Methionine Stimulates Motor Impairment And Cerebellar Mercury Deposition in Methylmercury-Exposed Mice

Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg–cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously exposed to MeHg and L-Met.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

HIV infection: pre-highly active antiretroviral therapy IL-7 plasma levels correlate with long-term CD4 cell count increase after treatment

Highly active antiretroviral therapy (HAART) in HIV patients generally increases the CD4 cell count, but the level of CD4 cell restoration remains very heterogeneous. IL-7 is the main cytokine controlling the size of the T-cell pool. We assessed the hypothesis that pre-HAART IL-7 plasma levels may affect CD4 cell restoration after treatment. A positive correlation was found in a cohort of 18 patients between pre-HAART IL-7 plasma levels and CD4 cell increases after 20 +/- 7.8 months of HAART.     

Does total knee arthroplasty modify flexion axis of the knee?

Purpose

To prospectively investigate whether preoperative functional flexion axis in patients with osteoarthritis- and varus-alignment changes after total knee arthroplasty and whether a correlation exists both between preoperative functional flexion axis and native limb deformity.

Methods

A navigated total knee arthroplasty was performed in 108 patients using a specific software to acquire passive joint kinematics before and after implant positioning. The knee was cycled through three passive range of motions, from 0° to 120°. Functional flexion axis was computed using the mean helical axis algorithm. The angle between the functional flexion axis and the surgical transepicondylar axis was determined on frontal (α ^F) and axial (α ^A) plane. The pre- and postoperative hip-knee-ankle angle, related to femur mechanical axis, was determined.

Results

Postoperative functional flexion axis was different from preoperative only on frontal plane, while no differences were found on axial plane. No correlation was found between preoperative α ^A and native limb deformity, while a poor correlation was found in frontal plane, between α ^F and preoperative hip-knee-ankle angle.

Conclusions

Total knee arthroplasty affects functional flexion axis only on frontal plane while has no effect on axial plane. Preoperative functional flexion axis is in a more varus position respect to the transepicondylar axis both in pre- and postoperative conditions. Moreover, the position of the functional axis on frontal plane in preoperative conditions is dependent on native limb alignment, while on axial plane is not dependent on the amount of preoperative varus deformity.

Level of evidence

IV.     

Adult onset Krabbe's leukodystrophy: a report of 2 cases

Krabbe's disease with adult onset is rare; neurological symptoms begin in childhood or at a juvenile age. Two brothers with adult onset of the disease are here reported; 1 sibling developed parapareto-ataxic gait while the other was asymptomatic. Magnetic resonance imaging showed areas of demyelination in the white matter of the brain, while nerve conduction was completely normal. In both patients deficiency of galactosylceramide beta-salactosidase was comnarable to the infantile form.