Antifungal activity and toxicological parameters of 8-hydroxyquinoline-5-sulfonamides using alternative animal models.

AIM: The purpose of this study was to evaluate the antifungal activity and toxicological parameters of 8-hydroxyquinoline derivatives PH151 and PH153 using alternative animal models, to understand their behaviour when subjected to in vivo experiments. METHODS AND RESULTS: We used Toll-deficient Drosophila melanogaster to test the protective effect of compounds against Candida albicans infection. Toxicological parameters were investigated in chicken and zebrafish embryos. PH151 and PH153 showed low toxicity and the treated flies with these compounds had a significantly higher survival rate than untreated flies after 7 days of infection. The compounds did not cause interruption of chicken embryogenesis. Zebrafish embryos exposed to compounds showed dose-dependent toxicity. CONCLUSIONS: The data supported the potential of PH151 and PH153 for the treatment of systemic candidiasis and demonstrated to be appropriate drug candidates for further studies using mammalian models. SIGNIFICANCE AND IMPACT OF THE STUDY: The increased incidence of Candida infections resistant to antifungals currently available requires acceleration of the discovery of new agents with properties of inhibiting this fungal pathogen. In this study, we have described the antifungal potential and toxicity of two 8-hydroxyquinoline derivatives using in vivo alternative models, and the results confirm their potential to be developed as new drug candidates.

The efficacy of 8-hydroxyquinoline derivatives in controlling the fungus Ilyonectria liriodendri, the causative agent of black foot disease in grapevines.

AIM: The purpose of this study was to evaluate the in vitro and in vivo efficiency of derivatives of 8-Hydroxyquinoline (8HQ) in controlling the fungus Ilyonectria liriodendri. METHODS AND RESULTS: The in vitro tests consisted of assessing its susceptibility to the minimal inhibitory concentration (MIC) and the inhibition of mycelial growth. While the in vivo tests consisted of applying and assessing the most effective products for the protection of wounds, in both preventive + curative and curative forms. The MIC values for PH 151 (6·25 µg ml-1 ) showed better results when compared to the fungicides tebuconazole (>50 µg ml-1 ) and mancozeb (12·5 µg ml-1 for strain 176 and 25 µg ml-1 for strain 1117). PH 151 significantly inhibited mycelial growth, while mancozeb did not differ from the control. In in vivo tests, PH 151 again demonstrated excellent results in vitro, especially when applied preventively. CONCLUSIONS: The derivative of 8HQ PH 151 was effective in controlling the fungus I. liriodendri in vitro and proved to be a promising option for protecting wounds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points to the prospect of an effective and safe preventive antifungal product, which would enable the use of pesticides in vine culture to be reduced.

Assessing an imidazolium salt's performance as antifungal agent on a mouthwash formulation.

AIMS: This study demonstrates the development of a mouthwash formulation containing the imidazolium salt (IMS) 1-n-hexadecyl-3-methylimidazolium chloride (C16 MImCl), considering its stability and efficacy against Candida sp. Biofilm formation. METHODS AND RESULTS: A variety of in vitro test methods were applied, assessing contaminated acrylic resin strip specimens before and after applying the mouthwash formulations. The formulation using C16 MImCl presented a similar antibiofilm activity to cetylpyridinium chloride one and a commercial mouthwash, but at a 10 times lower concentration. Scanning electron microscopy imaging demonstrated that the selected mouthwash preparation fully destroys the biofilm cells, while with the hypoallergenicity test no irritant effect was observed in ex vivo model. CONCLUSIONS: The results presented herein indicate a high potential for imidazolium salts application as mouthwash agents that can eliminate Candida biofilm growth at very low concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates a new and effective antibiofilm formulation containing the IMS C16 MImCl. These findings suggest the IMS' use as mouthwash formulations active ingredient against Candida biofilms on oral surfaces, as it outperforms the often used cetylpyridinium chloride at a 10 times lower concentration.

Growth and mortality of larval Myctophum affine (Myctophidae, Teleostei).

The growth and mortality rates of Myctophum affine larvae were analysed based on samples collected during the austral summer and winter of 2002 from south-eastern Brazilian waters. The larvae ranged in size from 2·75 to 14·00 mm standard length (L(S)). Daily increment counts from 82 sagittal otoliths showed that the age of M. affine ranged from 2 to 28 days. Three models were applied to estimate the growth rate: linear regression, exponential model and Laird-Gompertz model. The exponential model best fitted the data, and L(0) values from exponential and Laird-Gompertz models were close to the smallest larva reported in the literature (c. 2·5 mm L(S)). The average growth rate (0·33 mm day(-1)) was intermediate among lanternfishes. The mortality rate (12%) during the larval period was below average compared with other marine fish species but similar to some epipelagic fishes that occur in the area.

Using new tools to identify eggs of Engraulis anchoita (Clupeiformes, Engraulidae).

Efficiency of the identification of eggs of Engraulis anchoita can be greatly improved by a method developed from egg measurements, using photography and the ImageJ programme, analysed by discriminant analysis using R software.

Chagas' disease: carcinogenic activity of the antitrypanosomal nitroarenes in mice.

The carcinogenic activity of antitrypanosomal 2-nitroimidazole, 5-nitroimidazole and 5-nitrofuran derivatives was assessed in female Swiss mice of the same age group. A statistically significantly higher incidence of growths was seen in mice into which 2-nitro had been injected than in mice receiving 5-nitro derivatives intraperitoneally. A histologic type of lymphoblastic lymphoma that invades lymph nodes, spleen, liver, lungs and lymphatic tissue elsewhere was frequently found in nitroarene-treated mice. Further, it is shown that the potency of the drug, rather than the duration of its administration, was usually associated with the growth of lymphomas. The 2-nitro derivative which induced the highest incidence of lymphomas significantly decreased the survival of treated mice; this probably occurred because it undergoes enzymatic reduction of the nitro group more efficiently than the 5-nitro compounds used. The differences of incidence of lymphomas in mice receiving any of these nitroarenes and in control mice that received daily injections of 0.15 M saline were statistically significant (alpha = 0.05). The indiscriminate use of these nitroarenes to treat Trypanosoma cruzi infections in man could therefore induce a significant number of lymphomas.

[Tomodensitometry and radioisotopic methods in the study of unilateral lung hyperlucencies of vascular origin]. / Tomodensitometria e métodos radioisotópicos no estudo das hipertransparências pulmonares unilaterais de causa vascular.

Among the causes of the radiological entity known as unilateral or total hyperlucent lung is the decreased blood flow in the lungs. Unilateral and total hyperlucent lung results, among other factors, from the decreased intrapulmonary blood flow. Classically, the diagnosis and haemodynamic evaluation of these situations were usually made through invasive methods: right heart catheterism to perform angiopneumography and pressure evaluations as well as oximetry at several levels of the vascular network, thoracic aortography eventually associated with selective arteriography to detect the abnormalities of the systemic thoracic circulation. In this context, the authors propose for the diagnosis and study of this pathology, a new non-invasive methodology. In order to achieve this propose, we studied 8 patients, all of them performed clinical and laboratory evaluations, chest chi-ray, electrocardiographic and functional respiratory exams, as well angiopneumography, thoracic aortography tomodensitometry including qualitative (to study the lung arterial vasculature) and quantitative (to evaluate CT density of each lung in Hounsefield unit and two radioisotopic tests, including a ventilation/perfusion study with 133 chi e and HAM-99mTc, through an original software--four parameter histograms allowing simultaneous information of ventilation and perfusion at the pixel level and estimation of the V/Q; the other is the pulmonary gating through which it is possible to identify and quantify the arterio-arterial shunts.(ABSTRACT TRUNCATED AT 250 WORDS)

Histochemical and radioautographic study of glycoprotein secretion in the epithelium lining the uterine tubes of mice.

Two-month-old female Swiss mice that had come into estrus were injected intravenously with L-3H-fucose and killed at 5, 15, 40 min, and 4 h after injection. Pieces of the isthmus and of the ampulla of the uterine tubes were processed for light- and electron-microscopic radioautography. Incorporation of 3H-fucose was more intense in the isthmian secretory cells than in the ciliated cells of the ampulla. Electron-microscopic radioautography of the isthmian secretory cells demonstrated that 3H-fucose was incorporated into newly synthesized glycoproteins in the Golgi apparatus from where labelled glycoproteins migrated mainly to secretory granules and apical microvilli. The histochemical technique using ruthenium red confirmed the presence of glycoproteins in the contents of the secretory granules released to the lumen of the uterine tubes as demonstrated by radioautography. Other glycoproteins are transported inside small vesicles and most likely are related to the renewal of the plasma membrane. The role of the secretory glycoproteins in various events of mammalian reproduction is discussed.

Trypanosoma cruzi: histochemical characterization of parasitized skeletal muscle fibers.

C57B1/6 mice were infected with Brasil strain Trypanosoma cruzi trypomastigotes. The leg muscles of the mice were serial-sectioned with a cryostat, and individual fibers were classified histochemically as type I or type II on the basis of succinic dehydrogenase or adenosine triphosphatase activity. Although markedly more type II fibers were present in the leg muscles, the percentage of infected type I fibers was nearly five-fold higher than type II. This is the first demonstration of a preferential in vivo distribution of T. cruzi in muscle fibers based upon muscle type.

The immunology of experimental Chagas' disease. IV. Production of lesions in rabbits similar to those of chronic Chagas' disease in man.

Eight rabbits that received a single inoculation of trypomastigotes of a virulent strain of Trypanosoma cruzi first developed a transient acute illness associated with parasitemia; later, 4 of these rabbits died with chronic myocarditis and/or with megacolon in the absence of demonstrable parasitemia or encysted parasites in tissues. Two of these rabbits with chronic myocarditis died unexpectedly. Three of the inoculated rabbits that survived the infection were sacrificed 18 months later and showed similar but less severe microscopic lesions. The remaining rabbit is alive and well at the time of writing (26 months) with negative blood cultures but high hemagglutinating antibody titers to T. cruzi antigens. The natural course of T. cruzi infection in rabbits and the lesions observed postmortem are similar to those recorded for humans with chronic Chagas' disease. Multiple injections of particulate subcellular antigens of T. cruzi in rabbits resulted in microscopic lesions similar to those observed in rabbits that survived protozoan infection. Sera of rabbits inoculated with T. cruzi have antibodies to striated and smooth muscle structures. However, evidence provided in this and in other experiments strongly suggest that the lesions of chronic Chagas' disease are produced by delayed hypersensitivity to T. cruzi antigens.

Infeccao experimental de Calomys callosus (Rodentia-Cricetidae) com Leishmania donovani chagasi (Laison, 1982). / Exprimental infection of Calomys callosus (Rodentia-Cricetidae) with Leishmania donovani chagasi (Laison, 1982)

Foi descrita a infeccao experimental em Calomys callosus com uma cepa de Leishmania donovani chagasi de caso humano. Um grupo de 22 roedores foi inoculado por via intraperitoneal com 0,1 ml de um macerado de baco em salina, rico em amastigotas.Esses animais foram sacrificados tres meses apos as inoculacoes, tendo sido realizado: cultura "in vitro" em meio acelular (LIT e NNN) e esfregacos, corado pelo Giemsa, de figado, baco, medula ossea e sangue; cortes histologicos corados pelo Giemsa, de figado, baco, medula ossea e sangue; cortes histologicos corados com hematoxilina-eosina de figado e baco. Os resultados para figado e baco foram: 67% de positividade nas culturas "in vitro"; esfregacos ricos em amastigotas intra e extra celular (inclui medula ossea); reacoes teciduais traduzidas por hepatomegalia com proliferacao das celulas de Kupffer; reacao granulomatosa das areas portais, esplenomegalia com reacoes granulomatosas, abundancia de formas amastigotas. Os resultados para o sangue foram negativos em todas as investigacoes

Infeccao experimental de Calomys callosus (Rodentia Cricetidae) com Trypanosoma cruzi. / Experimental infection of Calomys callosus (Rodentia Cricetidae) with Trypanosoma cruzi

Sao apresentados resultados sobre a infeccao experimental de Calomys callosus (Rodentia) e duas cepas (Y e Berenice) de Trypanosoma cruzi, isoladas de casos humanos. O estudo da evolucao foi feito comparado com Mus musculus albino cepa "Swiss", quanto a prepatencia, parasitemia, patencia e letalidade. Analise histopatologica foi tambem conduzida em C.callosus, com o objetivo de verificar o tropismo tissular e agressividade das cepas neste roedor. Os experimentos mostraram que a evolucao da infeccao em C. callosus foi diferente para as duas cepas de T. cruzi. A cepa Y apresentou maior parasitemia do que a cepa Berenice. O periodo prepatente variou com as doses utilizadas tendo sido mais curto nos animais inoculados com a cepa Y (2, 2-5, 2 dias) do que naquelas com a cepa Berenice (3, 2-7 dias). Embora as duas cepas inoculadas nos C. callosus tenham-se mostrado miotropicas, as alteracoes tissulares foram mais acentuadas com a Y.Os resultados obtidos abrem perspectivas quanto a possibilidade do uso de C. callosus como animal experimental para T.cruzi

Estudo experimental de Zygodontomys lasiurus (Rodentia-Cricetidae) com cepas de Trypanosoma cruzi. / Experimental study of Zygodontomys lasiurus (Rodentia-Cricetidae) with strains of Trypanosoma cruzi

Sao apresentados resultados em relacao a infeccao experimental de Zygodontomys lasiurus (Rodentia-Cricetidae) com duas cepas de T. cruzi isoladas de casos humanos, Y e Berenice, e uma isolada de um triatomineo silvestre, chamada costalimai. Foram realizados estudos em relacao a evolucao da parasitemia, duracao da patencia e prepatencia da infeccao. Com o objetivo de verificar a agressividade e tropismo tissular das cepas de T. cruzi nesta especie de roedor, foram tambem realizados estudos histopatologicos. Os resultados obtidos mostraram que os niveis de parasitemias foram baixos para as tres cepas estudadas.A patencia da infeccao variou de 14 a 16 dias nos animais inoculados com a cepa Y, 26 a 29 dias com a Berenice e 9 a 13 dias com a costalimai. O periodo pre-patente variou de 3 a 5 anos nos animais inoculados com a cepa Y, de 2 a 6 dias com a cepa Berenice e de 6 a 8 dias com a costalimai.As tres cepas appresentaram em Z. lasiurus, comprometimento nitidamente muscular, provocando reacoes leves, moderadas e intensas