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Anticoccidial activity of 8-aminoquinolines, pamaquine, primaquine and several molecular complexes and salts of pamaquine, against Eimeria tenella, E. necatrix, E. acervulina, E. maxima, and E. brunetti in battery experiments.

Pamaquine and primaquine, the well known antimalarial 8-aminoquinolines, have not been reported for their anticoccidial activity. A series of battery experiments was conducted to investigate their activity against a laboratory strain of Eimeria tenella, E. necatrix, E. acervulina, E. maxima, or E. brunetti and revealed that both drugs were effective against E. tenella and E. necatrix, but not against the other three species. Pamaquine suppressed the symptoms of E. tenella induced coccidiosis at concentrations above 125 ppm in feed and primaquine controlled the clinical signs as well at levels above 31.2 ppm. The activity against E. necatrix was observed with pamaquine at 250 ppm and with primaquine at levels above 125 ppm. Pamaquine showed a tendency apparently to reduce body weight gain at 125-500 ppm, whereas primaquine showed the same tendency at 500 ppm. In a concomitantly conducted experiment, this adverse effect of pamaquine was averted in its molecular complexes with benzophenone, nitropyrazole, dinitrobenzoic acids and quinoline, and in its salts of sulfate or zinc chloride, and yet these compounds retained the same anticoccidial activity as of pamaquine. This suggests that these compounds had the broadened safety margin. Judging from their susceptibility to these compounds. E. tenella and E. necatrix will have similar metabolic functions to those of blood cell parasitizing protozoa like plasmodia and prioplasma, which are easily suppressed by this class of compound.

Aminoquinolines↗

Seasonal variations in the gastro-intestinal nematode populations of Scottish hil sheep.

In each of two consecutive years, groups of breeding ewes were removed from a hill farm in the west of Scotland on four occasions, namely late pregnancy, early lactation, autumn and early winter. At slaughter the major nematode genus present in the alimentary tract was Ostertagia, with O circumcincta the predominant species but three species previously found in Scottish hill sheep, Bunostomum trigonocephalum, Strongyloides papillosis and Chabertia ovina were absent. An absolute increase in total nematode burden and faecal egg count was apparent in the ewes commencing in late pregnancy, reaching a maximum during lactation and falling again in autumn and early winter. This peri-parturient increase in the nematode population could not be solely attributed to the maturation of previously inhibited larval stages but was primarily the result of the development of recently ingested infection; the latter situation thought to be due to a temporary relaxation of immunological response by the ewe at parturition or early lactation. Serum pepsinogen values in ewes remained elevated throughout the grazing season and were always higher than those of their lambs, suggesting that the ewe, although allowing few parasites to become established, was under considerable challenge in the autumn. The worm burdens of the lambs were always low in autumn and early winter with Ostertagia spp being the major genus present during the autumn and Trichostrongylus spp being the predominant genus during the early winter.

Abomasum↗

Scanning electron microscopy of the small intestine of rats experimentally infected with Cynodiplostomum azimi.

Scanning electron micrographs of the proximal intestine of rats infected with C. azimi showed mild villous changes and excessive mucus secretion as early as the first day after infection. On the second day the regular leaf-like pattern of the villi was not seen, the epithelial lining of the mucosa was damaged with large amounts of mucus. Goblet cell openings appeared either empty or filled with secretions. The mucosal damage persisted for three months. Four months after infection, villi regained part of their normal pattern. Their epithelial lining although less damaged, appeared delicate. Villi away from the worm were less affected. Pathological changes at different intervals of infection were discussed in relation to the surface structure of the parasite.

Animals↗

[The effects of intestinal parasites on enteric bacterial flora].

Intestinal parasites, can cause malabsorption syndromes and shifts in intestinal bacterial flora. In this study 200 cases with parasitic infestations were examined in regard to their intestinal flora. The series included 96 giardiasis. 58 Ascariasis, 20 Oxyuriasis and 17 H. nana 14 T. trichiura, 8 Tenia cases. The stool cultures yielded mainly E. coli, Strep. faecalis and other gram negative enteric bacteria, yeasts along with uncommon species as B. subtilis, Herellea, Shigella at low frequencies. The control group of 50 patients without parasitic infestations had the same distribution ratio for the same species. The observed frequencies of the isolated bacterial species showed no significant differences between the parasite positive and control cases.

Enterobacteriaceae↗

Modulation of porcine biotransformation enzymes by anthelmintic therapy with fenbendazole and flubendazole.

Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.

Alcohol Oxidoreductases↗

Swine infection with Trichinella spiralis: Comparative analysis of the mucosal intestinal and systemic immune responses.

The immune protective response developed by swine against Trichinella spiralis is not yet fully understood, particularly at the mucosal level. This study aimed to characterise intestinal immunity to T. spiralis by comparison with the systemic response in specifically pathogen-free pigs. For this purpose, the kinetics of cytokine and antibody production were assessed in the intestinal mucosa and serum of swine infected with T. spiralis for up to 60 days post-infection (dpi). An ex vivo model of jejunum mucosa culture was used to collect the supernatant as a source of antibodies (Abs). Mucosal antibodies were observed by Western blot from 15 dpi, while serum antibodies were expressed from 20 dpi. Both sources of antibodies initially recognized a 110 kDa protein, followed by the identification of 35, 43/46 and 55/59 kDa proteins. IgG1 and IgA antibodies were strongly expressed within the mucosa. The expression levels of Type 1 (IFN-gamma, IL-12), Type 2 (IL-4, IL-6), pro-inflammatory (TNF-alpha) and regulatory (IL-10, TGF-beta) cytokines were assessed by RT-PCR in the intestinal mucosa and spleen. Both IL-10 and IFN-gamma mRNA levels were increased in mucosa, whereas IL-6 and IL-12 mRNA were expressed in spleen. Taken together, these results demonstrated a mixed Type 1/Type 2 profile, the Type 2 profile being dominant in the mucosa.

Animals↗

Malabsorption associated with diarrhea and intestinal infections.

An episode of diarrhea causes weight loss and a temporary cessation of growth in infants and children. Diarrhea is accompained by malabsorption of sugars, nitrogen, fats, and micronutrients. The mechanisms by which acute diarrheal disease produce malabsorption have not been studied carefully. The nutritional costs of malabsorption may pose a major threat if diarrhea becomes chronic or recurrent. The hydrogen breath test for carbohydrate malabsorption does not require intubation or blood drawing and can be used in children to help clarify the importance of carbohydrate intolerance in the duration and perpetuation of acute diarrhea and intestinal bacterial overgrowth.

Bacterial Infections↗

Prevalence of Giardia spp. in beaver and muskrat populations in northeastern states and Minnesota: detection of intestinal trophozoites at necropsy provides greater sensitivity than detection of cysts in fecal samples.

Surveys of the prevalence of the intestinal protozoan Giardia spp. in animal populations have relied almost exclusively on the detection of cysts in fecal samples. We have determined the prevalence of Giardia spp. in beaver and muskrat populations in four northeastern states and Minnesota by using both the detection of trophozoites in mucosal scrapings from live-trapped animals at necropsy and the detection of cysts in fecal samples collected from kill-trapped animals. In muskrats the prevalence of Giardia infection was 36.6% by cyst detection in fecal samples (n = 790) from kill-trapped animals and 95.9% in live-trapped muskrats when the intestinal contents were analyzed for the presence of trophozoites (n = 219). Similarly, in beavers, Giardia infection was 9.2% by cyst detection in fecal samples (n = 662) from kill-trapped beavers and 13.7% in live-trapped animals examined for the presence of intestinal trophozoites (n = 302). The detection of trophozoites in mucosal scrapings from live-trapped animals consistently yielded a significantly higher prevalence for both muskrats and beavers than did the method based on detection of cysts in the fecal samples. The prevalence of Giardia infection in juvenile and adult live-trapped muskrats was similar (92.5 and 94.4%, respectively), but the prevalence in juvenile live-trapped beavers (23.2%) was significantly greater than that seen in the adult animals (12.6%). No difference in Giardia prevalence on the basis of sex was seen in either animal species. Regional variation, often statistically significant, was seen in the prevalence of Giardia in beavers in the northeastern states and Minnesota, but was not detected for muskrats.

Animals↗

Tikusnema javaense n. gen., n. sp. (Nematoda: Acuarioidea) and other nematodes from Rattus argentiventer collected in west Java, Indonesia.

Nematodes collected from the ricefield rat, Rattus argentiventer (Rodentia: Muridae), in Pusakanagara and Sukamandi, West Java, Indonesia, are reported. Tikusnema javaense n. gen., n. sp. (Nematoda:Acuariidae:Seuratiinae) is described from the small intestine. This new genus is distinguished readily from other genera of the subfamily Seuratiinae in having 4 strongly protruded cuticular leaves in the posterior cephalic portion and in having a pair of prominent cuticular ornamentations posterior to deirids. Besides T. javaense, Eucoleus bacillatus, Strongyloides ratti, Nippostrongylus brasiliensis, Syphacia muris, and Physaloptera sp. were detected.

Animals↗

Improved method for the recovery of Ascarus suum larvae from pig intestinal mucosa.

In the course of a comprehensive study on the population biology of Ascaris suum, it became necessary to determine quantitatively the migration of the larvae (L2) through the pig intestine. Because no satisfactory methods for recovering these larvae from the intestinal mucosa were apparently available in the literature, we undertook the development of such a procedure. Direct Baermannization of the intestine proved inadequate, so a series of studies was undertaken to find a method to solubilize the mucosa and free the larvae. Both pepsin digestion and mucus reduction with N-acetyl cysteine were evaluated. The highest recovery rates were obtained with short-term pepsin digestion (45-90 min), followed by a specific settling and washing procedure. A third alternative, migration of larvae out of agar-gel, was also tested. Although the recovery efficiency was low (10% of pepsin digestion), the larvae recovered were clean, with good motility. The agar-gel procedure could be useful when L2 larvae are needed for other purposes, such as antigen preparation or cultivation.

Acetylcysteine↗

Incidence of intestinal obstruction in children infected with Ascaris lumbricoides.

The most serious consequences of infection with the large roundworm, Ascaris lumbricoides, are complications requiring surgical intervention, particularly intestinal obstruction caused by a bolus of worms. A study was conducted to estimate the incidence of this complication among infected children in an area of the southeastern United States where ascariasis is endemic. A chart review at three rural Louisiana public hospitals revealed that 21 patients had been hospitalized with intestinal obstruction secondary to ascariasis over a 3-year period. The prevalence of ascariasis in three parishes (counties) served by these hospitals was calculated from the results of 2,360 stool examinations performed by the State Health Department and one hospital laboratory. The prevalence of ascariasis in 1- to 5-year-old children was similar to that in 6- to 12-year-olds and ranged from 8% to 28% in the three parishes. Prevalence rates were three times higher for blacks than for whites. It was found that most cases of intestinal obstruction occur in children in the 1- to 5-year age group and that this incidence approximates two such complications per 1,000 infected children per year.

Adolescent↗

Intestinal mucosal injury is associated with mast cell activation and leukotriene generation during Nippostrongylus-induced inflammation in the rat.

We examined mucosal injury in the jejunum of the rat during infection with the nematode parasite, Nippostrongylus brasiliensis (Nb). Injury was documented morphologically (increase in crypt length with or without villus atrophy) and biochemically (activities of digestive or proliferative enzymes) and related to mast cell activation and leukotriene generation. At day 4 crypt length and thymidine kinase activity were increased; no changes in villus parameters were recorded. No evidence of mast cell activation was found and leukotriene levels in the mucosa were normal. At day 7, the gut was acutely inflamed and edema was present at the tips of the villi. This progressed to enterocyte detachment, resulting in villus atrophy with decreased activities of brush border enzymes. At this stage mucosal histamine was decreased and rat mast cell protease II (RMCP II) was increased in serum, indicating mast cell activation. In addition, mucosal leukotrienes (LTB4, LTC4, LTE4) were present in significant quantities. Following worm expulsion, the villus abnormalities resolved and serum RMCP II returned to normal. However, the crypt hyperplasia persisted. Our results suggest that during Nb infection at least two components of injury can be identified. One component, epithelial injury at the villus tips, may be related to activation of mucosal mast cells.

Animals↗