Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma.

Current therapy for glioblastoma multiforme is insufficient, with nearly universal recurrence. Available drug therapies are unsuccessful because they fail to penetrate through the region of the brain containing tumor cells and they fail to kill the cells most responsible for tumor development and therapy resistance, brain cancer stem cells (BCSCs). To address these challenges, we combined two major advances in technology: (i) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery and (ii) repurposed compounds, previously used in Food and Drug Administration-approved products, which were identified through library screening to target BCSCs. Using fluorescence imaging and positron emission tomography, we demonstrate that brain-penetrating nanoparticles can be delivered to large intracranial volumes in both rats and pigs. We identified several agents (from Food and Drug Administration-approved products) that potently inhibit proliferation and self-renewal of BCSCs. When loaded into brain-penetrating nanoparticles and administered by convection-enhanced delivery, one of these agents, dithiazanine iodide, significantly increased survival in rats bearing BCSC-derived xenografts. This unique approach to controlled delivery in the brain should have a significant impact on treatment of glioblastoma multiforme and suggests previously undescribed routes for drug and gene delivery to treat other diseases of the central nervous system.

Development of a chemotherapeutic model for microfilaricidal drugs to Dirofilaria immitis.

Microfilariae obtained from in vitro culture of adult Dirofilaria immitis were inoculated into naive dogs and used to test the in vivo efficacy of the antimicrofilarial drug Dizan. Injection of 33 million microfilariae into a 3-month-old male beagle pup over a 5-day period resulted in a microfilaremia that peaked at 863 microfilariae per ml on day 30. Treatment with Dizan resulted in a rapid clearance of microfilariae from the peripheral circulation. Four additional male beagle pups that were each given a total of 31 million microfilariae over 100 days maintained an average of 25 microfilariae per ml for 2 months. Microfilaremias were monitored by ELISA, a modified Knott's method and selected blood chemistry tests. It was shown that after residing in the peripheral circulation the microfilariae were able to develop into infective larvae in mosquitoes; therefore, the system may be a reasonable model of the natural microfilaremic state.

Chemotherapy of filariasis in squirrel monkeys (Saimiri sciureus).

The effect of some known antifilarial drugs on naturally-occurring filariae in squirrel monkeys, Saimiri sciureus, was evaluated. Four drugs, dithiazanine iodide, naphuride sodium, thiacetarsamide sodium, and diethylcarbamazine were tested against Dipetalonema gracile and Tetrapetalonema marmosetae. Dipetalonema caudispina was included in some of the studies using diethylcarbamazine. These are the three most commonly encountered filarial species in squirrel monkeys. Dithiazanine iodide proved to be unsuitable for use because of lack of acceptance by the monkeys. Naphuride sodium (10 mg/kg/week for 5 weeks) did not exert filaricidal activity against the species tested during a 7-month evaluation period. Thiacetarsamide sodium (0.22 ml/kg twice daily for 2 days) had lethal effects on the adult parasites, but not the microfilariae, of all species tested. Diethylcarbamazine (50 mg/kg/day for 10 days) was found to be effective against both microfilaria and adults of all filarial species tested. Monkeys given this regimen were microfilaria-negative for 12-24 weeks following treatment.

Clinical laboratory evaluations of seven heartworm infected beagles: during disease development and following treatment.

Clinical laboratory evaluations were performed in 7 beagles for 12 months following experimental infection with Dirofilaria immitis and for 14 months following adulticide and microfilaricide treatment. Few abnormalities were detected. A mild basophilia and thrombocytopenia developed late during the year of infection and after arsenical treatment there were transient increases in eosinophils, SGPT, and SAP. Coagulation and blood gas studies were normal. The minimal changes were attributed to either: (1) the one year infection with 50 infective larvae was an insufficient insult or (2) an idiosyncrasy in the host-parasite relationship is required in order to produce marked alterations in clinical laboratory evaluations.

[Erythema cinitiensis perstans]. / Erythema cinitiensis perstans.

The authors report a case of Erythema Cinitiensis Perstans, in a thirty-one years old white man. This dermatosis, reported in the literature also es Ashy Dermatitis and Erythema Dyschromicum Perstans, is here in Brazil exceptional. Clinically this dermatosis is characterized by the presence of gray patches in a sometimes surrounded by an erythematous active border. The lesions may occur on any area of the integument, sparing the hair scalp, palms, soles and nails. The therapy has been ineffective in all the cases, but one reported by Stevenson and Miura and in our case, where the patients have improved after Dithiazanine iodide treatment due to intestinal parasitoses by the Tricocephalus trichiurus.

[Clinical study of strongyloidiasis]. / Contributii la studiul clinic al strongiloidozei.

Between 1961 and 1974 the authors had in their care 260 patients suffering from strongyloidiasis. The present paper deals with the clinical data evaluated from two points of view : the frequency of subjective and objective symptoms in the course of the disease, and the frequency of the groups of symptoms in terms of the clinical form of the disease. The frequency of the symptoms is listed according to the five evolutive stages of the disease (invasion, latency, pulmonary, gastrointestinal and neuropsychical phases). The following clinical forms were recorded : hepato-duodenovesicular, enterocolitic, pulmonary, neuropsychical, polymorphous and asymptomatic. Particularly efficient among the drugs used were gentian violet and dithiazanin (Telmid or Dilombrin).

Tricocefaliasis infantil

Se presenta 84 pacientes afectos de tricocefaliasis masiva. La mitad de los mismos es tratada con enemas a retener de yoduro de ditiazanina y la otra a base de hexilresorcinol por igual via......(AU)