Malignancy may adversely influence the quality and behaviour of oocytes

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age- matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.      

Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

Background  

The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.     

A further study on asymmetric cross-sensitization between MK-801 and phencyclidine-induced ambulatory activity.

Our previous study found that MK-801-sensitized rats showed cross-sensitization to the locomotor stimulant effects of phencyclidine, but phencyclidine sensitized rats did not show cross-sensitizaton to MK-801. This study was designed to determine whether the asymmetric cross-sensitization was due to injection-environment conditioning or possibly reduced phencyclidine-like effects following further repeated injections of phencyclidine. Adult female Sprague-Dawley rats were used in this study, and their activity was assessed with an automated photoelectric system. Results confirmed the early finding that four daily injections of phencyclidine (3.2 mg/kg) or MK-801 (0.32 mg/kg) produced locomotor sensitization, and that the two drugs showed asymmetric cross-sensitization. Moreover, injection-environment conditioning was ruled out as a possible cause for cross-sensitization from MK-801 to phencyclidine, and possibly reduced phencyclidine-like effects following further repeated injections was also ruled out as a cause for the failure of cross-sensitization from phencyclidine to MK-801. These additional results further confirm our previous finding, and indicate that there are significant differences in the neural mechanisms underlying phencyclidine- and MK-801-induced sensitization.     

Chemical dissociation of human awareness: focus on non-competitive NMDA receptor antagonists

Since the mid-1950s the pharmaceutical industry has developed a number of chemicals, including phencyclidine, ketamine and related arylcyclohexylamines (PCE and TCP), dizocilpine (MK-801), N-allylnormetazocine [ NANM, (±)SKF-10,047], etoxadrol, dioxadrol and its enantiomers dexoxadrol and levoxadrol, which produce a constellation of unusual behavioral effects in animals and man. The compounds best studied in humans are phencyclidine and ketamine. They produce a remarkable dose-dependent dissociation of awareness. All of these substances are now known to be non-competitive antagonists of NMDA receptors of glutamic acid. They act in the NMDA receptor ion channel. One can conclude, on the basis of the effects observed with these agents, that glutamic acid and related excitatory amino acids are extremely important in the maintenance of human awareness.     

Differential Service Utilization Associated With Trauma-informed Integrated Treatment for Women With Co-occurring Disorders

Women with co-occurring mental health and substance use disorders and trauma histories vary greatly in symptom severity and use of support services. This study estimated differential effects of an integrated treatment intervention (IT) across sub-groups of women in this population on services utilization outcomes. Data from a national study were used to cluster participants by symptoms and service utilization, and then estimate the effect of IT versus usual care on 12-month service utilization for each sub-group. The intervention effect varied significantly across groups, in particular indicating relative increases in residential treatment utilization associated with IT among women with predominating trauma and substance abuse symptoms. Understanding how IT influences service utilization for different groups of women in this population with complex needs is an important step toward achieving an optimal balance between need for treatment and service utilization, which can ultimately improve outcomes and conserve resources.     

Endotoxin-induced suppression of erythropoiesis: the role of erythropoietin and a heme synthesis stimulating factor

The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.