Aging‐ and vascular‐related pathologies

Our aging population is set to grow considerably in the coming decades. In fact, the number of individuals older than 65 years will double by 2050. This projected increase in people living with extended life expectancy represents an inevitable upsurge in the presentation of age‐related pathologies. However, our current understanding of the impact of aging on a number of biological processes is unfortunately inadequate. Cardiovascular, cerebrovascular, and neurodegenerative diseases are particularly prevalent in the elderly population. Intriguingly, these pathologies are all associated with vascular dysfunction, suggesting that the process of aging can induce structural and functional impairments in vascular networks. Together with elevated cell senescence, pre‐existing comorbidities, and the emerging concept of age‐associated inflammatory imbalance, impaired vascular functions can significantly increase one's risk in acquiring age‐related diseases. In this short review, we highlight some current clinical and experimental evidence of how biological aging contributes to three vascular‐associated pathologies: atherosclerosis, stroke, and Alzheimer's disease.     

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

The Haematopoietic Cell Transplantation‐Comorbidity Index (HCT‐CI) was designed as a predictor of non‐relapse mortality after HCT. Chronic graft‐versus‐host disease (GVHD) contributes to mortality after HCT. Here, we investigated whether the HCT‐CI could predict development of chronic GVHD or post‐chronic GVHD mortality. We retrospectively analysed data from 2909 patients treated with allogeneic HCT for malignant and non‐malignant haematological conditions at four institutions. In Cox regression models adjusted for potential confounders, increasing HCT‐CI was not statistically significantly associated with the development of chronic GVHD [hazard ratio (HR) = 1·02, P = 0·34]. Yet, the index was associated with an increased risk of non‐relapse mortality (HR = 1·29, P < 0·0001) as well as overall mortality (HR = 1·25, P < 0·001) following the development of chronic GVHD. The association between HCT‐CI and post‐chronic GVHD mortality was similar regardless of donor type or stem cell source. HCT‐CI scores could be incorporated in the design of clinical trials for treatment of chronic GVHD.     

Feasibility and acceptability of CD‐ROM‐based cognitive‐behavioural treatment for binge‐eating disorder

We compared preliminary feasibility and acceptability of CD‐ROM‐delivered CBT for overweight individuals with binge‐eating disorder (BED) to 10 weekly group CBT sessions (Group) and to a waiting list control (WL). Attrition was numerically greater in the Group than the CD‐ROM condition; although only Group differed significantly from WL in dropout rates. Those in the CD‐ROM condition reported continued use of their CD‐ROM after treatment. Also, the majority of WL participants elected to receive CD‐ROM over Group treatment at the end of the waiting period. Preliminarily, no significant differences emerged across the active treatment groups on most outcome measures. However, there was a significantly greater decline in binge days in the two active groups relative to WL. CD‐ROM appears to be an acceptable and at least initially preferred method of CBT delivery for overweight individuals with BED. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.     

Over‐expression of Toll‐like receptors and their ligands in small‐for‐size graft

Aim: Toll‐like receptors (TLRs) participate in several physiological and pathological processes of transplantation, including inflammation and allograft rejection, but the expression of TLRs and their ligands remains undetermined in small‐for‐size graft transplantation. Methods: A non‐arterialized partial liver transplantation model was used. The expression of TLR2 and TLR4 mRNA and protein, CD14 and Myeloid Differentiation‐2 (MD‐2) mRNA, as well as TLR2 and TLR4 exogenous ligands (endotoxin) and endogenous ligands [heat shock protein (HSP) 60 and 70] were assessed. The signaling pathways induced by TLR2 and TLR4 were also assessed. Results: In small‐for‐size liver graft, the expression of mRNA and protein of TLR2 and TLR4, CD14 and MD‐2 mRNA, as well as endogenous ligands of TLR2 and TLR4 such as HSP60 and HSP70 was quickly and significantly increased after reperfusion, and reached a peak at 3 h after reperfusion. The levels of exogenous ligands (endotoxin) were increased and reached a peak at 6 h after reperfusion. The appearance of TLR2 and TLR4 mRNA was accompanied by increased HSP 60 and 70 mRNA within 24 h after reperfusion. In the small‐for‐size group, the peak levels of TLRs and their endogenous ligands appeared earlier than those in the full size group; the peak levels of TLRs and their endogenous and exogenous ligands were higher than those in the full size group. Conclusion: TLR2 and TLR4, as well as their endogenous and exogenous ligands were activated in small‐for‐size liver graft transplantation.     

Spatiotemporal components of the 3‐D gait analysis of community‐dwelling middle‐aged and elderly Japanese: Age‐ and sex‐related differences

Aim: To describe age‐ and sex‐related differences in gait patterns of community‐living men and women using 3‐D gait analysis. Methods: Subjects (n = 2006) aged 40–84 years participated in the National Institute for Longevity Sciences‐Longitudinal Study of Aging (NILS‐LSA). Spatiotemporal components, including velocity, step length, step frequency, and double support time during a gait cycle, were calculated from 3‐D coordinates and vertical force data. Velocity, step length and step frequency were normalized by leg length and acceleration due to gravity, and double support time was normalized to gait cycle duration. Results: Spatiotemporal walking variables of brisk velocity and step length were significantly greater in men than in women, while comfortable velocity and comfortable and brisk step frequencies and double support times were greater in women than in men. Age‐related changes were marked at 70–84 years in most spatiotemporal variables in both sexes during comfortable walking. During brisk walking, age‐related changes were observed from a younger age than during comfortable walking, and there were sex‐related differences. Conclusion: The age‐related gait alteration was obvious among those aged 70 years and older, and it accelerated markedly in women's brisk walking intensity. Geriatr Gerontol Int 2011; 11: 39–49.     

Periplogenin‐3‐O‐ ‐D‐Glucopyranosyl ‐(1→6)‐ ‐D‐Glucopyaranosyl‐ ‐(1→4) ‐D‐Cymaropyranoside,Isolated from Aegle marmelos Protects Doxorubicin Induced Cardiovascular Problems and Hepatotoxicity in Rats

Doxorubicin is a common chemotherapeutic anticancer drug. Its use is associated with adverse effects including cardiotoxicity. Several therapeutics interventions have been attempted to reduce the toxicity and to improve the efficacy of the drug. However, on phytochemicals very few investigations have been made. In the present study we have evaluated the potential of a cardenolide, periplogenin, isolated from the leaves of Aegle marmelos in protecting the doxorubicin induced cardiotoxicity and lipid peroxidation (LPO) in rats. Doxorubicin induced cardiac and hepatotoxicity were characterized by marked biochemical changes including an increase in serum creatine kinase–MB (CK–MB), glutamate‐pyruvate transaminase (SGPT), and tissue LPO, with a decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). It also increased the levels of different serum lipids, but decreased the amount of high‐density lipoprotein (HDL). Cotherapy of the test cardenolide and doxorubicin for 4 weeks reversed all these adverse effects. However, out of three different concentrations (12.5, 25, and 50 mg/kg p.o.) of the test periplogenin, 25 mg/kg appeared to be most effective. When its efficacy was compared with that of vitamin E (α‐tocopherol) the isolated compound exhibited a better therapeutic potential. The isolated periplogenin from the leaves of A. marmelos could potentially inhibit doxorubicin‐induced cardiovascular problems in rats. However, its moderate dose was found to be most effective.     

Prognostic value of complete remission status at end‐of‐treatment FDG‐PET in R‐CHOP‐treated diffuse large B‐cell lymphoma: systematic review and meta‐analysis

This study systematically reviewed and meta‐analysed the prognostic value of complete remission status at end‐of‐treatment ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography (FDG‐PET) in diffuse large B‐cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP). The systematic PubMed/MEDLINE search yielded seven suitable studies comprising a total of 737 R‐CHOP‐treated DLBCL patients who were in complete remission at end‐of‐treatment FDG‐PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end‐of‐treatment FDG‐PET ranged from 7·0% to 20·0%, with a weighted summary proportion of 13·7%. Five of seven studies reported progression‐free survival (PFS) of these patients at various specific time points, i.e., 2‐year PFS (n = 1), estimated 3‐year PFS (n = 3) and 5‐year PFS (n = 1), which was 83%, 85–86·4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3‐year OS (n = 2) and estimated 5‐year OS (n = 1), which were 90%, 93·6% and 83%, respectively. In conclusion, a non‐negligible proportion of R‐CHOP‐treated DLBCL patients who achieve complete remission according to end‐of‐treatment FDG‐PET experiences disease relapse during follow‐up.