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.     

Population-based Studies of Childhood Disability in Developing Countries

This article reports the main health status differences between a representative sample of homeless people and an at-risk for homelessness group consisting of people who use services for the homeless such as soup kitchens and public baths but have and maintain a home. The variables analyzed include health problems by system, risk habits and behaviors, substance use, alcohol problems, general health status, suicidal thoughts and perceived health status. Because of the gender differences between groups, the data were analyzed independently for men and women. The results show that the homeless have worse health status compared with the at-risk group. Homeless men had significantly more risk habits and behaviors, substance use, and mental health problems. Homeless women had similar tendencies, although they also had significantly more general health illnesses (by systems and over the past year). Almost no differences were found in drug use (especially alcohol use) or in mental health—except for depression, which was significant. These results shed light on new data regarding the correlation between homelessness and health issues.     

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.     

Separation of T cell subpopulations capable of DNA synthesis, lymphotoxin release, and regulation of antigen and phytohemagglutinin responses on the basis of density and adherence properties.

T memory cells specifically responsive to ovalbumin and performing the diverse functions of DNA synthesis, lymphotoxin release, and regulation can be isolated in enriched numbers in the most buoyant fractions (A+B) of bovine serum albumin gradients on day 9 after sensitization. At least 20-30% of these cells are capable of mounting a blastogenic response to ovalbumin. A+B cells responding to ovalbumin with DNA synthesis have adherent properties and are further enriched on passage through glass wool. The subpopulations capable of entering into blastogenesis and DNA synthesis and of lymphotoxin release are unresponsive to T mitogens. A+B cells are capable of either potentiating or suppressing DNA synthetic responses to both phytohemagglutinin and antigen when added to 5 X 10(5) D cells in different proportions. Potentiation or suppression of phytohemagglutinin responses were observed with 1 X 10(5) A+B cells, and total suppression was observed with A+B in the range of 4 X 10(3) to 2 X 10(4). The response to antigen was sometimes inhibited in the same cell combinations that gave a potentiated response to phytohemagglutinin and vice versa. Regulatory cells in this system were not macrophages since their effect was not mimicked by addition of peritoneal macrophages, and ablation of macrophages by carrageenan affected neither the potentiation nor suppression.