Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination

S. J. Crocker, R. Bajpai, C. S. Moore, R. F. Frausto, G. D. Brown, R. R. Pagarigan, J. L. Whitton and A. V. Terskikh (2011) Neuropathology and Applied Neurobiology 37, 643–653 Intravenous administration of human embryonic stem cell‐derived neural precursor cells attenuates cuprizone‐induced central nervous system (CNS) demyelination Aims: Previous studies have demonstrated the therapeutic potential for human embryonic stem cell‐derived neural precursor cells (hES‐NPCs) in autoimmune and genetic animal models of demyelinating diseases. Herein, we tested whether intravenous (i.v.) administration of hES‐NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. Methods: C57Bl/6 mice were fed cuprizone (0.2%) for 2 weeks and then separated into two groups that either received an i.v. injection of hES‐NPCs or i.v. administration of media without these cells. After an additional 2 weeks of dietary cuprizone treatment, CNS tissues were analysed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC). Results: Cuprizone‐induced demyelination in the CC was significantly reduced in mice treated with hES‐NPCs compared with cuprizone‐treated controls that did not receive stem cells. hES‐NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or the astrocyte marker, glial fibrillary acidic protein. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES‐NPC‐treated mice. Conclusions: These findings indicated that systemically administered hES‐NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and the benefit of hES‐NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells.     

How clean is the toothbrush that cleans your tooth?

Abstract:  Until recently, little attention has been directed towards the role the toothbrush may play in human health, even though a report of toothbrush as a significant factor in the infection appeared in 1920. It is common knowledge that the human mouth harbours a wide variety of microorganisms, some of which, at any given time, can be assumed to be potential pathogens. This was not known when toothbrushes were originally designed, yet the common toothbrush has been used in basically the same form for about 200 years. In today's world of organ transplantation and alteration of the immune system, it is important to consider the toothbrush as a source of potential pathogens. Given the fact that very often people will traumatize themselves with their toothbrush, this trauma may become a potential portal of entry for organisms. In this article, we have attempted to demonstrate the importance of toothbrush disinfection, given tips on home toothbrush care and hope to motivate the dentists to educate the patients on the importance of toothbrush disinfection.     

The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis

In this study, we assessed the effectiveness of inflammatory markers to diagnose and monitor the treatment of osteomyelitis in the diabetic foot. We evaluated 35 consecutive patients admitted to our hospital with infected foot ulcers. Patients were divided in two groups based on the results of bone culture and histopathology: osteomyelitis and no osteomyelitis. The erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), procalcitonin (PCT), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), tumor necrosis factor alpha (TNFα), monocyte chemotactic protein‐1 (MCP‐1) and macrophage inflammatory protein‐1 alpha (MIP1α) were measured at baseline after 3 and 6 weeks of standard therapy. PCT levels in the osteomyelitis group were significantly higher at baseline than in the group with no osteomyelitis (P = 0·049). There were no significant differences between the two groups in the levels of the other markers. CRP, ESR, PCT and IL‐6 levels significantly declined in the group with osteomyelitis after starting therapy, while MCP‐1 increased (P = 0·002). TNFα and MIP1α levels were below range in 80 out of 97 samples and therefore not reported. Our results suggest that PCT might be useful to distinguish osteomyelitis in infected foot ulcers. CRP, ESR, PCT and IL‐6 are valuable when monitoring the effect of therapy.     

Human carcinoembryonic antigen cDNA expressed in rat carcinoma cells can function as target antigen for tumor localization of antibodies in nude rats and as rejection antigen in syngeneic rats.

We have tried to develop a new model consisting of rats transplanted with syngeneic colon carcinoma PROb cells transfected with cDNA coding for the carcinoembryonic antigen (CEA), the human tumor marker most commonly used as target for MAbs. The antigenic density of the 4 CEA-expressing clones selected for a precise characterization ranged from 5 x 10(4) to 1 x 10(6) CEA molecules per cell. In all clones the CEA was shown to be attached to the membrane by a phosphatidylinositol (PI) anchor. Using a panel of radiolabeled MAbs directed against the 5 major epitopes described on the CEA molecule, we showed that all these CEA epitopes were expressed by the 4 transfectants. Southern-blot analysis showed that the entire CEA cDNA was present in the transfectants. Western-blot analysis, however, showed that the size of the CEA expressed by the 4 transfectants was slightly smaller than that of CEA produced by 2 reference human colon-carcinoma cell lines. Two clones, expressing 1 x 10(5) and 1 x 10(6) CEA molecules per cell, respectively, were grafted s.c. in nude mice and rats. Injection of radiolabeled anti-CEA F(ab')2 fragments into these animals showed specific tumor localization with the highest percentages of injected doses for the transfectants expressing the highest CEA level. When grafted into immunocompetent syngeneic BDIX rats, the CEA-expressing clones induced a strong antibody response against CEA and tumor rejections in a majority of the animals. Although the analysis of the immune response against the CEA-cDNA-transfected carcinoma cells is under investigation, the present results demonstrate that human CEA could function as a rejection antigen when transfected into rat carcinoma cells.     

A comparative experimental study of pathogenic properties of new strains of California encephalitis virus serogroups]

Experiments in noninbred mice, Syrian hamsters and grey monkeys were made to characterize the pathogenic properties of new strain of the California encephalitis serogroup isolated for the first time on the island of Taimir, in the Murmansk, Leningrad, Tver regions and in Karelia. All the strains displayed marked tropism for the CNS. The strains isolated in the northern regions of this country turned out more pathogenic for the animals. The strain Leiv-12812 Kl (isolated in the Tver region) differed from the remaining ones in more pronounced pathogenicity for the monkeys, as well as in the site and intensity of brain lesions. The persistence of the virus in hamsters organs may play a role of a reservoir of infection in nature.     

Cancer fear and fatalism among ethnic minority women in the United Kingdom

Background:

Cancer fear and fatalism are believed to be higher in ethnic minorities and may contribute to lower engagement with cancer prevention and early detection. We explored the levels of cancer fear and fatalism in six ethnic groups in the United Kingdom and examined the contribution of acculturation and general fatalism.

Methods:

A cross-sectional survey of 720 White British, Caribbean, African, Indian, Pakistani, and Bangladeshi women (120 of each) was conducted. Three items assessed cancer fear and two cancer fatalism. Acculturation was assessed using (self-reported) migration status, ability to speak English, and understanding of health leaflets; general fatalism with a standard measure.

Results:

Relative to White British women, African and Indian women were more fearful of cancer, Bangladeshi women less fearful, and Pakistani and Caribbean women were similar to White British women. Cancer fatalism was higher in all the ethnic minority groups compared with White British women. Less acculturated women were less likely to worry (ORs 0.21–0.45, all P<0.05) or feel particularly afraid (ORs 0.11–0.31, all P<0.05) but more likely to feel uncomfortable about cancer (ORs 1.97–3.03, all P<0.05). Lower acculturation (ORs 4.30–17.27, P<0.05) and general fatalism (OR 2.29, P<0.05) were associated with the belief that cancer is predetermined.

Conclusions:

In general, cancer fear and fatalism are more prevalent among ethnic minority than White British women and even more so in less acculturated ethnic minorities. This may affect their participation in cancer prevention and early detection.