Increased reactivity to 5-hydroxytryptamine of portal veins from mice infected with Schistosoma mansoni (original) (raw)
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Parasitology Research, 2002
We previously reported that portal veins from mice infected with male Schistosoma mansoni exhibited an increased reactivity to 5-hydroxytryptamine (5-HT). Here, we extended our observations to mice infected by both male and female worms and we further investigated another constrictor agent and the mechanism(s) responsible for the enhanced maximal contraction (E max). Bisexual infection increased the E max of 5-HT (from 0.66±0.06 mN.s to 1.56±0.38 mN.s), in a similar way to the unisexual (male) infection. Infection with male worms increased portal vein reactivity to acetylcholine, as revealed by a higher E max (1.03±0.2 mN.s) in relation to non-infected control animals (E max = 0.54±0.08 mN.s). Sarcoplasmic/endoplasmic reticulum Ca 2+-ATPase (SERCA) inhibition with 100 nM thapsigargin reduced the E max of 5-HT by 35% in both tissues, discharging a deficiency of SERCA pump in infected animals. In contrast, the number of voltage-dependent Ca 2+ channels (L-type) was higher in portal veins from infected than non-infected control mice. Inhibition of Ca 2+-activated chloride channels (Cl Ca) with 10 lM niflumic acid reduced the E max of 5-HT in portal veins more from infected than non-infected animals (remaining tension = 60.9±2.2% and 70.4±2.3%, respectively). Histopathological analysis revealed an increased content of collagen and elastin in portal veins from male S. mansoni-infected mice, compatible with an increased intraluminal pressure. In conclusion, male S. mansoni altered portal vein physiology, increasing the E max of two vasoconstrictors, possibly by increasing membrane depolarisation through a more effective opening of Cl Ca channels, with calcium entering through L-type Ca 2+ channels.
Hepatosplenic schistosomiasis: a model for the study of portal hypertension
Annals of Hepatology, 2002
Annals of hepatology Schistosomiasis is an endemic disease of tropical areas. In American countries as Brazil, Venezuela, Puerto Rico, Antilles and Suriname the worm that causes schitosomiasis is the schistosoma mansoni. According to the World Health Orzganization more than 600 million people live in risk areas and about 200 million are infected in 75 countries. 1 The biological cicle of the worm corresponds to three phases: when human feces containing the eggs of the parasite fall in water, they rupture liberating the miracide. The intermediate cicle occurs in a snail of the gender biomphalaria. The parasite multiplies inside the snail and after 20 to 30 days gives origin to the cercariae, that spread in warm water of about 20 to 25 degrees Celsius. Free in the water the cercariae enter through the intact skin and mucosa, suffering modifications and achieving maturation in the portal system, where sexuated adult worms lay their eggs. From the portal system eggs can spread to tissues and organs, specially the liver and intestines. As eggs are elimianted with feces they may contaminate water, closing the cycle. Adults worms live in the portal system, where about 300 eggs per day are laid and about 2/3 of them carried to the liver. The typical egg has a characteristic lateral spine, useful for its diagnosis, not only in stools but also in the various tissues where the egg can be found (Figure 1). As various couples of adult worms can be found in the veins of the portal system, specially the mesenteric veins, this parasitic infection gives rise to a vascular disorder that may end up with an hepatic disease. Worms and eggs are responsible for the pathopysiology of the disease. In the initial phases there is formation of immune complexes, rarely with acute manifestations. The chronic forms are very common, due primarily to the deposition of eggs and dead worms in different organs and tissues, particularly intestines and liver. In the later they obliterate small vessels, forming granulomas in the portal tract, obstructing Concise Review
The Hepatoprotective Effect of Nitric Oxide on Murine Schistosomiasis Mansoni
2014
MANSOURA MEDICAL JOURNAL ABSTRACT Background: Schistosomiasis is a major public health problem in developing countries. Currently, praziquantel (PZQ) is the drug of choice for human schistosomiasis. Isosorbide-5-mononitrate (IS-5-MN) is a nitro compound that is used as an antianginal remedy. It must be enzymatically metabolized to release nitric oxide (NO) to exert its pharmacologic activities. This study evaluates the vasodilator effect of the NO donor IS-5-MN on hepatic bilharzial lesions caused by Schistosoma mansoni, and determines whether the combined use of IS-5-MN and PZQ is synergistic or antagonistic. Methods: Swiss albino female mice (CD I strain) were divided into five groups: (i) non-infected; (ii) infected non-treated; (iii) infected and treated with PZQ, 6 weeks post infection (WPI) in a dose of 500 mg/ kg/day for two successive days; (iv) infected and treated with IS-5-MN from the fourth to the tength WPI 5 days/week in a dose of 10.08 mg/kg; (v) infected and treated ...
Schistosoma mansoni: effects of anesthetics and antimonial drugs on worm shift in the mouse
Revista do Instituto de Medicina Tropical de São Paulo, 1986
Mice experimentally infected with Schistosoma mansoni were injected with sodium thiopental or sodium antimonyl gluconate (Triostib R), or submitted to halothane inhalation, with or without a previous injection of thiopental. Data obtained showed that halothane and thiopental induce worm shift to the liver (99 and 76%, respectively). Sodium gluconate and antimonium (Triostib R) shifted 52% of worms towards the liver. These results seem to indicate that the use of antimonium would be unnecessary, when surgical removal of schistosomules is carried out through the extracorporeal filtration technique, in patients with portal hypertension.
Microbes and Infection, 2007
Murine Schistosoma mansoni infection is related to an increased contraction of portal vein in response to 5-hydroxytryptamine (5-HT). The present study addressed a putative alteration of ion channels and enzymes involved in vascular contraction. In control group, either inhibition of K þ channels sensitive to ATP (K ATP) or Ca 2þ (BK Ca) increased 5-HT-induced contraction, but the same did not occur in infected mice. On the other hand, inhibition of p38 MAP kinase markedly decreased the vascular contraction to 5-HT in the infected mice with minor effects in the control group. Accordingly, we observed a higher density of phospho-p38 MAP kinase, that refers to the fully active state of the enzyme, in portal veins from infected mice as compared to control animals. These results suggest that the reduced function of K ATP and BK Ca channels along with an increased contribution of p38 MAP kinase contribute to the increased contraction of portal veins to 5-HT observed in murine schistosomiasis.
Journal of Clinical Investigation, 1991
We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of6 wk at a dose of 10 mgkg-'d-1, starting at 5 wk of schistosomal infection. 32 agematched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8±0.40 mmHg) was significantly lower (P < 0.001) in the propranololtreated animals (7.9±0.80 mmHg). Portal-systemic shunting was decreased by 79%, from 12.2±3.34% in controls to 2.5±0.99% in the propranolol group (P < 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50±0.73 ml/min; n = 6) compared with controls (4.00±0.34 ml/min; n = 8; P < 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system. (J. Clin.
British Journal of Clinical Pharmacology, 1980
The in vitro effect of histamine and its antagonists, cimetidine and clemastine fumarate, on natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities of human lymphocytes was investigated. The histamine 1 (HI) antagonist, clemastine fumarate, and the histamine 2 (H2) antagonist, cimetidine, but not histamine alone, inhibited the NK and ADCC activities of lymphocytes when added directly to the mixture of effector and target cells in a 5'Cr-release assay. This inhibition was proportional to the concentration of drugs added and was observed at various effector to target ratios against several targets. Hl and H2 antagonists also inhibited NK activities of T cells as well as Percoll-separated, NK-enriched effector cells. The inhibition was significantly reversed by histamine. In target binding assays, clemastine fumarate and cimetidine also decreased the target binding capacity of effector lymphocytes. Further, PBL precultured with histamine (1O-3-1O-4 M) for 24 hr showed a significant decrease in their NK and ADCC activities. In coculture experiments, PBL precultured with histamine suppressed the NK activity of normal autologous effector lymphocytes. PBL precultured with histamine showed an increased number of OKT8+ cells, as estimated using monoclonal antibodies. The suppression of cytotoxicity was not due to either direct toxicity, steric hindrance, crowding, or cell death, but by functionally viable suppressor cells. An immunoregulatory role for histamine in NK and ADCC reactions is proposed.
Central European Journal of Immunology, 2016
The effects of artesunate and myrrh on S. mansoni infection and the levels of some Th1 and Th2 cytokines were evaluated in the present study. Six weeks after infection, a group of mice was treated with 4 mg/kg of artesunate and other group was treated with 10 mg/kg of myrrh for 3 successive days. Worm burden was reduced with a percentage of 53.7 % and 58.78 % after treatment with myrrh and artesunate respectively as well as the levels of igG antibodies were significantly reduced compared with infected group. No obvious changes were observed in the level of interferon γ after treatment. after treatment with artesunate, interleukin 2 (il-2) level was significantly decreased, while no significant difference was observed in myrrh-treated group compared with the infected group. on the other hand, the level of il-10 was not significantly decreased after treatment with artesunate, but it was significantly increased after treatment with myrrh. however, il-12 levels were significantly decreased after treatment with artesunate. The results demonstrated that, artesunate or myrrh treatment could give a level of protection against S. mansoni infection and modulate the levels of some Th1 and Th2 cytokines in mice infected with S. mansoni.