as an inhibitor of sodium-potassium dependent ATPase. At the same time the activity of ATPase and phosphatase were determined in homogenates of intestinal mucosa. A significant effect on the concentration of the determined ions was demonstrated in the transport of these ions, and also an unquestionable participation of intestinal ATPase in the direction and intensity of this transport. It was found that the multidirectional effect of ouabain on the transport of cations depended on their concentration. In the case of concentrations of cations similar to those in the mean food rations it has been demonstrated that ouabain increased the absorption of sodium, potassium and calcium and inhibited the absorption of magnesium. With a threefold higher ions concentration the absorption of potassium and magnesium was inhibited, without changing the transport of sodium and calcium. The possible explanation of the mechanism of these effects is discussed.     

Net fluxes of electrolytes in the rat intestine infected with Moniliformis dubius (Acanthocephala).

The effect of Moniliformis dubius on fluxes of Na+, K+, Cl-, and HCO3-in the rat intestine was determined using a conventional in vivo single-pass perfusion technique. Results for ion and water movements in the uninfected gut were in agreement with previous studies. In the parasitized intestine the jejunal pH was significantly lower than that in control animals, matching the restriction of the parasites to this region of the small intestine. While parasitism did not affect Na+ transport in the distal ileum, Na+ absorption was reduced (pH 7.0), or secretion enhanced (pH 6.0), in the two proximal regions. Cl-absorption was reduced in the distal ileum, but secretion was enhanced in the other two segments. Parasitism also enhanced K+ secretion in all segments. Net H2O absorption was reduced at pH 7.0; at pH 7.0; at pH 6.0 net secretion was also reduced. These changes clearly indicate that a parasite restricted to the jejunum may significantly affect the absorptive and secretory activity of the intestine distal to the site of infection. The results are discussed in the light of current concepts of electrolyte transport. The effect of the parasites on mucosal function distal to their site of attachment is discussed in terms of the release by the parasite of toxin-like substances, changes in the physical-chemical characteristics of the intestinal lumen, and interference with neurohormonal control of gastrointestinal function.     

Local and Systemic Effects on Inflammation during Eimeria nieschulzi Infection1

Rats infected with Eimeria nieschulzi, a coccidium that inhabits intestinal epithelium, have a lower basal inflammatory state in their intestinal mucosa eight days postinoculation as reflected by a drop in mucosal peroxidase activity and a decrease in the number of granulocytes in the lamina propria. The reduction of systemic inflammation in infected rats was assessed from a reduction in the formation of granulation tissue around a sterile cotton string implanted under the abdominal skin of the hosts. This reduced inflammatory response, both locally and systemically, occurs during the development of gamonts by the parasite and the release of oocysts from the host. These results plus the presence of normal or slightly elevated numbers of granulocytes in peripheral blood lead to the conclusion that the parasite does not affect hematopoiesis but interferes with some phase in the directed migration of leukocytes to specific sites.     

Glycosaminoglycans in rat mucosal mast cells.

Rats were infected with the nematode Nippostrongylus brasiliensis, resulting in an approx. 5-fold increase in the number of mucosal mast cells and the histamine content of the intestinal (jejunum) wall. After injection of the infected animals with inorganic [35S]sulphate, a similar increase in the yield of labelled intestinal glycosaminoglycans was observed, compared with uninfected control rats. Autoradiography showed a highly selective labelling of the numerous mucosal mast cells and of the few connective-tissue mast cells in the subserosal region of the bowel. Analysis of the labelled polysaccharide from the infected animals showed that almost 60% of this material consisted of oversulphated galactosaminoglycan, whereas heparin-related polysaccharides accounted for only 13%. The galactosaminoglycan contained 4-monosulphated and 4,6-disulphated N-acetylgalactosamine residues in approx. 5:1 molar ratio, both being linked to D-glucuronic acid residues; the occurrence of L-iduronic acid units could not be excluded. No significant difference in structure was found between this polysaccharide and the corresponding component isolated from uninfected rats. It is concluded that the major polysaccharide produced by rat mucosal mast cells in vivo is an oversulphated galactosaminoglycan rather than heparin.     

Vitamin absorption in the in vivo intestine of normal and infected (Hymenolepis diminuta: Cestoda) rats

Uptake and serosal transfer of the vitamins thiamine, riboflavin and folic acid have been studied in vivo in normal and parasitized rats infected with Hymenolepis diminuta (Cestoda). Regional differences in intestinal uptake of all three vitamins in both uninfected and parasitized animals were not satistically significant. In the parasitized intestine mucosal uptake and serosal transfer of thiamine were significantly inhibited, with increased mucosal accumulation of the vitamin as luminal thiamine concentration increased. Apparent increased riboflavin mucosal uptake in parasitized animals, was not matched by the reduced serosal transfer, suggesting adsorption of the vitamin in the unstirred aqueous layers. Mucosal uptake of folic acid increased in the parasitized gut; serosal transfer and mucosal accumulation were not affected. These results, indicating vitamin malabsorption associated with infection by H. diminuta, are consistent with the parasite inhibiting mucosal passive transport mechanisms. This conclusion is supported by the changes in net water fluxes associated with vitamin uptake in the parasitized intestine.     

Anaphylaxis-mediated epithelial Cl- secretion and parasite rejection in rat intestine

Immunologically mediated expulsion of Trichinella spiralis infective larvae in the rat was used as a model to test the hypothesis that intestinal anaphylaxis induced by parasite antigen causes ion transport alterations in small intestinal epithelium, and that the small intestinal epithelium, by altering its physiologic state in response to mast cell-derived mediators, functions as an effector tissue in the expulsion process. Experimental results demonstrated that the rapid rejection response and antigen-inducible changes in net intestinal ion transport acquired through active immunization were transferable with serum containing a high titer of anti-trichinella homocytotropic antibody, as measured by the PCA test. Neither response was expressed in nonimmune hosts nor in recipients of serum in which the PCA-detectable antibody was reduced by heat treatment. Net ion transport by jejunal epithelium of both actively and passively immunized rats was measured in Ussing chambers by using the electrical correlate, short circuit current (Isc). Involvement of chloride secretion in antigen-induced alterations in Isc was deduced from the use of chemical agents that effectively and specifically blocked the antigen-induced Cl- secretory response. The results implicate anaphylaxis in both rapid worm rejection and altered epithelial ion transport.     

Effect of ethanol on intestinal lipid absorption in the rat

The effect of ethanol infusion on intestinal lipid absorption was studied in rats with a duodenal cannula. Rats were infused with ethanol overnight and ethanol was included in a trioleoylglycerol emulsion infusion given for 3 hr the next day. These rats were compared to control animals infused with glucose (isocalorically). The ethanol-infused rats had a greatly impaired lipid absorptive capacity. The monoacylglycerol and free fatty acid contents in the intestinal lumen in the ethanol-infused rats were 4- and 7-fold greater, respectively, than controls. The inhibition of absorption was not due to an effect of ethanol on lipolytic activity. The lipase content of the ethanol-infused rats was greater than controls and the separate infusion of monoacylglycerol and fatty acids demonstrated impaired absorption of these end products of lipolysis as compared to controls. To observe if these changes were due to an effect of ethanol on the enterocyte brush border membrane, the membrane lipids were analyzed. The phosphatidylcholine, lysophosphatidylcholine, and phosphatidylethanolanine content was reduced but not the neutral lipids, sphingomyelin, or phosphatidylserine. The uptake of fatty acid into intestinal rings was also shown to be impaired by ethanol infusion. Lastly, the specific activity of the neutral lipids remaining in the intestinal lumen after [3H]glycerol-labeled trioleoylglycerol-infusion was similar to controls even though the mass was much greater. It is concluded that ethanol impairs neutral lipid absorption due to an effect on the enterocyte brush border membrane and by increasing the efflux of low specific activity lipid from the enterocyte back out into the intestinal lumen. A potential pathway for this efflux is the recently described increased porosity of the apical junctional complex in response to ethanol infusion.     

Physiological responses of rats to primary infection with Nippostrongylus brasiliensis

The physiological responses of well-nourished rats to primary infection with the intestinal nematode Nippostrongylus brasiliensis were examined. Infected rats fed ad libitum were compared with uninfected control rats fed ad lib. and with uninfected rats which were pair-fed to the infected rats. Following infection with N. brasiliensis rat food intake was reduced from day 2 post infection (pi) and there were two periods of minimal food intake (days 2 to 3 and 8 to 9 pi). The water intake of infected rats was only reduced on days 2, 3 and 9 pi and not to the same extent as food intake. Muscle catabolism in infected rats was more severe than could be explained on the basis of their food intake reduction. The rectal temperature and rate of oxygen consumption per g body-weight of rats was not significantly altered by the infection. Host responses to N. brasiliensis are compared with those seen in microbial infections and some of them are found to be considerably different.     

Plasmodium falciparum: physiological interactions with the human sickle cell.

The malaria parasite, Plasmodium falciparum, enhances the rate and extent of sickling of infected hemoglobin S heterozygous human erythrocytes. Upon sickling of the host cell, the parasite is killed. Parasite-free lysates of highly infected cells were analyzed to determine the mechanism by which sickling is enhanced. The intraerythrocytic pH of the infected cell was estimated to be 0.4 units below that of the uninfected cell, a difference which could result in a 20-fold increase in the extent of sickling under physiological conditions. Sickle-cell hemoglobin (HbS) heterozygous (AS) erythrocytes had decreased intracellular potassium after 24 hr of culture under conditions which cause sickling and parasite death. When infected AS cells were cultured in high-potassium medium under these conditions the parasites were protected. The medium did not prevent sickling but did maintain normal intracellular potassium levels. It is suggested that sequestration of trophozoite-infected AS cells in the venules leads to the sickling of the host cell, loss of erythrocytic potassium, and parasite death. The resulting attenuation of parasite multiplication would favor the survival of the HbS heterozygote and maintain the HbS gene at high frequencies in areas endemic for falciparum malaria.     

Pomphorhynchus laevis: the intestinal acanthocephalan as a lead sink for its fish host, chub (Leuciscus cephalus).

Aqueous lead exposure of chub (Leuciscus cephalus) experimentally infected with the parasite Pomphorhynchus laevis resulted in a rapid accumulation of this metal in the intestinal acanthocephalans, reaching concentrations which were significantly greater than in the host muscle, liver, and intestine and approximately 1000 times higher than the exposure con centration. Parasitized chub accumulated significantly less lead in their intestinal wall than their uninfected conspecifics (Mann-Whitney U test, P 相似文献   

Effect of size of Trichinella spiralis (Nematode) infections on glucose and ion transport in the rat intestine

An in vivo perfusion technique, using 3 intestinal loops representing the anterior, mid and posterior regions of the rat small intestine, was used to determine intestinal glucose uptake 5 days after infection with Trichinella spiralis. At high levels of infection (3,000 and 6,000 larvae/rat) net glucose absorption by the intestinal mucosa was significantly impaired in all regions of the small intestine when compared to uninfected controls. At low levels of infection (50 larvae/rat) glucose uptake by the mucosa was significantly enhanced in all 3 regions of the small intestine. Intermediate levels of infections (200-1,000 larvae/rat) also enhanced glucose uptake, but only in the anterior regions of the small intestine. When washings from the small intestine of rats infected with 50 larvae/rat were added to the perfusion fluid used on uninfected rats, glucose uptake was also significantly enhanced. These results suggest that at low levels of infection the intestinal lumen contains a metabolite which may affect the mucosal transport of glucose and the related fluxes of H2O, Na+, Cl-, and K+, in the rat intestine. Luminal [H+] and pCO2 decreased from the proximal to distal regions of the small intestine following perfusion; pO2 was significantly decreased in the proximal and distal regions.     

The effects of Trichinella spiralis infection on social interactions in mixed groups of infected and uninfected male mice

The presence of Trichinella spiralis infection in groups of male mice caused behavioural changes in both infected and uninfected mice. Also, for some behaviours, the extent of behavioural change in infected mice appeared to be determined by the number of muscle larvae they harboured. Infected mice showed a reduced frequency of exploratory and social behaviours compared with uninfected mice while uninfected mice performed more social investigatory activities towards those that were infected. Social interactions between infected and uninfected mice were also affected by familiarity. Behavioural differences shown to result from infection in mice familiar with each other were similar but more pronounced when the mice were unfamiliar. These results suggest that other factors may influence the behavioural effects of parasites on their hosts. For some behaviours, the greatest alterations in behaviour apparently caused by infection coincided with the period of infectivity to another host. The significance of this in relation to parasite transmission is considered.     

Eimeria meleagrimitis, E. adenoeides, and E. dispersa: Severity of infection and changes in the intestinal mucosa of the Turkey

Glucose and methionine were malabsorbed in some intestinal regions of turkeys infected with Eimeria meleagrimitis, E. adenoeides, or E. dispersa. The decrease in absorption was not always related to the numbers of parasites in the cells or the extent of damage to the mucosa. With E. adenoeides, malabsorption was found in the jejunum even though parasites were not present. Conversely, with E. dispersa, no malabsorption was observed in the duodenum even though light microscopy showed numerous parasites. In many intestinal regions, damage to the mucosal surface visible with scanning electron microscopy (SEM) was slight or absent, although malabsorption was marked. No changes were noted with SEM in the structure and orientation of the brush border in these regions. Villar height was significantly reduced in the regions of heaviest infection when intestinal damage was visible. Conversely, the crypts of Lieberkühn were often two or three times as deep in infected poults as in uninfected poults. In general, no differences were found in the thickness of the circular and longitudinal muscle layers between the infected and uninfected poults. The dry weight of the intestinal tissue was less from infected poults than from uninoculated controls and was related to both region of the intestine and severity of the infection.     

Characterization of small intestinal water, sodium, and potassium transport and morphology in the pig.

The suitability of the young pig for studies of intestinal transport was investigated by determination of net water, sodium, and potassium absorption, and morphometry in jejunum and ileum. Active net absorption was seen in both jejunum and ileum. There was no difference in absorption between segments and there was a good correlation between water and electrolyte transport. Heart rate, arterial pressure, and absorption were constant with time. Villus height and width were similar to those of human, but crypt depth was greater, and the ratio of villus height to crypt depth less. The mucosa was partially permeable to polyethylene glycol 4000 and this marker is not suitable for studies of transport in young pigs.     

Coccidian-like Nature of Toxoplasma gondii

Specific pathogen-free domestic cats were fed with tissue cysts containing Toxoplasma gondii. In two infected cats large numbers of oocysts were produced in the faeces; no oocysts were observed in the faeces of the uninfected control cat. Five days after the feeding of the toxoplasms profuse schizogonic and gametogonic stages were observed in the epithelial cells of the small intestine of one infected cat. A single schizont was observed in an intestinal epithelial cell of a second cat six days after being fed the tissue cysts. There was no evidence of schizogony or gametogony in the uninfected control cat. The stages observed in the intestinal epithelium are identical with those of the well-known endogenous cycles of coccidian parasites. The appearance of these stages, together with the nature of the oocyst, indicates that T. gondii is a coccidian parasite closely related to the genus Isospora.     

Parasitized female mice display reduced aversive responses to the odours of infected males.

The present study showed that parasites influence both the responses of uninfected females to males and the responses of female hosts to infected males. In female laboratory mice one of the consequences of exposure to the olfactory cues associated with an infected male was a reduction of the reactivity to a thermal surface, i.e. pain inhibition or analgaesia. Uninfected oestrous and non-oestrous female mice displayed marked analgaesic responses after exposure to the odours of males infected with either the enteric single-host nematode parasite, Heligmosomoides polygyrus, or the protozoan parasite, Eimeria vermiformis. The uninfected oestrous females distinguished between infected and physically stressed males, displaying a greater analgaesic response to the odours of infected males. These analgaesic responses and their anxiety/ fearfulness-associated behavioural correlates could elicit either a reduced interest in, or avoidance of, parasitized males by females. Oestrous female mice infected with H. polygyrus displayed a reduced analgaesic response to the odours of the infected males and differentially responded to the odours of males infected with either the same (H. polygyrus) or a different parasite (E. vermiformis). An exposure time of 1 min elicited minimal responses to the odours of males infected with the same parasite, H. polygyrus, and an attenuated, though significant, non-opioid peptide-mediated analgaesic response to males infected with E. vermiformis. An exposure time of 30 min elicited similar markedly reduced endogenous opioid peptide-mediated analgaesic responses to the odours of both of the categories of infected males. The responses to the odours of a stressed male were, however, unaffected by the parasitic infection. The reduced analgaesic responses of the parasitized females to the odours of infected males may involve either enhanced odour familiarity and responses to group odour templates and/or neuromodulatory shifts resulting in reduced fearfulness and potentially greater interest in the infected males.     

Nippostrongylus brasiliensis: malabsorption in experimentally infected rats

Glucose absorption and net small intestinal water movement were examined in rats infected with Nippostrongylus brasiliensis at Days 4, 6, 9, 13, and 19 after inoculation. Rats were infected with 4 X 10(3) N. brasiliensis third stage larvae. The entire small intestine was divided into three segments and each segment perfused simultaneously in vivo with Krebs-Ringer phosphate buffer containing 80 mM glucose, 6 X 10(5) dpm/ml [3H]glucose, and 6.2 X 10(3) dpm/ml [14C]polyethylene glycol. Rats perfused on Days 6, 9, 13, and 19 after inoculation showed a significant (P less than 0.05) decrease in glucose absorption rates from all three segments of the small intestine when compared to uninfected controls. In the three segments of uninfected rat small intestine and those perfused on Days 4, 13, and 19 after inoculation, net absorption of water occurred. However, in the proximal and distal segments perfused on Day 6 and the proximal segment perfused on Day 9, net water movement into the lumen occurred. This is the first report of depressed glucose absorption along the entire length of the small intestine during nippostrongylosis and contradicts previous reports of unaltered net glucose absorption in response to this parasite.