Evaluación de formulaciones de ketoconazol para uso tópico en leishmaniasis cutánea por Leishmania(Viannia) / Evaluation of ketoconazole formulations for topical use in cutaneous leishmaniasis caused by Leishmania (Viannia)

RESUMEN Se evaluó la efectividad de diversas formulaciones farmacéuticas de ketoconazol en modelos experimentales de leishmaniasis cutánea (LC) en ratones BALB C. Fueron preparadas formulaciones tópicas tipo gel, lipogel y crema conteniendo potenciadores de la permeación y diferentes concentraciones de ketoconazol. Se determinó la estabilidad, la toxicidad y la actividad anti-Leishmania in vitro. Además, se evaluó in vivo la efectividad de las formulaciones aplicadas tópicamente en ratones con LC infectados con Leishmania (Viannia) braziliensis. Las formulaciones tipo crema fueron evaluadas adicionalmente en ratones infectados con L. (V.) panamensis. Los sistemas evaluados mantuvieron in vitro la actividad del ketoconazol contra los parásitos; sin embargo, ninguna de las formulaciones fue efectiva en curar las lesiones de LC en los ratones. El tratamiento tópico con miltefosina (utilizado como control) curó las lesiones. Se concluye que las formulaciones que contienen ketoconazol diseñados en este estudio, no fueron efectivos contra la LC en los ratones infectados.

ABSTRACT The effectiveness of various pharmaceutical formulations of ketoconazole was evaluated in experimental models of cutaneous leishmaniasis (LC) in BALB C mice. Topical gel, lipogel, and cream formulations containing permeation enhancers and different concentrations of ketoconazole were prepared. Stability, toxicity and anti-Leishmania activity were determined in vitro. In addition, the effectiveness of topically applied formulations in LC-infected mice infected with Leishmania (Viannia) braziliensis was evaluated in vivo. Cream formulations were additionally evaluated in mice infected with L. (V.) panamensis. The systems evaluated maintained in vitro the activity of ketoconazole against parasites; however, none of the formulations were effective in curing LC lesions in mice. Topical treatment with miltefosine (used as a control) cured the lesions. It is concluded that the ketoconazole-containing formulations designed in this study were not effective against LC in infected mice.

Open comparative study of efficacy and safety of ketoconazole soap and oral ketoconazole in tinea versicolor

To compare the efficacy and safety of 2% ketoconazole soap in treatment of tinea versicolor [TV] and to compare it with stat 400mg dose of ketoconazole. Patients of TV confirmed by potassium hydroxide [KOH] mount were divided by block randomization into 2 groups. Group 1 received 400mg of oral ketoconazole single dose and a non-medicated soap for daily bath. Group 2 received 2% ketoconazole soap for daily bath. The lather from the soap while bathing was to be left on the skin for 3 minutes. Patients were assessed at the end one month and KOH repeated from index lesion. Twelve patients out of 25 completed the study, 6 in each group. Four patients [66%] were mycologically cured in group 1 while two patients [34%] were mycologically cured in group 2. All these patients were compliant with the usage of soap. Ketoconazole soap is at best an adjunct in the treatment of TV. It might however be useful in the prophylactic management of patients with chronic TV as bathing is almost a daily routine in most patients especially in tropics. Further studies are required in this aspect

Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.

Colletotrichum graminicola keratitis: First case report from India.

Colletotrichum graminicola is a medically important fungus belonging to the order Melanconiales under the class Coelomycetes. The members of the genus Colletotrichum are primarily plant pathogens which cause anthracnoses (fungal infection in plants). In the past few decades, they are progressively being implicated as etiological agents of subcutaneous hyalohyphomycoses and keratomycoses. Of the five medically important members in the genus Colletotrichum, keratitis due to Colletotrichum graminicola is rare. We diagnosed Colletotrichum graminicola keratitis in a 44-year-old man who presented with a non-healing corneal ulcer since three weeks. Positive smears and cultures from the corneal scrapings established the causative organism as C. graminicola. The patient was treated with a combination of oral ketoconazole and topical fluconazole and natamycin. Infection resolved over 10 weeks and antimicrobials were stopped. We describe the clinical presentation and treatment outcome of Colletotrichum graminicola keratitis.

Rhabdomyomatous mesenchymal hamartoma clinical overview and report of a case with spontaneous regression / Hamartoma mesenquimal rhabdomiomatoso panorama clínico y reporte de un caso con regresión espontánea

A case of cutaneous rhabdomyomatous mesenchymal hamartoma in a 6-year old Afro-Caribbean girl is reported with review of the literature. The lesions were fine, located on the central face and became inapparent after six months. Spontaneous regression of these lesions has not been previously reported. Although rare, continued reporting will facilitate the elucidation of the clinical features and natural history of these lesions and the relationship to disordered embryogenesis.

Un caso de hamartoma mesenquimal rhabdomiomatoso cutáneo en una niña afrocaribeña de seis años de edad, se reporta junto con una revisión de la literatura. Las lesiones eran tenues, localizadas en la parte central de la cara, y se hicieron aparentes luego de seis meses. La regresión espontánea de estas lesiones no se ha reportado con anterioridad. Aunque sean raras, reportarlas de manera continuada facilitará la dilucidación de los rasgos clínicos y la historia natural de estas lesiones, así como su relación con una embriogénesis desordenada.

Effect of hypercortisolism control on high blood pressure in Cushing's syndrome / Efecto del control del hipercortisolismo sobre la hipertensión arterial en el síndrome de Cushing

Many hypertensive patients affected by endogenous Cushing's syndrome (CS) persist with high blood pressure (HBP) despite good control of cortisol excess. We assessed the effect of preoperative ketoconazole administration and of definitive treatment of CS on arterial hypertension and analysed the factors involved in the persistence of hypertension. We assessed retrospectively 71 patients with CS and HBP (60 women, 11 men; 50 pituitary, 21 adrenal) successfully treated by surgery and/or radiotherapy; 19 of them received ketoconazole (KNZ) before surgery. After treatment, patients were divided into those with persistent high blood pressure (PHBP) and those with normal blood pressure (NBP). As possible predictive factors for PHBP we analysed age, duration and family history of HBP, pre-treatment 24 hour urinary free cortisol (24h-UFC) and body mass index (BMI). HBP normalized in 53 out of 71 patients (74.6%), regardless of the origin of Cushing's syndrome. PHBP patients were older (p=0.003), had longer duration (p=0.007) and higher systolic blood pressure before treatment (p=0.046) than NBP patients. Thirteen out of 19 patients (68.4%) treated with ketoconazole, normalized their hypertension and remained normotensive after successful surgery. Five patients became normotensive only after surgery. In conclusion: a) blood pressure levels normalized in most patients after remission of CS; b) ketoconazole was effective for the control of HBP, and seems to be a good indicator of post-surgical outcome, and c) higher age at presentation, longer duration of hypertension and higher systolic blood pressure figures before treatment negatively influence normalization of blood pressure after resolution of Cushing's syndrome.

Muchos pacientes con síndrome de Cushing (SC) permanecen hipertensos a pesar del control del exceso glucocorticoideo. Investigamos el efecto de la administración de ketoconazol (KNZ) y del tratamiento definitivo del SC sobre la hipertensión arterial (HTA), analizando su relación con diversos factores. Evaluamos 71 pacientes con SC e HTA (60 mujeres, 11 varones; 50 pituitarios, 21 adrenales) exitosamente tratados por cirugía y/o radioterapia; 19 de ellos recibieron KNZ antes de cirugía. Luego del tratamiento, fueron divididos en pacientes con HTA persistente (HTAP) y normal (HTAN). Como posibles factores predictivos de HTAP se analizaron edad, duración, historia familiar de HTA, cortisol libre urinario de 24 hs pre-tratamiento e índice de masa corporal. La HTA normalizó en 53/71 pacientes (74.6%) independientemente del origen del síndrome de Cushing. Los pacientes con HTAP fueron de mayor edad (p=0.003), con mayor duración previa (p=0.007) y valores mayores de presión arterial sistólica antes de tratamiento (p=0.046) que aquellos con HTAN. Trece de 19 pacientes (68.4 %) tratados con ketoconazol normalizaron su tensión arterial y se mantuvieron normotensos luego de cirugía exitosa. Cinco pacientes se tornaron normotensos solo después de cirugía. En conclusión: a) la HTA se normalizó en la mayoría de pacientes luego de remisión del SC, b) el ketoconazol fue efectivo para el control tensional y aparenta ser indicador de la evolución pos-quirúrgica, y c) mayor edad, duración más prolongada de la HTA y valores más altos de presión sistólica influencian negativamente la normalización de la presión arterial luego de resolución del síndrome de Cushing.

Tiña negra: a propósito de tres casos en el estado Táchira-Venezuela / Tinea nigra: report of three cases in the state of Táchira-Venezuela

La tiña negra es una dermatomicosis superficial, poco frecuente, quiza subdiagnosticada, cuyo agente etiológico es el phaeonnellomyces werneckii. Considerada como enfermedad tropical y subtropical de distribución universal, afecta a personas de ambos sexos, a cualquier edad; siendo los niños y los adolescentes los más afectados. Manifestada clínicamente como maculas hiperpigmentadas, asintomáticas de evolución crónica, localizada en la palma de las manos, aunque también pueden estar presentes en la planta de los pies y otras superficies. El examen micológico directo y cultivo de la lesión confirman el diagnóstico y el tratamiento con topicos de formulación sencilla incluyendo imidazolicos ofrecen buenos resultados.

[ comparison between systemic fluconazol and ketoconazol effectivity in the treatment of tinea versicolor]

Tinea Versicolor is a common superficial fungal skin infection. Topical drugs are often effective in limited lesions; but in extensive cases, systemic drugs are more suitable. Previous studies have shown that Ketoconazole and Fluconazole are effective in 42-97% and 74-100% of lesions respectively. Theaim of this study is to compare the effectiveness of a single dose of 400mg Ketoconazole with two doses of 300mg of Fluconazole with 2 weeks interval. Sixty patients with extensive tinea versicolor [body involved area >/= 25%] were randomly assigned to treatment with either a single dose of 400mg of Ketoconazole or with two doses of 300mg of Fluconazole with 2 weeks interval. One month after the treatment, the improvement rate and side effects were evaluated by clinical examination and questionnaire. Sixty patients were participated initially in the study. Sixty cases [66.7%] completed the study. They were 51 males and 9 females, with a mean age of 30 years. At the follow up visit [one month after the end of treatment], the improvement rate for Ketoconazole [87.9%] was not significantly different from Fluconazole [81.5%]. [Fisher test: P=0.37]. Fluconazole has shown to be as effective as Ketoconazole in the treatment of extensive tinea versicolor. Due to the hepatotoxicity of Ketoconazole, Fluconazole appears to be more suitable in the treatment of extensive tinea versicolor

Comparative study of 2% ketoconazole cream and 1% hydrocortisone cream in the treatment of infantile seborrheic dermatitis.

OBJECTIVE: To compare efficacy of 2% ketoconazole cream with 1% hydrocortisone cream in the treatment of infantile seborrheic dermatitis (ISD). This study recruited infants of 2 weeks to 2 years old with a clinical diagnosis of infantile seborrheic at the Department of Pediatrics, King Chulalongkorn Memorial Hospital from December 2001 to November 2003. METHOD: The severity of the rash of the patients was examined in terms of erythema, scale and crust before treatment based on a scoring system comparing two sides (left and right) of the lesion with numeral representation for it a severity, namely: Ofor no lesion; 1, mild; 2, moderate; and 3, severe. They were treated with 2% ketoconazole cream on the left side of the lesion and 1% hydrocortisone cream on the right side of the lesion, twice a day. RESULTS: The responses of treatment of 2% ketoconazole cream compared with 1% hydrocortisone cream in 48 patients had no statistical significant difference at 2-3 days of treatment and 4-7 days of treatment. By one week, both 2% ketoconazole cream and 1% hydrocortisone cream have significant clinical improvement of the lesion. The skin lesions were cleared in 31% of the ketoconazole group and 35% of the hydrocortisone group. All skin lesions were cleared by the end of the second week. CONCLUSION: The efficacy of 2% ketoconazole cream and 1% hydrocortisone cream in the treatment of ISD was not significantly different. Ketoconazole is another option for the treatment of ISD, to avoid the side effects of topical corticosteroid in long-term use and on large surface area of treatment.

Estudio comparativo entre terbinafina en crema contra ketoconazol en crema; eficacia y tolerancia en el tratamiento de la candidiosis de la zona del pañal en lactantes / Terbinafine versus Ketoconazole cream in the treatment of diaper zone candidiasis. A clinical trial of tolerability and efficacy

Introducción. La dermatitis de la zona del pañal (DZP), común en lactantes, se agrava frecuentemente con infecciones, principalmente por Candida albicans. Objetivo. Comparar la eficacia y tolerancia a la terbinafina en crema contra la de ketoconazol en crema en candidiosis de la zona del pañal. Material y métodos. Se realizó un ensayo clínico abierto, comparativo, aletorizado, separando 2 grupos, indicandoseles aplicar terbinafina en crema una vez al día durante 14 días al primer grupo y ketoconazol 2 veces al día, por mismo periodo, al segundo grupo. El seguimiento se realizó por 4 semanas. Resultados. Ingresaron 52 pacientes; 28 en el grupo de terbinafina, 24 en el ketoconazol; 28 del sexo masculino y 24 del femenino. Hubo un sólo caso de reacción adversa en el grupo de terbinafina y consistió en incremento del eritema y prurito. El resto de parámetros evolucionó en forma similar. Conclusiones. Los análisis estadísticos no reportan diferencia significativa. Se considera a la terbinafina como alterativa en una circunstancia clínica no estudiada antes

Vaginal Candidiasis: An incomprehensible Challege

A infecçäo recorrente da mucosa vaginal pela Candida albicans foi abordada realçando-se os mecanismos de interaçäo entre o fungo e o epitélio vaginal, com ênfase para os aspéctos imunológicos que controlam a proliferaçäo fúngica. Destaca-se o papel da imunidade celular mediada neste processo de eqüilibrio entre agente e hospedeiro, reforçando a importância via Th1, de resposta imune, onde há uma liberaçäo de citocinas como interferon-gama, interleucina-1 e 12. Por outro lado, a via Th2 que libera citocinas estimulantes da produçäo de anticorpos (interleucinas-4, 5 and 10) tera valor limitado na defesa da mucosa contra este agente. Comenta-se também o aspécto fisiopatogênico envolvendo resposta imune ligada aos processos alérgicos individuais e em decorrência de interaçäo como parceiro sexual. O diagnóstico principal "arma" para o tratamento adequado, é enfocado com ênfase na prática, reforçando-se o uso de bacterioscopias simples, sem esquecer que técnicas sofisticadas, como PCR, podem vir a ser útil para determinados casos. O tratamento da fase aguda e de manutençäo foi sugerido na tentativa de diminuir as recorrências, alertando-se principalmente para necessidade de tomar atitudes que visem näo somente o combate ao fungo, mas que também e fudamentalmente, priorize a identificaçäo e eliminaçäo de possíveis alérgenos

Adiaspiromicose pulmonar disseminada: relato de caso / Disseminated pulmonary adiaspiromycosis: a case report

Relata-se caso de adiaspiromicose causando infiltrado pulmonar retículo-nodular difuso e bilateral, em lavrador de 26 anos. O diagnóstico etiológico foi estabelecido através de biópsia por toracoscopia. Tratado com cetoconazol, o paciente evoluiu bem, retornando às atividades profissionais um mês após a alta.

A case of thoracoscopic lung biopsy proven diffuse human adiaspiromycosis is reported. The patient, a 26-year-old male farm worker presented with a three-week history of fever, sweating, dyspnea and unproductive cough. Radiographic findings were those of granulomatous pulmonary interstitial disease. Treated with ketoconazole he improved very well, resuming work normal activities a month later.

Monoartrite de joelho como manifestação isolada de paracoccidioidomicose / Monoarthritis of the knee as an isolated manifestation of paracoccidioidomycosis

Artrite como manifestação isolada de paracoccidioidomicose, tem sido raramente descrita na literatura médica. O presente relato, descreve mulher de 46 anos de idade, com monoartrite crônica do joelho em tratamento com anti-inflamatórios não hormonais durante 4 anos, cujo diagnóstico definitivo foi obtido apenas por biópsia da membrana sinovial, que revelou uma inflamação crônica granulomatosa de tipo tuberculóide, com abundantes elementos leveduriformes do Paracoccidioides brasiliensis. A terapêutica específica (iniciada com ketoconazol e seguida por cotrimoxazol) levou à completa recuperação funcional da articulação acometida. Não se detectou a presença de outros sítios acometidos pela doença, apesar da utilização de vários métodos propedêuticos, incluindo tomografia axial computadorizada do tórax e abdome. Os autores chamam a atenção para a raridade do caso e discutem os possíveis fenômenos fisiopatológicos responsáveis por esta monoartrite fúngica.

Osteoarthritis in paracoccidioidomycosis has been rarely reported. The present case describes a 36-[quot ]year[quot ]-old woman, with chronic monoarthritis in the knee lasting 4 years. The diagnosis was achieved only after synovial biopsy, by anatomopathological examination showing granulomatous reaction with a large number of the characteristic [quot ]pilot wheel[quot ]Paracoccidioides brasiliensis yeast cells. Specific therapy, initially with ketoconazole and followed by cotrimoxazole led to complete functional recovery of the compromised joint. No other affected site was detected by various propaedeutic methods, including computed axial tomography of the thorax and abdomen. The authors emphasize the rarity of the case and discuss its possible pathophysiology.

Chromoblastomycosis murine model and in vitro test to evaluate the sensitivity of Fonseca pedrosoi to ketoconazole, itraconazole and saperconazole

An experimental model of murine chromoblastomycosis and in vitro tests with Fonsecaea pedrosoi were used to test the sensitivity of this fungus to three different antimycotics. The experimental model was standardized in BALB/c mice inoculated intraperitoneally with a 10 6 CFU/ml suspension of a F.pedrosoi isolate. Clinical infection was evident after 5 days of inoculation. Three groups of 27 mice each were used in the experiment. One group was treated with ketoconazole (KTZ), another with itraconazole (ITZ) and the other with saperconazole (SPZ). Antimycotic therapy was continued for 21 days. The control group consisted of 40 mice which were inoculated, but not treated. Infection was documented by macroscopic and microscopic examination of affected tissue in addition to culture of tissue macerates. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) for the F.pedrosoi strain used were done. The in vitro results showed that SPZ was the most active with MIC 0.01 µg/ml and MFC 0.1 µg/ml, followed by ITZ, SPZ was also the most effective in vivo since 63 per cent of the trated animals (p=0.01) showed a curative effect after the observation period. We concluded that SPZ ha the best in vitro and in vivo activity against F. pedrosoi.

Profilaxis del síndrome de insuficiencia respiratoria progresiva aguda (SIRPA) con ketoconazol en pacientes con sepsis / Prophylaxis of the acute respiratory distress syndrome (ARDS) with ketoconazole in patients with sepsis

Introducción. Los tromboxanos son mediadores de la inflamación que contribuyen al edema pulmonar del SIRPA en los pacientes con sepsis. Objetivo. Estudiar los efectos del ketoconazol (un inhibidor de la tromboxano-sintetasa) en la profilaxis del SIRPA en pacientes con sepsis. Pacientes y métodos. Estudiamos en una UCI 24 pacientes (grupo problema) tratado con ketoconazol (400 mg/día) y 24 pacientes (grupo control) tratados con placebo al ingreso y durante su estancia en la UCI. Diariamente se realizó evaluación clínica, gases arteriales y venosos, y radiografías de tórax; el monitoreo hemodinámico se inició cuando se hizo el diagnóstico de SIRPA. Resultados. El SIRPA se estableció en siete pacientes del grupo problema y en nueve del grupo control). La PaO2, relación PaO2/FIO2, distensibilidad pulmonar, niveles de PEEP y presión de oclusión de la arteria pulmonar fueron similares en ambos grupos. Conclusión. Es necesario evaluar el papel de ketoconazol en la profilaxis del SIRPA con series más grandes de pacientes

Ketoconazol al 1 por ciento champú vs. climbazole champú en el tratamiento de la dermatitis seborreica en piel cabelluda / Ketoconazole 1 por ciento shampoo vs climbazole shampoo on the treatment of seborrhoeic dermatitis in scalp skin

La dermatitis seborreica de piel cabelluda (caspa) es un padecimiento crónico, recidivante y frecuente que se presenta entre los 18 y 40 años de edad y es más común en hombres adultos que en mujeres. Para tratar este padecimiento se ha empleado ketoconazol al 1 por ciento en champú y actualmente se ha propuesto climbazole champú. Por lo anterior, los objetivos del estudio fueron conocer la eficacia de climbazole y compararla con ketoconazol. El diseño del estudio fue doble ciego, comparativo, prospectivo y longitudinal, con una duración de seis semanas de tratamiento por pacientes. Se estudiaron 60 pacientes con diagnóstico clínico de dermatitis seborreica en piel cabelluda, edades entre 16 y 45 años, y que otorgaron su consentimiento para participar en el protocolo. A los pacientes se les asignó en forma aleatoria a una de las dos pociones de tratamiento, realizándose una valoración inicial del padecimiento, y posteriormente se les citó para revisión al final de la primera, tercera y sexta semanas de tratamiento. Se encontró que ambos medicamentos fueron efectivos en el tratamiento de los síntomas como prurito, descamación, piel reseca o grasosa, pero ketoconazol al 1 por ciento champú mostró una eficacia superior, con una diferencia estadísticamente significativa en todos los síntomas. El 80 por ciento de los pacientes del grupo ketoconazol y el 13 por ciento de los del grupo climbazole se calificaron como curación clínica al final del tratamiento (p=0.0001)

Piedra blanca: informe de un caso / White piedra: report of 1 case

The most common superficial mycosis caused by trichosporon beigelii is white piedra. We report a 18 years old male that had in several hairs of the scalp, white-yellowish nodules of 1 mm diameter, agglutinated or forming chains, even forming threads, with a greasy aspect. Trichosporon beiglii was identified in cultures. Oral and topical antimycotics were prescribed and the patient was lost from follow up

Acanthamoeba keratitis.

Acanthamoeba keratitis, common in soft lens wearers, is not commonly isolated. The reports of Acanthamoeba keratitis in Indian literature are few. We report here a case of Acanthamoeba Keratitis in a medical student using soft contact lenses, initially diagnosed and treated as a bacterial and later as a viral corneal ulcer, who responded extremely well to medical line of therapy.