SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
We present a case report of invasive hepatic fascioliasis. Ramified hypodense lesions with peripheral distribution were found in the CT-scan. These lesions disappeared after treatment with Bithionol. CT-scan plays an important role in the diagnosis of invasive fascioliasis whereas ultrasound is useful in the chronic phase. Both are helpful to evaluate response to treatment.
A 68-year-old woman and her 28-year-old son ate some rare fresh-water crabs (Eriocheir japonicus). The son became ill one month later with pleural effusion. After 10 months the mother's symptoms included cough, hemosputum and a nodular shadow on her chest X-ray. Eosinophilia was present and the Ouchterlony test showed strong bands toward Paragonimus westermani antigen in both patients. They were diagnosed as having Paragonimiasis westermani. The symptoms stopped after Bithionol administration and the bands of the Ouchterlony test also disappeared. The difference in the latent stage and clinical symptoms of these patients, who were infected at the same time, is interesting as it highlights the importance of observing other people who may have been infected with Paragonimus westermani.
The present review has the objective to identify clinical epidemiologic characteristics and evolution for four children with Fasciola hepatica evaluated at the Pediatric Gastroenterology Unit at the Children's Health Institute, Lima, Peru, between 1988 and 1992. The first patient was a 9-year old girl who had fever, leg edema, collateral circulation and hepatomegaly, predominantly at the right lobe. The second was a 6-year old by who had upper gastrointestinal hemorrhage and fever; endoscopic diagnosis demonstrated hemobilia. The third case was a 12-year old boy who presented generalized edema. The fourth patient was a 9-year old boy with jaundice, fever and upper gastrointestinal hemorrhage. Esophageal varices and cirrhosis were present. In the four patients the diagnosis was made by the identification of parasite eggs in the feces. The first three cases responded satisfactorily to treatment with bithionol; the fourth patient died because of systemic failure.
A method for determinations of triclosan (TCS) and hexachlorophene (HCP) disinfectants in medical waste water by selected ion monitoring (SIM) using bithionol (BTN) as an internal standard compound has been developed. The method consists of the following procedures. (i) TCS and HCP in medical waste water were extracted and purified by an Extrelut column with ethyl acetate. (ii) The eluted TCS, HCP and BTN were converted to trimethylsilyl (TMS) derivatives with N,O-bis(trimethylsilyl)trifluoroacetamide-ethyl acetate (1:4). (iii) The TMS derivatives of TCS, HCP and BTN were identified and determined by SIM. Recoveries of these compounds added to medical waste water were more than 88% in amounts ranging from 1 to 10 micrograms. In the waters from our medical waste water treatment plant, TCS and HCP concentrations were found to be 0.43-8.01 and 0.24-4.69 micrograms l-1, respectively. The present method is superior to the pre-existing ones in quick separation, specificity and sensitivity.
PURPOSE: The aim of this retrospective study was to analyze the sonographic features of hepatic lesions in patients with fascioliasis to help determine the utility of sonography in diagnosing this disorder in patients from areas in which Fasciola hepatica infestation is endemic. METHODS: Seven patients with acute-phase (hepatic) fascioliasis had been identified among a previously reported series of 37 patients with fascioliasis who had been evaluated sonographically at Donostia Hospital in San Sebastián (Guipúzcoa), Spain. The 4 men and 3 women ranged in age from 29 to 69 years (mean, 49 years). A history of ingestion of watercress had been confirmed in 6 of the patients. RESULTS: Sonographically, the hepatic lesions appeared as focal areas of increased echogenicity in the right lobe (2 cases), multiple nodular or irregular lesions of variable echogenicity, ranging from 5 to 25 mm in diameter, in both lobes (4 cases), and a single 6-cm complex mass in the right hepatic lobe (1 case). Therapy with dehydroemetine, praziquantel, or bithionol resulted in complete remission, although 2 patients required an additional treatment cycle. One patient also underwent surgery. CONCLUSIONS: Sonography can be useful in the detection and follow-up of hepatic lesions in human fascioliasis and can facilitate the diagnosis of this condition, particularly in areas where it is endemic.
The acute toxicity of five antiparasitic drugs used in the veterinary field-amprolium hydrochloride (APH), bithionol (BT), levamisole hydrochloride (LVH), pyrimethamine (PYM) and trichlorfon (TRC)-to the aquatic organisms Oryzias latipes, Daphnia magna, and Brachionus calyciflorus was examined. The toxicity test with O. latipes was conducted in accordance with the OECD Guidelines for the Testing of Chemicals (1993) to determine the 24-, 48-, 72-, and 96-h LC(50) values. In addition, 24- and 48-h EC(50) values for D. magna and a 24-h EC(50) for B. calyciflorus were determined with the DAPHTOXKIT F(trade mark) magna (Creasel, Belgium) and the ROTOXKIT F(trade mark) (Creasel, Belgium), respectively. High-performance liquid chromatographic analysis revealed that APH, LVH, and PYM were stable in water, but BT was unstable, decreasing by 84% on average at 24 h. TRC rapidly decomposed, with only 0.7% of the initial concentration remaining after 96 h, forming dichlorvos. The toxicity of TRC to O. latipes was determined in two ways: exposure to the same medicated water for 96 h (static test) and exposure to medicated water replaced every 24 h (semistatic test). AMP, LVM, and PYM were tested in the static condition, and BT was tested in the semistatic condition. BT was most toxic to O. latipes, with a 96-h LC(50) of 0.24 mg L(-1), followed by PYM, with a 96-h LC(50) of 5.6 mg L(-1). The 24-, 48-, 72-, and 96-h LC(50) values of TRC in the static test were 92.0, 45.2, 29.5, and 17.6 mg L(-1), respectively, which tended to be lower than those in the semistatic test, especially late in the observation period. D. magna was the most susceptible to TRC, with a 48-h EC(50) as low as 0.00026 mg L(-1). The 48-h EC(50) values of BT, PYM, and LVH for D. magna were 0.3, 5.2, and 64.0 mg L(-1), respectively. B. calyciflorus was the most susceptible to BT, with an EC(50) of 0.063 mg L(-1), followed by PYM, with an EC(50) of 15.0 mg L(-1). Among the test compounds, APH was the least toxic to all the freshwater organisms tested, with a 96-h LC(50) of >600 mg L(-1) for O. latipes, a 48-h EC(50) of 227 mg L(-1) for D. magna, and an EC(50) of 403 mg L(-1) for B. calyciflorus.
Six fasciolicides, bithionol, bromofenofos, DS-6, nitroxynil, oxyclozanide and tribromsalan, were tested for mutagenicity in the Salmonella reverse mutation test using S. typhimurium tester strains TA100, TA98, TA1535, TA1537 and TA1538 and the micronucleus test in mice. None of the fasciolicides increased the number of revertant colonies in any tester strain in the presence and absence of S9 mix, nor did they induce a significant increase of the micronuclei in erythrocytes. Taking the high correlation between mutagenicity and carcinogenicity into consideration, these results suggest that the fasciolicides tested in this investigation are devoid of carcinogenic action.
A 57-year-old man with a history of having consumed fresh-water crab 8 months previously presented with a solitary mass lesion in the left lung without any symptoms. Since neoplastic disease could not be ruled out, an open biopsy was performed, and histological examination confirmed a definite diagnosis of paragonimiasis. A high level of the anti-Paragonimus westermani antibody was detected in the sera of the patient, but this level decreased substantially 3 months after chemotherapy with bithionol.
Hepatobiliary and pulmonary trematodes continue to cause significant morbidity and mortality worldwide. This article provides a selected update on the clinical features, diagnosis, immunology, treatment, and control of infections caused by Clonorchis sinensis, Opisthorchis species, Fasciola hepatica, and Paragonimus species. Although recent molecular studies have elucidated novel mechanisms of immune evasion in Paragonimus westermani and F. hepatica, there are no immediate prospects for a vaccine for any of these trematodes. Although treatment of paragonimiasis, clonorchiasis, and opisthorchiasis was simplified with praziquantel in the 1980s, eradication of fascioliasis remains difficult because of the limited availablity of bithionol. Several experimental drugs have been tested as possible alternatives. Despite successful pilot public health programs designed to decrease transmission of these trematodes, their prevalence remains high and underlines the importance of allocating resources to control them.
The effects of a wide range of fasciolicides on the in vitro motility of Fasciola hepatica have been determined by means of an isometric transducer system. Carbon tetrachloride and diamphenethide do not affect movement at concentrations up to 500 and 100 micrograms/ml, respectively; at 1000 micrograms/ml, however, carbon tetrachloride induces a rapid tonic paralysis. Brotianide and the deacetylated metabolite of diamphenethide cause a rapid flaccid paralysis of the fluke at concentrations of 1.0 micrograms/ml and above. In contrast, the effect of MK-401 is a long-term one, a flaccid paralysis occurring after 20 hr only at 200 micrograms/ml. Praziquantel also produces a flaccid paralysis of the fluke, but this follows an initial increase, then decrease in muscle tone. The effect is rapid at 500 micrograms/ml, but long-term at 100 and 200 micrograms/ml; at these lower concentrations there is also a stimulation of activity. Oxyclozanide , rafoxanide, niclofolan , bithionol, and hexacholorophene induce a rapid spastic paralysis of the fluke at concentrations of 1.0 micrograms/ml and above. Both phasic and tonic components are evident in the response at concentrations of 1.0 micrograms/ml and below; the phasic component disappears at higher concentrations. Nitroxynil produces a similar effect, evident at higher concentrations. Among the benzimidazoles, mebendazole, oxfendazole, and albendazole sulphoxide cause a suppression of motility, whilst thiabendazole and albendazole produce a stimulation of movement. The effects are not rapid, however, for only mebendazole at 500 micrograms/ml causes total inactivity of the fluke within a 12-hr period. Possible explanations for these effects on fluke motility are discussed.
The biochemical properties of the enzyme responsible for nematode "activated L-serine sulphydrase" activity (L-cysteine + R-SH----cysteine thioether + H2S) have been investigated using primarily the gastro-intestinal nematodes Nippostrongylus brasiliensis and Haemonchus contortus. The activated L-serine sulphydrase enzyme was found to be cytosolic in origin and exhibited maximal activity at pH 9.0. Enzyme activity was widely distributed amongst the major tissues of adult female Ascaris suum but was particularly abundant in longitudinal muscle. The enzyme appeared to have a rigid specificity for L-cysteine as the primary thiol substrate, but was capable of utilising a number of sulphur amino acids (and derivatives) and nonphysiological thiols as second substrates. The best second thiol substrates were nonphysiological, hydroxyl-containing thiols that showed some structural similarity to the standard second substrate, 2-mercaptoethanol. Kinetic analyses revealed that the enzyme operates by a sequential catalytic mechanism, and the absolute Michaelis constants were: KL-cysteine = 0.21 +/- 0.02 mM and K2-mercaptoethanol = 5.58 +/- 0.59 mM. The enzyme was relatively insensitive to inhibition by a variety of substrate analogues and known inhibitors of pyridoxal 5'-phosphate dependent enzymes, whilst plant phenols caused significant levels of inhibition. The most potent inhibitors discovered were the anthelmintics bithionol, dichlorophene and hexachlorophene. Further characterisation revealed that hexachlorophene was a parabolic competitive inhibitor of the activated L-serine sulphydrase enzyme.
The latex agglutination test (LAT) was compared with the complement fixation test (CFT), double diffusion test (DDT) and enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of South American paragonimiasis. Sera from 17 Peruvian and Ecuadorian patients with paragonimiasis, from 15 Japanese patients with other helminthiases, and from 100 healthy students were analyzed. The tests were also compared using serum samples from patients treated with bithionol. There was remarkable agreement among the methods and it was concluded that the LAT could be a useful serodiagnostic technique for paragonimiasis, especially in field surveys.
Trichomonas vaginalis growing in complex medium produced volatile thiols at a rate of 0.7 nmol min-1 (mg protein)-1 and the parasite suspended in PBS with L-methionine excreted volatile thiols, including methanethiol, and alpha-keto acid. Cell-free extracts of the parasite also produced volatile thiols from L-methionine, at the rate of 5.4 nmol min-1 (mg protein)-1. Thiol production was not detectable with living cells or cell-free extracts of Tritrichomonas foetus, Trichomitus batrachorum or Pentatrichomonas hominis and homogenates of a range of trypanosomatids and mouse liver also failed to produce volatile thiols from L-methionine. Approximately equimolar concentrations of alpha-keto acid and volatile thiols were produced from L-methionine by cell-free extracts of Trichomonas vaginalis; the release of ammonia, however, was not detectable. The parasite enzyme catabolised a range of substrates and was inhibited by several compounds, including bithionol and DL-propargylglycine. Parasites grown in the presence of 10(-5) M DL-propargylglycine had no detectable L-methionine-catabolising enzyme activity. These findings indicate that T. vaginalis is significantly different from other trichomonads, a range of trypanosomatids and mouse liver in L-methionine catabolism, and that the parasite enzyme responsible for the breakdown of L-methionine in T. vaginalis appears to be similar in several ways to bacterial L-methionine-gamma-lyase (EC 4.4.1.11) and trichomonal homocysteine desulphurase (EC 4.4.1.2).
A 13-kDa fatty acid binding protein (FABP) (Fh13) has been isolated from the cytosol of adult Fasciola hepatica and its physicochemical and binding characteristics determined. Fh13 appears to exist as a dimer in native solution. Binding of the fluorescent fatty acid analogue 11-((5-dimethyl aminonaphthalene-1-sulfonyl) amino) undecanoic acid (DAUDA) to Fh13 results in changes in the emission spectrum, which are reversed by oleic acid. The binding activity for DAUDA determined from titration experiments revealed a single binding site per monomeric unit with Kd of 1.5 microM. The displacement of DAUDA by competitive nonfluorescent ligands allowed Kd values for oleic (2.5 microM), retinoic (2.8 microM), palmitic (4.1 microM) and arachidonic acid (6.1 microM) to be calculated. Ten commonly used anthelmintics were evaluated for binding to Fh13, but only bithionol showed binding activity commensurate with those of the putative natural ligands (Kd 6.8 microM).
A variety of compounds including classical anthelmintics and avermectin analogs were screened for their effects on movements of adult heartworms (HW) (Dirofilaria immitis). Contractile activity was measured by tension recording of spontaneous movements of intact HW coil preparations (6 min compound exposure) and motility was evaluated by observation of spontaneous, free movements in culture (3 and 7 days compound exposure). Results for female HW indicated that some compounds caused spastic paralysis of contractile activity and inhibition of motility in culture (bephenium, DL-tetramisole, and pyrantel); some caused only spastic paralysis of contractile activity (methyridine and disophenol); and some caused only inhibition of motility in culture (chlorpromazine, dithiazanine, 1-ethoxycarbonylmethyl-1-methylpyrrolidinium, and 4-methyltropolone). Effects on motility in culture appeared to be lethal. The following compounds lacked effects: amprolium, 2-amino-2-thiazoline, bithionol, bitoscanate, bitriben, hexachlorophene, ivermectin, and 10 H-phenothiazine. A group of avermectin analogs was screened for effects only on motility in culture of both adult female and male HW. Several of the analogs affected motility, but the effects appeared to be non-lethal. Microfilaria release into the culture media was suppressed by two of the analogs (an aglycone and avermectin B2). The HW maintenance system used in the present study facilitated screening of compounds for effects on this parasite.
Type II fatty acid biosynthesis represents an attractive target for the discovery of new antimalarial drugs. Previous studies have identified malarial ENR (enoyl acyl-carrier-protein reductase, or FabI) as the target for the antiseptic triclosan. In the present paper, we report the biochemical properties and 1.5 A (1 A=0.1 nm) crystal structure of OAR (3-oxoacyl acyl-carrier-protein reductase, or FabG), the second reductive step in fatty acid biosynthesis and its inhibition by hexachlorophene. Under optimal conditions of pH and ionic strength, Plasmodium falciparum OAR displays kinetic properties similar to those of OAR from bacteria or plants. Activity with NADH is <3% of that with NADPH. Fluorescence enhancement studies indicate that NADPH can bind to the free enzyme, consistent with kinetic and product inhibition studies suggesting a steady-state ordered mechanism. The crystal structure reveals a tetramer with a sulphate ion bound in the cofactor-binding site such that the side chains of the catalytic triad of serine, tyrosine and lysine are aligned in an active conformation, as previously observed in the Escherichia coli OAR-NADP+ complex. A cluster of positively charged residues is positioned at the entrance to the active site, consistent with the proposed recognition site for the physiological substrate (3-oxoacyl-acyl-carrier protein) in E. coli OAR. The antibacterial and anthelminthic agent hexachlorophene is a potent inhibitor of OAR (IC50 2.05 microM) displaying non-linear competitive inhibition with respect to NADPH. Hexachlorophene (EC50 6.2 microM) and analogues such as bithionol also have antimalarial activity in vitro, suggesting they might be useful leads for further development.
Chlorinated bisphenol antibacterial and antifungal agents are potent inhibitors of torula yeast glucose-6-phosphate dehydrogenase (G6PD). Several compounds were tested, including hexachlorophene [HCP; 2,2'-methylenebis(3,4,6-trichlorophenol)]; 2,2'-oxybis(tetrachlorophenol); 2',4-dihydroxy-2,3,3',5,5',6-hexachlorodiphenylmethane; 2,2'-methylenebis(3,4-dichlorophenol) (3,4-TCP); bithionol [2,2'-thiobis(4,6-dichlorophenol)]; 2,2'-methylenebis(3,5-dichlorophenol); 2,2'-dihydroxy-3,3',5,6,6'-pentachlorodiphenylmethane; 2,2'-methylenebis(4-chlorophenol) (DCP); 2,2'-methylenebis(4,6-dichlorophenol); and the related uncoupler 2,4-dinitrophenol. The relative inhibitory activity of the chlorinated bisphenols tended to increase with degree of chlorination of the aromatic rings. the concentrations of the bisphenols that caused 50% inhibition ranged from 2.5 micrometers for 2,2'-oxybis(tetrachlorophenol) to 40 micrometers for 2,2'-methylenebis(4,6-dichlorophenol) under comparable assay conditions. More detailed kinetic analysis showed that, as with HCP, the inhibition of G6PD by 3,4-TCP and DCP followed noncompetitive kinetics. Calculations from the kinetic data gave apparent inhibition constant (Ki) values for 3,4-TCP of 267 micrometers with G6P and 308 micrometers with NADP, and for DCP of 697 micrometers with both G6P and NADP.
Paragonimiasis was diagnosed in eight patients: five with sputum specimens positive for characteristic ova and three with only stool specimens positive for ova. Clinical symptoms, roentgenograms and serologic findings appeared to correlate with severity of disease. All eight patients were treated with praziquantel (oral dose, 75 mg/kg of body weight daily for two consecutive days). Of seven patients who completed the treatment, six had ova-negative sputum and stool specimens by day 90; the seventh patient's specimens became ova negative by day 120. The eighth patient, who had failed to respond to prior treatment with bithionol, could not tolerate the daily dosage of 75 mg/kg because of nausea. Although he received the same total dose (150 mg/kg) over four days his specimens remained ova positive on day 90. Adverse effects included nausea (two patients), headache (one patient), and urticaria (two), the last effect possibly secondary to release of antigen from drug-damaged parasites. A review of the epidemiology, clinical presentation, and treatment of pulmonary paragonimiasis is presented.