Anturan for secondary prophylaxis of myocardial infarction

273 patients suffering from ischemic heart disease were treated with Anturan for one year at a daily dosage of 800 mg. The number of cardiovascular complications was significantly reduced, compared to the control group.     

Diminution of antifungal activity of fluconazole associated with ibuprofen and piroxicam in experimental histoplasmosis of hamsters (Mesocricetus auratus)

The aim of this study was to determine if tha association of non-steroid antiinflammatory drugs (piroxicam and ibuprofen) with fluconazole, affects the antifungal activity of the azole compound, in an experimental model histoplasmosis in hamsters (Mesocricetus auratus). Sixty hamsters were intracardially inoculated with 4x10(6) yeasts of Histoplasma capsulatum var. capsulatum. Treatments began one week after the challenge and continued for three weeks. The hamsters were divided in six groups of ten animals each and received the following treatment: 1- fluconazole 8 mg/kg/day; 2- ibuprofen 20 mg/kg/day; 3- piroxicam 20 mg/kg/day; 4- fluconazole+ibuprofen; 5- fluconazole+piroxicam and 6- only received the solvent of these drugs. One week after ending the treatment, all the animals were sacrified and the evaluation of the treatments was based on the results of blood cultures, on the determination of colony forming units per gram of spleen, and the histopathologic studies of the same organ. The animals treated with fluconazole plus ibuprofen or piroxicam showed more colony colony forming units per gram (3.9x10(7) and 3.3x10(7)) when compared with the animals treated with fluconazole alone (0.9x10(7)). The histopathologic results of the hamsters that received fluconazole showed well-organized granulomas with few yeast-like elements inside the macrophages. In contrast, those which received fluconazole associated with antiinflammatory drugs presented lax granulomas containing numerous yeast-like elements. These findings let us to conclude that non-steroids antiinflammatory drugs diminish the antifungal efficacy of fluconazole in this animal model.     

Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis

Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms) would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP), giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM) experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC), 600 (C. albicans -5-FC) or 1000 (S. cerevisiae - CSP) fold higher than the spontaneous mutation frequency, the experimental data for C. albicans -5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.     

播散型组织胞浆菌病研究进展

组织胞浆菌病是由组织胞浆菌引起的深部真菌疾病。播散型组织胞浆菌病为所有临床分型中最为凶险的类型,其特点为起病急、发展快、死亡率高,诊断及治疗也颇为棘手。该病既往被认为是一种地方流行性疾病,多见于美国中西部等西半球地区,我国少见且多为输入性病例。但现阶段我国本土病例也屡有报道,故本文在复习相关文献基础上总结了播散型组织胞浆菌病的流行病学现状、易感人群、临床表现、诊断方法及治疗进展,以飨读者。     

Occurrence of histoplasmosis in Asia

The occurrence of histoplasmosis in Asia has been reviewed. Authentic cases of histoplasmosis in man are known from India, Malaysia, Singapore, Indonesia, Thailand, South Vietnam and Japan, but the autochthonous nature of the cases reported has not been established unequivocally. Of the 30 cases of human histoplasmosis recorded from Asia, 15 were confirmed by positive cultures, and their country-wise distribution is as follows: Malaysia — 4, Indonesia — 3, Singapore — 2, Thailand — 2, South Vietnam — 2 and one each from India and Japan. Authentic cases of histoplasmosis in animals are currently unknown from Asia, and likewise there is no information on the natural habitats of the etiologic agentH. capsulatum in this part of the world except for a solitary isolation from soil in bat-infested cave in Malaysia.The available data on the prevalence of cutaneous hypersensitivity to histoplasmin indicates that histoplasmin sensitivity is absent in Israel, Syria, Saudi Arabia, Lebanon and Qatar; sensitivity is negligible or of a very low order in Iran, Iraq, Pakistan and India, and for these countries it has been even suggested that the positive reactors observed may represent cross-sections with some unknown fungus/fungi which may be antigenically related toH. capsulatum. In Japan the frequency of histoplasmin positive reactors has been negligible except in groups of persons working near a U.S. Army base and in factories which used soil and sand imported from overseas including the U.S.A. In Burma and Taiwan the bulk of positive reactions in which the induration did not exceed 8 mm in diameter has been considered probably non-specific. In Indonesia and South Vietnam, on the other hand, where less than 10 per cent of the reactions tended to concentrate around an induration of 16 mm sensitivity to histoplasmin may represent specificH. capsulatum infection in certain cases. Likewisef the requently large reactions reported from the Philippines have also been interpreted to represent specific histoplasmosis infection.The recovery ofH. capsulatum from soil coupled with the finding of well-documented cases of histoplasmosis in Malaysia suggests that the disease is endemic in that country. It is not unlikely that histoplasmosis is endemic in other parts of Asia although this has not been demonstrated so far. Comprehensive mycological, serological and soil studies are indicated in order to investigate the prevalence and incidence of histoplasmosis and to map out the endemic areas of the disease in Asia.Paper read at the Eighth International Congresses for Tropical Medicine and Malaria, September 1968, Teheran (Iran).     

Serology of histoplasmosis

We admit that the complete understanding of the serology of histoplasmosis has not as yet been realized. However, as laboratories continue to produce new and better techniques, not only for qualitative but also for quantitative assessment, we may be able to view a relatively complete picture in the near future.Paper read at the Eighth International Congresses for Tropical Medicine and Malaria, September 1968, Teheran (Iran).     

Treatment of disseminated histoplasmosis in hamsters

A comparative study between itraconazole, ketoconazole and amphotericin B in the treatment of experimental histoplasmosis in hamsters was carried out.Seventy five animals were inoculated intracardiacally with the yeast-phase of Histoplasma capsulatum. They were divided in 5 groups: 1) treated with itraconazole by gavage (g) at a daily dose of 16 mg/kg; 2) treated with ketoconazole by (g) at a daily dose of 80 mg/kg; 3) treated with amphotericin B intraperitoneally (i.p.) at 6 mg/kg every other day; 4) control animals receiving distilled water i.p. and 5) control animals receiving P.E.G. 200 by (g). All the treatments were started one week after the challenge inoculation and they were given for 21 days. The results were evaluated by autopsy of all the animals one week after the end of the treatments. The following determinations were taken into account: microscopic examinations of spleen, liver and lungs and cultures of the spleen with determination of colony forming units/g.All the antifungal drugs used in this study were able to cause negative microscopic examinations of the liver, spleen and lungs; but only amphotericin B produced culture negative results. Itraconazole and ketoconazole presented 66% and 86% of positive cultures respectively, nevertheless the C.F.U. were lower than those obtained in control groups.In these experimental conditions amphotericin B seems to be more active than the azolic compounds and itraconazole is slightly superior to ketoconazole at a lower dose.     

The status of histoplasmosis in Brazil

Thirty four cases of the progressive form of histoplasmosis, five epidemics of the mycosis, many histoplasmin skin test surveys and few clinical or histological evidences of the benign form of the disease were reported in Brazil. The occurrence of the infection in animals and the isolation ofH. capsulatum from soil have also been reported.Pesquisador 1 B do CNPq.     

Current diagnosis of histoplasmosis

Histoplasmosis is a common infection endemic in many regions of America, Asia, India and Africa, with sporadic cases also occurring throughout the world. Although excellent laboratory methods for diagnosis are available, there are deficiencies that must be met by continued research. Clinicians and laboratory directors must be familiar with the uses and limitations of a battery of serologic and mycological tests to accurately diagnose histoplasmosis. Research is needed to reduce false-negative and false-positive results, and to improve the identification of the organism in tissues. Approaches to the diagnosis of histoplasmosis and areas that require further research will be reviewed.     

An epizootic of histoplasmosis duboisii (African histoplasmosis) in an American baboon colony.

Histoplasmosis duboisii, a chronic granulomatous disease caused by Histoplasma capsulatum var. duboisii, was diagnosed in 21 baboons at a large primate colony in San Antonio, Texas. Diagnosis was based on finding 8 to 15 microns-diameter yeast cells in histologic sections. Therapy with drugs was unsuccessful. Surgical removal of lesions was the primary treatment. Epidemiologic data suggest the incubation period to be at least 9 months. The most likely route of infection was oral and happened during grooming by the baboons.