Efficacy of quorum sensing and growth inhibitors alone and in combination against avian pathogenic Escherichia coli infection in chickens.

Avian pathogenic E. coli (APEC), a causative agent of colibacillosis, is associated with high mortality and morbidity which results in severe economic losses to the poultry industry worldwide. APEC can be transmitted to humans through the consumption of contaminated poultry products. The limited effect of the current vaccines and the advent of drug-resistant strains have necessitated the development of alternative therapies. Previously, we identified 2 small molecules (SMs; [quorum sensing inhibitor; QSI-5] and [growth inhibitor; GI-7]) with high efficacy in vitro and in chickens subcutaneously challenged with APEC O78. Here, we optimized the oral challenge dose of APEC O78 in chickens to mimic the infection in the natural settings, evaluated the efficacy of the GI-7, QSI-5, and combination of GI-7 and QSI-5 (GI7+ QSI-5) in chickens orally infected with APEC, and compared their efficacy to sulfadimethoxine (SDM), an antibiotic currently used to treat APEC. Using the optimized dose of each SM in drinking water, GI-7, QSI-5, GI7+ QSI-5, and SDM were evaluated in chickens challenged with the optimized dose of APEC O78 (1 × 109 CFU/chicken; orally; d 2 of age) and grown on built-up floor litter. Reduction in mortality was 90, 80, 80, and 70% in QSI-5, GI-7+QSI-5, GI-7, and SDM treated groups compared to the positive control (PC), respectively. GI-7, QSI-5, GI-7+QSI-5, and SDM reduced the APEC load in the cecum by 2.2, 2.3, 1.6, and 0.6 logs and in the internal organs by 1.3, 1.2, 1.4, and 0.4 logs compared to PC (P < 0.05), respectively. The cumulative pathological lesions scores were 0.51, 0.24, 0.0, 0.53, and 1.53 in GI-7, QSI-5, GI-7+QSI-5, SDM, and PC groups, respectively. Overall, GI-7 and QSI-5 individually have promising effects as a potential antibiotic-independent approach to control APEC infections in chickens.

A signal "on-off-on"-type electrochemiluminescence aptamer sensor for detection of sulfadimethoxine based on Ru@Zn-oxalate MOF composites.

An "on-off-on"-type electrochemiluminescence (ECL) aptamer sensor based on Ru@Zn-oxalate metal-organic framework (MOF) composites is constructed for sensitive detection of sulfadimethoxine (SDM). The prepared Ru@Zn-oxalate MOF composites with the three-dimensional structure provide good ECL performance for the "signal-on." The MOF structure with a large surface area enables the material to fix more Ru(bpy)32+. Moreover, the Zn-oxalate MOF with three-dimensional chromophore connectivity provides a medium which can accelerate excited-state energy transfer migration among Ru(bpy)32+ units, and greatly reduces the influence of solvent on chromophore, achieving a high-energy Ru emission efficiency. The aptamer chain modified with ferrocene at the end can hybridize with the capture chain DNA1 fixed on the surface of the modified electrode through base complementary pairing, which can significantly quench the ECL signal of Ru@Zn-oxalate MOF. SDM specifically binds to its aptamer to separate ferrocene from the electrode surface, resulting in a "signal-on" ECL signal. The use of the aptamer chain further improves the selectivity of the sensor. Thus, high-sensitivity detection of SDM specificity is realized through the specific affinity between SDM and its aptamer. This proposed ECL aptamer sensor has good analytical performance for SDM with low detection limit (27.3 fM) and wide detection range (100 fM-500 nM). The sensor also shows excellent stability, selectivity, and reproducibility, which proved its analytical performance. The relative standard deviation (RSD) of SDM detected by the sensor is between 2.39 and 5.32%, and the recovery is in the range 97.23 to 107.5%. The sensor shows satisfactory results in the analysis of actual seawater samples, which is expected to play a role in the exploration of marine environmental pollution.

Ultrasensitive evanescent wave optical fiber aptasensor for online, continuous, type-specific detection of sulfonamides in environmental water.

Sensors capable for online continuous monitoring of total sulfonamides in environmental waters are highly desired due to their adverse effects on ecosystem, unexpected concentration fluctuation, and diversity. At present, no sensor with this capability has been reported. In this study, we evaluated the cross reactivity (CR) of the previously reported sulfadimethoxine-binding aptamer using DNase I assay and found that the aptamer was type-specific to sulfonamides. We then fabricated the first type-specific sulfonamide sensor, where the aptamer was immobilized on the optical fiber of the evanescent wave sensor, followed by the surface coating with Tween 80. The competitive binding of sulfonamides and Cy5.5 labeled complementary DNA enabled the low femtomolar to picomolar sensitivity and the detection of total 14 sulfonamides spiked in the lake water. The sensor also exhibited high selectivity, regeneration capability (40 cycles), stability (65 days), and short detection time (5 min). In addition, we found that the CRs were greatly dependent on the buffer composition. By performing the parallel detections in two buffers, the sensors detected 18 out of the 24 sulfonamides with the diversity coverage higher than commercial ELISA kits. Our aptasensor fills the technical gap for continuous monitoring of total sulfonamides in environmental waters.

Assessment of Binding Affinity between Drugs and Human Serum Albumin Using Nanoporous Anodic Alumina Photonic Crystals.

In this study, we report an innovative approach aiming to assess the binding affinity between drug molecules and human serum albumin by combining nanoporous anodic alumina rugate filters (NAA-RFs) modified with human serum albumin (HSA) and reflectometric interference spectroscopy (RIfS). NAA-RFs are photonic crystal structures produced by sinusoidal pulse anodization of aluminum that present two characteristic optical parameters, the characteristic reflection peak (λPeak), and the effective optical thickness of the film (OTeff), which can be readily used as sensing parameters. A design of experiments strategy and an ANOVA analysis are used to establish the effect of the anodization parameters (i.e., anodization period and anodization offset) on the sensitivity of HSA-modified NAA-RFs toward indomethacin, a model drug. To this end, two sensing parameters are used, that is, shifts in the characteristic reflection peak (ΔλPeak) and changes in the effective optical thickness of the film (ΔOTeff). Subsequently, optimized NAA-RFs are used as sensing platforms to determine the binding affinity between a set of drugs (i.e., indomethacin, coumarin, sulfadymethoxine, warfarin, and salicylic acid) and HSA molecules. Our results verify that the combination of HSA-modified NAA-RFs with RIfS can be used as a portable, low-cost, and simple system for establishing the binding affinity between drugs and plasma proteins, which is a critical factor to develop efficient medicines for treating a broad range of diseases and medical conditions.

Promoting effects of carminic acid-enriched cochineal extracts on capsular invasive thyroid carcinomas through targeting activation of angiogenesis in rats.

Cochineal extracts (CE) is a coccid-derived natural food colorant containing carminic acid (CA) as an active ingredient that potentiates inhibition of tissue proteolysis mediated by activation of plasma hyaluronan-binding protein (PHBP). In our previous study, dietary administered CE (CA: 28.5% in CE) has shown to promote the macroscopic development of capsular invasive carcinomas (CICs) associated with up-regulation of angiogenesis-related genes in an intracapsular invasion model of experimental thyroid cancers using rats. However, the promoting effect of CE could not be confirmed histopathologically. The purpose of the present study was to confirm the promoting effect of CE through direct injections to animals on the development of CICs using this cancer invasion model. One week after initiation with N-bis(hydroxypropyl)nitrosamine, male F344/NSlc rats were administered CA-enriched CE (CA: 52.6% in CE) by intraperitoneal injections every other day (10 mg/kg body weight) during the promotion with 0.15% sulfadimethoxine in the drinking water for 8 weeks. The multiplicities of macroscopical CICs and the mean area of early capsular invasive foci estimated by Tenascin (TN)-C-immunoreactivity in the thyroid significantly increased with CE-treatment, while the number of TN-C-positive foci did not change with CE. Transcript level of Phbp and downstream genes unchanged; however, transcript level of angiogenesis-related genes, i.e, Vegfb and its transcription factor gene, Hif1a, those being downstream of phosphatase and tensin homolog (PTEN)/Akt signaling, up-regulated in the thyroid tissue with CE-administration. These results suggest that CE potentiates promotion activity by facilitating angiogenesis through activation of PTEN/Akt signaling without accompanying modification of PHBP-related proteolysis.

Clinical and microbial efficacy of antimicrobial treatments of experimental avian colibacillosis.

The clinical and microbial efficacy of antimicrobial treatments of avian colibacillosis was studied, using an experimental model on chickens previously inoculated with multiresistant commensal Escherichia coli strains. One E. coli with pMG252 plasmid containing bla(FOX5) and qnrA1 genes and another E. coli with pMG298 plasmid containing bla(CTX-M15) and qnrB1 genes were first orally inoculated to chickens Both isolates were also resistant to chloramphenicol, sulphamethoxazole, trimethoprim, streptomycin, gentamicin, kanamycin, and tetracycline. The birds were then experimentally infected with an avian pathogenic E. coli (APEC), via the air sac. Treatments (oxytetracycline (OTC), trimethoprim-sulfadimethoxin (SXT), amoxicillin (AMX) or enrofloxacin (ENR) were then offered at the therapeutic doses. Symptoms, lesions in dead or sacrificed birds, and isolation and characterization of APEC from internal organs were studied. Results showed that OTC, SXT or ENR treatments could control the pathology. AMX worsened the disease, possibly due to endotoxin shock. All APEC re-isolated from internal organs showed the same antimicrobial susceptibility as the APEC inoculated strain, except for one APEC isolate from an infected OTC-treated bird, which acquired tetracycline resistance only, and one APEC isolate recovered from the air sacs of a chicken in the infected SXT-treated group, which acquired the pMG252 plasmid and became multi-resistant. Thus three antimicrobials could control the disease but the experimental model enabled, to our knowledge, the first observation of plasmid transfer from a bacterium of the intestinal tract to a pathogenic isolate from the respiratory tract.

A multifactorial test of the effects of carotenoid access, food intake and parasite load on the production of ornamental feathers and bill coloration in American goldfinches.

It has been well established that carotenoid and melanin pigmentation are often condition-dependent traits in vertebrates. Expression of carotenoid coloration in birds has been shown to reflect pigment intake, food access and parasite load; however, the relative importance of and the potential interactions among these factors have not been previously considered. Moreover, carotenoid and melanin pigmentation have been proposed to signal fundamentally different aspects of individual condition but few data exist to test this idea. We simultaneously manipulated three environmental conditions under which American goldfinches (Cardeulis tristis) grew colorful feathers and developed carotenoid pigmentation of their bills. Male goldfinches were held with either high or low carotenoid supplementation, pulsed or continuous antimicrobial drug treatment, or restricted or unlimited access to food. Carotenoid supplementation had an overriding effect on yellow feather coloration. Males given more lutein and zeaxanthin grew yellow feathers with hue shifted toward orange and with higher yellow chroma than males supplemented with fewer carotenoids. Parasites and food access did not significantly affect yellow feather coloration, and there were only minor interaction effects for the three treatments. By contrast, bill coloration was significantly affected by all three treatments. Carotenoid supplementation had a significant effect on yellow chroma of bills, drug treatment and food access both had a significant effect on bill hue, and food access had a significant effect on the yellow brightness of bills. Neither the size nor blackness of the black caps of male goldfinches was affected by any treatment. These results indicate that pigment intake, food access and parasite load can have complex and variable effects on color displays, and that feather and bill coloration signal different aspects of male condition.

Comparative efficacy of enrofloxacin, oxytetracycline, and sulfadimethoxine for the control of morbidity and mortality caused by Escherichia coli in broiler chickens.

The purpose of the present study was to compare the ability of enrofloxacin, oxytetracycline, and sulfadimethoxine to reduce morbidity and mortality caused by Escherichia coli (colibacillosis) in broiler chickens. The chickens were raised in 80 pens (20 birds per pen) with 20 pens representing each treatment group under simulated commercial conditions that produced a colibacillosis challenge scenario. Each group of 20 randomized pens (replicates) was given one of four water treatments. Chickens that received enrofloxacin had significantly less mortality (P < 0.01), lower average gross pathology (colibacillosis) scores (P < 0.01), and better feed-conversion ratios (P < 0.05) than did chickens that received either oxytetracycline or no medication. Chickens that received enrofloxacin had significantly less mortality and lower pathology scores than those that received sulfadimethoxine and numerically lower feed conversion than the sulfadimethoxine group. Results from the present study show that enrofloxacin is superior to oxytetracycline and sulfadimethoxine for the control of morbidity and mortality caused by E. coli in broiler chickens. Our findings will help veterinarians choose and prescribe the most efficacious antimicrobial when treating colibacillosis.

Specificity of co-promoting effects of caffeine on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine.

The specificity of copromotion effects of caffeine with known goitrogenic factors on thyroid carcinogenesis was examined in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 8 groups, each consisting of 10 animals, and received a single sc injection of 2,800 mg/kg DHPN. From one week after the DHPN initiation, they were given basal diet, iodine deficiency (ID) diet, 500 ppm phenobarbital (PB) solution or 1,000 ppm sulfadimethoxine (SDM) solution with or without 1,500 ppm caffeine feeding for 12 weeks. The caffeine, PB, SDM, and ID treatments significantly (p < 0.05 or 0.01) increased the relative thyroid weights, and the increases with PB or ID were further (p < 0.05 or 0.01) enhanced in combination with caffeine. SDM drastically promoted thyroid carcinogenesis in association with increased serum TSH levels regardless of the caffeine treatment. Thyroid follicular carcinomas and adenomas were more frequently observed in the additional caffeine groups than in the ID alone groups. The incidence and multiplicity of focal thyroid follicular hyperplasias in the ID-treated groups were significantly (p < 0.05 and 0.01) elevated in the case of combination with caffeine. Increases in serum TSH levels with PB or ID were also further enhanced in combination with caffeine. Serum thyroid hormone levels were significantly (p < 0.01) decreased by SDM but significantly (p < 0.05 or 0.01) increased by caffeine, PB or ID. Our results clearly indicate that dietary caffeine at a high dose of 1,500 ppm interacts with ID, but neither SDM nor PB, to promote rat thyroid carcinogenesis although the combined caffeine + PB treatment somewhat affected thyroid weights as well as thyroid hormone levels.

Efficacy of oral sulfadimethoxine against two gregarine parasites, Protomagalhaensia granulosae and Gregarina cubensis (Apicomplexa: Eugregarinida), infecting the Death's Head cockroach, Blaberus discoidalis.

Gregarines are common parasites of insects in culture, but no effective chemotherapeutic or prophylactic control protocol has been demonstrated. Sulfadimethoxine was administered in 5- and 7-day treatments to Death's Head cockroaches (Blaberus discoidalis) infected with Gregarina cubensis and Protomagalhaensia granulosae to test the efficacy of this sulfonamide against gregarine infection. Sulfadimethoxine significantly reduced the mean intensity of both G. cubensis and P. granulosae. Sulfadimethoxine treatment reduced gregarine intensity by 80% to 85% but had no significant effect on gametocyst production, suggesting that sulfonamide toxicity is directed primarily at sporozoites, trophozoites, and perhaps young gamonts. The possible use of sulfadimethoxine to produce gregarine-free insect cultures and the potential utility of gregarines as target organisms for screening pharmacologically active compounds for use against other intestinal apicomplexans are discussed.

Synergistic effects of high-dose soybean intake with iodine deficiency, but not sulfadimethoxine or phenobarbital, on rat thyroid proliferation.

The specificity and dose dependence of the synergistic effects of soybean intake with iodine deficiency on the induction of thyroid proliferation were investigated in female F344 rats. In the first experiment, rats were divided into 6 groups, each consisting of 5 animals, and fed a basal diet containing 20% gluten, an iodine-deficient basal diet alone or an iodine-deficient diet containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding synergistically induced thyroid hyperplasias with iodine deficiency only at the 25% dose. In the second experiment, rats were also divided into 6 groups, each consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05% phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM treatments significantly (P < 0.05 - 0.01) increased the thyroid weights, but this increase rate was less prominent in the SDM + soybean group than in the SDM alone group. The PB treatment was also associated with a tendency for increase in thyroid weight, but again this was smaller in the PB + soybean group than in the PB alone group. Although the SDM or PB treatments reduced the serum triiodothyronine and thyroxine levels and consequently increased the serum thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or rather attenuated these changes. Our results clearly indicate that soybean feeding does not synergistically enhance the effects of SDM or PB on the rat thyroid. Thus it can be concluded that soybean intake specifically interacts with iodine deficiency in induction of thyroid proliferative lesions in rats, only at high doses.

Oral bioavailability and disposition of sulphadimethoxine in lobster, Homarus americanus, following single and multiple dosing regimens.

1. Single and multiple oral doses of sulphadimethoxine or sodium sulphadimethoxine were administered by gavage to lobster, and sequential samples of haemolymph were taken for analysis of parent sulphadimethoxine. Single doses of sodium sulphadimethoxine were given over a dose range of 14-70 mg/kg. Five 42-mg/kg doses of sulphadimethoxine on alternate days were administered for the multiple-dose studies. Some experiments were conducted with radiolabelled (35S or 14C) sulphadimethoxine, and the tissue distribution of radioactivity was determined at different killing times. 2. Pharmacokinetic parameters were obtained by fitting sulphadimethoxine concentrations in haemolymph to a one-compartment model. Oral bioavailability at the 42-mg/kg dose, calculated from the area under the haemolymph concentration-time curve (AUC) relative to the AUC from intravascular administration, was between 47 and 52% for single or multiple doses of the free drug. The bioavailability of sodium sulphadimethoxine was dose dependent, at 97% for the 14 mg/kg dose, and 25% for the 70-mg/kg dose. The low bioavailability at the high dose probably resulted from poor absorption due to the limited solubility of sulphadimethoxine at the low pH of the lobster gastrointestinal tract. 3. Sulphadimethoxine and several polar metabolites were excreted in lobster urine. Polar metabolites were also found in the hepatopancreas and haemolymph. At least 20% of the 42-mg/kg dose was metabolized. The major vertebrate metabolite of sulphadimethoxine, N-acetylsulphadimethoxine, was a very minor metabolite in lobster. The identities of the polar metabolites were not established. 4. Elimination of sulphadimethoxine residues from muscle to < 0.1 microgram sulphadimethoxine equivalent/g tissue required 40 days after a single dose, or 44 days after the last of multiple doses. Concentrations of sulphadimethoxine residues in all other tissues were always greater than muscle concentrations. Data showed that sulphadimethoxine residues were very persistent in lobster tissues.

[Sulfadimethoxine as a promising drug in the treatment of infections caused by Mycobacterium kansasii and Mycobacterium xenopi--differentiation between M. kansasii and M. marinum and between M. gordonae and M. scrofulaceum by the susceptibility testing to sulfadimethoxine].

Susceptibility testing to sulfadimethoxine of various mycobacteria was made using Ogawa egg medium containing various concentrations of the drug. Each medium was inoculated by a 0.02 ml-sample of bacterial suspensions (10 mg wet weight per ml) prepared from 10 day-old (M. tuberculosis, 14 day-old) cultures growing on Ogawa egg medium after homogenizing the bacteria by shaking with glass beads. The media inoculated were incubated at 37 degrees C for 14 days (M. marinum, at 28 degrees C). The minimal inhibitory concentration (MIC) was determined as the lowest drug concentration on which the growth of bacteria was completely inhibited. However, residual growth occurred often. This was regarded as negative growth, because control medium containing no drug always exhibited abundant membraneous growth. Of the mycobacteria tested, M. kansasii (MICs, 0.8-3.2 micrograms/ml) and M. xenopi (MICs, 0.2-3.2 micrograms/ml) were most susceptible to this drug. Other mycobacteria showed the MICs higher than 3.2 micrograms/ml. The drug seemed to be useful in the treatment of infections caused by M. kansasii and M. xenopi. Furthermore, the susceptibility testing to sulfadimethoxine was considered to be useful for differentiation between two photochromogens, M. kansasii and M. marinum and for differentiation between two scotochromogens, M. scrofulaceum and M. gordonae (Fig. 3 and 4).

Pharmacokinetics of sulphadimethoxine in the lobster, Homarus americanus, following intrapericardial administration.

1. The pharmacokinetics and tissue distribution of intrapericardially administered sulphadimethoxine were studied in the lobster Homarus americanus. 2. Pharmacokinetic analysis of haemolymph concentration-time data indicated that a two compartment model best described sulphadimethoxine disposition, and that there were no apparent sex differences in the lobster. Analysis of total body clearance (Clb), apparent steady-state volume of distribution (Vss), area under the curve, and plasma protein binding in lobsters receiving 21, 42 and 55 mg/kg sodium sulphadimethoxine indicated that the pharmacokinetics were independent of dose. 3. Mean parameter estimates for Clb, Vss, and terminal half life were 13.8 ml/h/kg, 1369 ml/kg, and 76.7 h, respectively. Binding of sulphadimethoxine to haemolymph proteins was linear, with a mean of 53.5% bound. 4. Analysis of the tissue distribution of radiolabelled sulphadimethoxine at 4, 48 and 336 hours after a 42 mg/kg dose indicated that sulphadimethoxine was excreted slowly by the lobster, with the muscle, shell and haemolymph holding the largest fraction of the dose at early times. After 2 weeks, 9.5% of the radiolabel remained in the animal, with the hepatopancreas and digestive tract holding the greatest concentration of the dose.

Disposition of sulfadimethoxine in the lobster (Homarus americanus).

The long-acting sulfonamide antibacterial, sulfadimethoxine, has the potential for use in pen-held lobsters, Homarus americanus for treatment of gaffkemia. We evaluated the disposition of sulfadimethoxine after intrapericardial, oral or multiple oral administration of unlabelled or radiolabelled sulfadimethoxine (42 mg/kg) to 500 g lobsters. Elimination of parent sulfadimethoxine from hemolymph was very slow compared with elimination of the drug from blood of vertebrate species; the beta phase half-life was 77 hr in lobster as opposed to 7-40 hr in several vertebrate species. The pharmacokinetics of sulfadimethoxine after intrapericardial administration were linear up to 55 mg/kg, and binding of sulfadimethoxine to hemolymph proteins was constant over the range 14-200 micrograms/ml. During the first week after dosing, concentrations of sulfadimethoxine and metabolites (total radioactivity) were similar in all non-excretory tissues, such that muscle, shell and hemolymph contained the largest percentage of the administered dose. By 2 weeks and later, hepatopancreas and digestive tract contained the highest concentration and percentage of the dose, by total radioactivity. Part of the dose of sulfadimethoxine was excreted unchanged in urine and part was metabolized in hepatopancreas to unknown polar metabolites. The major vertebrate metabolite, N-acetylsulfadimethoxine, was a very minor metabolite in lobster. Although sulfadimethoxine was extensively metabolized in hepatopancreas, the polar metabolites were very slowly excreted, suggesting inefficient excretion mechanisms for elimination of polar xenobiotic metabolites in the lobster.

Displacing effects of chenodeoxycholic acid, ursodeoxycholic acid and sulfadimethoxine on plasma protein binding of tolbutamide.

The interactions between chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA) and tolbutamide including its displacement from plasma protein binding sites were investigated pharmacokinetically. An increasing concentration of unbound tolbutamide was observed in the in vitro experiment, conducted by equilibrium dialysis method at 30 degrees C after the addition of CDCA and UDCA to human serum albumin (HSA), bovine serum albumin (BSA) and rabbit plasma containing tolbutamide. Small changes in total plasma concentration of tolbutamide were noted after high dose (0.167 mg/kg/min) intravenous infusion of CDCA to rabbits receiving a constant intravenous infusion of tolbutamide, but, such an observation was not obtained with low dose (0.083 mg/kg/min) of CDCA or with either high or low dose of UDCA. These results seem to indicate the displacement of high doses of CDCA. The coadministration of sulfadimethoxine which not only displaces tolbutamide from binding sites but also inhibits its metabolism was investigated. A different plasma pattern was obtained under the same intravenous infusion conditions, as compared with the plasma pattern resulting from tolbutamide-CDCA or UDCA combination.

Açäo da anfotericina B e Levamisole em camundongos albinos inoculados com Paracoccidioidomicose Brasiliensis / Study on anphotericin B and levamisole in albino mice inoculated with paracoccidioides brasiliensis

Paracoccidioidomicose experimental, em camundongos albinos de 3-4 semanas de idade. Inoculaçäo de 0,5 ml de suspensäo, contendo 1x10(devada a sexta potência) células/ml de Paracoccidioides brasiliensis e tratamento com anfotericina B (1 mg/Kg) em doses diárias; com levamisole (3 mg/Kg) administrada em intervalos de 15 dias e em séries de uma dose por dia, em três dias consecutivos; e com anfotericina B e levamisole associadas, de maneira a cobrir o período de 50, 80 e 95 dias para necrópsia. Estudo comparativo do quadro histológico de fígado e baço, com ênfase em granulomas, parasitas, células de Küpffer, células gigantes, reaçäo linforreticular, folículos e amioloidose. O animal revela-se satisftório, como modelo experimetnal, porém de uso limitado, devido ao fenômeno de auto-cura. Isoladamente, anfotericina B é menos eficiente do que quando em associaçöes com levamisole, para a reduçäo do número de parasitas. Animais com amiloidose esplênica apresentam alto número de parasitas. O quadro reativo revela qe a açäo de levamisole, isolada ou combinadamente com anforicina B, induz aumento de defesa com notável incremento da açäo de células fagocitárias

Antimalarial activity of saccharidic polymers of dapsone and sulfadimethoxine.

With the purpose of obtaining pro-drugs of dapsone and sulfadimethoxine, those chemotherapeutic agents were attached through covalent bonding to starch polymeric dialdehyde (Sumstar-190). The antimalarial activity of the two resulting compounds - the dapsone saccharidic polymer (PS6) and the sulfadimethoxine saccharidic polymer (PS7) - in mice experimentally inoculated with Plasmodium berghei was significantly increased with this molecular modification. Mice infected with malaria and kept without treatment together with others which received different doses of PS6 and PS7 were also partially or totally cured, possibly due to the ingestion of excrements containing the parent chemotherapeutic agents.