LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

Long term treatment of a thyrotropin-secreting microadenoma with somatostatin analogues / Tratamento de longa duração com análogos da somatostatina de um microadenoma tirotrofinoma

Thyrotropin (TSH) secreting pituitary adenomas (TSH-omas) account for < 1 percent of all pituitary adenomas and are a rare cause of hyperthyroidism. The diagnosis is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. First line therapy is transsphenoidal resection of the tumor, which can cure one-third of the patients completely. However, if surgery is not possible or curative, pituitary radiotherapy and/or somatostatin analogs (SSA) can be useful. We report the case of a 54-year-old woman treated 20 years earlier for a mistakenly suspected primary hyperthyroidism. Given the persistence of symptoms she was studied further and was diagnosed with a thyrotropinoma. Despite the delay in diagnosis and prior thyroid ablation, a microadenoma was found. As transsphenoidal surgery was not considered effective, medical therapy with a somatostatin analogue was initiated. Currently, at four years of follow-up, the patient continues on this treatment and remains euthyroid and asymptomatic. We report a case of successful long-term treatment with SSA, after unsuccessful surgery.

Tirotrofinomas (TSH-omas) representam < 1 por cento dos adenomas hipofisários. Eles são uma causa muito rara de hipertireoidismo. O diagnóstico é frequentemente feito na fase de macroadenoma em consequência da natureza agressiva do tumor e do feito de que os doentes são tratados inicialmente por engano e por um longo tempo para hipertireoidismo primário. A terapêutica de primeira linha é a ressecção transesfenoidal do tumor, que cura um terço dos pacientes completamente. Contudo, se a cirurgia não for possível ou curativa, a radioterapia da pituitária e/ou o tratamento com análogos da somatostatina (SSA) podem ser úteis. Relatou-se o caso de uma mulher de 54 anos, tratada há 20 anos por uma suspeita equivocada de hipertireoidismo primário. Dada a persistência dos sintomas, foram realizados mais exames e a paciente foi diagnosticada com TSH-oma. Apesar do diagnóstico tardio e da ablação prévia com iodo radioativo, encontrou-se um microadenoma. Como a cirurgia transesfenoidal não foi considerada eficaz, iniciou-se o tratamento da paciente com SSA. Atualmente, após quatro anos de acompanhamento, a paciente continua com o tratamento e permanece eutireoidea e assintomática. Neste artigo, relatou-se a eficácia da terapia medicamentosa com SSA em longo prazo, após cirurgia não eficaz.

Cost-effectiveness analysis of somatostatin analogues in the treatment of acromegaly in Brazil / Análise de custo-efetividade de análogos da somatostatina no tratamento de acromegalia no Brasil

This study aims to compare economic and patient impacts of the treatment of acromegaly with two different somatostatin analogues (octreotide LAR and lanreotide SR) in Brazil. A cost-effectiveness analysis was carried out under the Brazilian Public Health Care System (SUS) perspective. A decision analytical model was developed based on the Brazilian Public Health Care System Clinical Guideline for Acromegaly. A hypothetical cohort of 276 patients was followed for two years. Data were extracted from literature and administrative databases. Based on the analytical model, treatment with octreotide LAR would avoid 12 and 17 cases of GH and IGF-I elevated serum levels, respectively. Octreotide LAR was a cost-saving strategy, with net savings of R$10,448,324 (US$4,465,096) to SUS. Annual net savings per patient were R$ 18,928 (US$8,089). Treatment of acromegaly with octreotide LAR is a dominant strategy when compared to the treatment with lanreotide SR in Brazil. Sensitivity analysis did not alter the cost-saving status.

O objetivo deste estudo é comparar o impacto econômico e o impacto nos pacientes com acromegalia do tratamento com dois diferentes análogos de somatostatina (octreotida LAR e lanreotide SR) no Brasil. Um estudo de custoefetividade foi realizado a partir da perspectiva do Sistema Único de Saúde (SUS). Foi desenvolvido um modelo analítico de decisão baseado no Protocolo Clínico e Diretrizes Terapêuticas de Acromegalia do SUS. Uma coorte hipotética de 276 pacientes foi seguida por dois anos. Dados foram obtidos da literatura e bases de dados oficiais do SUS. Baseado no modelo analítico, o tratamento com octreotida LAR evitaria 12 e 17 casos com níveis elevados de GH e IGF-I, respectivamente. Octreotida LAR foi uma estratégia econômica, gerando economia de R$10.448.324 (US$4.465.096) para o SUS. A economia anual por paciente foi de R$18.928 (US$8.089). O tratamento de acromegalia com octreotida LAR é estratégia dominante quando comparado com o tratamento com lanreotida SR no Brasil. A análise de sensibilidade não alterou seu status de econômica.

Mucormicosis renal aislada / Isolated renal mucormicosis

La mucormicosis es una infección causada por hongos de la clase Zygomycetes. Existen varias formas de presentación clínica, siendo las más comunes la rinocerebral y la pulmonar. La mucormicosis renal aislada es un tipo de mucormicosis muy poco frecuente hasta el momento; se han reportado 25 casos en la literatura. Se presenta el caso de una paciente con leucemia aguda que desarrolló mucormicosis renal aislada, y se revisa la literatura.

Mucormycosis is an infection caused by a class Zygomycetes fungi. The rhinocerebral and pulmonary are the most common clinical presentations. Renal mucormycosis is a very rare form. To date, only 25 cases have been reported in the literature. We describe the case of a patient with leukemia who developed isolated renal mucormycosis and review the literature.

Atualização no uso de agentes antifúngicos / An update on the use of antifungal agents

Aborda-se sumariamente o espectro de ação, aspectos farmacológicos e toxicológicos e eficácia clínica de anfotericina B lipossomal, anfotericina B em dispersão coloidal, complexo lipídico de anfotericina B, voriconazol e caspofungina. Discute-se o uso desses antifúngicos mais recentes considerando a segurança, a eficiência e o custo da terapia. Sugestões para o uso clínico dessas drogas em infecções pulmonares e sistêmicas são apresentadas, destacando-se a menor toxicidade das formulações lipídicas da anfotericina B em relação à medicação convencional, a possibilidade de terapia primária da aspergilose invasiva, scedosporiose e fusariose com voriconazol e a caspofungina como opção terapêutica na candidíase disseminada e na aspergilose invasiva.

We summarize here data regarding the spectrum of action, the pharmacological aspects, the toxicological aspects and the clinical efficacy of liposomal amphotericin B, amphotericin B in colloidal dispersion, amphotericin B lipid complex, voriconazole and caspofungin. We discuss the use of these more recently introduced antifungal agents in terms of their safety, efficiency and cost. We also offer suggestions for the clinical use of these drugs in pulmonary and systemic infections, with an emphasis on the lower toxicity of the lipid formulations of amphotericin B in comparison with conventional medications. In addition, we explore the possibility of using voriconazole as the primary treatment for invasive infections such as aspergillosis, as well as those caused by Scedosporium spp. and Fusarium spp., together with that of using caspofungin to treat disseminated candidiasis and invasive aspergillosis.

Antibiotics for treatment of resistant gram-positive coccal infections.

Vancomycin is considered the workhorse for the treatment of most drug-resistant gram-positive bacterial infections. However, concerns have been raised regarding the increasing rates of vancomycin-resistant enterococci and the clinical shortcomings of vancomycin in the treatment of invasive Staphylococcus aureus infections. Resources have been committed to the development of antimicrobial agents with activity against these organisms. This review will focus on the newer antibacterial agents that have been developed for the treatment of resistant gram-positive pathogens. Included in this review are the agents: quinupristin-dalfopristin, linezolid, daptomycin, telithromycin, and tigecycline.

Successful treatment of disseminated Aspergillosis in a leukemic child

The incidence of severe fungal infections in the immunocompromised patient with malignancies has increased in recent years. This appears to be associated to the profound periods of immunosuppression and the extended use of broad spectrum antibiotics. Aspergillosis is the second most common fungal infection reported in the immunocompromised cancer patients. In patients with advanced immunosupression, the mortality due to invasive aspergillosis approaches 100despite treatment with antifungal agents. Reports of complete or partial response to echinocandins are well demonstrated in adults, but very limited in the pediatric population. This report describes the case of a child with relapsed acute lymphoblastic leukemia (ALL) who developed cutaneous aspergillosis and subsequent multiorgan dissemination during therapeutic induction and was treated successfuly with caspofungin acetate.

Tratamiento con caspofungina de endocarditis por Candida tropicalis resistente a fluconazol / Treatment with caspofungin of Candida tropicalis endocarditis resistant to fluconazol

Fungal endocarditis, in particular due to Candida species, requires medical and surgical treatment and amphotericin B is the drug of choice. Caspofungin is an echinocandin very effective against Candida and Aspergillus. We present a patient with Candida tropicalis endocarditis, fluconazol resistant, treated with caspofungin, on a compassional basis as a result of adverse effects with amphotericin B. The patient had a microbiological response.

Las endocarditis causadas por hongos, (Candida en particular), requieren tratamiento médico-quirúrgico,siendo la anfotericina B la droga de elección. Caspofungina es una equinocandina con gran actividadsobre Candida y Aspergillus. Se presenta un paciente con una endocarditis por Candida tropicalis resistente a fluconazol tratado con caspofungina bajo un esquema de salvataje, luego de haber presentado efectos adversos por anfotericina B. El paciente tuvo respuesta microbiológica.