外阴阴道假丝酵母菌病的阴道清洁度观察

目的观察外阴阴道假丝酵母菌病阴道清洁度的情况。方法用湿片法进行阴道分泌物检查,随机选取1000例念珠菌阳性分泌物,对其阴道清洁度进行观察。结果1000例念珠菌阳性分泌物中,阴道清洁度Ⅳ度有606例,阴道清洁度Ⅲ度有279例,阴道清洁度Ⅱ度有82例,阴道清洁度Ⅰ度有33例。结论虽然大多数念珠菌阳性分泌物（88．5％）阴道清洁度异常（Ⅲ～Ⅳ度）,但仍然有少数念珠菌阳性分泌物（11．5％）阴道清洁度属于正常（Ⅰ～Ⅱ度）。这一结果应有助于临床妇产科医生在为患者做常规妇检、在外观性状上对阴道分泌物作判断时采取更加谨慎的态度。     

Vaginal microflora in girls of prepuberal age

The bacteriological study of vaginal microflora in 24 clinically healthy girls aged 7-8 years was carried out. Two criteria of normal vaginal biocenosis in girls of prepuberal age were proposed. The proportion of hemolytic bacteria in the vagina of a girl of prepuberal age could reach 100% of all microflora, provided the total bacterial count (TBC) exceed average values. A high proportion of hemolytic bacteria in the vaginal microflora of girls of prepuberal age in combination with a high level of TBC (even with TBC not exceeding the upper limit of its normal value) could probably by regarded as a border state. No fungi of the genus Candida should be isolated from vagina in girls of prepuberal age. Facultative anaerobic microflora was represented mainly by Staphylococcus epidermidis and S. saprophyticus. In 64.3 +/- 12.8% of cases bifidobacteria were detected in the girls vagina.     

Are Echinocandins Better Than Azoles for Invasive Candidiasis?

Antifungal therapy has advanced tremendously in the past decade, with multiple new agents for systemic fungal infections that have a broad spectrum of activity and are well-tolerated. There is usually more than one acceptable therapeutic option for many diseases, and this is true in particular of candidiasis. Fluconazole has been the drug of choice for most clinical syndromes of candidiasis, due to its tolerability, effectiveness, and ease of administration. However, the echinocandin class of antifungals, comprised of caspofungin, micafungin and anidulafingin, has emerged as the preferred choice in the therapy of invasive candidiasis and candidemia. Their potent fungicidal activity and minimal toxicity have made them first-line drugs for this indication. In certain clinical settings, they may even be agents of first choice. Nevertheless, recent trends in echinocandin resistance demonstrated with Candida glabrata mandate ongoing surveillance, and continued trends may impact upon future antifungal selection.     

La micafungina en el tratamiento de la candidiasis invasiva en pacientes sometidos a trasplante de órgano sólido

BackgroundMicafungin is an echinocandin approved for the prevention of Candida spp. infection in hematopoietic stem cell transplantation and therapy of oesophageal candidiasis, disseminated candidiasis and candidemia in adults, children and neonates.AimsTo evaluate the role of micafungin for candidiasis therapy in solid organ transplant recipients.MethodsA medical literature review according to micafungin role for candidiasis therapy in transplant patients is performed.ResultsMicafungin has shown fungicide activity against Candida species, including strains resistant or poorly susceptible to fluconazole. No dose adjustment is required when micafungin is administered in combination with other drugs used in transplant patients, excluding sirolimus, nifedipine and itraconazol. With these drugs, a minimal dose reduction is recommended. The results observed in transplant patients included in clinical trials are favourable and similar to results obtained in other kind of patients.ConclusionsThe clinical results, its safety profile and the low grade of medical interactions permit micafungin to be considered for therapy in specific groups of transplant patients.     

The role of pharmacogenetics in treating central nervous system disorders

Symptoms of central nervous system (CNS) disorders include abnormalities in both physical and psychological domains. Many drugs indicated for the treatment of CNS disorders are fraught with side effects and/or poor efficacy which impact patients' quality of life and drives non-compliance. Moreover, for many CNS drugs such as antidepressants and antipsychotics, it takes time to determine whether a particular drug is efficacious in an individual patient. To optimize drug treatment for each patient, prescribing physicians often need to raise or lower doses, switch drug classes, or prescribe additional drugs to mitigate side effects, often in a "trial and error" fashion. Pharmacogenetic (PGx) testing, particularly in the realm of CNS therapy, can reduce the unpredictability of this process. By determining a patient's genetic profile, individual therapy parameters may be predicted pre-treatment for drug efficacy, optimal drug dose, and the risk of adverse drug reactions (ADRs). The intent of this review is to highlight the power of PGx testing to predict the likelihood of ADRs and efficacy during the treatment of the following CNS disorders: epilepsy, bipolar disorder, schizophrenia and depression.     

1800例妇科门诊患者阴道分泌物的病原学分析

目的了解妇科门诊患者中阴道分泌物的病原学。方法用湿片法进行阴道分泌物及细菌性阴道病（BV）检查,革兰染色法检查G^-双球菌。观察分泌物的病原体分布情况。结果1800例妇科门诊患者中,其阴道分泌物假丝酵母菌阳性549例,阳性率为30．50％;阴道毛滴虫阳性34例,阳性率为1．89％;BV399例,阳性率为22．17％;G^-双球菌16例,阳性率为0．89％。混合感染：假丝酵母菌合并阴道毛滴虫感染2例（0．11％）;假丝酵母菌合并BV192例（10．67％）;假丝酵母菌合并G^-双球菌5例（0．28％）;假丝酵母菌合并BV和G^-双球菌3例（0．17％）。结论妇科门诊患者阴道分泌物的病原体构成复杂,阴道炎主要以外阴阴道假丝酵母菌病和BV为主,部分可多种病原体混合感染。     

Health Canada/BIOTECanada Summit on regulatory and clinical topics related to subsequent entry biologics (biosimilars), Ottawa,Canada, 14 May 2012

In May 2012, Health Canada and other participants held a National Summit on Subsequent Entry Biologics (SEBs). Health Canada released a guidance document in March 2010 describing policy positions and data requirements for approval of SEBs. While Health Canada and health agencies in other regulatory jurisdictions are aligned on many scientific principles related to biosimilar drugs, Health Canada's specific requirements may not be widely understood by many Canadian stakeholders. The Summit provided an opportunity for education and dialog among physicians who prescribe biologics, provincial payers, and industry on the following topics: preclinical and clinical comparability studies; manufacturing and other product differences; extrapolation of indications; substitution and interchangeability of SEBs with reference biologic drugs in clinical practice; payers' current perspective; pharmacovigilance and naming. It is anticipated that the consensus reached at this meeting will further educate Canadian healthcare professionals, provincial payers, and insurers about the appropriate use of SEBs, and may be of general interest to others internationally.     

The continuous changes in the aetiology and epidemiology of invasive candidiasis: from familiar <Emphasis Type="Italic">Candida albicans</Emphasis> to multiresistant <Emphasis Type="Italic">Candida auris</Emphasis>

Recent changes in the aetiology and epidemiology of invasive candidiasis have serious implications for current and future diagnosis, treatment and prognosis. The aim of the current review was to discuss the epidemiology of invasive candidiasis, the distribution of Candida species in different regions of the world, the medical concerns of the changing aetiology and the emergence of antifungal resistance. Overall burden of invasive candidiasis remains high, especially in vulnerable persons, such as the elderly, immunosuppressed or debilitated patients. Moreover, there is a progressive shift in the aetiology of invasive candidiasis from Candida albicans to other species of Candida, probably related to the increased use of azole drugs with a clear trend towards increased antifungal resistance. Finally, the emergence and rise of multiresistant species, such as Candida auris or Candida glabrata, is a major threat making necessary invasive candidiasis worldwide surveillances. These changes have serious implications for the diagnosis, treatment and prognosis of invasive candidiasis. Updated knowledge of the current local epidemiology of invasive candidiasis is critical for the clinical management.     

Role of genetics and drug metabolism in human cancer risk

The research field concerning responses to drugs having a hereditary basis is called 'pharmacogenetics'. At least 5 dozen pharmacogenetic polymorphisms have been described in clinical medicine; many are responsible for marked differences in genetic predisposition toward toxicity or cancer. Three are detailed here: the acetylation, the debrisoquine, and the AH locus polymorphism. All 3 are very common among the United States' population: 1 in 2 is a 'slow acetylator', 1 in 12 is a 'poor metabolizer' for more than 2 dozen commonly prescribed drugs in the debrisoquine panel, and the CYP1A1 and CYP1A2 (cytochromes P(1)450 and P(3)450) genes are highly inducible by cigarette smoke in 1 of 10 patients. Differences in xenobiotic metabolism between individuals in the same family can be greater than 200-fold, suggesting that occupationally hazardous chemicals, as well as prescribed drugs having a narrow therapeutic window, might cause strikingly dissimilar effects between patients of differing genotypes. Our ultimate goal is 'preventive toxicology', i.e. the development of simple, inexpensive, unequivocal and sensitive assays to predict individual risk of toxicity or cancer. These tests could help the individual in choosing a safer life style or place of work and might aid the physician in deciding which drug to prescribe.     

The role of antifungal susceptibility testing in the management of patients with invasive mycoses

The availability of standardized antifungal susceptibility testing methodologies as well as the definition of interpretative breakpoints have made possible the establishment of useful correlations between in vitro testing data and clinical results with antifungal drugs such as fluconazole and itraconazole in patients with oropharyngeal candidiasis. The results obtained in these studies, however, can not be extrapolated to other organisms or clinical syndromes. Although there has been some recent progress, the interpretations of in vitro and in vivo results obtained in patients suffering cryptococcosis or invasive candidiasis needs to be further defined in order to establish meaningful clinical-laboratory correlations. Furthermore, the method needs to be fully standardized in case of filamentous fungi. It can be anticipated that the development, standardization and validation of in vitro antifungal susceptibility testing will guide clinicians in the management of patients with invasive mycoses.     

Candidiasis — Do we need to fight or to tolerate the<Emphasis Type="Italic">Candida</Emphasis> fungus?

Candidiases, infections caused by germination forms of the Candida fungus, represent a heterogeneous group of diseases from systemic infection, through mucocutaneous form, to vulvovaginal form. Although caused by one organism, each form is controlled by distinct host immune mechanisms. Phagocytosis by polymorphonuclears and macrophages is generally accepted as the host immune mechanism for Candida elimination. Phagocytes require proinflammatory cytokine stimulation which could be harmful and must be regulated during the course of infection by the activity of CD8+ and CD4+ T cells. In the vaginal tissue the phagocytes are inefficient and inflammation is generally an unwanted reaction because it could damage mucosal tissue and break the tolerance to common vagina antigens including the otherwise saprophyting Candida yeast. Recurrent form of vulvovaginal candidiasis is probably associated with breaking of such tolerance. Beside the phagocytosis, specific antibodies, complement, and mucosal epithelial cell comprise Candida eliminating immune mechanisms. They are regulated by CD4+ and CD8+ T cells which produce cytokines IL-12, IFN-gamma, IL-10, TGF-beta, etc. as the response to signals from dendritic cells specialized to sense actual Candida morphotypes. During the course of Candida infection proinflammatory signals (if initially necessary) are replaced successively by antiinflammatory signals. This balance is absolutely distinct during each candidiasis form and it is crucial to describe and understand the basic principles before designing new therapeutic and/or preventive approaches.     

乳杆菌制剂和(或)达克宁治疗外阴阴道假丝酵母菌病的疗效比较

目的探讨乳杆菌制剂治疗外阴阴道假丝酵母菌病(VVC)的疗效。方法将2006年5月至7月在温州医学院附属二院确诊为VVC的患者分为3组,单纯使用达克宁栓者(A组)40例,联合使用达克宁栓及定君生阴道栓者(B组)40例,单纯使用定君生者40例(C组),进行对照。对3组的临床症状及真菌学检查结果进行分析讨论。结果停药3~5 d时,A、B组患者的疗效差异无显著性(P>0.05),C组患者的疗效明显低于A、B两组(P<0.05);停药30~37 d时,A、C组患者的疗效差异无显著性(P>0.05),B组患者的疗效明显高于A、C两组(P<0.05)。结论在应用阴道用乳杆菌治疗VVC时,应首先应用抗真菌药物,当真菌感染得以控制之后再使用乳杆菌,帮助恢复阴道内菌群环境。     

Studies on detection of Candida antigen in the sera of mice inoculated orally with Candida albicans

Summary The authors succeeded in establishing a murine model of systemic candidiasis being disseminated from the primary gastrointestinal lesions caused by oral inoculation of Candida albicans. Using this model, an attempt was made for detecting the Candida antigen by enzyme-linked immunosorbent assay using avidin-biotin (AB-ELISA) from the serum of infected mice.Gastrointestinal candidiasis was formed in all of the 20 mice treated with the drugs (antibiotics, antineoplastic agents, hydrocortisone, etc.) and inoculated orally with C. albicans. Fourteen of these mice suffered from submucosal candidiasis, and C. albicans was cultured from the visceral organs in 12 of them. The assay by AB-ELISA was able to detect 1.0 ng/ml Candida mannan in the mouse serum. The Candida antigen was detected in the sera of 11 of the 14 mice with submucosal candidiasis. However, the antigen could not be detected in the sera of the 6 mice with intramucosal candidiasis.The assay by AB-ELISA is more sensitive and specific for the diagnosis of systemic candidiasis than other serological assays.     

A D-octapeptide drug efflux pump inhibitor acts synergistically with azoles in a murine oral candidiasis infection model

Clinical management of patients undergoing treatment of oropharyngeal candidiasis with azole antifungals can be impaired by azole resistance. High-level azole resistance is often caused by the overexpression of Candida albicans efflux pump Cdr1p. Inhibition of this pump therefore represents a target for combination therapies that reverse azole resistance. We assessed the therapeutic potential of the D-octapeptide derivative RC21v3, a Cdr1p inhibitor, in the treatment of murine oral candidiasis caused by either the azole-resistant C. albicans clinical isolate MML611 or its azole-susceptible parental strain MML610. RC21v3, fluconazole (FLC), or a combination of both drugs were administered orally to immunosuppressed ICR mice at 3, 24, and 27 h after oral inoculation with C. albicans. FLC protected the mice inoculated with MML610 from oral candidiasis, but was only partially effective in MML611-infected mice. The co-application of RC21v3 (0.02 μmol per dose) potentiated the therapeutic performance of FLC for mice infected with either strain. It caused a statistically significant decrease in C. albicans cfu isolated from the oral cavity of the infected mice and reduced oral lesions. RC21v3 also enhanced the therapeutic activity of itraconazole against MML611 infection. These results indicate that RC21v3 in combination with azoles has potential as a therapy against azole-resistant oral candidiasis.     

Unacceptable face of private practice: prescription of controlled drugs to addicts.

Self administered questionnaires completed by 69 out of 100 consecutive drug addicts attending two drug dependence clinics suggested that some private general practitioners were easily persuaded to prescribe controlled drugs. These drugs were usually methadone, dipipanone-cyclizine (Diconal), and methylphenidate (Ritalin). Numbers of new narcotic addicts notified to the Home Office confirmed the practice, which may lead to a severe spread of addiction, as occurred in the 1960s with heroin and cocaine. If the General Medical Council or a tribunal set up in accordance with the Misuse of Drugs Act 1971 cannot stop the practice, then the present licensing system should be extended to include all controlled drugs.     

Induction of secretory aspartyl proteinase of <Emphasis Type="Italic">Candida albicans </Emphasis>by HIV-1 but not HSV-2 or some other microorganisms associated with vaginal environment

The most common type of candidiasis involves mucosal sites such as the oral cavity, the gastrointestinal tract and the vagina. Among many of virulence factors, the production of secretory aspartyl proteinase (Sap) by Candida albicans (C. albicans) has gained much attention, and factors leading to Sap induction are thus under intense study. The aim of this study was to examine whether some microorganisms such as Lactobacillus, Gardnerella vaginalis (G. vaginalis), human immunodeficiency virus type-1 (HIV-1) and human herpes simplex virus type-2 (HSV-2) had any Sap inducing effect on C. albicans. Here we showed that among the microorganisms tested in vitro only HIV-1 induced Sap production from C. albicans.     

Investigacion de levaduras en vulva y vagina

Resumen Se estudiaron 200 mujeres de primera consulta, sin tratamiento, que asistieron a la consulta externa de Ginecología del Hospital Universitario de Caracas, con el objeto de investigar la presencia de levaduras en vulva y vagina.Se tomaron 4 muestras de cada paciente: 2 de vulva y 2 del fondo de saco vaginal. Una muestra de vulva y una de vagina se destinaron al exámen directo (en fresco y con NaoH + tinta Parker Super Quink) y las otras muestras de vulva y vagina se utilizaron para cultivo en bilis-agar y lactritmel.Se encontraron 71 casos positivos especificados así:Trichomonas vaginalis, 38 (19 %);Candida albicans, 21 (10.5 %);Candida parapsilosis, 6 (3 %);Candida tropicalis, 5 (2.5 %);Torulopsis (holmii 2,candida 1) = 3 (1.5 %);Saccharomyces delbrueckii, 2 (1 %);Debaryomyces hansenii, 1 (0.5 %);Candida tenuis, 1 (0.5 %).Para el diagnóstico de la candidiasis y/o tricomoniasis vulvovaginal las manifestaciones clínicas no tienen ningún valor. El exámen directo, cuando es positivo, con presencia de filamentos y blastosporos, confirma el diagnóstico de candidiasis; pero su negatividad no excluye la presencia deCandida albicans como habitante de la vulvovagina en mujeres aparentemente normales.Los autores recomiendan la toma de la muestra des de la vulva para la investigación deCandida albicans, lo que facilita el exámen por no hacerse necesario el uso delspeculum; en cambio, paraTrichomonas vaginalis recomiendan la toma de la muestra desde el fondo de saco vaginal.El medio bilis-agar es el más apropiado para la rápida identificación deCandida albicans en el cultivo naciente, ya que en él se forman las clamidosporas en 24–48 horas.

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The cases of 200 women, without treatment, who attended the first gynecological external consultation at the Hospital Universitario, Caracas, Venezuela, were studied for the purpose of investigating the presence of yeast — like fungi in the vulva and in the vagina.Four samples were taken from each patient: two from the vulva and two from the posterior fornix. One sample each from the vulva and from the vagina were used, in direct examination, under microscope with NaOH + Parker/Super Quink ink; the remaining vulva and vagina samples were utilized in bilis-agar and lactritmel cultivation.71 positives cases were found, specified as follows:Trichomonas vaginalis, 38 (19 %);Candida albicans, 21 (10.5 %);Candida parapsilosis, 6 (3 %);Candida tropicalis, 5 (2.5 %);Torulopsis (holmii 2,candida 1) = 3 (1.5 %);Saccharomyces delbrueckii, 2 (1 %);Debaryomyces hansenii, 1 (0.5 %);Candida tenuis, 1 (0.5 %).In the diagnosis of vulvo-vaginal candidiasis and/or trichomoniasis the clinical signs have no significance. The direct examination, when positive, with presence of mycelium and blastospores confirms the diagnosis of candidiasis. However, if negative, it does not exclude the presence ofCandida albicans as habitant of the vulvo-vagina among apparently normal women.The authors recommended the taking of samples from the vulva for the purpose of investigation ofCandida albicans, which would facilitate the examination, inasmuch as it would be unnecessary to use the speculum. On the other hand, in the examination ofTrichomonas vaginalis the taking of samples from the posterior fornix is recommended.The bilis-agar medium is the most appropriate for the rapid identification ofCandida albicans from original cultures, as clamydospores are becoming present in 24 to 48 hours.

     

白念珠菌耐药的分子机制研究进展

近年来,免疫受损人群不断增多,该人群念珠菌病发病率呈上升趋势。随着抗真菌药物的广泛应用,临床分离到的白念珠菌耐药株增多,有关白念珠菌对抗真菌药物的耐药机制的研究又有了进一步的进展。就白念珠菌对唑类、多烯类、5-氟胞嘧啶、棘白菌素类等抗真菌药物的耐药机制方面的研究进展,作了介绍。     

Mouse Strain-Dependent Differences in Estrogen Sensitivity During Vaginal Candidiasis

The animal models available for studying the immune response to genital tract infection require induction of a pseudo estrous state, usually achieved by administration of 17-β-estradiol. In our experimental model of vaginal candidiasis, under pseudo estrus, different strains of mice were used. We observed major differences in the clearance of Candida albicans infection among the different strains, ascribable to differing susceptibility to estradiol treatment. In the early phase of infection CD1, BALB/c, C57BL/6 albino and C57BL/6 mice were colonized to similar levels, while in the late phase of infection, BALB/c mice, which are considered genetically resistant to C. albicans infection, exhibited greater susceptibility to vaginal candidiasis than CD1 and C57BL/6 albino strains of mice. This was because estradiol induced “per se” enlarged and fluid-filled uteri, more pronounced in infected mice and consistently more evident in BALB/c and C57BL/6 mice than in CD1 mice. Unlike CD1, BALB/c and C57BL/6 mice showed a heavy fungal colonization of the uterus, even though C57BL/6 mice apparently cleared C. albicans from the vagina. The presence of C. albicans in the vagina and uterus was accompanied by a heavy bacterial load. Collectively these observations prompted us to carry out a careful analysis of estradiol effects in a mouse model of vaginal infection.