Super aggregated amphotericin B with a thermoreversible in situ gelling ophthalmic system for amoebic keratitis treatment.

Acanthamoeba spp. are the causative agents of a sight-threatening infection of the cornea known as Acanthamoeba keratitis (AK). Amphotericin B - deoxycholate (AB) is used in the treatment of infectious keratitis, however, its topical administration has side effects as blepharitis, iritis, and painful instillation. In this context, the preheating of AB can decrease its toxicity by the formation of super aggregates (hAB). hAB associated with a thermoreversible in situ gelling ophthalmic system is a promising option due to the latter biocompatibility, low toxicity, and high residence time on the ocular surface. Our objective was to develop a topical ocular formulation of hAB for the treatment of AK. After heating at 70°C for 20 min, hAB was incorporated into a thermoreversible gelling system. The amebicidal activity of AB and hAB was evaluated against trophozoites and cysts of A. castellanii (ATCC 50492) and a regional clinical isolate (IC01). The results showed that the preheating of AB did not change the pharmacological action of the drug, with the amebicidal effect of AB and hAB under trophozoites and cysts of Acanthamoeba spp. The thermoreversible system remained stable, allowing the increase of drug retention time. For assessment of cytotoxicity, HUVEC (ATCC® CRL-1730) cells were challenged with AB and hAB for 48h. Cell viability was assessed, and hAB did not show cytotoxicity for HUVEC cells. As far as we know this was the first study that showed the preheated AB associated with a thermoreversible in situ gelling ophthalmic system as a promising system for topical ocular topical administration of hAB for AK therapy.

Bariatric surgery improves clinical outcomes and adiposity biomarkers but not inflammatory cytokines SAA and MCP-1 after a six-month follow-up.

Obesity is a global health problem and is associated with a chronic low-grade inflammatory state. Surgical obesity treatment is being increasingly common due to its efficacy. From this, we evaluate the metabolic state improvement and inflammation remission in patients with obesity undergoing bariatric surgery. Methods: The clinical data and serum levels of leptin and adiponectin were assessed in patients with obesity before and one, three and six months after bariatric surgery. Also, serum amyloid A (SAA), monocyte chemoattractant protein-1 (MCP-1) levels were measured during the follow-up surgery and compared with a lean group of individuals. Results: Weight loss decreased body mass index (BMI), comorbidities percentage, drugs use and leptin levels. Adiponectin levels increased after surgery. SAA and MCP-1 showed no difference after surgery, but a trend decrease for MCP-1 and a significant decrease was observed when the patients with obesity were compared to the lean participants. Conclusion: Bariatric surgery alters metabolic status improving obesity-related comorbidities and the adiposity biomarkers leptin and adiponectin, but not inflammatory cytokines SAA and MCP-1.

Complement component 3 (C3) as a biomarker for insulin resistance after bariatric surgery.

OBJECTIVES: Since complement system has been recently associated with metabolic and cardiovascular diseases, and closely related to insulin resistance, we investigated the association of plasma complement factor 3 (C3) and factor 4 (C4) with insulin sensibility and weight loss after bariatric surgery. METHODS: Serum levels of C3, C4, total cholesterol, triacylglycerol, HDL-cholesterol, LDL-cholesterol and homeostatic model assessment (HOMA-IR) measurements were assessed in morbidly obese patients before and after bariatric surgery, including a 6-month follow-up period, as well as a comparison with a lean group. RESULTS: Weight loss decreased body mass index (BMI), serum triacylglycerol, and increased serum HDL-cholesterol and insulin sensitivity, as expected. C3 and C4 were significantly higher in obese individuals when compared to lean subjects (p<0.001). In addition, C3 and C4 positively correlated with BMI and HOMA-IR, however, only C3 were significantly decreased 6months after surgery. CONCLUSION: C3 was strongly associated with insulin sensitivity after bariatric surgery.

[Prevalence of disorders detected by newborn screening in Santa Catarina]. / Prevalência de patologias detectadas pela triagem neonatal em Santa Catarina.

OBJECTIVE: To evaluate the prevalence of the diseases phenylketonuria (PKU), congenital hypothyroidism (CH), cystic fibrosis (CF), hemoglobinopathies (HB), and congenital adrenal hyperplasia (CAH), in the state of Santa Catarina, in order to delineate the local population profile for these diseases. MATERIALS AND METHODS: A survey of data from the Newborn Screening Program of the Ministry of Health of Santa Catarina, in the period 2004 to 2008 was carried out. RESULTS: During the study period, the following prevalences were obtained: 1:28,862 children screened for PKU; 1:2,876 children screened for CH; 1:5,121 children screened for CF; 1:14,446 children screened for HB S; and 1:11,655 children screened for CAH. CONCLUSIONS: The prevalence of PKU proved to be lesser than the national prevalence, while CAH prevalence was greater. On the other hand CH prevalence was similar to the global and national prevalence. Moreover, the predominance of the Caucasian population in the state resulted in reduced prevalence of HB S and increased prevalence of CF in relation to the rest of the country.

Prevalência de patologias detectadas pela triagem neonatal em Santa Catarina / Prevalence of disorders detected by newborn screening in Santa Catarina

OBJETIVO: Avaliar a prevalência das patologias fenilcetonúria (FNC), hipotireoidismo congênito (HC), fibrose cística (FC), hemoglobinopatias (HB) e hiperplasia adrenal congênita (HAC), no Estado de Santa Catarina, a fim de delinear o perfil da população catarinense em relação a essas patologias. MATERIAIS E MÉTODOS: Foi realizado um levantamento de dados do Programa de Triagem Neonatal da Secretaria de Estado da Saúde de Santa Catarina, no período de 2004 a 2008. RESULTADOS: No período de estudo, foram obtidas as seguintes prevalências: FCN 1:28.862, HC 1:2.876, FC 1:5.121, HB S 1:14.446 e para HAC 1:11.655 crianças triadas. CONCLUSÕES: A prevalência média da FNC mostrou-se inferior à prevalência nacional, ao passo que a da HAC foi superior; por sua vez, a do HC mostrou-se semelhante às prevalências mundial e nacional. Além disso, o predomínio da população caucasiana no Estado resultou em uma prevalência reduzida da HB e uma prevalência aumentada da FC em relação ao restante do país.

OBJECTIVE: To evaluate the prevalence of the diseases phenylketonuria (PKU), congenital hypothyroidism (CH), cystic fibrosis (CF), hemoglobinopathies (HB), and congenital adrenal hyperplasia (CAH), in the state of Santa Catarina, in order to delineate the local population profile for these diseases. MATERIALS AND METHODS: A survey of data from the Newborn Screening Program of the Ministry of Health of Santa Catarina, in the period 2004 to 2008 was carried out. RESULTS: During the study period, the following prevalences were obtained: 1:28,862 children screened for PKU; 1:2,876 children screened for CH; 1:5,121 children screened for CF; 1:14,446 children screened for HB S; and 1:11,655 children screened for CAH. CONCLUSIONS: The prevalence of PKU proved to be lesser than the national prevalence, while CAH prevalence was greater. On the other hand CH prevalence was similar to the global and national prevalence. Moreover, the predominance of the Caucasian population in the state resulted in reduced prevalence of HB S and increased prevalence of CF in relation to the rest of the country.

[Acute renal failure in patient treated with ATRA and amphotericin B: case report]. / Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso.

This is a report of the case of a patient with acute promyelocytic leukemia treated with all trans-retinoic acid (ATRA), who had suspected all-trans retinoic acid syndrome (ATRA syndrome). The nonspecific febrile leukopenia observed justified the association with antimicrobial and antifungal therapy. Signs and symptoms contributed to the suspicion of ATRA syndrome, and renal function was impaired by the combination with antifungal agents. The decrease in renal function observed initially contributed to the suspicion of ATRA syndrome and was aggravated by antifungals. Thus, the use of ATRA was discontinued. Eight days after the pneumonia characterization, the possibility of ATRA syndrome was dismissed. In this context, ATR's nephrotoxicity and the synergic adverse effect by the use of nephrotoxic antifungal agents were discussed, particularly amphotericin B, as well as the importance of differential diagnosis between ATRA syndrome and infectious diseases.

Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso / Acute renal failure in patient treated with ATRA and amphotericin B: case report

O presente relato apresenta o caso clínico de uma paciente com leucemia promie-locítica aguda tratada com ácido todo-transretinoico (ATRA), que apresentou suspeita de síndrome do ácido transreti-noico (síndrome de ATRA). Com a ocor-rência de leucopenia febril inespecífica, foram associados ao tratamento antimi-crobianos e antifúngicos. A diminuição da função renal, observada inicialmente, contribuiu para a suspeita de síndrome de ATRA, que foi agravada pelos antifúngi-cos. Assim, o uso de ATRA foi suspenso, mas somente 8 dias depois foi caracteriza-da pneumonia e descartada a hipótese de síndrome de ATRA. Nesse contexto, foi discutida a nefrotoxicidade do ATRA e a potencialização desse efeito adverso pelo uso de antifúngicos nefrotóxicos, em par-ticular da anfotericina B, assim como a im-portância do diagnóstico diferencial entre síndrome de ATRA e doença infecciosa.

This is a report of the case of a patient with acute promyelocytic leukemia treated with all trans-retinoic acid (ATRA), who had suspected all-trans retinoic acid syndrome (ATRA syndrome). The nonspecific febrile leukopenia observed justified the association with antimicrobial and antifungal therapy. Signs and symptoms contributed to the sus-picion of ATRA syndrome, and renal func-tion was impaired by the combination with antifungal agents. The decrease in renal function observed initially contributed to the suspicion of ATRA syndrome and was aggravated by antifungals. Thus, the use of ATRA was discontinued. Eight days after the pneumonia characterization, the possibil-ity of ATRA syndrome was dismissed. In this context, ATRA's nephrotoxicity and the syn-ergic adverse effect by the use of nephrotoxic antifungal agents were discussed, particularly amphotericin B, as well as the importance of differential diagnosis between ATRA syn-drome and infectious diseases.

Eficiência terapêutica das formulações lipídicas de anfotericina B / Therapeutic efficacy of amphotericin B lipid formulations

A anfotericina B, fármaco descoberto em 1953, ainda permanece como substância fungicida de escolha no tratamento da maioria das micoses sistêmicas que acometem pacientes imunocomprometidos. Mesmo com a sua toxicidade e a introdução de antifúngicos azólicos sistêmicos na década de 1980, a potência, o espectro de ação e os quase 50 anos de experiência clínica asseguram sua efetividade tanto para o tratamento das infecções fúngicas quanto para a profilaxia fúngica sistêmica em pacientes neutropênicos. Sua eficácia tem sido julgada a cada medicamento antifúngico novo apresentado aos profissionais de saúde e, por esta razão, numerosas tentativas para reduzir sua nefrotoxicidade específica surgiram nos últimos anos. Adicionalmente, a necessidade de se instituírem tratamentos agressivos para as micoses sistêmicas invasivas com dosagens necessariamente mais altas motivou o desenvolvimento de diferentes veículos para a administração de anfotericina B. Dentre eles, o encapsulamento de base lipossômica, a formação de complexos lipídicos e dispersões coloidais destacam-se com os melhores resultados na diminuição da toxicidade e aumento da eficácia terapêutica. Serão descritos diversos trabalhos direcionados ao desenvolvimento de preparações lipídicas como veículo para anfotericina B, tendo como intuito a utilização dos mecanismos farmacocinéticos dessas formulações a fim de melhorar a distribuição do fármaco nos órgãos-alvo

Amphotericin B, discovered in 1953, has been the antifungal drug of choice for the most fungal infections in immonosupressed patients. Despite its toxicity and the introduction of new azolic antifungal agents in the 1980's, the therapeutic potencial, the spectrum of action, and almost 50 years of clinical experience, determine its efficacy for the treatment of fungal infections and secondary prophylaxis in neutropenic patients. Its efficacy has been challenged in every new antifungal drug presented for the scientists and doctors and, for this purpose, a wide range of new studies were performed in order to reduce its nephrotocixity. In addition to the necessity of establishing strong treatments with higher doses for systemic mycoses, the development of different ways of amphotericin B delivery has been encouraged. Among on them, the entrapping amphotericin B into liposomes, the formation of lipid complex and colloidal dispersions produced successful results in reducing the tocixity and improving efficacy. Therefore, many studies demostrating new lipid preparations and delivery systems will be cited, focused on pharmacokinetics and mechanisms to improve the delivery of active drugs to sites of infections

Serum beta2-microglobulin values among healthy Brazilians using a DPC IMMULITE assay.

PURPOSE: The present study was designed to determine the normal range of serum beta 2-microglobulin (Sb2M) levels among healthy volunteers in Brazil. Levels of Sb2M are elevated in human immunodeficiency virus (HIV)-infected patients and have been shown to be the best predictor of HIV infection status and of some malignant disorders, especially multiple myeloma. In order to achieve its optimal use in Brazilian clinical diagnosis, an adequate reference interval study was performed for Sb2M IMMULITE assay, based on the fact that its reference range limits were evaluated among European populations. METHODS: Ninety-six healthy blood donors were evaluated, and Sb2M levels were measured by chemiluminescent enzyme immunoassay using the IMMULITE automated analyzer. RESULTS: A normal range of Sb2M values, established by a nonparametric statistical method, was 1.05 to 3.9 mg/mL, with the upper limit being higher than that reported elsewhere. CONCLUSIONS: This study presented new data indicating that there is a significant difference between the current reference limits for Sb2M IMMULITE assay and those found in Brazil, providing evidence that significant differences in range of normal values may occur among different populations, and that these new values should be considered for Brazilian individuals.

Novas formas comerciais de anfotericinina B / New commercial formulations of amphotericin B

A anfotericinina B permanece como o padrão ouro para o tratamento de infecções fúngicas invasivas. Para melhorar a eficácia terapêutica desse fármaco e reduzir sua toxidade aguda e crônica, diversas formulações lipídicas de anfotericinina B foram desenvolvidas, entre elas: anfotericinina B lipossômica (AmBisome), complexo lipídico de anfotericinina B (ABLC, Abelcet) e dispersão coloidal de anfotericinina B (ABCD, Amphocil). Essas novas formulações são efetivas em várias infecções fúngicas sistêmicas, incluindo candidíase, aspergilose invasiva, mucormicose, criptococose, fusariose, sendo também eficientes no tratamento da leishmaniose. As três formulações apresentam baixa toxidade renal, sendo mais seguras que a anfotericina B convencional. Raros são os trabalhos que comparam as formulações lipídicas. Estudos de triagem clínica em ampla escala podem esclarecer a eficácia relativa em várias formas de infecções fúngicas. A presente revisão analisa os dados disponíveis na literatura, faz uma comparação entre as três formulações lipídicas e discute a questão custo e benefício do tratamento para o paciente.

Serum beta2-microglobulin values among healthy Brazilians using a DPC IMMULITE® assay

OBJETIVO: O objetivo do presente estudo foi determinar valores de referência de beta2-Microglobulina sérica (Sb2M) em voluntários saudáveis. Sabe-se que tal parâmetro apresenta-se elevado em pacientes infectados com o vírus da imunodeficiência humana (HIV) e tem se mostrado melhor marcador da infecção por HIV e de desordens malignas, especialmente mieloma múltiplo. De forma a se obter o melhor diagnóstico clínico, um intervalo de referência adequado de Sb2M para a população brasileira foi determinado empregando-se o ensaio IMMULITE®; já que este tem como parâmetro uma faixa de referência determinada a partir de populações européias. MÉTODOS: Noventa e seis doadores de sangue saudáveis foram avaliados e os valores de Sb2M foram medidos por método enzima imunoensaio quimiluminescente usando analisador automatizado IMMULITE®. RESULTADOS: Os valores de Sb2M, estabelecidos por método estatístico não paramétrico, apresentaram-se entre 1.05 e 3.9 mg/ml, sendo que o limite superior obtido foi maior que o relatado em outros trabalhos. CONCLUSÃO: Este estudo apresentou novos valores, indicando que existe uma diferença significante entre os limites de referência de Sb2M disponibilizados para o IMMULITE® e os encontrados no presente trabalho, evidenciando a ocorrência de variações importantes entre diferentes populações e que novos valores devem ser considerados para brasileiros.

Comparação entre o perfil lipídico de pacientes atendidos em laboratórios privados e públicos da 18ª Regional de Saúde de Santa Catarina / Patient's lipid profile comparison among private and public laboratory from the 18th Health Zones of Santa Catarina State

As doenças cardiovasculares são uma das maiores causas de morbidade e mortalidade no mundo Ocidental. Assim, o perfil lipídico da população residente na 18ª Regional de Saúde do Estado de Santa Catarina foi analisado através de resultados secundários, obtidos do banco de dados de Laboratórios Clínicos Públicos e Privados, possibilitanto a comparação entre pacientes de diferentes classes sociais. No laboratório particular, o colesterol, para ambos os sexos, apresentou uma frequencia superior a 60% nas faixas acima da concentração limítrofe, enquanto nos laboratórios públicos estes valores apresentaram um equilíbrio com aproximadamente 50% nas faixas inferiores ao limítrofe, exceto para o sexo feminico, onde os resultados foram semelhantes aos dos pacientes do laboratório privado. O LDL-COL em todos os estabelecimentos, obteve mais de 50% dos resultados abaixo da faixa desejável. O HDL-COL foi o dado mais divergente, no laboratório particular, para ambos os sexos, os valores ficaram entre 40 e 60 mg/dL, seguidos de faixa alta, nos laboratório público as concentrações <40mg/dL predominaram para o sexo feminino e ignorado as concentrações entre 40 e 60mg/dL foram seguidas das baixas. Em todos os estabelecimentos para concentrações de triglicerídeos predominou a faixa ótima em mais de 55% dos pacientes.