Comparative evaluation of fluconazole 50 mg and 100 mg versus itraconazole 100 mg in the treatment of dermatomycoses

In the above double-blind multicenter study the efficacy and tolerability of 50 and 100 mg doses of fluconazole were compared with 100 mg itraconazole in 178 patients with T. corporis, T. cruris, and T. pedis infections. All patients were submitted to clinical and mycological examination before starting, at weekly intervals during treatment, and 4 and 8 weeks after its conclusion. Duration of the three therapeutic regimes was 15 days for T. corporis and T. cruris, and 30 days for T. pedis infection. The percentage of symptomatic cure was 85% and 86.5%, respectively for 50 and 100 mg fluconazole, and 83% for itraconazole. Mycologic cure was achieved in 81.4% of patients treated with 50 mg fluconazole, 83.3% in those treated with 100 mg fluconazole, and 67.9% in those treated with 100 mg itraconazole. None of the groups showed changes in laboratory parameters. It is concluded that all three treatment schemes had high antimycotic activity, but fluconazole both 50 and 100 mg daily was superior. Both drugs were well tolerated and compliance was good.     

Clotrimazole is an inhibitor of inflammatory angiogenesis and the metabolic activity in sponge granuloma

BACKGROUND: Recently, the automated cardiac output method (ACM) was introduced for the calculation of blood flow at the left ventricular outflow tract (LVOT). This study was performed to examine the possibility of using ACM for flow calculation at the level of the mitral valve and for the quantification of mitral regurgitation (MR) in vitro and in vivo. METHODS AND RESULTS: In a computer-controlled in vitro model of the human heart, aortic and mitral normal bioprosthetic valves were inserted. ACM and electromagnetic probe flow measurements correlated well at the LVOT and at the mitral level (r2 = 0.79 and 0.77, respectively). For stroke volumes ranging from 30 to 100 ml/beat, there was no statistically significant bias between ACM and electromagnetic flow probe (-1.5 and 1.3 ml for LVOT and mitral level, respectively). Limits of agreement were [-14; +11] ml and [-18; +16] ml, respectively. We evaluated 68 patients in our in vivo study. They were divided into three groups according to the results of "standard" echocardiographic Doppler methods for the semiquantification of MR: echocardiographic color Doppler cartography, intensity of the continuous wave Doppler spectra, and in some patients, pulmonary venous flow, conventional Doppler, and proximal isovelocity surface area quantitative data. Group 1 consisted of 35 patients without MR or a physiologic one; the 17 patients in group 2 had a mild MR (1-2/4) and in group 3, 16 patients with MR 3-4/4 were included. Regurgitant volume (RV) was calculated as the difference between ACM mitral flow and ACM aortic flow, and regurgitant fraction (RF) was defined as the ratio between RV and ACM mitral flow. When mitral flow was measured only from the four-chamber view, we found in group 1, RV = -0.57 (0.67) L/min and RF = -16% (19%); in group 2, RV = -0.31 (1.06) L/min and RF = -8% (19%); and in group 3, RV = 1.53 (0.94) L/min and RF = 23% (13%). RV and RF were statistically higher in group 3 compared with group 2 or group 1 (p < 0.0005), but no significant difference was found between groups 1 and 2. When mitral flow was measured by the mean value of ACM four-chamber and two-chamber views, this resulted in group 1, RV = -0.26 (0.63) L/min and RF = -8% (15%); in group 2, RV = 0.01 (1.04) L/min and RF = -2% (18%); and in group 3, RV = 2.07 (1.21) L/min and RF = 34% (19%). RV and RF were again significantly higher in group 3 (p < 0.0001). There was no significant difference between group 1 and group 2, but in group 1 RF was no longer statistically different from 0%. CONCLUSIONS: (1) In our in vitro setting, ACM is reliable both at the LVOT and at the mitral valve. (2) In the in vivo situation, some overlapping does exist between the three groups of MR. However, ACM is a very easy, rapid, and objective method to differentiate hemodynamic nonsignificant (<3/4) from significant (> or =3/4) MR. Together with other well-known methods for the quantification of MR, it should facilitate the gradation of MR in the clinical setting. The absence of significant differences between group 1 and group 2 proves that the accuracy of ACM measurements at the mitral valve needs to be ameliorated before ACM can be used as a gold standard for the noninvasive measurement of RV and RF.     

Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis

PURPOSE: To evaluate the roles of fibroblast proteins in the remodeling of the subconjunctival connective tissue, we immunohistochemically assessed the expression of matrix metalloproteinases (MMP)-1 and -2, and the tissue inhibitors of matrix metalloproteinases (TIMP)-1 and -2 in cultured human subconjunctival fibroblasts and in normal and healing human subconjunctival connective tissue. METHODS: Cultured fibroblasts derived from human subconjunctival connective tissue and surgical specimens of normal and healing conjunctiva were immunostained with monoclonal antibodies directed against human MMPs and TIMPs and examined by light and electron microscopy. RESULTS: In the cultured fibroblasts, MMP-1 and TIMP-1 antibodies stained the cytoplasm in a fine granular pattern, suggesting localization of those proteins in the endoplasmic reticulum (ER) and Golgi apparatus. Antibodies to MMP-2 and TIMP-2 reacted with fibroblast cytoplasm in a granular pattern. Electron microscopy of those fibroblasts revealed MMP-1 and TIMP-1 immunoreactivity in the ER cisternae or on the membrane of the ER. In surgical samples, MMP-1 and TIMP-1 were immunohistochemically detected in healing subconjunctival tissue, but not in conjunctival epithelium or normal subconjunctival tissue. CONCLUSIONS: MMPs and TIMPs may be involved in remodeling of subconjunctival connective tissue and in fibroblast population after surgical interventions. These proteins may play a crucial role in the post-operative fibrotic process occurring during scar formation in subconjunctival tissue.     

Clotrimazole, an antimycotic drug, inhibits the sarcoplasmic reticulum calcium pump and contractile function in heart muscle

Clotrimazole (CLT), an antimycotic drug, has been shown to inhibit proliferation of normal and cancer cell lines and its systemic use as a new tool in the treatment of proliferative disorders is presently under scrutiny (Benzaquen, L. R., Brugnara, C., Byers, H. R., Gattoni-Celli, S., and Halperin, J. A. (1995) Nature Med. 1, 534-540). The action of CLT is thought to involve depletion of intracellular Ca2+ stores but the underlying mechanism has not been defined. The present study utilized membrane vesicles of rabbit cardiac sarcoplasmic reticulum (SR) to determine the mechanism by which CLT depletes intracellular Ca2+ stores. The results revealed a strong, concentration-dependent inhibitory action of CLT on the ATP-energized Ca2+ uptake activity of SR (50% inhibition with approximately 35 microM CLT). The inhibition was of rapid onset (manifested in <15 s), and was accompanied by a 7-fold decrease in the apparent affinity of the SR Ca2+-ATPase for Ca2+ and a minor decrement in the enzyme's apparent affinity toward ATP. Exposure of SR to CLT in the absence or presence of Ca2+ resulted in irreversible inhibition of Ca2+ uptake demonstrating that the Ca2+-bound and Ca2+-free conformations of the Ca2+-ATPase are CLT-sensitive. Introduction of CLT to the reaction medium subsequent to induction of enzyme turnover with Ca2+ and ATP resulted in instantaneous cessation of Ca2+ transport indicating that an intermediate enzyme species generated during turnover undergoes rapid inactivation by CLT. The inhibition of Ca2+ uptake by CLT was accompanied by inhibition of Ca2+-stimulated ATP hydrolysis and Ca2+-induced phosphoenzyme intermediate formation from ATP in the ATPase catalytic cycle. Phosphorylation of the Ca2+-deprived enzyme with Pi in the reverse direction of catalytic cycle and Ca2+ release from Ca2+-preloaded SR vesicles were unaffected by CLT. It is concluded that CLT depletes intracellular Ca2+ stores by inhibiting Ca2+ sequestration by the Ca2+-ATPase. The mechanism of ATPase inhibition involves a drug-induced alteration in the Ca2+-binding site(s) resulting in paralysis of the enzyme's catalytic and ion transport cycle. CLT (50 microM) caused marked depression of contractile function in isolated perfused, electrically paced rabbit heart preparations. The contractile function recovered gradually following withdrawal of CLT from the perfusate indicating the existence of mechanisms in the intact cell to inactivate, metabolize, or clear CLT from its target site.     

复发性假丝酵母菌性阴道炎复发相关性因素及疗效分析

目的:为了提高复发性假丝酵母菌性阴道炎的治愈率.方法:对复发性假丝酵母菌性阴道炎患者阴道分泌物进行真菌培养、真菌基因分型及药敏试验、针对药敏试验结果进行治疗.结果:81例对照组标本分离出白假丝酵母菌42例、平滑念珠菌14例、热带念珠菌11例、克柔念珠菌12例及其他念珠菌2例;42例白假丝酵母菌基因分型A型13株,B型22株,C型7株.进行药敏试验提示氟康唑对A型较B型、C型白假丝酵母菌敏感,对咪康唑耐药性强;B型、C型白假丝酵母菌对制霉菌素、酮康唑、伊曲康唑的耐药性明显低于A型菌株.结论:四联递进治疗复发性假丝酵母菌性阴道炎时将氟康唑分别与制霉菌素、酮康唑、伊曲康唑联合使用可提高该病的治愈率.     

Longitudinal investigation of candida vaginitis in pregnancy: role of superimposed antibiotic use

Two Escherichia coli isolates were studied. MIC patterns and hydrolysis assays suggested that they hyperproduced AmpC beta-lactamase, but synergy between ceftazidime and tazobactam was greater than between ceftazidime and Ro 48-1256, whereas the converse pattern is typical of AmpC hyperproducers. Studies with purified beta-lactamase from one of the isolates confirmed that tazobactam was a 100-fold stronger inhibitor than for the classical E. coli AmpC enzyme. Moreover, in contrast to typical AmpC types, the new enzyme had greater affinity for cephaloridine than for benzylpenicillin.     

In-vitro activity of purpuromycin and MDL 63,604 against microorganisms that cause vaginitis and vaginosis

Purpuromycin and its semi-synthetic derivative MDL 63,604 had in-vitro activity similar to that of amphotericin B against isolates of Candida albicans. MDL 63,604 had activity similar to that of metronidazole against Trichomonas vaginalis. Both compounds were very active against most species of Gram-positive and Gram-negative anaerobes and against Gardnerella vaginalis. MDL 63,604 had significantly lower MICs than purpuromycin against T. vaginalis and most of the bacteria, probably due to antagonism of purpuromycin's activity by medium supplements (blood or serum). Purpuromycin or related compounds may have a potential role in the topical treatment of vaginitis and vaginosis.     

Protective role of antimannan and anti-aspartyl proteinase antibodies in an experimental model of Candida albicans vaginitis in rats

The role of antibodies (Abs) in the resistance to vaginal infection by Candida albicans was investigated by using a rat vaginitis model. Animals receiving antimannoprotein (anti-MP) and anti-aspartyl proteinase (Sap) Ab-containing vaginal fluids from rats clearing a primary C. albicans infection showed a highly significant level of protection against vaginitis compared to animals given Ab-free vaginal fluid from noninfected rats. Preabsorption of the Ab-containing fluids with either one or both proteins MP and Sap sequentially reduced or abolished, respectively, the level of protection. A degree of protection against vaginitis was also conferred by postinfectious administration of anti-Sap and anti-MP monoclonal antibodies (provided the latter were directed against mannan rather than protein epitopes of MP) and by intravaginal immunization with a highly purified, polysaccharide-free Sap preparation. Postinfectious administration of pepstatin A, a potent Sap inhibitor, greatly accelerated the clearance of C. albicans from rat vagina. No anti-MP or anti-Sap Abs were elicited during a C. albicans vaginal infection of congenitally athymic nude rats. Although they were as able as their euthymic counterparts to clear the primary infection, these animals did not show increased resistance to a rechallenge, demonstrating that induction of anticandidal protection in normal rats was a thymus-dependent Ab response. Overall, our data strengthen the concept that Abs against some defined Candida antigens are relevant in the mechanism of acquired anticandidal protection in vaginitis. The T-cell dependence of this protection may also provide a link between cell-mediated and humoral immunity in vaginal infection.     

Control of Candida albicans murine vaginitis by topical administration of polycarbophil-econazole complex

The complexation of econazole with the mucoadhesive polycarbophil was found to significantly improve the therapeutic benefit of the drug in the topical treatment of experimental vaginal candidiasis in mice, while no difference in the antimycotic activity exerted by econazole and polycarbophil-econazole could be detected in vitro.     

The role of vaginal pH. Importance of its normalization in the prevention of recurrent vaginitis

BACKGROUND: A sample of 100 women was clinically examined for a very various vulvovaginal symptomatology and an individual diagnosis of vulvovaginitis of different aetiology was established. METHODS: All women were treated with antibiotic and/or antimycotic drugs on the basis of individual diagnosis. Sixty women had only this treatment, while 40 women had also a supplementary treatment with a cleanser emulsion characterized by physiologic pH value and an antiseptic activity due to a vegetable extract (Saugella Attiva, Lab. Guieu). The symptomatologic changes due to the two treatments were compared. RESULTS AND CONCLUSIONS: Combined treatment (drug + antiseptic) obtained better results mostly in subjective symptomatology; this combined treatment was very useful in the recovery of the Doderlein population.     

Ingestion of yogurt containing Lactobacillus acidophilus compared with pasteurized yogurt as prophylaxis for recurrent candidal vaginitis and bacterial vaginosis

To compare and assess ingestion of yogurt that contained live Lactobacillus acidophilus with pasteurized yogurt as prophylaxis for recurrent bacterial vaginosis (BV) and candidal vaginitis, we designed a crossover trial during which patients were examined monthly for candidal infection and BV while they were receiving either a pasteurized yogurt or a yogurt that contained live L acidophilus. Forty-six patients in 2 groups of 23 were randomly assigned to each of the study groups. At least 28 (61%) participated during the first 4 months of the study. Seven patients completed the entire study protocol. We concluded that daily ingestion of 150 mL of yogurt, enriched with live L acidophilus, was associated with an increased prevalence of colonization of the rectum and vagina by the bacteria, and this ingestion of yogurt may have reduced episodes of BV.