Pedometria aplicada a estudo comparativo entre morfina e tramadol em bovinos / Pedometry applied to a comparative study using morphine and tramadol in bovine

A analgesia com opioides é limitada ou indefinida em ruminantes. Neste trabalho, objetivou-se a realização de um estudo comparativo entre dois analgésicos opioides: a morfina e o tramadol, com base nas avaliações clínica e pedométrica de animais submetidos a artrite e sinovite experimental transitórias, desenvolvidas na articulação interfalângica distal, após administração intra-articular de anfotericina B. Utilizou-se seis animais, em dois tratamentos distintos, com morfina, na dose de 0,5 mg/kg e 20 dias depois com tramadol, na dose de 1,8 mg/kg, ambos via intramuscular. Os animais foram avaliados em intervalos de três horas, num total de 27 horas, observando-se parâmetros fisiológicos, deambulação e atividade pedométrica. Claudicação e alterações pedométricas foram observadas para ambos os fármacos. Por meio das variáveis da atividade pedométrica, observou-se um padrão de inquietação compatível com nocicepção podal, não havendo a interferência dos fármacos sobre a claudicação. Concluiu-se que a morfina e o tramadol, nas doses testadas, foram incapazes de interferir na atenuação do grau de claudicação no momento de máxima estimulação dolorosa, frente ao modelo experimental de dor ortopédica.

The use of opioids for analgesia is limited or undefined in ruminants. The aim of this study was to compare two analgesics opioids, morphine and tramadol, based on the clinical and pedometric evaluations of animals submitted to a temporary experimental arthritis and synovitis, developed at the distal interphalangeal joint after an intra-articular administration of amphotericin B. Six animals were used in two different treatments, using morphine, dose of 0,5 mg/kg, and twenty days later, tramadol, dose of 1,8 mg/kg, both intramuscularly. The animals were evaluated at 3-hour intervals for a total of 27 hours, observing the physiological parameters, ambulation and pedometer activity. Lameness and pedometer variations were observed in both treatments. Based on the variables of pedometric activity, a pattern of restlessness compatible with podal nociception was observed, and there was no interference of any of the drugs on lameness. It was concluded that morphine and tramadol, at the tested doses, were incapable of interfering in the lameness attenuation during the maximum painful stimulation moment in this experimental protocol of orthopedic pain.

Pedometria aplicada a estudo comparativo entre morfina e tramadol em bovinos / Pedometry applied to a comparative study using morphine and tramadol in bovine

A analgesia com opioides é limitada ou indefinida em ruminantes. Neste trabalho, objetivou-se a realização de um estudo comparativo entre dois analgésicos opioides: a morfina e o tramadol, com base nas avaliações clínica e pedométrica de animais submetidos a artrite e sinovite experimental transitórias, desenvolvidas na articulação interfalângica distal, após administração intra-articular de anfotericina B. Utilizou-se seis animais, em dois tratamentos distintos, com morfina, na dose de 0,5 mg/kg e 20 dias depois com tramadol, na dose de 1,8 mg/kg, ambos via intramuscular. Os animais foram avaliados em intervalos de três horas, num total de 27 horas, observando-se parâmetros fisiológicos, deambulação e atividade pedométrica. Claudicação e alterações pedométricas foram observadas para ambos os fármacos. Por meio das variáveis da atividade pedométrica, observou-se um padrão de inquietação compatível com nocicepção podal, não havendo a interferência dos fármacos sobre a claudicação. Concluiu-se que a morfina e o tramadol, nas doses testadas, foram incapazes de interferir na atenuação do grau de claudicação no momento de máxima estimulação dolorosa, frente ao modelo experimental de dor ortopédica.(AU)

The use of opioids for analgesia is limited or undefined in ruminants. The aim of this study was to compare two analgesics opioids, morphine and tramadol, based on the clinical and pedometric evaluations of animals submitted to a temporary experimental arthritis and synovitis, developed at the distal interphalangeal joint after an intra-articular administration of amphotericin B. Six animals were used in two different treatments, using morphine, dose of 0,5 mg/kg, and twenty days later, tramadol, dose of 1,8 mg/kg, both intramuscularly. The animals were evaluated at 3-hour intervals for a total of 27 hours, observing the physiological parameters, ambulation and pedometer activity. Lameness and pedometer variations were observed in both treatments. Based on the variables of pedometric activity, a pattern of restlessness compatible with podal nociception was observed, and there was no interference of any of the drugs on lameness. It was concluded that morphine and tramadol, at the tested doses, were incapable of interfering in the lameness attenuation during the maximum painful stimulation moment in this experimental protocol of orthopedic pain.(AU)

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity

Abstract Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

Resumo A anfotericina B é o tratamento de escolha para a maioria das infecções fúngicas sistémicas que afetam os doentes imunocomprometidos. No entanto, efeitos secundários graves têm limitado a utilidade desta droga. O objetivo deste estudo foi avaliar o efeito antifúngico da combinação de anfotericina B com chá preto ou chá branco, bem como o efeito citotóxico desta combinação sobre hemáceas. O presente estudo demonstra que o chá branco e preto de Camellia sinensis têm efeitos aditivos com anfotericina B contra algumas espécies de Candida sp. Além disso, a combinação de chá branco e preto com anfotericina B pode reduzir a toxicidade da anfotericina B em hemáceas. Nossos resultados sugerem que o chá branco e preto são agentes potenciais para associação com anfotericina B contribuindo para eficácia antifúngica, bem como redução de toxicidade.

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity / Chá preto e branco de Camellia sinensis como potenciais agentes para associar com anfotericina B

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.(AU)

A anfotericina B é o tratamento de escolha para a maioria das infecções fúngicas sistémicas que afetam os doentes imunocomprometidos. No entanto, efeitos secundários graves têm limitado a utilidade desta droga. O objetivo deste estudo foi avaliar o efeito antifúngico da combinação de anfotericina B com chá preto ou chá branco, bem como o efeito citotóxico desta combinação sobre hemáceas. O presente estudo demonstra que o chá branco e preto de Camellia sinensis têm efeitos aditivos com anfotericina B contra algumas espécies de Candida sp. Além disso, a combinação de chá branco e preto com anfotericina B pode reduzir a toxicidade da anfotericina B em hemáceas. Nossos resultados sugerem que o chá branco e preto são agentes potenciais para associação com anfotericina B contribuindo para eficácia antifúngica, bem como redução de toxicidade.(AU)

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity

Abstract Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

Resumo A anfotericina B é o tratamento de escolha para a maioria das infecções fúngicas sistémicas que afetam os doentes imunocomprometidos. No entanto, efeitos secundários graves têm limitado a utilidade desta droga. O objetivo deste estudo foi avaliar o efeito antifúngico da combinação de anfotericina B com chá preto ou chá branco, bem como o efeito citotóxico desta combinação sobre hemáceas. O presente estudo demonstra que o chá branco e preto de Camellia sinensis têm efeitos aditivos com anfotericina B contra algumas espécies de Candida sp. Além disso, a combinação de chá branco e preto com anfotericina B pode reduzir a toxicidade da anfotericina B em hemáceas. Nossos resultados sugerem que o chá branco e preto são agentes potenciais para associação com anfotericina B contribuindo para eficácia antifúngica, bem como redução de toxicidade.

Quercetin and rutin as potential agents antifungal against Cryptococcus spp / Quercetina e rutina: potenciais agentes para terapia antifúngica

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with quercetin or rutin and as a protective of citotoxic effect. The antifungal activity to amphotericin B, quercetin and rutin alone and in combination was determined in Candida sp and Cryptococcus neoformans strains. Cytotoxicity test on erythrocytes was performed by spectrophotometric absorbance of hemoglobin. The amphotericin B MIC was reduced when used in combination with quercetin or rutin to C. neoformans ATCC strain and reduced when combined with rutin to a clinical isolate of C. neoformans. In addition, the combination of quercetin with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that quercetin and rutin are potential agents to combine with amphotericin B in order to reduce the amphotericin dose to lessen side effects and improve antifungal efficacy.(AU)

A anfotericina B é uma substância fungicida e é o tratamento de escolha para a maioria das infecções fúngicas sistêmicas que afetam os pacientes imunocomprometidos, como a criptococose. No entanto, as severas reações adversas têm limitado a utilização desta droga. O objetivo deste estudo foi avaliar o efeito antifúngico e o potencial efeito protetor de citotoxicidade da combinação de anfotericina B com quercetina ou rutina. A atividade antifúngica de anfotericina B, quercetina e rutina, isoladamente e em combinação foi determinada em cepas de Candida sp e Cryptococcus neoformans. O teste de citotoxicidade em eritrócitos foi realizado por espectrofotometria, através da determinação da absorbância da hemoglobina. A concentração inibitória mínima da anfotericina B foi reduzida quando utilizada em combinação com a quercetina e rutina em C. neoformans ATCC e reduzida quando combinados com rutina em um isolado clínico de C. neoformans. Além disso, a combinação de quercetina com anfotericina B pode reduzir a toxicidade da droga em eritrócitos. Os resultados sugerem que quercetina e rutina são potenciais agentes para combinação com anfotericina B, a fim de reduzir a dose de anfotericina, diminuindo os efeitos colaterais e melhorando sua eficácia antifúngica.(AU)

Topical treatment using amphotericin b and dmso for an atypically located equine cutaneous Pythiosis / Pitiose cutânea equina de localização atípica tratada topicamente com solução de anfotericina B e DMSO

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at fl ooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdômen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes.Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left fl ank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomoris methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at fl ooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdômen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes.Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left fl ank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomoris methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated

Pitiose cutânea equina de localização atípica tratada topicamente com solução de anfotericina B e DMSO / Topical treatment using amphotericin B and DMSO for an atypically located equine cutaneous pythiosis

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at flooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdômen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes. Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left flank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomori's methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated as initial treatment, and due to financial reasons, the owners elected only the topical antifungal therapy to control the fungus infection after surgery. Flunixin meglumine was also administrated for five days aiming the control of pain and inflammation. The wound was cleaned with povidone-iodine solution and rinsed with a solution containing 50 mg of amphotericin B in 10 mL of sterile water and 10 mL of DMSO. This procedure was carried out twice a day. The wound healed fast due to an excellent centripetal epithelialization, and the horse was discharged after 64 days showing only 5% of the initial wound area. The owner reported by telephone the complete healing and hair growth 10 days after discharge. Discussion: Despite the atypical location of the tumoral lesion described at the present report, the history and clinical manifestations, especially the intense pruritus, showed similarity with other characteristic reports of equine cutaneous pythiosis. The diagnosis was confirmed by the histopathological examination showing hyphae structures, as described to be evidences of the presence of Pythium insidiosum in the tissue. The surgical procedure was the first step to provide remission of clinical signs, and one day after surgery the pruritus desapeared. After excision of the granulomatous tissue and cauterization, daily topical administration of amphotericin B associated with DMSO was effective in destroying the infectious agent, as observed by the excellent epithelization. A pink granulation tissue grew up providing an ideal surface for epithelial migration and the healing process progressed quickly. Centripetal epithelialization reduced the wound area until 3% of the initial area in 64 days of treatment, when the remaining wound was found almost completely healed and covered with hair. At the present report, the horse presenting pythiosis was only topically treated. The recommended therapy using amphotericin B and DMSO solution was effective, economically viable and low risk, considering that the systemic antifungal therapy usually suggested is expensive and extremely nephrotoxic. The atypical location of the lesion on the left flank shows that any anatomical region can be affected by the fungus, since the conditions for its development were present.

Atividade in vitro de formulações de lípides catiônicos contra bactérias multirresistentes, fungos e microalgas de interesse médico humano e veterinário

Bentivoglio ECRO. Atividade in vitro de formulações de lípides catiônicos contra bactérias multirresistentes, fungos e microalgas de interesse médico humano e veterinário. Dissertação (Mestrado em Microbiologia) Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 2016. Infecções microbianas podem ser causadas por bactérias, fungos, vírus, parasitas e algas. O presente estudo avaliou a atividade in vitro de formulações de lípides catiônicos contra bactérias multirresistêntes (MRs), fungos e microalgas de interesse médico humano e veterinário. A atividade biocida de bicelas de brometo de dioctadecildimetilamônio (DBB) foi avaliada contra bactérias gram-negativas produtoras de -lactamases de amplo espectro e carbapenemases mundialmente disseminadas. Para fungos (Candida albicans, Trichophyton rubrum) e microalgas (Prototheca zopfii), a atividade biocida de DBB, sem e com a associação a drogas antifúngicas (ex., miconazol, terbinafina e anfotericina B), foi avaliada determinando-se adicionalmente a atividade sinérgica. Nanodispersões catiônicas de DBB exibiram atividade bactericida, fungicida e algicida, mesmo para patógenos MRs, sendo que a sua associação com outros antimicrobianos resultou em uma atividade sinérgica que poderia favorecer a produção de formulações com potencial para aplicação clínica humana e veterinária.

Microbial infections can be caused by bactérias, fungi, virus, parasites and algae. This study evaluated in vitro activity from cationic lipds formulations against multiresistant bacterias (MRs), fungi and e microalgae from human and veterinary. The Biocidal activity from bromide dioctadecildimetilammonium biceles (DBB) was evaluated against gram-negative bactérias lactamases producers and carbapenemases from broad spectrum with wide spread dissemination. For fungi (Candida albicans, Trichophyton rubrum) and microalgae (Prototheca zopfii), the biocidal activity from DBB wuth and without antifungal drugs (ex., miconazole, terbinafine e amphotericin B), was also evaluated by synergistic activity. Cationic nanodispertions of DBB has shown bactericidal, fungicidal and algicidal activity, even for MRs patogens, thus , the association with the others antimicrobials resulted in a synergistic activity wich could foment the production of the formulations with a potential application in human and veterinary medicine.

Acompanhamento laboratorial da função renal de cães sadios tratados experimentalmente com doses terapêuticas de anfotericina B

The objective of this experiment was to assess the renal function of ten healthy male adult dogs submitted to therapeutic doses of amphotericin B, whose use has been limited due to its high nephrotoxic potential, as well as to evaluate the more sensitive and early method to diagnose kidney lesions. The renal function was evaluated through daily urinalysis, fractioned excretion of sodium and potassium, serum concentration of creatinine and blood urea nitrogen (BUN) and urinary activity of gamma-glutamyltransferase (GGT). It was concluded that amphotericin b provokes lesions in both proximal and distal tubules, inducing type I renal tubular acidosis and nephrogenic Diabetes insipidus in dogs. Renal function evaluation, preferably by serum creatinine, BUN and potassium dosage is recommended before each drug application. Urinalysis proved to diagnose kidney lesions in its earliest stage through a modification of the density parameters. Urinary GGT was not effective as an earliest diagnose kidney lesions caused by amphotericin B.

O presente trabalho objetivou avaliar a função renal de dez cães adultos saudáveis submetidos à administração de doses terapêuticas do antifúngico anfotericina B, cuja utilização tem sido limitada pelo seu elevado potencial nefrotóxico, e avaliar o método laboratorial mais sensível e precoce de diagnóstico de lesão renal. Foram realizadas, diariamente, urinálise, excreção fracionada de sódio e potássio, dosagem sérica de creatinina e uréia e atividade urinária de gama-glutamiltransferase (GGT). Concluiu-se que a anfotericina B provoca lesões nos túbulos proximal e distal, induzindo acidose tubular renal do tipo I e Diabetes insipidus nefrogênico em cães. Avaliação da função renal, preferencialmente por dosagens de creatinina, uréia e potássio séricos, é recomendada antes de cada aplicação do fármaco. A densidade urinária foi o parâmetro mais precocemente alterado pela lesão renal. A GGT urinária não foi eficaz para o diagnóstico precoce de lesão induzida por anfotericina B.

Acompanhamento laboratorial da função renal de cães sadios tratados experimentalmente com doses terapêuticas de anfotericina B

The objective of this experiment was to assess the renal function of ten healthy male adult dogs submitted to therapeutic doses of amphotericin B, whose use has been limited due to its high nephrotoxic potential, as well as to evaluate the more sensitive and early method to diagnose kidney lesions. The renal function was evaluated through daily urinalysis, fractioned excretion of sodium and potassium, serum concentration of creatinine and blood urea nitrogen (BUN) and urinary activity of gamma-glutamyltransferase (GGT). It was concluded that amphotericin b provokes lesions in both proximal and distal tubules, inducing type I renal tubular acidosis and nephrogenic Diabetes insipidus in dogs. Renal function evaluation, preferably by serum creatinine, BUN and potassium dosage is recommended before each drug application. Urinalysis proved to diagnose kidney lesions in its earliest stage through a modification of the density parameters. Urinary GGT was not effective as an earliest diagnose kidney lesions caused by amphotericin B.

O presente trabalho objetivou avaliar a função renal de dez cães adultos saudáveis submetidos à administração de doses terapêuticas do antifúngico anfotericina B, cuja utilização tem sido limitada pelo seu elevado potencial nefrotóxico, e avaliar o método laboratorial mais sensível e precoce de diagnóstico de lesão renal. Foram realizadas, diariamente, urinálise, excreção fracionada de sódio e potássio, dosagem sérica de creatinina e uréia e atividade urinária de gama-glutamiltransferase (GGT). Concluiu-se que a anfotericina B provoca lesões nos túbulos proximal e distal, induzindo acidose tubular renal do tipo I e Diabetes insipidus nefrogênico em cães. Avaliação da função renal, preferencialmente por dosagens de creatinina, uréia e potássio séricos, é recomendada antes de cada aplicação do fármaco. A densidade urinária foi o parâmetro mais precocemente alterado pela lesão renal. A GGT urinária não foi eficaz para o diagnóstico precoce de lesão induzida por anfotericina B.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

PURPOSE: Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon (AmB-D) and two new different AmB formulations. METHODS: three products were studied: Fungizon, and two Fungizon /Lipofundin admixtures, which were diluted through two methods: in the first one, Fungizon was previously diluted with water for injection and then, in Lipofundin (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). RESULTS: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. CONCLUSION: The Fungizon-Lipofundin admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.

OBJETIVO: A anfotericina B é um agente antifúngico de largo espectro bastante empregado na terapia antifúngica. Entretanto, esta molécula apresenta um alto nível de toxicidade que, na maioria das vezes, impede o seu uso contínuo na terapêutica médica. O objetivo deste artigo foi comparar a eficácia e a toxicidade in vitro do Fungizon (AmB-D) e de dois sistemas carreadores de AmB. MÉTODOS: Três produtos foram avaliados: o Fungizon , e dois sistemas oriundos da mistura entre o Fungizon e o Lipofundin , uma emulsão de uso parenteral. Tais sistemas foram obtidos por duas técnicas: Na primeira diluiu-se previamanete o Fungizon com água para injetáveis e em seguida inseriu-se o Lipofundin (AmB-DAL); o segundo método consistiu na diluíção extemporânea do Fungizon com a referida emulsão (AmB-DL). Dois modelos celulares foram empregados no estudo: os eritrócitos (RBC) oriundos de doadores humanos e a Candida tropicalis (Ct). A avaliação in vitro (liberação de K+ e hemoglobina, e o índice de sobrevivência celular-CSR) foi realizado com quatro concentrações de AmB (entre 50 e 0.05mg.L-1). RESULTADOS: Os resultados demonstram que a ação da AmB não só foi dependente da concentração como também variou de acordo com o modelo celular e o veículo que diluiu o Fungizon . Nas concentrações de 50 mg.L-1, apesar da liberação de hemoglobina ser quase que total para AmB-D (99.51), para a AmB-DAL e AmB-DL este valor tendeu a zero. Um p = 0.000 demonstrou que AmB-D foi significativamente mais hemolítico. CONCLUSÃO: A mistura Fungizon -Lipofundin aparenta ser um bom sistema para carrear a AmB tendo em vista seu elevado índice terapêutico demonstrado.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

PURPOSE: Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon (AmB-D) and two new different AmB formulations. METHODS: three products were studied: Fungizon, and two Fungizon /Lipofundin admixtures, which were diluted through two methods: in the first one, Fungizon was previously diluted with water for injection and then, in Lipofundin (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). RESULTS: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. CONCLUSION: The Fungizon-Lipofundin admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.

OBJETIVO: A anfotericina B é um agente antifúngico de largo espectro bastante empregado na terapia antifúngica. Entretanto, esta molécula apresenta um alto nível de toxicidade que, na maioria das vezes, impede o seu uso contínuo na terapêutica médica. O objetivo deste artigo foi comparar a eficácia e a toxicidade in vitro do Fungizon (AmB-D) e de dois sistemas carreadores de AmB. MÉTODOS: Três produtos foram avaliados: o Fungizon , e dois sistemas oriundos da mistura entre o Fungizon e o Lipofundin , uma emulsão de uso parenteral. Tais sistemas foram obtidos por duas técnicas: Na primeira diluiu-se previamanete o Fungizon com água para injetáveis e em seguida inseriu-se o Lipofundin (AmB-DAL); o segundo método consistiu na diluíção extemporânea do Fungizon com a referida emulsão (AmB-DL). Dois modelos celulares foram empregados no estudo: os eritrócitos (RBC) oriundos de doadores humanos e a Candida tropicalis (Ct). A avaliação in vitro (liberação de K+ e hemoglobina, e o índice de sobrevivência celular-CSR) foi realizado com quatro concentrações de AmB (entre 50 e 0.05mg.L-1). RESULTADOS: Os resultados demonstram que a ação da AmB não só foi dependente da concentração como também variou de acordo com o modelo celular e o veículo que diluiu o Fungizon . Nas concentrações de 50 mg.L-1, apesar da liberação de hemoglobina ser quase que total para AmB-D (99.51), para a AmB-DAL e AmB-DL este valor tendeu a zero. Um p = 0.000 demonstrou que AmB-D foi significativamente mais hemolítico. CONCLUSÃO: A mistura Fungizon -Lipofundin aparenta ser um bom sistema para carrear a AmB tendo em vista seu elevado índice terapêutico demonstrado.

Tratamento da pitiose em membros de equinos por meio de perfusão regional intravenosa com anfotericina B

Avaliaram-se os efeitos da perfusão regional intravenosa com anfotericina B, um antimicótico, em membros de equinos acometidos por pitiose, combinada com a excisão cirúrgica. Foram utilizados 16 equinos, jovens e adultos, da raça pantaneira, com pitiose em membro torácico ou pélvico, distalmente às articulações do cotovelo ou joelho, distribuídos em dois grupos experimentais. Um constituído de 12 equinos tratados, após excisão cirúrgica e termocauterização, por perfusão regional intravenosa do membro com anfotericina B (Ganf) e outro constituído de quatro equinos não tratados (controle, Gc). As feridas foram fotografadas e avaliadas antes do início do tratamento (D0) e após sete (D7), catorze (D14), vinte e um (D21), vinte e oito (D28), trinta e cinco (D35) e sessenta (D60) dias e foi realizado exame do aparelho locomotor. No Ganf, 92% dos animais apresentaram cicatrização das feridas de pitiose e no Gc 100% apresentaram recrudescência da afecção. No Ganf, 58% exigiram administração única de anfotericina B pela técnica de perfusão regional do membro e 42% exigiram uma readministração, após 14 dias. No Ganf, 33% apresentaram ulceração no local da administração da anfotericina B e 42% apresentaram aumento de volume do membro e dor à palpação na região perfundida pela anfotericina B. No Ganf, 100% dos animais apresentavam claudicação severa no D0 e 92% não apresentavam claudicação no D21. Conclui-se que a administração de anfotericina B, por perfusão regional intravenosa, promove a cura da pitiose, com mínimas reações adversas, sendo uma alternativa terapêutica para o tratamento de pitiose em membros de equinos

The effects of intravenous regional perfusion with amphotericin B, an antifungal drug, in equine limbs with pythiosis associated with surgical excision were evaluated. 16 horses, young and adults, pantaneira breed, with pythiosis in thoracic or pelvic limbs, distally to the elbow or knee joints, were allocated into two experimental groups. One constituted by 12 horses treated, after surgical excision and thermocauterization, by intravenous regional limb perfusion with amphotericin B (Ganf) and other constituted by four not treated horses (control, Gc). The wounds were photographed and evaluated before the beginning of the treatment (D0) and after seven (D7), fourteen (D14), twenty-one (D21), twenty-eight (D28), thirty-five (D35) and sixty (D60) days and examination of the locomotor system was performed. 92% of the animals with pythiosis presented wound healing in Ganf and, in Gc, 100% presented recrudescence of the disease. In the Ganf, 58% of the animals needed single administration of amphotericin B by regional limb perfusion and 42% of the animals needed one more administration after 14 days. In the Ganf, 33% of the animals presented ulceration in the amphotericin B injection site and 42% of the animals presented limb edema and pain during palpation of the amphotericin B perfused region. In Ganf, 100% of the animals presented severe lameness at D0 and 92% of the animals presented no lameness at D21. It can be concluded that the administration of amphotericin B by intravenous regional perfusion promotes pythiosis remission with minimal side effects, being a therapeutic alternative to the pythiosis treatment in equine limbs

DROGAS ANTIFÚNGICAS PARA PEQUENOS E GRANDES ANIMAIS

The antifungal drugs are classified in classic and current chemical agents and in antibiotics. The chemists classic agents are those medicines that present in a general way reduced action spectrum against fungi, having a fungistatic effect in an indirect way when modifying the local conditions, as for instance the iodine, acids fat and derived, acid salicilic, tolnaftate and tolciclate. The current chemical agents are represented by imidazole and triazole, flucytosine and allylamines and the antibiotics represented by the polyene (amphotericin B, nystatin and natamycin) and the griseofulvin. The discretion of each antifungal drug will be presented in the work.

As drogas antifúngicas são classificadas em agentes químicos clássicos e atuais e em antibióticos. Os agentes químicos clássicos são aqueles medicamentos que apresentam de maneira geral espectro de ação reduzido contra fungos, atuando como fungistático de modo indireto ao modificar as condições locais, como por exemplo o iodo, os ácidos graxos e derivados, ácido salicílico, tolnaftato e tolciclato. Os agentes químicos atuais são representados pelos imidazóis e triazóis, flucitosina e alilaminas e os antibióticos representados pelos poliênicos (anfotericina B, nistatina e natamicina) e a griseofulvina. A descrição de cada antifúngico considerado será apresentada no trabalho.

Drogas antifúngicas para pequenos e grandes animais

The antifungal drugs are classified in classic and current chemical agents and in antibiotics. The chemists classic agents are those medicines that present in a general way reduced action spectrum against fungi, having a fungistatic effect in an indirect way when modifying the local conditions, as for instance the iodine, acids fat and derived, acid salicilic, tolnaftate and tolciclate. The current chemical agents are represented by imidazole and triazole, flucytosine and allylamines and the antibiotics represented by the polyene (amphotericin B, nystatin and natamycin) and the griseofulvin. The discretion of each antifungal drug will be presented in the work.

As drogas antifúngicas são classificadas em agentes químicos clássicos e atuais e em antibióticos. Os agentes químicos clássicos são aqueles medicamentos que apresentam de maneira geral espectro de ação reduzido contra fungos, atuando como fungistático de modo indireto ao modificar as condições locais, como por exemplo o iodo, os ácidos graxos e derivados, ácido salicílico, tolnaftato e tolciclato. Os agentes químicos atuais são representados pelos imidazóis e triazóis, flucitosina e alilaminas e os antibióticos representados pelos poliênicos (anfotericina B, nistatina e natamicina) e a griseofulvina. A descrição de cada antifúngico considerado será apresentada no trabalho.

Topical treatment using amphotericin b and dmso for an atypically located equine cutaneous Pythiosis / Pitiose cutânea equina de localização atípica tratada topicamente com solução de anfotericina B e DMSO

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at fl ooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdômen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes.Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left fl ank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomoris methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at fl ooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdômen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes.Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left fl ank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomoris methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated