IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L. braziliensis Infection.

Cutaneous leishmaniasis (CL) is characterized by high production of pro-inflammatory cytokines and development of pathology. Individuals with subclinical L. braziliensis infection (SC) have a positive skin test to leishmania, but do not develop disease. We evaluated whether the downregulation of inflammatory response in SC is mediated by IL-10 and IL-27 and whether IL-17 is associated with control of infection. Participants include SC individuals, patients with CL and healthy subjects. Cytokines protein and mRNA were detected by ELISA and real-time PCR. IFN-γ and TNF-α levels were higher in CL than in SC group. The IL-10 levels and mRNA for IL-10 were similar in both SC and CL. mRNA for IL-27 was increased in cells from SC after stimulation with L. braziliensis antigen. There was a tendency for increased levels of IL-17 in SC compared to CL. The weak type 1 immune response observed in SC L. braziliensis infection is not because of the regulatory effects of IL-10 and IL-27. The control of Leishmania infection may be mediated by innate immune response with participation of IL-17. The results from this pilot study warrant further larger studies to investigate the potential contributions of IL-17 and IL-27 to the control of L. braziliensis infection.

A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies.

BACKGROUND: To determine the maximum tolerated dose (MTD), safety, potential pharmacokinetic (PK) interactions, and effect on liver histology of trabectedin in combination with pegylated liposomal doxorubicin (PLD) for advanced malignancies. PATIENTS AND METHODS: Entry criteria for the 36 patients included normal liver function, prior doxorubicin exposure <250 mg/m(2), and normal cardiac function. A 1-h PLD (30 mg/m(2)) infusion was followed immediately by one of six trabectedin doses (0.4, 0.6, 0.75, 0.9, 1.1, and 1.3 mg/m(2)) infused over 3 h, repeated every 21 days until evidence of complete response (CR), disease progression, or unacceptable toxicity. Plasma samples were obtained to assess PK profiles. RESULTS: The MTD of trabectedin was 1.1 mg/m(2). Drug-related grade 3 and 4 toxic effects were neutropenia (31%) and elevated transaminases (31%). Six patients responded (one CR, five partial responses), with an overall response rate of 16.7%, and 14 had stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) >4 months (39%). Neither drug had its PK affected significantly by concomitant administration compared with trabectedin and PLD each given as a single agent. CONCLUSION: Trabectedin combined with PLD is generally well tolerated at therapeutic doses of both drugs in pretreated patients with diverse tumor types and appears to provide clinical benefit. These results support the need for additional studies of this combination in appropriate cancer types.

Cysticidal therapy: impact on seizure control in epilepsy associated with neurocysticercosis.

OBJECTIVE: To evaluate the clinical features and seizure control of epilepsy related to neurocysticercosis. METHOD: 18 patients with partial epilepsy and neurocysticercosis were treated with albendazol or praziquantel and followed from 3 months to 12 years. We analyzed results from the CSF exam, interictal electroencephalogram (EEG), head computerized tomography and/or magnetic resonance imaging. RESULTS: The patients' mean age was 36.4 years. The mean duration of epilepsy was 16 years. 83% patients had simple partial seizures; 17% had complex partial seizures. All patients underwent routine EEGs: 62% had abnormalities and 38% were normal. A relationship was observed between focal EEG abnormality and the location of cyst in 28% of the patients. The CSF exams showed pleocytosis in 33% of the patients, and 28% had elevated protein levels. Only 22% of patients had positive titer for cysticercosis in the CSF. In all patients who had somatosensory and special sensory seizures there was a relationship between location of the cysts and seizure semiology (n=11). After cysticidal therapy, 83% patients had a significant improvement in controlling seizures. CONCLUSION: In this group, we found a predominance of simple partial seizures and a relationship between somatosensory and special sensory seizures and the location of the cysts. Cysticidal therapy was effective in controlling seizures in these patients and should be considered for patients with partial seizures and semiology related to cyst location.