Attenuation of LPS-induced changes in synaptic activity in rat hippocampus by Vasogen's Immune Modulation Therapy

Systemic injection of lipopolysaccharide (LPS) blocks the expression of long-term potentiation in the hippocampus of the rat. This is coupled with increased IL-1beta concentration and c-Jun NH(2)-terminal kinase activity, as well as an increase in the number of cells displaying apoptotic characteristics in the hippocampus. Vasogen's Immune Modulation Therapy (IMT) is a procedure involving intramuscular administration of syngeneic blood which has been exposed ex vivo to elevated temperature, oxidation and ultraviolet light. We report that Vasogen's IMT significantly abrogates these LPS-induced effects with a concomitant increase in the concentration of the anti-inflammatory cytokine IL-10. These data suggest that Vasogen's IMT may play a protective role against the deleterious effects of immune insults in the brain.     

The significance of environmental factors in the etiology of Alzheimer's disease

The proposition that environmental agents, such as diet, aluminum, and viruses, are as important as genetic factors in the etiology of Alzheimer's disease (AD) was advanced by the authors at the Challenging Views of Alzheimer's Disease meeting held in Cincinnati on July 28 and 29, 2001. Diet, dietary fat, and to a lesser extent, total energy (caloric intake), were found to be significant risk factors for the development of AD in a dozen countries, while fish consumption was found to be a significant risk reduction factor. An acid-forming diet, such as one high in dietary fat or total energy, can lead to increased serum and brain concentrations of aluminum and transition metal ions, which are implicated in oxidative stress potentially leading to the neurological damage characteristic of AD. Many of the risk factors for AD, such as cholesterol and fat, and risk reduction factors, such as whole grain cereals and vegetables, are shared with ischemic heart disease. Aluminum may cause neurological damage and a number of studies have linked aluminum to an increased risk for developing AD. The evidence for viral agents playing a role in AD is the strong association between the presence of HSV1 in brain and carriage of an apoE-epsilon4 allele in the case of AD patients but not of controls; statistical analysis shows the association is causal. Diet, aluminum, and viral infections may increase the prevalence of AD by eliciting inflammation, which may cause the neurological damage that results in AD.     

The integrin family of cell adhesion molecules has multiple functions within the CNS

Integrins comprise a large family of cell adhesion molecules that mediate interactions between the extracellular environment and the cytoplasm. During the last decade, analysis of the expression and function of these molecules has revealed that integrins regulate many aspects of cell behavior including cell death, proliferation, migration, and differentiation. Within the central nervous system (CNS), most of the early studies focused on the role of integrins in mediating adhesive and migratory events in two distinct processes: neural development and CNS inflammation. Interestingly, recent analysis of transgenic mice has provided some surprising results regarding the role of integrins in neural development. Furthermore, a large body of evidence now supports the idea that in addition to these well-described functions, integrins play multiple roles in the CNS, both during development and in the adult in areas as diverse as synaptogenesis, activation of microglia, and stabilization of the endothelium and blood-brain barrier. Many excellent reviews have addressed the contribution of integrins in mediating leukocyte extravasation during CNS inflammation. This review will focus on recently emerging evidence of novel and diverse roles of integrins and their ligands in the CNS during development and in the adult, in health and disease.     

Striking the right balance in colorectal cancer care--a qualitative study of rural and urban patients

BACKGROUND: Colorectal cancer is the second most common cause of cancer-related death in Scotland. For patients, the journey from diagnosis through treatment is complex and there are inequalities in survival rates. OBJECTIVES: The aim of the present study was to explore how patients with colorectal cancer perceive their care. METHODS: This was a qualitative study involving 95 patients and relatives of patients with colorectal cancer in the North, Northeast and Northern Isles, Scotland. Focus groups (32 participants) were conducted in hospital, and interviews (63 participants) in patients' own homes in order to explore their experiences of health services for cancer-what was good, what was bad and what was needed. Analysis was inductive, with exploration of similar and divergent perspectives within themes. RESULTS: Patients wanted rapid diagnosis, specialist treatment and good communication, but their experiences of and perspectives on these areas were often divergent. Delays in diagnosis could stem from late presentation by patients, but also from early presentation when the cancer could go undetected. GP continuity was desirable, but sometimes implicated in delays. Patients preferred their GPs to be advocates, not gatekeepers. The context, however, was one where some patients pursued their care tenaciously while others did not. For some, speed of progress through the system was everything, but others found this could be impersonal. Outlying patients had to balance transport difficulties with the benefits of distant specialist treatment. Some patients wanted full information to be provided directly, but others could not cope with this. CONCLUSIONS: From patients' perspectives, ideal cancer care cannot be achieved in a uniform way. For some of the key goals of cancer treatment to be met, including rapid access to specialist treatment for all and good communication of bad news and test results, a balance must be struck which tailors care to individuals.     

Peer education,gender and the development of critical consciousness: participatory HIV prevention by South African youth

Despite the growing popularity of participatory peer education as an HIV-prevention strategy worldwide, our understandings of the processes underlying its impact on sexual norms are still in their infancy. Starting from the assumption that gender inequalities play a key role in driving the epidemic amongst young people, we outline a framework for conceptualizing the processes underlying successful peer education. We draw on the inter-locking concepts of social identity, empowerment (with particular emphasis on Freire's account of critical consciousness) and social capital. Thereafter we provide a critical case study of a school-based peer education programme in a South African township school, drawing on a longitudinal case study of the programme, and interviews and focus groups with young people in the township. Our research highlights a number of features of the programme itself, as well as the broader context within which it was implemented, which are likely to undermine'the development of the critical thinking and empowerment which we argue are key preconditions for programme success. In relation to the programme itself, these include peer educators' preference for didactic methods and biomedical frameworks, unequal gender dynamics amongst the peer educators, the highly regulated and teacher-driven nature of the school environment and negative learner attitudes to the programme. In relation to the broader context of the programme, we point to factors such as limited opportunities for communication about sex outside of the peer educational setting, poor adult role models of sexual relationships, poverty and unemployment, low levels of social capital and poor community facilities. We discuss the implications of our findings for the design of peer educational activities, and point to a number of broader social and community development initiatives that would maximize the likelihood of programme success.     

Brainstem auditory evoked response in adolescents with acoustic mycotic neuroma due to environmental exposure to toxic molds

Indoor air contamination with toxic opportunistic molds is an emerging health risk worldwide. Some of the opportunistic molds include: Stachybotrys chartarum, Aspergillus species (A. fumigatus, A. flavus, A. niger, A. versicolor etc.), Cadosporium, Alternaria, Penicillium, Trichoderma, Fusarium graminearum etc. These molds flourish in homes that are moist and damp. Reports of floods are now evident in many parts of the world. With these global changes in climatic conditions that favor the opportunistic mode of living among these molds, some health authorities are beginning to feel concerned about the diversity and the extent to which opportunistic molds can cause adverse health effects in humans. Mycotoxicosis is the collective name for all the diseases caused by toxic molds. Frequently, we have cases of acoustic neuroma due to mycotoxicity in our Center. Mycotic neuroma probably has not been reported before and the application of brainstem auditory evoked response (BAER) techniques in acoustic mycotic neuroma have not been reported either. The aim of this study, therefore, was to report cases and measurements of acoustic mycotic neuroma in adolescents using the brainstem auditory evoked response. The patients' case history, clinical neurological and neurobehavioral questionnaires were assessed. Then, the BAERs were recorded between Cz and Ai, with a second channel, Cz-Ac. The case histories and the questionnaires were analyzed in conjunction with the outcome of the objective brainstem auditory evoked response measurements. The prevalent subjective findings in the patients were headaches, memory loss, hearing loss, lack of concentration, fatigue, sleep disturbance, facial swelling, rashes, nosebleeds, diarrhea, abdominal pains and respiratory difficulties. Objective BAER showed overall abnormalities in all the patients. Although the waveform abnormalities varied, 1-3 interpeak latencies were abnormal in all the patients. Overall results showed the presence of acoustic mycotic neuroma and confirmed the sensitivity and usefulness of BAER in screening acoustic mycotic neuroma and sensorineural auditory dysfunction.     

Breast cancer-race,ethnicity, and survival: a literature review

A review of the literature on breast cancer was conducted to identify gaps in knowledge as it relates breast cancer risk, race, and survival. The discussion has been divided into three broad categories: (1) breast cancer basics and the relationships between risks, race, and survival; (2) influence of race and socioeconomic status on breast cancer morbidity and mortality; and (3) relationship between age and mammography screening. All of the cited studies reveal evidence of a linkage between race and breast cancer survival, however, the effects of socioeconomic factors and race needs to be examined. Results suggest that African-American women and lower income women need to be targeted for early detection. Many of the analyses among younger women (20–39 years) reported that very little disease occurrence in young black women was associated with the socioeconomic factors studied. Conclusions from all studies indicate that more aggressive screening and public education programs directed toward younger black women is warranted. The gaps in knowledge identified included the lack of an explanation of early onset breast cancer with high penetrance as well as an explanation of African-American women's resistance to self-examination and mammography screening and other barriers to diagnostic treatment. Future studies should also examine the link between familial breast cancer and genetic mutations.     

Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma

Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (P 相似文献   

Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors

Tumor vessels possess unique physiological features that might be exploited for improving drug delivery. In the present study, we investigate the possibility of modifying polyethylene glycol-ylated liposome cationic charge of polyethylene glycol coated liposomes to optimize delivery to tumor vessels using biodistribution studies and intravital microscopy. The majority of liposomes accumulated in the liver, and increasing charge resulted in lower retention in the spleen and blood. Although overall tumor uptake was not affected by charge in the biodistribution studies, intravital microscopy showed that increasing the charge content from 10 to 50 mol % doubled the accumulation of liposomes in tumor vessels, suggesting a change in intratumor distribution; no significant effect of charge on interstitial accumulation could be detected, possibly attributable to spatial heterogeneity. Increased vascular accumulation of cationic liposomes was similar in two different tumor types and sites. Our results suggest that optimizing physicochemical properties of liposomes that exploit physiological features of tumors and control the intratumor distribution of these drug carriers should improve vascular-specific delivery.