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Tumor necrosis factor alpha augments nitric oxide-dependent macrophage cytotoxicity against Entamoeba histolytica by enhanced expression of the nitric oxide synthase gene.

Nitric oxide (NO measured as nitrite, NO2-) is the major effector molecule produced by activated macrophages for in vitro cytotoxicity against Entamoeba histolytica trophozoites. In this study, we determine whether tumor necrosis factor alpha (TNF-alpha) produced by activated bone marrow-derived macrophages (BMM) is involved in the induction of the inducible NO synthase gene (mac-NOS) for NO-dependent amebicidal activity. TNF-alpha alone did not directly induce macrophage NO2- production to kill amebae; however, in combination with increasing concentrations of TNF-alpha and gamma interferon (IFN-gamma), BMM amebicidal activity and NO2- production progressively increased and showed a significant linear correlation. Antiserum to TNF-alpha and the NO synthase inhibitor NG-monomethyl L-arginine (L-NMMA) inhibited the synergistic effects of TNF-alpha and IFN-gamma. BMM activated with increasing concentrations of lipopolysaccharide (LPS) and IFN-gamma showed a significant linear correlation between TNF-alpha release and NO2- production. Antiserum to TNF-alpha suppressed TNF-alpha release, NO2- production, and amebicidal activity by 93, 53, and 86%, respectively. L-NMMA diminished NO2- production by 74% and macrophage amebicidal activity by 83% but had no effect on TNF-alpha release. Quantification by Northern (RNA) blot analyses demonstrated that IFN-gamma in combination with TNF-alpha or LPS increased markedly the accumulation of mac-NOS and TNF-alpha mRNAs in a time-dependent manner with a concomitant increase in NO and TNF-alpha production. Peak induction of mac-NOS occurred after 24 h, whereas TNF-alpha mRNA was rapidly expressed after 4 h and remained stable for 48 h. Taken together, these data argue that TNF-alpha augments NO-dependent macrophage cytotoxicity against E. histolytica via elevated levels of mac-NOS mRNA expression which may be associated with the accumulation of TNF-alpha mRNA.

Amino Acid Oxidoreductases↗

Ruptured amebic liver abscess.

Fifteen cases of extrahepatic rupture of amebic liver abscess have been reviewed. Five patients had thoracic rupture and ten had intra-abdominal rupture. Celiotomies were performed in five patients, with a preoperative diagnosis of acute appendicitis with perforation in four patients and generalized peritonitis of unknown origin in one patient. All 15 patients were treated with amebicides, including three patients with documented free intraperitoneal perforation who were not treated surgically. Twelve patients recovered uneventfully. Two patients with thoracic rupture developed secondary bacterial complications and in one case of free intraperitoneal rupture, a mistaken diagnosis of ruptured pyogenic abscess was made. Amebicidal therapy was delayed for four days. The patient died of multisystem organ failure. Amebicidal therapy is effective in the treatment of both unruptured and extrahepatic rupture of amebic liver abscess. Surgery should be required only for secondary bacterial complications.

Adult↗

Uncomplicated amebic liver abscess: prospective evaluation of percutaneous therapeutic aspiration.

The performance of therapeutic aspiration in the treatment of amebic liver abscess, advocated and practiced in many centers, is controversial. Previously, this practice has been evaluated in retrospective analyses. To test the potential benefit of therapeutic aspiration, the authors undertook a prospective randomized trial in 57 patients admitted for suspected amebic liver abscess during a 15-month period. Sixteen patients were excluded from the trial. The remaining 41 patients were randomly included in one of two study groups to receive amebicidal therapy alone or amebicidal therapy coupled with image-guided percutaneous therapeutic aspiration. All patients in the trial recovered. No statistically significant benefit was demonstrated in the aspiration group for the two objective parameters evaluated: length of hospitalization and duration of time to becoming afebrile. Subjective improvement in symptoms after aspiration was greater in the aspiration group at a marginally statistically significant level. These data do not support the adjunctive performance of percutaneous therapeutic aspiration in the treatment of uncomplicated amebic liver abscess. Amebicidals alone were equally efficacious in treating the group studied.

Humans↗

[Amebic liver abscess and amebic colitis in a couple].

Amebiasis is a disease commonly extended all around the world, its prevalence depending on the population under study. In Spain, most cases published are of exotic acquisition. We present the case of a married couple from Venezuela presenting two different forms of invasive amebiasis: acute colitis and hepatic abscess. In our environment, once the diagnosis of amebiasis is established, a close follow-up of the patients must be made, including the evaluation of the closest contacts. Regarding the treatment, we think that the asymptomatic forms must be treated with a luminal amebicidal and the symptomatic forms, with hystic amebicidal followed by luminal amebicidal.

Abdomen, Acute↗

Chemotherapeutically active anthraquinones. I. Aminoanthraquinones.

Basically substituted 2,6-diacetaminoanthraquinones proved to have an interesting in vivo effect against Entameba histolytica, but this effect was markedly exceeded by that of the series of the 2,6-diamidinoanthraquinones. A number of compounds of this series revealed a significantly stronger extraintestinal effect in the golden hamster than the standard amebicides metronidazole and tinidazole, but they were not superior to these compounds in their trichomonacidal effect, which was in general only a moderate one. In both substance classes, the amebicidal effect was confined to 2,6-disubstitution. Variations of the anthraquinone system resulted in a loss of activity. The structure-activity relationships are discussed.

Amebicides↗

[Severe forms of hemorrhagic rectocolitis. Predisposing role of the amebic graft?].

Severe forms of ulcerative colitis are somewhat rare but have a severe prognosis. Apart from the usual predisposing factors, the amebic graft must be especially emphasized, at least in those countries where the parasite is endemic. Entamoeba histolytica was consistently identified in 19 cases of the severe form that we found out of a total of 126 cases of ulcerative colitis. Usually the parasite was found in the shape of massive infestation and in most cases it proved to be resistant to the amebicides currently available. The clinical picture shown by the 19 patients was identical to that given in the literature for severe forms of ulcerative colitis. Therapeutically, it was essential to combine one (or, if necessary, several) course(s) of treatment with amebicides with the usual therapeutic measures until the parasite was destroyed in the intestine. This work suggests that any attack on ulcerative colitis must automatically include an anti-amebic course of treatment, and this should strictly precede any corticosteroid therapy, even administered as enemas.

Adolescent↗

A study with quinfamide in the treatment of chronic amebiasis in adults.

Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-mg doses, each given three times daily. A cure rate of 100% was found at a dosage of 100 mg/8 hr and of 93.3% at 200 mg/8 hr. These results indicate that quinfamide is an effective luminal amebicide at the doses studied.

Adolescent↗

[Amebic liver abscess: review of 13 cases].

Amebian hepatic abscess (AHA) is the most frequent extraintestinal localization of infection by Entamoeba histolytica. Despite being a disease mainly of tropical zones, it is currently also observed with higher frequency in Spain. Thirteen cases of AHA diagnosed in the authors' hospital over the last 11 years were retrospectively analyzed comparing the data in this series with that of other published series and undertaking a review of this subject. The diagnosis of AHA was established on the basis of the clinical picture together with specific positive serology and compatible echographic imaging. The series was composed of 9 males and 4 females with a mean age of 38.7 years (range 25-55). Five were Spanish, and 8 were immigrants from tropical countries. In 61.5% of the cases echographically guided aspiration puncture was performed with placement of percutaneous drainage being carried out in 38%. Eighty-five percent of patients were treated with more than one amebicide drug (metronidazole or tinidazole together with chloroquine and dehydroemetine). Luminal amebicides were administered lastly. Laparotomy was required in 3 cases due to the presence of complications. No deaths were observed.

Adult↗

Hepatic abscess.

Hepatic abscess--amebic or pyogenic--can be diagnosed with great accuracy by either ultrasonography or computed tomographic (CT) scanning. Ultrasound is the modality of choice and will detect almost 100% of abscesses. Confirmation of a diagnosis of amebic liver abscess is made by the indirect hemagglutination test that should be positive in almost 100% of cases. Cultures of pus from the abscess and from the blood must be obtained in cases of pyogenic liver abscess. A positive culture of pus from the abscess has been achieved in 90% of cases. Ultrasound or CT guidance is utilized in aspiration of a hepatic abscess. In the treatment of an amebic liver abscess, metronidazole is the amebicide of choice. Open drainage is contraindicated. For cases that fail to respond to therapy with amebicides, closed drainage guided by CT or ultrasound is performed. Secondary bacterial infection of an amebic liver abscess is an extremely rare event. The identification and determination of the antibiotic sensitivity of organisms responsible for pyogenic liver abscess is a crucially important step. Unless a celiotomy is necessary to correct an intraabdominal process or the abscess is extremely large, the initial treatment of pyogenic liver abscess is a 2 week course of appropriate antibiotics followed by a 1 month course of oral antibiotics. The majority of pyogenic liver abscesses will respond to such treatment. If drainage of a pyogenic abscess is required, the preferable technique is with a percutaneous CT- or ultrasound-directed catheter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of magainins on ameba and cyst stages of Acanthamoeba polyphaga.

Amebic keratitis produced by Acanthamoeba spp. is an increasingly important ocular infection in extended-use contact lens wearers. Problems associated with the infection are compounded by the lack of effective and well-tolerated chemotherapeutic agents. The magainins, a group of naturally occurring and synthetic membrane-active peptide compounds, have been shown to be active in vitro against a clinical isolate of Acanthamoeba polyphaga. Two magainins tested extensively had minimal inhibitory and minimal amebicidal values of 20 and 25 micrograms/ml for magainin MSI-103 and 25 and 40 micrograms/ml for magainin MSI-94, respectively. Both amebastatic and amebicidal activities are enhanced by combining the magainins with silver nitrate (200 micrograms/ml) and/or other marginally effective antimicrobial agents. These combinations have activity against both trophic and cystic stages in the Acanthamoeba life cycle and have promise as antimicrobial agents in the treatment of amebic keratitis.

Acanthamoeba↗

The prognostic factors of severe amebic liver abscess: a retrospective study of 125 cases.

One hundred twenty-five cases of amebic liver abscess were diagnosed at Chang Gung Memorial Hospital in Taiwan from January 1981 to December 1989. An analysis of possible prognostic factors for severe amebic liver abscess was done retrospectively. The majority of the patients came from the southern part of Taiwan. Severe amebic liver abscess was defined as the rupture of an abscess that was resistant to 72 hr of medical treatment, or complicated by secondary bacterial infection. The results showed significant differences between patients with severe liver abscess and those with more moderate forms of amebic liver abscess in indices such as jaundice, hemoglobin and serum bilirubin levels, and dyspnea, as well as in pulmonary changes (right diaphragm elevation, right pleural effusion) seen on chest radiographs. Those patients with diabetes mellitus also had greater evidence of severe liver abscess. Moderate cases that were treated with amebicides showed excellent responses (no mortality). Severe cases required, in addition to amebicide therapy, either percutaneous or surgical drainage of pus, especially in those patients with ruptured abscesses. Those patients with abscesses that ruptured into the thoracic cavity were treated by either thoracostomy or needle aspiration, and all were cured. Three patients died of abscess rupture into the abdominal cavity, associated with secondary bacterial infection. The overall mortality rate was 2.4%. These symptoms and signs of severe liver abscess are indicators of the need for intensive treatment such as aspiration or surgical drainage.

Adult↗

[Clinical and therapeutic study of a group of 217 patients with intestinal giardiasis and amebiasis].

In 15 months of the years 1979-1980, 158 patients with giardiasis and 69 patients with intestinal amebiasis were diagnosed and treated in the outpatient department of the Swiss Tropical Institute. Repeated examination of merthiolate-iodine-formol-fixed stools was the method of choice for detecting intestinal protozoa. Parasitological investigation of duodenal fluid (Enterotest) was less effective. Fewer than 30% of the cases were symptomatic, usually mentioning diarrhea (73-85%) or abdominal discomfort (20-44%). Treatment was by ornidazole single dose (2 g in adults; 40 mg/kg in children) for asymptomatic cases and a five-day treatment schedule (2 X 500 mg/day in adults, 20 mg/day in children) for symptomatic cases. In amebiasis a luminal amebicide (diloxanide furoate) was prescribed in all instances after the first stool examination. Parasitological cure rates were excellent (95%) in all cases of giardiasis but only 59 and 65% respectively in cases of asymptomatic and symptomatic amebiasis. Drug tolerance was excellent. Ornidazole is the drug of choice for all forms of giardiasis, even in a single dose. As a luminal amebicide, however, its efficacy is not superior to other nitroimidazole derivatives.

Drug Administration Schedule↗

Mutagenicity of urine from mice exposed orally to nitrite and various aminated antiparasitic drugs.

Mutagenic N-nitroso compound formation from the in vitro reaction of amebicides and anthelmintic drugs, which are pyrimidine derivatives or contain secondary aliphatic amines or heterocyclic nitrogens, has been previously described (Arriaga Alba et al.: Environmental and Molecular Mutagenesis 12:65-73, 1988). Under similar conditions, antiparasitic drugs containing halogenated derivatives of tertiary amines or quaternary ammonium salts do not form mutagenic nitrosated compounds. In the present study the mutagenic activity of mouse urine was determined after oral administration of sodium nitrite and the two above-mentioned groups of drugs (pyrantel pamoate, chloroquine, piperazine and dehydroemetine/iodochlorhydroxyquin and bephenium hydroxynaphthoate, respectively). Results show that the simultaneous administration of piperazine or chloroquine with sodium nitrite produced urinary mutagens that appeared conjugated as glucuronides, whereas pyrantel pamoate and dehydroemetine in the presence of nitrite caused only slightly mutagenic urine. No mutagenic activity was detected in the urine of mice to which halogenated derivatives of tertiary amines (iodochlorhydroxyquin) or quaternary ammonium salts (bephenium hydroxynaphthoate) were administered together with nitrite.

Amebicides↗

Surgical management of hepatic abscesses.

Amebic and pyogenic hepatic abscesses are rare liver lesions that may require surgical intervention. Amebic liver abscesses are more common in subtropical and tropical climates and in areas with poor sanitation. The majority of pyogenic liver abscesses are caused by infections in the biliary or intestinal tracts. These lesions can be differentiated on clinical grounds and by amebic serology. Ultrasound and computed tomography are the imaging techniques of choice. The initial management of amebic hepatic abscesses is treatment with amebicidal agents. Most patients respond rapidly so that surgery is reserved for patients with complications including secondary bacterial infection, impending rupture, or rupture into the pericardium or peritoneum. Patients with pyogenic hepatic abscesses require a prolonged course of antibiotics and appropriate drainage. Selected solitary abscesses can be managed with percutaneous abscess drainage. Similarly, some abscesses of biliary origin will respond to percutaneous biliary drainage. Surgical drainage has several advantages including: the ability to explore the abdomen for a source, excellent exposure of the entire liver, accurate assessment, sometimes with ultrasound, of the best drainage site, and access to the biliary tree for cholangiography and drainage.

Amebicides↗

Mutagenicity of antiamebic and anthelmintic drugs in the Salmonella typhimurium microsomal test system.

4 amebicides (chloroquine diphosphate, diiodohydroxyquin, iodochlorohydroxyquin and dehydroemetine) and 6 anthelmintics (bephenium hydroxynaphthoate, 4-hexylresorcinol, mebendazole, niclosamide, pyrantel pamoate and pyrvinium pamoate) were tested for mutagenicity in the Salmonella typhimurium microsomal test system. Frameshift mutations were induced by dehydroemetine and niclosamide following activation by microsomal enzymes, while pyrvinium pamoate induced both frameshift and base-pair substitution mutations with or without metabolic activation. The urine of mice treated with dehydroemetine or pyrvinium pamoate showed no mutagenic activity. However, urine obtained from mice treated with niclosamide was mutagenic in strains TA98 and TA1538. The fluctuation assay showed chloroquine diphosphate to be mutagenic in TA1537, a strain which detects frameshift mutations.

Amebicides↗

Influence of the Uvr repair system on the mutagenicity of antiparasitic drugs.

One amebicide (chloroquine diphosphate) and 2 anthelmintic compounds (niclosamide and pyrvinium pamoate) were found to be mutagenic for Salmonella typhimurium TA1537, TA1538, TA100 and TA98 Uvr- strains respectively. Drugs tested on homologous Uvr+ strains (TA1977, TA1978, UTH8414 and UTH8413) showed decreased mutagenic activity of the compounds. This indicates that premutational damage induced by the drugs was totally or partially repaired. Furthermore, results obtained in the present study suggest that niclosamide and pyrvinium pamoate induce premutational lesions by adduct formation, and that chloroquine diphosphate, known as an intercalating agent, behaves as an adduct-forming compound as regards its effects on Uvr- and Uvr+ S. typhimurium strains.

Amebicides↗

Therapy of entamebiasis.

Therapy of entamebiasis is critical in that, if untreated, the disease can be fatal. Recently, a new method for differentiating pathogenic and non-pathogenic amebae has been standardized. This method relies upon the electrophoretic analysis of 4 isoenzymes which allow the identification of 20 different zymodemes. It is now widely accepted that non-pathogenic strains of Entamoeba histolytica are not a hazard for humans and therefore don't need therapy. As a consequence, treatment must be addressed only toward infections caused by pathogenic strains. As there are different drugs available for treating amebiasis, from a therapeutical point of view the disease must be divided into two forms: intestinal and extraintestinal. For the former, drugs which reach therapeutical levels in the gut are required. The mainstay for the treatment of asymptomatic carriage of pathogenic strains is DILOXANIDE FUROATE, a very well tolerated luminal amebicide. METRONIDAZOLE and other 5-nitroimidazole compounds such as ORNIDAZOLE are indicated for the treatment of symptomatic intestinal infections as they reach good concentrations in tissues, including the bowel where ulcerations develop. In order to ensure the clearance of amebae from the gut, a subsequent cycle with diloxanide furoate is advisable. Extraintestinal forms include amebic abscesses which can develop in many sites, but most commonly in the liver. Metronidazole and related compounds are the drugs of choice; in case of liver abscess, the addition of CHLOROQUINE is indicated because of its good concentration in tissues. A subsequent cycle with diloxanide furoate is also indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Amebiasis↗

Structural basis for the inhibition of protein biosynthesis: mode of action of tubulosine.

A structural model for the inhibition of protein biosynthesis was previously formulated on the basis of a topochemical analogy between the ipecac alkaloids and the glutarimide antibiotics. The structure of tubulosine satisfies the requirements of this model. The prediction that such a compound would exhibit amebicidal activity and act by selectively inhibiting the transfer reaction in protein biosynthesis is confirmed.

Alkaloids↗