MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy

The biochemical targets for antidepressants are relatively well established, but we lack a clear understanding of how actions at these proteins translate to clinical benefits. This study used a novel rodent assay to investigate how different antidepressant drugs act to modify affective biases that have been implicated in depression. In this bowl-digging task, rats encounter two equal value learning experiences on separate days (one during an affective manipulation and the other during control conditions). This induces an affective bias that is quantified using a preference test in which both digging substrates are presented together and the individual rats’ choices recorded. The assay can be used to measure affective biases associated with learning (when the treatment is given at the time of the experience) or examine the modification of previously acquired biases (when the treatment is administered before the preference test). The rapid-onset antidepressant ketamine, but not the delayed-onset antidepressant, venlafaxine, attenuated the previously acquired FG7142-induced negative bias following systemic administration. Venlafaxine but not ketamine induced a positive bias when administered before learning. We then used local drug infusions and excitotoxic lesions to localize the effects of ketamine to the medial prefrontal cortex and venlafaxine to the amygdala. Using a modified protocol we also showed that positive and negative biases amplified further when the numbers of substrate–reinforcer associations are increased. We propose that this pattern of results could explain the delayed onset of action of venlafaxine and the rapid onset of action but lack of long-term efficacy seen with ketamine.     

Expression of phosphatase of regenerating liver-3 (PRL-3) in endometrioid cancer and lymph nodes metastases

PurposeWe identify the expression of PRL-3 in primary endometrioid endometrial cancer and metastases in relation to the clinicopathological characteristics.Material/MethodsThe study involved 30 patients with type I endometrial cancer. Twelve of them were diagnosed with metastases in various localization of abdomen. The PRL-3 expression was evaluated on the basis of immunohistochemistry results by the use of monoclonal antibody anti-PRL3 clone 3B6.ResultsThe intensity of PRL-3 expression in correlation with tumor stage was statistically significant (p = 0.024). The strongest reaction was noted in cases classified as a 1a and 1b stage defined by FIGO. The strength of PRL-3 expression is significantly associated with the degree of histological tumor grade (p = 0.035).ConclusionsThe strong expression of PRL-3 in the primary tumor that was significantly correlated with the grade and clinical stage suggest that PTP4A3 participates in the process of endometrial carcinogenesis.     

Systemic complement activation, lung injury, and products of lipid peroxidation.

Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxidation products (conjugated dienes) as well as increased concentrations of lactic dehydrogenase (LDH) and one of its isoenzymes (LDH-4). After injection of CVF, extracts of lungs also showed elevated levels of conjugated dienes, whereas no elevations were found in extracts of liver, kidney, and spleen. There was no evidence in CVF-injected rats of renal or hepatic injury as reflected by the lack of development of proteinuria and the failure to detect increased serum levels of liver-related enzymes. Other peroxidation products identified in plasma of CVF-injected rats involved hydroperoxides and fluorescent compounds with features of Schiff bases. Not surprisingly, malondialdehyde was not found to be a reliable plasma indicator of lipid peroxidation associated with oxygen radical-mediated lung vascular injury. In using a model of oxygen radical-independent lung injury induced by oleic acid, although large amounts of LDH and LDH-4 were found in the plasma, no increases in plasma levels of conjugated dienes were detected. In CVF-injected animals treated with interventions protective against lung injury (neutrophil depletion, catalase, hydroxyl radical scavengers, or iron chelators), there were striking reductions in the plasma levels of conjugated dienes, hydroperoxides, and fluorochromic products. Morphometric analysis of lung sections revealed that the protective interventions did not interfere with the accumulation of neutrophils in lung interstitial capillaries after systemic activation of complement. In vitro studies with phorbol-stimulated neutrophils failed to demonstrate appearance of conjugated dienes, suggesting that the dienes appearing in plasma of CVF-injected animals are not the result of autotoxic changes in neutrophils. The data presented in this paper suggest that acute lung injury mediated by oxygen radicals derived from phagocytic cells can be monitored by the appearance in plasma of products of lipid peroxidation.     

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.