nystatin-a1 and Disease-Models--Animal

Topics: Animals; Anti-Bacterial Agents; Bacitracin; Bird Diseases; Birds; Chlamydia; Chlamydia Infections; Chloramphenicol; Conjunctivitis, Inclusion; Cycloserine; Disease Models, Animal; Erythromycin; Glycosides; Humans; Lymphogranuloma Venereum; Nystatin; Penicillins; Polymyxins; Psittacosis; Sulfonamides; Tetracycline; Trachoma; Vancomycin

Vulvovaginal candidiasis (VVC) affects approximately 75% of all women of during their reproductive years. Previously, we reported that recombinant human IFN α-2b (rhIFNα-2b) protects vaginal epithelial cells from candidal injury in vitro. In the current study, we examined the effects of rhIFNα-2b (1.25 mg/mL, 10% inhibition concentration) on fungal clearance, immunocompetent cytokine responses, non-B IgG production, and tissue repair in a rat model of VVC. Following rhIFNα-2b treatment, the negative pathogen conversion rate reached 50.0% (3/6). Although rhIFNα-2b exhibited a limited ability to decrease inflammation and injury progression (P > 0.05), the Flameng mitochondrial injury scores were significantly reduced (P < 0.001) compared with those of the Model rats. After rhIFNα-2b treatment, the levels of IFN-γ and epithelial-derived IgG (tested by RP215) in vaginal tissues were significantly increased with those in the Control and Model groups (both P < 0.001), while there were no significant differences in the levels of IL-4 and IL-17 (P > 0.05). This is the first study to address the efficacy of rhIFNα-2b in treating VVC in a rat model, providing a theoretical basis for development of this promising treatment for clinical use.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Cytokines; Disease Models, Animal; Epithelial Cells; Female; Humans; Immunoglobulin G; Inflammation; Interferon alpha-2; Interferon Type I; Interleukin-17; Interleukin-4; Nystatin; Rats; Rats, Sprague-Dawley; Vagina

Vulvovaginal candidiasis (VVC) is a common infectious disease of the lower genital tract. Nystatin, a polyene fungicidal antibiotic, is used as a topical antifungal agent for VVC treatment. The aim of the current study was to investigate the possible immunomodulatory effects of nystatin on the vaginal mucosal immune response during Candida albicans infection and examine its role in protection of vaginal epithelial cell (VEC) ultrastructure.. Following infection with C. albicans, IFN-γ and IL-17 levels in VECs were significantly elevated, while the presence of IgG was markedly decreased as compared to uninfected controls (P <  0.05). No significant differences in IL4 expression were observed. After treatment with nystatin, the level of IFN-γ, IL-17 and IgG was dramatically increased in comparison to the untreated group (P <  0.05). Transmission electron microscopy revealed that C. albicans invades the vaginal epithelium by both induced endocytosis and active penetration. Nystatin treatment protects the ultrastructure of the vaginal epithelium. Compared with the untreated C. albicans-infected group, Flameng scores which measure mitochondrial damage of VECs were markedly decreased (P <  0.001) and the number of adhesive and invasive C. albicans was significantly reduced (P <  0.01) after treatment with nystatin.. Nystatin plays a protective role in the host defense against C. albicans by up-regulating the IFN-γ-related cellular response, the IL-17 signaling pathway and possibly through enhancing VEC-derived IgG-mediated immunity. Furthermore, nystatin notably improves the ultramorphology of the vaginal mucosa, partially through the protection of mitochondria ultrastructure in VECs and inhibition of adhesion and invasion by C. albicans. Together, these effects enhance the immune response of the vaginal mucosa against C. albicans and protect the ultrastructure of vaginal epithelium in VVC rats.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Disease Models, Animal; Epithelial Cells; Female; Immunologic Factors; Interferon-gamma; Interleukin-17; Mitophagy; Nystatin; Rats; Rats, Sprague-Dawley; Vagina

In patients with a perforated tympanic membrane, topically administered medication reaches the middle ear and thus creates a risk of ototoxicity. The aim of the present study was to evaluate the possible ototoxic effect of the antifungal medication nystatin when administered to the rat middle ear cavity.. Three groups (negative control, positive control, and study groups), each containing eight rats, were formed. Before the drug administration, distortion product otoacoustic emissions were recorded in both ears of each rat. Saline (0.09% NaCl), gentamycin, and nystatin solutions were transtympanically injected into the middle ear cavities of the negative control, positive control, and study groups, respectively, for five consecutive days. Seven days after the last infiltration, the control otoacoustic emission was measured, and the data of the 2, 3, 4, 6, 8 kHz frequencies were statistically analyzed.. There were no significant changes between the 1st and 2nd measures in the negative control group (0.09% NaCl) (p>0.05), whereas there were significant changes between the 1st and 2nd measures in the positive control group (gentamycin) and study group (nystatin) (p<0.05).. Ototopical medications carry a risk of ototoxicity in patients with perforated ear drums. In the present study, it was shown that nystatin, an antifungal that can be ototopically used in the treatment of otomycosis, may cause a decrease in otoacoustic emissions in rats when administered into the middle ear cavities.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Cochlea; Disease Models, Animal; Ear, Middle; Gentamicins; Nystatin; Otoacoustic Emissions, Spontaneous; Random Allocation; Rats; Tympanic Membrane; Tympanic Membrane Perforation

The wide use of topical and systemic antifungal agents as the conventional treatment for oral candidiasis has caused Candida albicans to develop resistance to these agents. The aims of this study were to evaluate the effects of photodynamic therapy (PDT) and chitosan on buccal candidiasis and study the possible enhancive effect of chitosan on the photosensitizer methylene blue.. Thirty-five DBA/2 immunosuppressed mice were orally inoculated with a suspension of Candida albicans. The animals were randomized into seven groups (n = 5 per group): Group 1 (control); Group 2 (nystatin); Group 3 (PDT); Group 4 (chitosan 1.5 mg/ml); Group 5 (chitosan 3 mg/ml); Group 6 (PDT + chitosan 1.5 mg/ml); and Group 7 (PDT + chitosan 3 mg/ml). The Candida albicans count was evaluated on days 3, 5, 7, and 11 after inoculation. At last, macroscopic and microscopic analyses of the tongue dorsa were performed.. On day 7 after inoculation, the control group showed a greater number of Candida albicans (5.25 ± 0.41 log10 CFU/ml), with significant differences compared to all other groups (P ≤ 0.05). On day 11 after inoculation, animals treated with PDT showed lower CFU/ml count. Groups 2, 3, 4, 5, and 6 showed fewer microscopic candidiasis lesions than Groups 1 and 7.. PDT has an antifungal effect, even greater than nystatin. Chitosan has a powerful fungicide effect but did not possess any enhancive effect on methylene blue.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis, Oral; Chitosan; Disease Models, Animal; Epithelium; Female; Methylene Blue; Mice; Mice, Inbred DBA; Mucous Membrane; Nystatin; Photochemotherapy; Photosensitizing Agents; Random Allocation

Several bicyclic compounds, 3-azabicyclo[3.2.2]nonanes, have been prepared. The new compounds were tested for their activities against one strain of the causative organism of Malaria tropica, Plasmodium falciparum K1, which is resistant against chloroquine and pyrimethamine. In addition, their cytotoxicity and their activity against the pathogen of the East African form of sleeping sickness, Trypanosoma brucei rhodesiense, were investigated. Structure-activity relationships are discussed considering data of readily prepared compounds. For the first time, a distinct in vivo activity was observed against Plasmodium berghei in a mouse model. The active compound was further investigated.

Topics: Administration, Oral; Animals; Antiprotozoal Agents; Azabicyclo Compounds; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Intravenous; Male; Mice; Molecular Structure; Parasitic Sensitivity Tests; Plasmodium berghei; Plasmodium falciparum; Rats; Structure-Activity Relationship; Tissue Distribution; Trypanosoma brucei rhodesiense; Trypanosomiasis, African

In this study, we developed a nanoparticulate nystatin formulation and performed a comparative evaluation against a commercial nystatin preparation of its in vitro and in vivo antifungal activities.. A nystatin nanosuspension was prepared from a commercially available suspension by wet-media milling. The nanosuspension was characterized for particle size by laser diffraction and assayed for content by HPLC. Its in vitro activity was evaluated against Candida albicans strains SC5314 and LAM-1 (12.5-5000 μg/mL) using an agar plate assay and its in vivo efficacy was evaluated using a murine model of oral candidiasis. Briefly, DBA/2 mice were immunosuppressed with cortisone acetate, orally infected with C. albicans strain LAM-1, and treated for 14 days with conventional nystatin suspension, nystatin nanosuspension or saline control. Efficacy endpoints were oral fungal burden, mouse survival and organ histopathology. A single-dose pharmacokinetic study was also performed.. The median particle size of the nystatin suspension was reduced from 6577 to 137 nm. The HPLC assay demonstrated a nystatin content of 98.7% ± 0.8% of the label claim. In vitro activity was superior to that of the conventional nystatin suspension at 100-5000 μg/mL concentrations. Beginning on day 3 of treatment, lower oral burdens of C. albicans were found in the nanosuspension group compared with the suspension and control groups. Mouse survival was also superior in the nanosuspension group. No systemic absorption was observed.. Taken together, these data reveal that nanonization of nystatin provides a novel approach to enhancing its efficacy in the treatment of oral candidiasis.

Topics: Animal Structures; Animals; Antifungal Agents; Candida albicans; Candidiasis, Oral; Colony Count, Microbial; Disease Models, Animal; Humans; Male; Mice; Mice, Inbred DBA; Microbial Sensitivity Tests; Mouth; Nanoparticles; Nystatin; Survival Analysis; Treatment Outcome

To assess and compare the effect of commonly used topical antimycotic agents and their solvents on the function of the vestibular and cochlear parts of the sand rat's inner ear.. Prospective, controlled, animal study.. Forty-five fat sand rats were randomly assigned to five major groups, each receiving topical application of a different agent: saline (control), gentamicin (ototoxic control), and three antimycotic agents: nystatin, clotrimazole solution (Agisten), and bifonazole solution (Agispor). All animals underwent a right labyrinthectomy, and a polyethylene tube was inserted into the left middle ear followed by baseline recording of vestibular evoked potentials (VsEPs) and auditory nerve and brainstem responses (ABR). Subsequently, each animal received five consecutive daily applications of the specific agent into the left middle ear. Evoked potential recordings were repeated 3 and 10 days after the last application and compared to baseline. For clotrimazole and bifonazole solutions, the effect of the solvents was assessed by comparing ABR recordings at similar intervals.. Administration of saline did not affect VsEPs or ABR. Both could not be recorded following gentamicin application. In all three antimycotic agents, no statistically significant difference was found between VsEPs recordings before and after application. Clotrimazole and bifonazole solutions caused a significant ABR threshold elevation similar to that caused by their solvents. Nystatin caused a less significant ABR threshold elevation.. The three commonly used topical antimycotic agents investigated here did not affect vestibular function but had a toxic effect on inner ear cochlear function. It seems the main offenders were the solvents.

Topics: Animals; Antifungal Agents; Clotrimazole; Cochlea; Disease Models, Animal; Ear, Inner; Evoked Potentials, Auditory; Gentamicins; Gerbillinae; Imidazoles; Nystatin; Rats; Sodium Chloride; Solvents; Vestibule, Labyrinth

The aim of this study is to evaluate the oral colonization by Candida albicans in experimental murine immunosuppressed DBA/2 and treatment with probiotic bacteria. To achieve these objectives, 152 DBA/2-immunosuppressed mice were orally inoculated with a suspension of C. albicans containing 10(8) viable yeast cells, the animals were treated with nystatin or with the probiotics (Lactobacillus acidophilus and Lactobacillus rhamnosus). Evaluations were performed by Candida count from oral mucosa swabbing. The oral mucosa colonization by C. albicans started at day 1 after inoculation, remained maximal from day 3 until day 7, and then decreased significantly. Probiotics reduced the C. albicans colonization significantly on the oral mucosa in comparison with the untreated animal group. In the group treated with L. rhamnosus, the reduction in yeast colonization was significantly higher compared with that of the group receiving nystatin. Immunosuppressed animal model DBA/2 is a relevant model for experimental Candida oral colonization, and the treatment with probiotics in this model may be an effective alternative to prevent it.

Topics: Animals; Antifungal Agents; Candida; Candidiasis, Oral; Colony Count, Microbial; Cyclophosphamide; Disease Models, Animal; Immunosuppression Therapy; Immunosuppressive Agents; Lacticaseibacillus rhamnosus; Lactobacillus acidophilus; Male; Mice; Mice, Inbred DBA; Mouth Mucosa; Nystatin; Palate; Probiotics; Random Allocation; Tongue

Cryptococcus neoformans infection is a common fungal infection in persons infected with human immune deficiency virus (HIV) or those with defective cell-mediated immunity. Since treatment of cryptococcal meningitis poses a big challenge, the present study aimed to develop a novel liposomal therapeutic formulation against cryptococcosis. Treatment with tuftsin-incorporated liposomes increased the anti-cryptococcal activity of murine peritoneal macrophages. Prophylactic treatment of mice with tuftsin-incorporated liposomes reduced the dissemination of C. neoformans to brain tissues. Moreover, the co-administration of tuftsin with nystatin liposomes augmented the anti-cryptococcal activity of nystatin, as mice treated with tuftsin-incorporated nystatin liposomes showed the highest survival and least fungal burden in their brain tissues. The results of the present study favour the use of immune-stimulating molecules along with antifungal agents in the treatment of opportunistic fungal infections.

Topics: Animals; Antifungal Agents; Brain; Cells, Cultured; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Immunologic Factors; Liposomes; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Nystatin; Survival Analysis; Treatment Outcome; Tuftsin

In this experimental animal study, the effects of three different topical antimicrobial dressings on Candida albicans contaminated full-thickness burn in rats were analyzed.. In total 32 adult Wistar rats (body weight 200-220 g) were used. Silver-coated dressing (Acticoat™®), chlorhexidine acetate 0.5% (Bactigrass®) and Mycostatine (Nystatin®) were compared to assess the antifungal effect of a once-daily application on experimental rat 15% full-skin thickness burn wound seeded 24h earlier with a 10(8) CFU/mL standard strain of C. albicans ATCC 90028. All the animals were sacrificed at post burn day 7. The quantitative counts of seeded organism in burn eschar and subjacent muscle were determined, in addition to the cultures of left ventricle blood and lung biopsies.. While there were significant differences between Acticoat™® group (4 ± 10 × 10(4)) and control group (5 ± 6 × 10(6)), and between Nystatin group (4 ± 4 × 10(4)) and control group (P=0.01, P=0.01), there were no significant differences between chlorhexidine acetate 0.5% group (2 ± 3 × 10(4)) and control group (P=0.7) respectively. Acticoat™® and Nystatin were sufficient to prevent to C. albicans from invading to the muscle and from causing systemic infection.. The animal data suggest that nystatin is the most effective agents in the treatment of C. albicans-contaminated burn wounds, and Acticoat™® is a choice of treatment on fungal burn wound infection with antibacterial effect and the particular advantage of limiting the frequency of replacement of the dressing.

Topics: Administration, Topical; Animals; Anti-Infective Agents, Local; Antifungal Agents; Bandages; Burns; Candida albicans; Candidiasis; Chlorhexidine; Disease Models, Animal; Male; Nystatin; Polyesters; Polyethylenes; Rats; Rats, Wistar

Nonionic surfactant (NIS) vesicles (niosomes) formed from self-assembly of hydrated synthetic NIS monomers are capable of entrapping a variety of drugs and have been evaluated as an alternative to liposomes. Nystatin (NYS) is a polyene antifungal drug that has been used in the treatment of cutaneous, vaginal and oral fungal infections since the 1950s. The aim of this work is to encapsulate NYS in niosomes to obtain a safe and effective formula administered parenterally for neutropenic patients. NYS niosomes were prepared by the thin-film hydration method using Span 60 or Span 40 and cholesterol (CHOL). Stearylamine and dicetyl phosphate were added as the positive and negative charge-inducing agents (CIA), respectively. Two molar ratios were used, namely NIS/CHOL/CIA (1:1:0.1 and 2:1:0.25). Neutral and positively charged niosomes gave the highest encapsulation efficiencies. NYS niosomes were characterized using transmission electron microscopy, differential scanning calorimetry and dynamic light scattering. The release of neutral and negatively charged NYS niosomes was estimated, and it showed a slow sustained release profile. A 25-kGy γ-irradiation dose was sufficient to sterilize the investigated vesicles. NYS niosomes exerted less nephrotoxicity and hepatotoxicity in vivo, showed higher level of drug in vital organs and revealed pronounced efficacy in elimination of the fungal burden in experimental animals infected with Candida albicans compared with those treated with free NYS. Niosomal encapsulation thus provided means for parenteral administration of NYS, reducing its toxicity and making it a more active antifungal agent.

Topics: Analysis of Variance; Animals; Antifungal Agents; Candidiasis; Disease Models, Animal; Drug Delivery Systems; Female; Liposomes; Male; Mice; Nystatin; Random Allocation; Rats; Rats, Wistar

In this prospective controlled animal study, the authors investigated the potential ototoxic effects of ototopical application of nystatin through a tympanostomy tube, using their established chinchilla animal model. Each of the 10 animals used had ventilation tubes inserted in both ears; 1 ear was randomly assigned to receive nystatin suspension, whereas the other ear did not receive any medication, serving as control. Distortion product otoacoustic emissions (DPOAEs) were measured in each animal before application of nystatin and at 45 and 60 days after application. Each cochlea was also processed for scanning electron microscopy (SEM) at the end of the experiment. There was no significant difference in the DPOAEs and SEM appearances of the experimental and control ears over the 60-day period of the experiment. The authors conclude that transtympanic nystatin did not produce any long-term ototoxic effects detectable by DPOAEs or SEM.

Topics: Administration, Topical; Animals; Chinchilla; Cochlea; Disease Models, Animal; Female; Immunohistochemistry; Microscopy, Electron, Scanning; Middle Ear Ventilation; Nystatin; Otoacoustic Emissions, Spontaneous; Random Allocation; Reference Values; Sensitivity and Specificity; Tympanic Membrane

The effects of aqueous and alkaline extracts from Agaricus blazei Murill, an edible mushroom used as folk medicine in Brazil, Japan, and China to treat several illnesses, were investigated on the basis of the inflammatory process induced by different agents. Oral administration of A. blazei extracts marginally inhibited the edema induced by nystatin. In contrast, when complete Freund's adjuvant was used as the inflammatory stimulus, both extracts were able to inhibit this process significantly (P < .05, analysis of variance followed by Tukey-Kramer multiple comparison post hoc test), although it inhibited the granulomatous tissue induction moderately. These extracts were able to decrease the ulcer wounds induced by stress. Also, administration of extracts inhibited neutrophil migration to the exudates present in the peritoneal cavity after carrageenin injection. Therefore, it is possible that A. blazei extracts can be useful in inflammatory diseases because of activation of the immune system and its cells induced by the presence of polysaccharides such as beta-glucans.

Topics: Adjuvants, Immunologic; Agaricus; Analysis of Variance; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Arthritis; Carrageenan; Disease Models, Animal; Edema; Freund's Adjuvant; Granuloma; Male; Neutrophil Infiltration; Nystatin; Plant Extracts; Rats; Rats, Wistar; Stomach Ulcer

Present study was performed to evaluate the efficacy, toxicity and pharmacokinetics of antifungal drug nystatin incorporated in immunomodulator tuftsin-bearing liposomes. In vitro toxicity of free nystatin and nystatin incorporated in tuftsin-free or tuftsin-loaded liposomes was assessed by incubation of nystatin formulations with human erythrocytes. The toxicity profile of free nystatin and liposomal formulations of nystatin with or without tuftsin was also analyzed by monitoring the level of blood urea nitrogen (BUN) and serum creatinine in the treated BALB/c mice. The results of the present work showed that tuftsin-loaded nystatin liposomes like conventional nystatin liposomes exerted less toxicity to human erythrocytes as compared with free nystatin. Moreover, mice treated with tuftsin-loaded nystatin liposomes showed insignificant elevation in the biochemical values of serum creatinine and blood urea. The stability of nystatin liposomes upon incorporation of tuftsin was evaluated by monitoring the leakage of the entrapped drug in human serum. Tuftsin-loaded liposomes held nystatin for longer duration in the presence of serum than identical nystatin liposomes without tuftsin. Pharmacokinetics of the both tuftsin-free or tuftsin-loaded liposomal formulations nystatin was analyzed by determining the level of nystatin in the systemic circulation of mice at different time points. Mice injected with tuftsin-loaded nystatin liposomes showed higher level of the drug in the systemic circulation compared with those treated with conventional nystatin liposomes. The efficacy of tuftsin-loaded nystatin liposomes against A. fumigatus was evaluated by assessing the fungal burden in the lungs of treated mice. Treatment with tuftsin-loaded nystatin liposomes was most effective in eliminating fungal burden from lung tissues of infected mice compared to those treated with free nystatin or nystatin liposomes without tuftsin. The immunopotentiating activity, increased stability and less toxicity of tuftsin-incorporated nystatin liposomes, supports the idea for its prophylactic and therapeutic use in the clinical setting.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Disease Models, Animal; Humans; Immunologic Factors; Liposomes; Male; Mice; Microbial Sensitivity Tests; Nystatin; Treatment Outcome; Tuftsin

The objective of this research was the evaluation of the activity of admixtures of amphotericin B (AMB)--intralipid (AMB-IL) and nystatin (Ny)--intralipid (Ny-IL) against experimental systemic aspergillosis in immunocompromised mice. ICR mice were transiently immunosuppressed by intraperitoneal (i.p.) administration of cyclophosphamide (CY). Three days post CY administration the mice were inoculated intravenously (i.v.) with Aspergillus fumigatus conidia. The animals were treated with various doses of AMB-IL or Ny-IL admixtures administered i.v. for 5 consecutive days, starting 2 h after infection. The mean survival rate (MSR) and mean survival time (MST) were evaluated during an observation period of 30 days in comparison to untreated infected mice and to animals treated with conventional formulations of these drugs. These experiments showed that AMB-IL increased significantly the MSR. Specifically, the MSR ranged in dependence of dose, between 48 and 65.7% vs. 0% of the untreated (P < 0.001, anova analysis) and 39.7% of AMB-treated animals (P < 0.01). The MSR of the Ny-IL-treated mice ranged between 16.2 and 40% in comparison to 0% of the untreated group (P < 0.001). Treatment with both admixtures prolonged the MST of the mice (AMB-IL: 17.3-23.07 days; Ny-IL: 8.61-16.8 days) in comparison to either untreated (6.13 days) or AMB treated animals (15.23 days). The data obtained in this study show that both AMB-IL and Ny-IL formulations, particularly AMB-IL at the highest dose, were effective in the treatment of experimental systemic aspergillosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Fat Emulsions, Intravenous; Female; Immunocompromised Host; Immunosuppressive Agents; Mice; Mice, Inbred ICR; Nystatin; Phosphatidylcholines; Phosphatidylglycerols; Polyenes

The anti-inflammatory effect of Arnica montana 6cH was evaluated using acute and chronic inflammation models. In the acute, model, carrageenin-induced rat paw oedema, the group treated with Arnica montana 6cH showed 30% inhibition compared to control (P < 0.05). Treatment with Arnica 6cH, 30 min prior to carrageenin, did not produce any inhibition of the inflammatory process. In the chronic model, Nystatin-induced oedema, the group treated 3 days previously with Arnica montana 6cH had reduced inflammation 6 h after the inflammatory agent was applied (P < 0.05). When treatment was given 6 h after Nystatin treatment, there was no significant inhibitory effect. In a model based on histamine-induced increase of vascular permeability, pretreatment with Arnica montana 6cH blocked the action of histamine in increasing vascular permeability.

Topics: Acute Disease; Analysis of Variance; Animals; Anti-Inflammatory Agents; Arnica; Carrageenan; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Foot Diseases; Granulation Tissue; Inflammation; Male; Nystatin; Phytotherapy; Plant Extracts; Random Allocation; Rats; Rats, Wistar; Time Factors

The vegetal species Pterodon emarginatus Vog. (Leguminosae/Papilonaceae), popularly known in Brazil as 'sucupira branca', is widely used by domestic medicine as an anti-inflammatory. From these observations, the hexanic crude extract (HCE) of the fruits was obtained and submitted for assessment of its anti-inflammatory activity. For this purpose, the following tests were used: (1) Determination of ED50 and LD50; (2) Paw edema induced by carrageenin, dextran, histamine and nystatin; (3) Peritonitis caused by carrageenin and (4) Granuloma test. The ED50 (oral) in the edema induced by carrageenin was 500 mg/kg, and LD50 (oral) was 4.02 g/kg. In the edema caused by nystatin, there was a significant inhibition by 45% (P < 0.05 student's t-test) at the 6th hour following the treatment. In the granuloma test performed in animals treated with HCE, there was an inhibition of the granulomatous tissue formation by 22%. The migration of neutrophils towards the peritoneal cavity was inhibited in HCE treated animals by 43% (P < 0.05). However, in the edema caused by dextran and histamine, there was no significant response in HCE treated animals.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Dextrans; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Fabaceae; Fruit; Male; Mice; Nystatin; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar

The activity of liposomal nystatin (L-Nys) against subacute disseminated candidiasis was investigated in persistently neutropenic rabbits. Antifungal therapy was administered for 10 days starting 24 h after intravenous inoculation of 10(3) blastoconidia of Candida albicans. Responses to treatment were assessed by the quantitative clearance of the organism from blood and tissues. Treatments consisted of L-Nys at dosages of 2 and 4 mg/kg of body weight/day (L-Nys2 and L-Nys4, respectively) amphotericin B deoxycholate at 1 mg/kg/day (D-AmB), and fluconazole at 10 mg/kg/day (Flu). All treatments were given intravenously once daily. Compared to the results for untreated but infected control animals, treatment with L-Nys2, L-Nys4, D-AmB, and Flu resulted in a significant clearance of the residual burden of C. albicans from the kidney, liver, spleen, lung, and brain (P < 0.0001 by analysis of variance). When the proportion of animals infected at at least one of the five tissue sites studied was evaluated, a dose-dependent response to treatment with L-Nys was found (P < 0.05). Compared to D-AmB-treated rabbits, mean serum creatinine and blood urea nitrogen levels at the end of therapy were significantly lower in animals treated with L-Nys2 (P < 0.001) and L-Nys4 (P < 0.001 and P < 0.01, respectively). L-Nys was less nephrotoxic than conventional amphotericin B and had dose-dependent activity comparable to that of amphotericin B for the early treatment of subacute disseminated candidiasis in persistently neutropenic rabbits.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Disease Models, Animal; Drug Carriers; Fluconazole; Liposomes; Nystatin; Rabbits; Treatment Outcome

A new model for the evaluation of antifungal compounds against oropharyngeal and gastrointestinal mucosal colonization by Candida albicans was developed. To simulate the immune deficiency observed in AIDS patients, mice were depleted of CD4+ T lymphocytes by the injection of either GK1.5 hybridoma cells or purified anti-CD4+ T lymphocytes by the injection of either GK1.5 hybridoma cells or purified anti-CD4+ monoclonal antibody derived from GK1.5 hybridoma cells in tissue culture. Fluorescence-activated cell sorter analysis of splenic lymphocytes confirmed the elimination of the CD4+ T-cell population. Gentamicin, a broad-spectrum, nonabsorbable aminoglycoside antibiotic, was given via the drinking water to reduce the normal gastrointestinal microflora, allowing less competition for colonization of the gastrointestinal tract by the C. albicans isolates. Mice were challenged by gavage and swabbing their oral mucosae with a pure culture of C. albicans. Gentamicin was withdrawn 3 days postchallenge, and antifungal compounds were administered via the drinking water ad libitum at concentrations ranging from 25 to 400 micrograms/ml. L-693989, a water-soluble phosphorylated cyclic lipopeptide prodrug of pneumocandin Bo, and L-733560, a semisynthetic derivative of pneumocandin Bo, are inhibitors of 1,3-beta-D-glucan synthesis that exhibit potent in vivo anti-Candida spp. and anti-Pneumocystis carinii activities. The efficacies of L-693989, L-733560, fluconazole, ketoconazole, and nystatin were evaluated in this new oropharyngeal and gastrointestinal model of mucosal colonization. L-693989, L-733560, fluconazole, and ketoconazole showed superior efficacies in reducing the numbers of C. albicans CFU per gram of feces and the numbers of oral CFU relative to those in sham-treated controls in this model, while nystatin was moderately effective in reducing oral and fecal colonization by C. albicans in this model.

Topics: Animals; Anti-Bacterial Agents; Antibodies, Monoclonal; Antifungal Agents; Candida albicans; CD4-Positive T-Lymphocytes; Digestive System; Disease Models, Animal; Female; Fluconazole; Ketoconazole; Mice; Mice, Inbred DBA; Microbial Sensitivity Tests; Nystatin; Oropharynx; Peptides; Peptides, Cyclic

Relatively simple and rapid procedures have been developed for evaluating the local efficacy of vaginal antifungal agents in vivo in a vaginal candidiasis model in ovariectomized rats. The results of this investigation indicate that the model and methods described are quite suitable for screening potential antifungal substances and for assessing the chemotherapeutic effectiveness of new antifungal agents and formulations before carrying out clinical studies.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Clotrimazole; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Miconazole; Nystatin; Rats; Vagina

The effect of synthetic salmon calcitonin was studied on adjuvant arthritis, pertussis vaccine edema, tuberculin skin reaction, passive direct Arthus reaction and nystatin edema. The results show that calcitonin inhibits these inflammatory processes.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthus Reaction; Calcitonin; Dermatitis, Atopic; Disease Models, Animal; Edema; Inflammation; Nystatin; Pertussis Vaccine; Rats; Time Factors; Tuberculin

Cyclophosphamide (5 or 10 mg/kg p.o.) and Gold sodium thiomalate (0 or 40 mg/kg i.m.) inhibit after repeated administrations (5 days) all the phases of Nystatin edema, whereas a single administration is ineffective. D-Penicillamine (25 or 100 mg/kg p.9.) inhibits the early phases of Nystatin edema after a single administration whereas repeated administrations are almost ineffective. An early treatment with Cyclophosphamide (2.5 mg/kg p.o.) simply delays the appearance of the secondary lesions of adjuvant arthritis but inhibit the development of the primary lesions. A late treatment with Cyclophosphamide as both the types of treatment with Gold sodium thiomalate (10 mg/kg i.m.) are effective against primary and secondary lesions. The only effect of D-Penicillamine (50 mg/kg p.o.) in adjuvant arthritis is a significant increase of the intensity of secondary lesions during the late treatment. It is suggested that the anti-inflammatory activity of Cyclophosphamide does not depend exclusively upon its immunosuppressant activity and that D-Penicillamine is effective on some cell population committed in the inflammatory reactions.

Topics: Animals; Arthritis; Arthritis, Experimental; Cyclophosphamide; Disease Models, Animal; Female; Gold Sodium Thiomalate; Inflammation; Nystatin; Penicillamine; Rats; Time Factors

Topics: Animals; Disease Models, Animal; Edema; Female; Inflammation; Nystatin; Rats