Imidazoles in the treatment of ocular mycoses

The use of a new class of broad spectrum antifungal drugs i.e. imidazoles and in particular ketoconazole in treatment of severe affections of the eye such as mycoses is described. The clinical trials included 40 patients with various forms of mycosis: mycotic canaliculitis (6 patients), mycotic blepharitis (4 patients), mycotic conjunctivitis (7 patients), keratomycosis (17 patients) and mycotic endophthalmitis (6 patients). Ketoconazole was used in the form of tablets and instillations. The combined treatment included nonsteroid antiinflammatory drugs and antibacterial agents. The clinical trials showed that ketoconazole had pronounced antifungal activity and was rather efficient in treatment of ocular mycoses. Its broad spectrum and low toxicity were recorded.     

Inhibition of immune-mediated meningoencephalitis in persistently Borna disease virus-infected rats by cyclosporine A

In rats persistently infected with Borna disease virus (BDV), severe neurologic disorders and occasional death are the consequences of a T cell-mediated immunopathologic reaction in the brain. It is shown here that the pathologic alterations in the brain and as a result, Borna Disease (BD) can be prevented if animals are treated with the immunosuppressive drug cyclosporine A (CSA) under the following optimal conditions: greater than or equal to 25 mg/kg/day of CSA, started before infection and given for 4 wk. Rats treated with lower doses of CSA, for shorter periods or after infection displayed encephalitic lesions and developed BD. When CSA treatment was begun even as early as 1 day after infection, encephalitis and disease were not influenced. Immune spleen cells passively transferred into CSA-treated rats induced the disease in the recipients, whereas lymphoid cells from CSA-treated rats did not induce BD in infected cyclophosphamide-treated recipients. Antibodies were not involved in BD because rats treated with CSA revealed an inhibition of the synthesis of virus-specific antibodies for all regimens of treatment used (whether successful in preventing BD or not). After i.v. challenge of CSA-treated healthy rats with BDV, antiviral antibodies at low titers could be induced in some animals; however, no encephalitis or disease symptoms could be observed at any time after infection. The same was true for rats reinfected intracerebrally with BDV after discontinuation of CSA. These results support the hypothesis that unresponsiveness and even tolerance can be induced by CSA in the presence of the foreign Ag, demonstrating the beneficial effect of this immunosuppressive drug during a persistent viral infection.     

Experimental mycotic ulceration

Summary The experimental production of mycotic ulceration (in guinea pigs) is recorded for the first time. Prior or concurrent damage to the epithelium of the mucosal membrane appears to be necessary for the establishment of infection. Histologically, lesions produced were similar to those found in spontaneous cases in other animals. It is postulated that mycotic ulcers provide a primary lesion from which fungal elements are disseminated to other organs of the body.     

Dermatophytes and other keratinophilic fungi from coypus (Myocastor coypus) and brown rats (Rattus norvegicus)

The occurrence of mycotic agents was investigated by hair-brush technique on the coat of 162 naturalized coypus (Myocastor coypus) and 64 indigenous brown rats (Rattus norvegicus) originating from the same protected area in Central Italy. The isolates from positive coypus (29.6%) were identified as Microsporum gypseum (14.8%), Trichophyton terrestre (9.8%), Alternaria sp. (3.7%), Trichophyton mentagrophytes (2.5%), Cladosporium sp. (1.8%), Scopulariopsis sp. (1.2%), and Chrysosporium keratinophilum (0.6%), whereas the isolates from positive rats (46.7%) were identified as M. gypseum (28.1%), T. mentagrophytes (12.5%), Chrysosporium tropicum and T. terrestre (3.1% each), and Chrysosporium inops (1.6%). Statistically, brown rats were more likely to harbor fungal agents (P < 0.05) on their coat than coypus, especially T. mentagrophytes (P < 0.01) and M. gypseum (P < 0.05). No positive animal showed dermatological lesions. The present results are the first providing basic information on the coat’s mycoflora of a wild coypu population. It is concluded that the coypu, an allochthonous rodent in Italy, can play a role as natural animal reservoir of dermatophytes and as carrier of keratinophilic and saprophytic fungi within its new habitat, though to a lesser extent than indigenous rats. Therefore, people who are exposed to the risk of contact with the coat of rats and coypus should take all the cautions needed to protect themselves from mycotic agents potentially transmissible to humans.     

Recent advances on mycotic keratitis caused by dematiaceous hyphomycetes

Dematiaceous hyphomycetes (DH) are darkly pigmented fungi ubiquitously found all over the world as plant pathogens and saprophytes, and many of the members of this group have emerged as opportunistic pathogens. These fungi are responsible for a wide variety of infections including mycotic keratitis, which is considered as one of the major causes of corneal blindness, particularly in tropical and subtropical countries with an annual global burden of about 1 000 000 patients. The infection is more common in workers working in an outdoor environment. Moreover, trauma is found to be the most important predisposing cause of mycotic keratitis. Considerable delay in diagnosis and scarcity of effective pharmacological drugs are the major factors responsible for increased morbidity and visual impairment. Considering the crucial role of DH in mycotic keratitis, in the present review, we have focused on major DH with special emphasis on their pathogenicity, diagnosis and treatment strategies.     

Measles virus nucleocapsid protein protects rats from encephalitis.

Lewis rats immunized with recombinant vaccinia virus expressing the nucleocapsid (N) protein of measles virus were protected from encephalitis when subsequently challenged by intracerebral infection with neurotropic measles virus. Immunized rats revealed polyvalent antibodies to the N protein of measles virus in the absence of any neutralizing antibodies as well as an N protein-specific proliferative lymphocyte response. Depletion of CD8+ T lymphocytes did not abrogate the protective potential of the N protein-specific cell-mediated immune response in rats, while protection could be adoptively transferred with N protein-specific CD4+ T lymphocytes. These results indicate that a CD4+ cell-mediated immune response specific for the N protein of measles virus is sufficient to control measles virus infections of the central nervous system.     

Mycotic morbidity — An occupational risk for mycologists

Classical mycologists may be at a greater risk for infection with organisms under investigation than medical mycologists. The methods of infection of human beings by systemic mycotic pathogens is known. These principles can be used to develop good laboratory practices for classical mycological investigators. Newly recognized fungal pathogens and a more susceptible population may cause more laboratory infections. Minimal safety practices to prevent mycotic morbidity are described.     

120例婴幼儿外耳道炎分泌物细菌培养及药敏分析

目的通过对婴幼儿外耳道分泌物做细菌培养和药物敏感试验,指导临床用药。方法取120例患耳外耳道脓性分泌物,菌株经ATB express自动微生物分析仪进行鉴定和药敏试验。结果 120例菌株中,33例真菌感染,18例细菌和真菌合并感染,69例细菌感染。真菌耐药率不高,葡萄球菌对青霉素和红霉素耐药率接近100%。结论外耳道真菌感染率增高,细菌对抗生素耐药性增强,临床医生应参照药敏试验合理谨慎应用抗生素。     

Mycotic keratitis caused by Curvularia brachyspora (Boedjin)

Curvularia brachyspora has been identified for the first time as a cause of mycotic keratitis. Mycotic infections of the eye have assumed increasing importance in ophthalmology, resulting in a need for fungal identification and early specific treatment for the successful management of cases. A case of mycotic keratitis caused by C. brachyspora is described against the background of other Curvularia species causing mycoses.     

Diagnostic and clinical characteristics of mycotic vaginitis caused by Candida glabrata (Torulopsis glabrata)

In this study an evaluation of frequency of occurrence of C. glabrata, its diagnosis, sensitivity to antifungal drugs and its significance in pathogenesis of mycotic vaginosis was performed. Strains belonging to C. glabrata genus constituted 12.1% of total of 852 isolated strains and 39.2% of strains other than C. albicans. During fungal vaginosis caused by C. glabrata Lactobacillus sp. was present and normal pH values of vaginal secretion were seen. In direct preparations single or few leukocytes were observed and usually numerous blastospores were present. During evaluation of the sensitivity of C. glabrata strains to antimycotic agents a decreased sensitivity of these strains to clotrimazole and ketoconazole was found what speaks for their low usefulness in the treatment of mycotic vaginosis. Significance of C. glabrata in pathogenesis of mycotic vaginosis is not questioned since release of complaints and clinical symptoms in patients with positive therapeutic effect is seen and their persistence in a group of patients with treatment failure.     

Brain Catecholamine Alterations and Pathological Features with Aging in Parkinson Disease Model Rat Induced by Japanese Encephalitis Virus

We analyzed two disease model groups with rats infected by Japanese encephalitis virus (JEV), a 90-day group and a 180-day group after JEV infection. The time measured by the modified pole test showed that motor activities in these two groups were slower than those of age-matched control groups. Striatal dopamine (DA) levels were significantly decreased in all JEV-infected rats. Norepinephrine concentration in brain regions in the 180-day group was significantly decreased in the medulla oblongata and hypothalamus as compared with the control and 90-day group. Tyrosine hydroxylase-positive neurons were significantly decreased in both JEV-infected rat groups. These results suggest that DA decrease and pathological changes in JEV-infected model rats persist for a long time, at least up to 180 days, and this model will be useful for the evaluation of new anti-parkinsonian agents.     

Book review

Book review in this article:
Reiss, E. Molecular immunology of mycotic and actinomycotic infections     

Virus-neutralizing monoclonal antibody expressed in milk of transgenic mice provides full protection against virus-induced encephalitis

Neutralizing antibodies represent a major host defense mechanism against viral infections. In mammals, passive immunity is provided by neutralizing antibodies passed to the offspring via the placenta or the milk as immunoglobulin G and secreted immunoglobulin A. With the long-term goal of producing virus-resistant livestock, we have generated mice carrying transgenes that encode the light and heavy chains of an antibody that is able to neutralize the neurotropic JHM strain of murine hepatitis virus (MHV-JHM). MHV-JHM causes acute encephalitis and acute and chronic demyelination in susceptible strains of mice and rats. Transgene expression was targeted to the lactating mammary gland by using the ovine beta-lactoglobulin promoter. Milk from these transgenic mice contained up to 0.7 mg of recombinant antibody/ml. In vitro analysis of milk derived from different transgenic lines revealed a linear correlation between antibody expression and virus-neutralizing activity, indicating that the recombinant antibody is the major determinant of MHV-JHM neutralization in murine milk. Offspring of transgenic and control mice were challenged with a lethal dose of MHV-JHM. Litters suckling nontransgenic dams succumbed to fatal encephalitis, whereas litters suckling transgenic dams were fully protected against challenge, irrespective of whether they were transgenic. This demonstrates that a single neutralizing antibody expressed in the milk of transgenic mice is sufficient to completely protect suckling offspring against MHV-JHM-induced encephalitis.     

Characterisation and inhibition effect of cetrimide on collagenase produced byAspergillus flavus, isolated from mycotic ulcers

Collagenase was found to be the most important enzyme, produced by mycotic keratitis fungi. Therefore,Aspergillus flavus collagenase enzyme has been purified by ammonium sulphate precipitation, Sephadex G25 and DEAE-cellulose chromatography. Electrophoretic analysis for the purified enzyme indicated one subunit of molecular weight of 70–90 KDa when examining on SDS-PAGE. Cetrimide (cetyl trimethyl ammonium bromide) has been tested against the purified collagenase enzyme and indicated reversible competitive inhibitor (kis=0.15 mg/ml) with high promising activity. Cetrimide might be used to inhibit mycotic keratitis fungi.     

Hepatic and subcutaneous abscesses due to aspergillosis. Initial diagnosis of a case by intraoperative fine needle aspiration cytology

Laparotomy of a 64-year-old woman with bleeding caused by a perforated anastomotic peptic gastric ulcer disclosed a mycotic abscess in the lower surface of the left hepatic lobe covering the ulcer. Fine needle aspiration (FNA) of the abscess produced a clear milky liquid that was positive for Aspergillus fungi by cytology and subsequent microbiologic and cultural studies. Postoperative diffusion of the aspergillosis into the subcutaneous tissue was similarly confirmed by cytology and Sabouraud solid medium culture. This appears to be the first case of disseminated aspergillosis diagnosed by intraoperative FNA cytology; it confirms that FNA cytology is a rapid, sensitive and important tool for the diagnosis of mycotic infections.     

Arbovirus infections in man in British Columbia

During the summer of 1971, the first laboratory-proved cases of acute encephalitis in man due to any of the known arboviruses occurred in the south-central region of British Columbia. Five human cases of encephalitis with two deaths were diagnosed; three of these patients, including one of the fatalities, were proven in the laboratory to have contracted western equine encephalitis.During 1968 and 1969, a human serum survey undertaken in approximately 2000 life-long residents of the province discovered low levels of hemagglutinin-inhibiting and/or complement-fixing as well as neutralizing antibodies for western equine encephalitis, St. Louis encephalitis, Powassan encephalitis, California encephalitis and Colorado tick fever. Evidence of recent sub-clinical infection was detected in some cases.     

动态脑电图与常规脑电图应用于病毒性脑炎诊断的效果分析

目的:探讨动态脑电图与常规脑电图应用于病毒性脑炎的应用价值。方法:选取150例病毒性脑炎患者,随机分为两组,每组各75例,常规脑电图(REEG)组采用常规脑电图检查,动态脑电图(AEEG)组采用动态脑电图检查;观察并记录脑电图异常率,不同程度病情脑电图异常率的例数,评价动态脑电图与常规脑电图对病毒性脑炎的检测灵敏度和准确度。结果:AEEG组检出的脑电图异常率明显高于REEG组(P0.05)。不同程度病情脑电图检出的患者比例,两组相比,差异没有统计学意义(F=-0.085,P0.05)。REEG组中,轻度与中度病毒性脑炎检出率相比,差异没有统计学意义(P0.05),中度与重度病毒性脑炎检出率相比,差异没有统计学意义(P0.05),重度病毒性脑炎检出率明显高于轻度(P0.05)。AEEG组中,轻度与中度病毒性脑炎检出率相比,差异没有统计学意义(P0.05),重度病毒性脑炎检出率明显高于中度和轻度(P0.05),AEEG组重度病毒性脑炎检出率明显高于REEG组(P0.05)。结论:动态脑电图作为一种无创性检查,对于病毒性脑炎具有极好的检出率,灵敏度高,适用于病毒性脑膜炎的早期辅助诊断。     

Borna disease: association with a maturation defect in the cellular immune response.

Borna disease virus (BDV) is a negative-strand RNA virus which produces persistent infection in a variety of experimental animals. In the rat, the presence or absence of clinical signs of Borna disease, a characteristic, biphasic neurobehavioral illness, depends on host-related factors. A window of opportunity exists after birth wherein inoculation with BDV produces a persistently infected rat without signs of Borna disease or encephalitis (persistent, tolerant infection-newborn [PTI-NB] rat). Although immunopathological destruction of the nervous system does not occur in the PTI-NB rat, significant alterations in the development of the nervous system were noted, including site-specific lysis of neurons. Unlike the case with other pharmacologically produced, persistent, tolerant BDV infections, adoptive transfer of spleen cells from BDV-infected rats did not produce disease in the PTI-NB rats. PTI-NB rats developed Borna disease after being connected by parabiosis to rats with Borna disease. Bone marrow transplantation experiments revealed that bone marrow cells from PTI-NB rats produced Borna disease in lethally irradiated, BDV-infected recipient rats. Bone marrow from PTI-NB rats contained a complement of inflammatory cells capable of inducing Borna disease. Thus, the loss of BDV-specific cellular immunity appeared to occur after the release of cells from the bone marrow.