Metabolic Syndrome and Risk for Incident Alzheimer's Disease or Vascular Dementia: The Three-City Study

OBJECTIVE—Associations between metabolic syndrome and its individual components with risk of incident dementia and its different subtypes are inconsistent

Earlier age of dementia onset and shorter survival times in dementia patients with diabetes

Diabetes is a risk factor for dementia, but relatively little is known about the epidemiology of the association. A retrospective population study using Western Australian hospital inpatient, mental health outpatient, and death records was used to compare the age at index dementia record (proxy for onset age) and survival outcomes in dementia patients with and without preexisting diabetes (n = 25,006; diabetes, 17.3%). Inpatient records from 1970 determined diabetes history in this study population with incident dementia in years 1990–2005. Dementia onset and death occurred an average 2.2 years and 2.6 years earlier, respectively, in diabetic compared with nondiabetic patients. Age-specific mortality rates were increased in patients with diabetes. In an adjusted proportional hazard model, the death rate was increased with long-duration diabetes, particularly with early age onset dementia. In dementia diagnosed before age 65 years, those with a ≥15-year history of diabetes died almost twice as fast as those without diabetes (hazard ratio = 1.9, 95% confidence interval: 1.3, 2.9). These results suggest that, in patients with diabetes, dementia onset occurs on average 2 years early and survival outcomes are generally poorer. The effect of diabetes on onset, survival, and mortality is greatest when diabetes develops before middle age and after 15 years’ diabetes duration. The impact of diabetes on dementia becomes progressively attenuated in older age groups

Topical immunotherapy of severe alopecia areata with diphenylcyclopropenone (DPCP): experience in an Iranian population

BACKGROUND: Highly variable results of topical diphenylcyclopropenone (DPCP) in the treatment of alopecia areata have been reported so far. The purposes of the present study were to evaluate the efficacy and tolerability of DPCP treatment in severe alopecia areata. METHODS: Twenty-eight patients (16 female and 12 male, 10–35 years old, mean age 25 years) with extensive alopecia areata were enrolled in an open-label clinical trial. After sensitization with 2% DPCP, progressively higher concentrations beginning at 0.001% were applied weekly for 6 months to one side of the scalp, after which, if terminal hair growth was noted, the entire scalp was then treated under the same weekly protocol. The maximum concentration of DPCP in acetone was 2%. RESULTS: Twenty-seven of 28 patients completed therapy. The overall response rate was 81.5% (22/27), complete remission (90%-100% terminal hair re-growth) was obtained 22.2% (6/27) and partial remission (10%-90% terminal hair re-growth) in 59.3% (16/27). In all patients an eczematous reaction consisting of erythema, itching, and scaling at the site of application were observed. During therapy, other side effects including, occipital lymphadenopathy 40.7% (11/27), severe eczema/blister formation 40.7% (11/27), hyperpigmentation 18.5% (5/27) were observed, but no hypopigmentation, vitiligo, contact urticaria, and erythema multiforme-like reaction were seen in the patients. Nineteen of 27 (70.4%) patients had at least one side effect, other than eczematous reaction. Notably, partial recurrence was observed in 50.9% (13/22) of these patients after 6 to 12 months of follow-up. During the follow-up time the maintenance DPCP immunotherapy was continued. CONCLUSION: Topical DPCP treatment for alopecia areata is an effective therapy with a slightly high relapse rate during bilateral maintenance treatment. According to the author's knowledge this is the first experience with DPCP in Iran

Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

Background: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Methodology/Principal Findings: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPOtreated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Conclusions/Significance: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fa

Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21

BACKGROUND: Down syndrome (DS) is caused by trisomy 21 (+21), but the aberrations in gene expression resulting from this chromosomal aneuploidy are not yet completely understood. METHODS: We used oligonucleotide microarrays to survey mRNA expression in early- and late-passage control and +21 fibroblasts and mid-gestation fetal hearts. We supplemented this analysis with northern blotting, western blotting, real-time RT-PCR, and immunohistochemistry. RESULTS: We found chromosome 21 genes consistently over-represented among the genes over-expressed in the +21 samples. However, these sets of over-expressed genes differed across the three cell/tissue types. The chromosome 21 gene MX1 was strongly over-expressed (mean 16-fold) in senescent +21 fibroblasts, a result verified by northern and western blotting. MX1 is an interferon target gene, and its mRNA was induced by interferons present in +21 fibroblast conditioned medium, suggesting an autocrine loop for its over-expression. By immunohistochemistry the p78(MX1 )protein was induced in lesional tissue of alopecia areata, an autoimmune disorder associated with DS. We found strong over-expression of the purine biosynthesis gene GART (mean 3-fold) in fetal hearts with +21 and verified this result by northern blotting and real-time RT-PCR. CONCLUSION: Different subsets of chromosome 21 genes are over-expressed in different cell types with +21, and for some genes this over-expression is non-linear (>1.5X). Hyperactive interferon signaling is a candidate pathway for cell senescence and autoimmune disorders in DS, and abnormal purine metabolism should be investigated for a potential role in cardiac defects

Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model

YesAlopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60–70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.Canadian Institutes of Health Researches (Funding Reference Number: 134214 and 136945)