CCS
Copper chaperone for superoxide dismutase (Superoxide dismutase copper chaperone)
Publications[править]
Frailty is a condition of elderly characterized by increased vulnerability to stressful events. Frail patients are more likely to have adverse events. The purposes of this study were to define frailty in patients aged ≥ 70 years with chronic coronary syndrome (CCS) and to evaluate mortality and prognostic significance of frailty in these patients. We included 99 patients, ≥ 70 years old (mean age 74±5.3 years), with diagnosis of CCS. They were followed-up for up to 12 months. The frailty score was evaluated according to the Canadian Study of Health and Aging (CSHA). All patients were divided as frail or non-frail. The groups were compared for their characteristics and clinical outcomes. Fifty patients were classified as frail, and 49 patients as non-frail. The 12-month Major Adverse Cardiac Events (MACE) rate was 69.4% in frail patients and 20% in non-frail patients. Frailty increases the risk for MACE as much as 3.48 times. Two patients died in the non-frail group and 11 patients died in the frail group. Frailty increases the risk for death as much as 6.05 times. When we compared the aforementioned risk factors by multivariate analysis, higher CSHA frailty score was associated with increased MACE and death (relative risk [RR] = 22.94, 95% confidence interval [CI] 3.33-158.19, P=0.001, for MACE; RR = 7.41, 95% CI 1.44-38.03, P=0.016, for death). Being a frail elderly CCS patient is associated with worse outcomes. Therefore, frailty score should be evaluated for elderly CCS patients as a prognostic marker.
Keywords
- Aging
- Canada
- Confidence Intervals
- Death
- Frail Elderly
- Frailty
- Heart
- Multivariate Analysis
- Prognosis
- Risk Factors
Childhood cancer survivors (CCS) demonstrate features of premature aging in a multitude of organ systems. The aim of this pilot study is to determine the presence of premature ocular aging features in CCS, specifically childhood acute lymphoblastic leukemia (ALL) survivors. This prospective case-control study was conducted over a period of 21 months, starting July 2015 till March 2017. A total of 59 childhood ALL survivors who attended the Paediatric Oncology Clinic of University Malaya Medical Centre (UMMC) and 48 age, race, and gender-matched controls went through a series of ocular examinations and tests. Inclusion criteria used to recruit survivors were age above 16 years, history of ALL in childhood, completion of treatment for ALL, and a remission period of at least 5 years. Patients with ocular disease and those who received hematopoietic stem cell transplantation were excluded. The parameters measured were visual acuity, amplitude of accommodation, pupil cycle time (PCT), and tear break-up time (TBUT). Survivors of childhood ALL demonstrated significant differences in amplitude of accommodation, PCT, and TBUT compared to age-matched controls. Survivors had a lower median (interquartile range [IQR]) amplitude of accommodation compared to controls (11.0 D [9.0-13.0] vs. 12.0 D [10.5-15]; [i]p[/i] = 0.045). Survivors also showed a longer median (IQR) PCT in comparison to controls (931.00 mseconds (857.00-1063.00) vs. 875.50 mseconds (825.75-966.00); [i]p[/i] = 0.024). In addition, median (IQR) TBUT was worse in survivors in comparison to the control group (9 seconds [6-13] vs. 11 seconds [10-15]; [i]p[/i] = 0.001). Survivors of childhood ALL demonstrate premature ocular aging features compared to age-matched controls. Thus, survivors may benefit from having ocular examinations as part of their routine late-effects screening to detect age-related ocular morbidities early in its course.
Keywords
- acute lymphoblastic leukemia survivors
- childhood cancer survivors
- ocular changes
- premature ocular aging
The cognitive trajectories in normal aging may be affected by medial temporal atrophy (MTA) and amyloid burden, as well as vascular pathologies such as cortical microbleeds (CMB) and white matter hyperintensities (WMH). We addressed here the role of imaging markers in their prediction in a real-world situation. We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, MTA estimated with the Schelten's scale, number of CMB, and WMH evaluated with the Fazekas score at inclusion and follow-up, visual rating of amyloid PET and glucose hypometabolism at follow-up, and APOE genotyping. Regression models were built to explore the association between the continuous cognitive score (CCS) and imaging parameters. The number of strictly lobar CMB at baseline (4 or more) was related to a 5.5-fold increase of the risk of cognitive decrement. This association persisted in multivariable models explaining 10.6% of the CCS decrease variance. MTA, and Fazekas score at baseline and amyloid positivity or abnormal FDG PET, were not related to the cognitive outcome. The increase of right MTA at follow-up was the only correlate of CCS decrease both in univariate and multivariable models explaining 9.2% of its variance. The present data show that the accumulation of more than four CMB is associated with significant cognitive decrement over time in highly educated elderly persons. They also reveal that the progressive deterioration of cognitive performance within the age-adjusted norms is also related to the increase of visually assessed MTA.
Keywords
- Atrophy
- cognition
- imaging markers
- medial temporal lobe
- microbleeds
- normal aging
Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions. We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL. There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele. The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.
MeSH Terms
- Aged
- Aged, 80 and over
- Amyloid beta-Peptides
- Apolipoprotein E4
- Brain
- Cognitive Aging
- Female
- Hippocampus
- Humans
- Longitudinal Studies
- Magnetic Resonance Imaging
- Male
- Positron-Emission Tomography
Keywords
- APOE
- Aging
- Amyloid
- Hippocampus
Amyloid imaging, gray matter (GM) morphometry and diffusion tensor imaging (DTI) have all been used as predictive biomarkers in dementia. Our objective was to define the imaging profile of healthy elderly controls as a function of their cognitive trajectories and explore whether amyloid burden and white matter (WM) microstructure changes are associated with subtle decrement of neuropsychological performances in old age. We performed a 4.5-year longitudinal study in 133 elderly individuals who underwent cognitive testing at inclusion and follow-up, amyloid PET, MRI including DTI sequences at inclusion, and APOE epsilon 4 genotyping. All cases were assessed using a continuous cognitive score (CCS) taking into account the global evolution of neuropsychological performances. Data processing included region of interest analysis of amyloid PET analysis, GM densities and tract-based spatial statistics (TBSS)-DTI. Regression models were built to explore the association between the CCS and imaging parameters controlling for significant demographic and clinical covariates. Amyloid uptake was not related to the cognitive outcome. In contrast, GM densities in bilateral hippocampus were associated with worst CCS at follow-up. In addition, radial and axial diffusivities in left hippocampus were negatively associated with CCS. Amyloid load was associated with decreased VBM and increased radial and axial diffusivity in the same area. These associations persisted when adjusting for gender and APOE4 genotype. Importantly, they were absent in amygdala and neocortical areas studied. The progressive decrement of neuropsychological performances in normal aging is associated with volume loss and WM microstructure changes in hippocampus long before the emergence of clinically overt symptoms. Higher amyloid load in hippocampus is compatible with cognitive preservation in cases with better preservation of GM densities and WM microstructure in this area.
Keywords
- APOE genotyping
- amyloid deposition
- magnetic resonance imaging
- normal aging
- positron emission tomography
Osteoporosis and coronary heart disease (CHD) are very common conditions among elderly people, and both represent a public health concern due to their prognostic consequences. Osteoporosis and CHD share many risk factors and pathophysiological mechanisms, such as calcification pathways. Clinical evidence associates lower bone mass with cardiovascular diseases and endothelial dysfunction. Hence, this study aims to investigate whether bone mass density is associated with subclinical atherosclerosis and/or endothelial dysfunction in the very elderly. We performed a cross-sectional study of cohort enrolled individuals, ages 80 years or older (n = 208), who had never manifested cardiovascular diseases. Medical evaluation, blood tests, flow-mediated dilation (FMD), carotid intimal-media thickness (IMT), Dual Energy X-ray Absorptiometry (DEXA) and Coronary Calcium Score (CCS) were obtained. Odds Ratio (OR) was calculated by multivariate logistic regression models using CCS, FMD and IMT categories. Adjustments for covariates were done. Overall bone mass was independently and inversely associated with CCS categories [OR:1.68(1.16-8.85); p = 0.024] and IMT categories [OR:2.97(1.11-7.90); p = 0.030]. Conversely, overall bone mass was independent and directly associated with FMD categories [OR:2.73(1.36-70.39); p = 0.023]. This study indicates that overall bone mass is independently and inversely associated with subclinical atherosclerosis, endothelial dysfunction and thickness of carotid in the very elderly.
Keywords
- Aging
- Endothelial dysfunction
- Osteoporosis
- Subclinical atherosclerosis
Human diploid fibroblasts (HDFs) cultured in vitro have limited capacity to proliferate after population doubling is repeated several times, and they enter into a state known as replicative senescence or cellular senescence. This study aimed to investigate the effect of Chlorella vulgaris on the replicative senescence of HDFs by determining the expression of senescence-associated genes. Young and senescent HDFs were divided into untreated control and C. vulgaris-treated groups. A senescence-associated gene transcription analysis was carried out with qRT-PCR. Treatment of young HDFs with C. vulgaris reduced the expression of SOD1, CAT and CCS (p < 0.05). In addition, the expression of the SOD2 gene was increased with C. vulgaris treatment in young, pre-senescent and senescent HDFs (p < 0.05). Treatment of senescent HDFs with C. vulgaris resulted in the downregulation of TP53 gene expression. The expression of the [[CDKN2A]] gene was significantly decreased upon C. vulgaris treatment in young and senescent HDFs. C. vulgaris treatment was also found to significantly upregulate the expression of the MAPK14 gene in pre-senescent HDFs. In addition, the expression of MAPK14 was significantly upregulated compared to that in the untreated senescent HDFs (p < 0.05). In summary, the expression of senescence-associated genes related to antioxidants and the insulin/insulin-like growth factor-1 signalling, DNA damage-associated signalling, cell differentiation and cell proliferation pathways was modulated by C. vulgaris during replicative senescence of human diploid fibroblasts.
MeSH Terms
- Antioxidants
- Catalase
- Cell Differentiation
- Cell Proliferation
- Cells, Cultured
- Cellular Senescence
- Chlorella vulgaris
- DNA Damage
- Diploidy
- Fibroblasts
- Gene Expression
- Genes, p53
- Humans
- Male
- Mitogen-Activated Protein Kinase 14
- Molecular Chaperones
- Primary Cell Culture
- Signal Transduction
- Superoxide Dismutase
- Superoxide Dismutase-1
Keywords
- Chlorella vulgaris
- Fibroblasts
- Replicative senescence
- Senescence-associated genes
Hypertensive disorders of pregnancy (HDP) comprise an independent, sex-specific risk factor for cardiovascular disease (CVD) in women. This study examined the utility of CVD risk models proposed in the 2016 Canadian Cardiovascular Society (CCS) lipid guidelines to identify women requiring further screening or lipid treatment following HDP. Using data collected from the postpartum Maternal Health Clinic (MHC) at Kingston General Hospital in Kingston, Ontario and the Preeclampsia New Emerging Team (PE-NET) cohort study, the study investigators used the models recommended by the CCS guidelines and the cardiometabolic model of life expectancy in each cohort to estimate CVD risk in women after HDP. (Canadian Task Force Classification II-2). Using the 10-Year Modified Framingham Risk Score, all women were classified by the 2016 CCS Guidelines as low risk, requiring no follow-up. The 30-Year and Lifetime Risk Scores resulted in significant reclassification of women at risk in the PE-NET control and HDP groups (P < 0.001 and P < 0.0001, respectively); 49.2% of women with HDP were classified as high risk, requiring follow-up, compared with 14.3% of control subjects. Using the cardiometabolic model, median life expectancy was significantly lower and expected onset of CVD was earlier in the HDP group compared with the control group (P < 0.0001). The 2016 CCS lipid guidelines' risk classification recommendations significantly underestimated lifelong CVD risk in the HDP group compared with the control group. Women with HDP also had a significant decrease in cardiometabolic life expectancy and an earlier predicted age at onset of CVD. Early primary prevention in this at-risk population may improve CVD outcomes and reduce the future burden on the health care system.
MeSH Terms
- Adult
- Age of Onset
- Body Mass Index
- Cardiovascular Diseases
- Female
- Follow-Up Studies
- Humans
- Hyperlipidemias
- Hypertension, Pregnancy-Induced
- Life Expectancy
- Pregnancy
- Primary Prevention
- Prospective Studies
- Risk Assessment
- Risk Factors
Keywords
- Pregnancy-induced hypertension
- cardiovascular diseases
- pregnancy complications
Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory diseases in cancer survivors. To test this hypothesis, we established the epigenetic and transcriptomic profiles of immune cells from 44 childhood cancer survivors (CCS, > 16 years old) on full remission (> 5 years) who had received chemotherapy alone or in combination with total body irradiation (TBI) and hematopoietic stem cell transplant (HSCT). We found that more than 10 years post-treatment, CCS treated with TBI/HSCT showed an altered DNA methylation signature in T cell, particularly at genes controlling immune and inflammatory processes and oxidative stress. DNA methylation remodeling in T cell was partially associated with chronic expression changes of nearby genes, increased frequency of type 1 cytokine-producing T cell, elevated systemic levels of these cytokines, and over-activation of related signaling pathways. Survivors exposed to TBI/HSCT were further characterized by an Epigenetic-Aging-Signature of T cell consistent with accelerated epigenetic aging. To investigate the potential contribution of irradiation to these changes, we established two cell culture models. We identified that radiation partially recapitulated the immune changes observed in survivors through a bystander effect that could be mediated by circulating factors. Cancer treatments, in particular TBI/HSCT, are associated with long-term immune disturbances. We propose that epigenetic remodeling of immune cells following cancer therapy augments inflammatory- and age-related diseases, including metabolic complications, in childhood cancer survivors.
MeSH Terms
- Adolescent
- Aging
- Cancer Survivors
- Child
- Child, Preschool
- DNA Methylation
- Epigenesis, Genetic
- Epigenomics
- Female
- Gene Expression Profiling
- Humans
- Infant
- Infant, Newborn
- Jurkat Cells
- Oxidative Stress
- T-Lymphocytes
Keywords
- DNA methylation
- Epigenetic aging
- T cell
- cancer survivors
- inflammation
Neurobiology is regulated by miRNA. Here circulating plasma miRNAs were assayed on a 754 miRNA OpenArray platform using 90 monozygotic elderly twins (73-95 year of age) and associated with mini mental state examination (MMSE) and a five-component cognitive score (CCS) in an explorative study. Both ordinary individual and twin-pair analyses were performed with level of cognitive scores. Candidate miRNAs were further associated with cognitive decline over 10 years using up to six repeated assessments. A total of 278 miRNAs were expressed in plasma from at least ten participants and 23 miRNAs were nominally associated (i.e., at an uncorrected p < 0.05) with CCS or MMSE in the paired analyses. Generally, elderly individuals with poor cognitive function had increase miRNA expression compared with equivalent individuals who performed better on the cognitive scale. Three miRNAs, miR-151a-3p, miR-212-3p and miR-1274b were associated with CCS both in the paired and the individual analysis. Four miRNAs found to be associated with CCS in cross-sectional analysis were also found to show an association in longitudinal analysis such that increase miRNA expression was associated with steeper cognitive decline. We propose a shared biological path underlies dementia and normative cognitive aging.
MeSH Terms
- Aged
- Aging
- Cognition
- Female
- Humans
- Male
- MicroRNAs
- Twins, Monozygotic
Cancer and its treatment in childhood and young adulthood can cause hypogonadism, leading to increased risk of long-term morbidity and mortality. The aim of this study was to evaluate the risk of presenting with biochemical signs of hypogonadism in testicular cancer survivors (TCS) and male childhood cancer survivors (CCS) in relation to the type of treatment given. Case-control study. Ninety-two TCS, 125 CCS (mean age 40 and median age 34 years, respectively; mean follow-up time 9.2 and 24 years, respectively) and a corresponding number of age-matched controls. Fasting morning blood samples were analysed for total testosterone (TT), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The odds ratios (OR) for hypogonadism, defined as primary, secondary, compensated or ongoing androgen replacement, were calculated for TCS and CCS and for subgroups defined by diagnosis and treatment. Hypogonadism was found in 26% of CCS and 36% of TCS, respectively (OR: 2.1, P = .025 and OR = 2.3, P = .021). Among CCS, the OR was further increased in those given testicular irradiation (OR = 28, P = .004). Radiotherapy other than cranial or testicular irradiation plus chemotherapy, or cranial irradiation without chemotherapy, associated also with increased ORs (OR = 3.7, P = .013, and OR = 4.4, P = .038, respectively). Among TCS, those receiving >4 cycles of cisplatin-based chemotherapy had OR = 17, P = .015. Biochemical signs of testosterone deficiency are recognized as markers of decreased life expectancy. Thus, the risk of hypogonadism in TCS and CCS should be recognized and emphasizes the need of long-term follow-up for these men.
MeSH Terms
- Adolescent
- Adult
- Cancer Survivors
- Case-Control Studies
- Child
- Cisplatin
- Humans
- Hypogonadism
- Life Expectancy
- Male
- Risk Factors
- Testicular Neoplasms
- Testosterone
- Young Adult
Keywords
- childhood cancer
- cytotoxic drugs
- hypogonadism
- radiotherapy
- testicular neoplasms
Tocotrienols have been known for their antioxidant properties besides their roles in cellular signalling, gene expression, immune response and apoptosis. This study aimed to determine the molecular mechanism of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs) by targeting the genes in senescence-associated signalling pathways. Real time quantitative PCR (qRT-PCR) was utilized to evaluate the expression of genes involved in these pathways. Our findings showed that SOD1 and CCS-1 were significantly down-regulated in pre-senescent cells while CCS-1 and PRDX6 were up-regulated in senescent cells (p<0.05). Treatment with TRF significantly down-regulated SOD1 in pre-senescent and senescent HDFs, up-regulated SOD2 in senescent cells, CAT in young HDFs, GPX1 in young and pre-senescent HDFs, and CCS-1 in young, pre-senescent and senescent HDFs (p<0.05). TRF treatment also caused up-regulation of FOXO3A in all age groups of cells (p<0.05). The expression of TP53, PAK2 and [[CDKN2A]] was significantly increased in senescent HDFs and treatment with TRF significantly down-regulated TP53 in senescent cells (p<0.05). MAPK14 was significantly up-regulated (p<0.05) in senescent HDFs while no changes was observed on the expression of JUN. TRF treatment, however, down-regulated MAPK14 in young and senescent cells and up-regulated JUN in young and pre-senescent HDFs (p<0.05). TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.
MeSH Terms
- Antioxidants
- Cell Differentiation
- Cell Proliferation
- Cells, Cultured
- Cellular Senescence
- DNA Damage
- Diploidy
- Down-Regulation
- Fibroblasts
- Genetic Markers
- Humans
- Insulins
- Real-Time Polymerase Chain Reaction
- Signal Transduction
- Tocotrienols
- Up-Regulation
Keywords
- Cellular senescence
- Genes expression
- Senescence-associated signalling pathways
- Tocotrienol-rich fraction
To evaluate contrast-color sensitivity (CCS) of central vision, contrast-frequency sensitivity (CFS) and dynamic visual acuity (DVA) in healthy people and patients with ischemic optic neuropathy (ION). The study was performed for 115 eyes with normal static visual acuity (1.0) in 111 healthy people; 25 patients (39 eyes) with acute anterior ION and 26 patients (26 eyes) with chronic ION. Assessment of static visual acuity and refraction as well as ophthalmoscopy of the eye fundus were performed. Based on the data analysis of CFS, DVA and photometry of CCS, the quantitative estimation of age-related changing in light sensitivity and changing sensitivity of ill and healthy eyes of patients with acute and chronic ION has been carried out. The differences between changing of these functional parameters are used for discussion of the role of age-related changes of visual system hemodynamics in decreasing of light sensitivity. The possibility of usig the data of light sensitivity decreasing in the early diagnostics of visual system ischemic impairment is discussed.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aging
- Color Vision
- Female
- Hemodynamics
- Humans
- Male
- Middle Aged
- Ophthalmoscopy
- Optic Neuropathy, Ischemic
- Photometry
- Photophobia
- Refraction, Ocular
- Visual Acuity
- Young Adult
Frailty, a phenotype reported among 9.9% of individuals 65 years old and older (9.6% of women; 5.2% of men), has not been assessed among adult childhood cancer survivors (CCS). We estimated the prevalence of frailty and examined associations with morbidity and mortality. Participants included 1,922 CCS at least 10 years from original cancer diagnosis (men, 50.3%; mean age, 33.6 ± 8.1 years) and a comparison population of 341 participants without cancer histories. Prefrailty and frailty were defined as two and ≥ three of the following conditions: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Morbidity was defined as grade 3 to 4 chronic conditions (Common Terminology Criteria for Adverse Events version 4.0). Fisher's exact tests were used to compare, by frailty status, percentages of those with morbidity. In a subset of 162 CCS who returned for a second visit, Poisson regression was used to evaluate associations between frailty and new onset morbidity. Cox proportional hazards regression was used to evaluate associations between frailty and death. The prevalence of prefrailty and frailty were 31.5% and 13.1% among women and 12.9% and 2.7% among men, respectively, with prevalence increasing with age. Frail CCS were more likely than nonfrail survivors to have a chronic condition (82.1% v 73.8%). In models adjusted for existing chronic conditions, baseline frailty was associated with risk of death (hazard ratio, 2.6; 95% CI, 1.2 to 6.2) and chronic condition onset (relative risk, 2.2; 95% CI, 1.2 to 4.2). The prevalence of frailty among young adult CCS is similar to that among adults 65 years old and older, suggesting accelerated aging.
MeSH Terms
- Adolescent
- Adult
- Aging
- Child
- Chronic Disease
- Cohort Studies
- Energy Metabolism
- Fatigue
- Female
- Humans
- Male
- Middle Aged
- Morbidity
- Muscle Weakness
- Neoplasms
- Poisson Distribution
- Prevalence
- Proportional Hazards Models
- Survivors
- United States
- Walking
- Young Adult
Survival rates among childhood cancer survivors (CCS) have enormously increased in the last 40 years. However, this improvement has been achieved at the expense of serious late effects that frequently involve the endocrine system. To evaluate the cumulative incidence of endocrine diseases in a cohort of long-term CCS. We analyzed the clinical data of 310 adults, followed for a median time of 16.0 years after the first cancer diagnosis. The monitoring protocols applied to each patient were personalized on the basis of cancer diagnosis and previous treatments, according to the Children's Oncology Group guidelines. The cumulative incidence of endocrine late effects steadily increased over time. At the last follow-up visit available, 48.46% of females and 62.78% of males were affected by at least one endocrine disease. The most common disorders were gonadal dysfunction, primary hypothyroidism, and GH deficiency (GHD). The main risk factors for endocrine disease were male sex (hazard ratio (HR)=1.45, 95% confidence interval (95% CI) 1.05-1.99), radiotherapy (HR=1.91, 95% CI 1.28-2.84), hematopoietic stem cells transplantation (HR=3.11, 95% CI 2.23-4.34), and older age at cancer diagnosis (HR=1.89, 95% CI 1.25-2.85). Male sex was associated with a higher risk of gonadal disorders, whereas radiotherapy specifically increased the risk of GHD and thyroid dysfunction. Endocrine disorders among CCS have a high prevalence and increase over time. Thus, endocrinologists need to cope with an increasing demand for health care in a field that is still little developed and that, in perspective, could also be extended to some selected types of adult cancer survivors.
MeSH Terms
- Adult
- Aging
- Cohort Studies
- Endocrine System Diseases
- Female
- Follow-Up Studies
- Humans
- Incidence
- Italy
- Male
- Neoplasms
- Outpatient Clinics, Hospital
- Practice Guidelines as Topic
- Prevalence
- Proportional Hazards Models
- Radiation Injuries
- Retrospective Studies
- Risk Factors
- Sex Factors
- Survivors
Histopathological features of the cardiac conducting system (CCS) in the Turkish population have not been investigated previously. We examined CCS of 202 autopsy heart specimens dissected between the years 2004 and 2005 in Bursa Forensic Medicine Institution. Of the 202 cases from all age groups, 154 were males and 48 were females. In our cases, an increase in fibrous and adipose tissue concordant with age, indicating an age-related nature, were detected. Fibrous and fatty tissue infiltration appeared at the age of 35. Fatty infiltration started between the ages 20 and 34 years at the sinoatrial node (SAN). There was no relationship between obesity and fatty tissue infiltration in SAN and atrioventricular node (AVN). In 4 cases calcification and in 19 cases inflammation was observed. Amyloid accumulation was not present. In 7 cases myocardial infarction not involving CCS was seen. In 1 case fibroelastoma was detected. In the Turkish population age-related fibrosis and fatty infiltration in CCS appeared at the age of 35 years and increased with age. Fatty infiltration in the SAN started at a younger age than that reported in the literature. In cases where the cause of death could not be determined, we could not detect lethal pathological features. However, we think that examination of the CCS will improve the quality of autopsy diagnosis.
MeSH Terms
- Adipose Tissue
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Atrioventricular Node
- Autopsy
- Calcinosis
- Child
- Child, Preschool
- Female
- Fibrosis
- Humans
- Male
- Middle Aged
- Sinoatrial Node
- Turkey
A sensitive and reliable biomarker has yet to be identified for marginal copper deficiency in humans. The need for such a biomarker is critical, because increased cases of human copper deficiency evolve following bariatric surgery and other secondary factors besides diet. Four experiments were devised to induce marginal copper deficiency through copper-deficient (CuD) diets (5 wk for mice and 4 wk for rats). In Expt. 1 and 2, male postweanling mice were raised in either solid-bottom plastic cages (Expt. 1) or stainless steel hanging cages (Expt. 2) and compared. Postweanling rats (Expt. 3) and adult mice (Expt. 4) were also studied using stainless steel cages. Copper-adequate controls were fed a semipurified diet containing 9 mg Cu/kg. CuD rats exhibited the most severe changes in biomarkers due to copper limitation, including major reductions in plasma ceruloplasmin (Cp) and erythrocyte superoxide dismutase (Sod1) and augmentation in copper chaperone for Sod1 (CCS). The CuD mice in Expt. 2 were more deficient than the CuD mice in Expt. 1, likely due to coprophagia differences. In fact, the CuD mice in Expt. 1 had unaltered Sod1 or Cp levels. Importantly though, these marginally deficient mice and CuD adult mice that had no changes in Cp activity or liver copper level had robust augmentation of CCS. Erythrocyte CCS was the only consistent biomarker to change in copper deficiency for all dietary groups, suggesting that CCS may be an excellent biomarker for human confirmation of marginal copper deficiency.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Ceruloplasmin
- Copper
- Diet
- Erythrocytes
- Gene Expression Regulation
- Liver
- Male
- Mice
- Molecular Chaperones
- Rats
- Rats, Sprague-Dawley
To investigate stapled transanal rectal resection (STARR) procedures as surgical techniques for obstructed defecation syndrome (ODS) by analyzing specimen evaluation, anorectal manometry, endoanal ultrasonography and clinical follow-up. From January to December 2007, we have treated 30 patients. Fifteen treated with double PPH-01 staplers and 15 treated using new CCS 30 contour. Resected specimen were measured with respect to average surface and volume. All patients have been evaluated at 24 mo with clinical examination, anorectal manometry and endoanal ultrasonography. Average surface in the CCS 30 group was 54.5 cm² statistically different when compared to the STARR group (36.92 cm²). The average volume in the CCS 30 group was 29.8 cc, while in the PPH-01 it was 23.8 cc and difference was statistically significant. The mean hospital stay in the CCS 30 group was 3.1 d, while in the PPH-01 group the median hospital stay was 3.4 d. As regards the long-term follow-up, an overall satisfactory rate of 83.3% (25/30) was achieved. Endoanal ultrasonography performed 1 year following surgery was considered normal in both of the studied groups. Mean resting pressure was higher than the preoperative value (67.2 mmHg in the STARR group and 65.7 mmHg in the CCS30 group vs 54.7 mmHg and 55.3 mmHg, respectively). Resting and squeezing pressures were lower in those patients not satisfied, but data are not statistically significant. The STARR procedure with two PPH-01 is a safe surgical procedure to correct ODS. The new Contour CCS 30 could help to increase the amount of the resected tissue without differences in early complications, post-operative pain and in hospital stay compared to the STARR with two PPH-01 technique.
MeSH Terms
- Defecation
- Digestive System Surgical Procedures
- Female
- Follow-Up Studies
- Humans
- Longevity
- Manometry
- Middle Aged
- Pain, Postoperative
- Prevalence
- Rectal Diseases
- Rectum
- Retrospective Studies
- Surgical Stapling
- Treatment Outcome
- Ultrasonography
Keywords
- Contour CCS
- Obstructed defecation
- Stapled transanal rectal resection
Copper,zinc superoxide dismutase (SOD1) in mammals is activated principally via a copper chaperone (CCS) and to a lesser degree by a CCS-independent pathway of unknown nature. In this study, we have characterized the requirement for CCS in activating SOD1 from Drosophila. A CCS-null mutant (Ccs(n)(29)(E)) of Drosophila was created and found to phenotypically resemble Drosophila SOD1-null mutants in terms of reduced adult life span, hypersensitivity to oxidative stress, and loss of cytosolic aconitase activity. However, the phenotypes of CCS-null flies were less severe, consistent with some CCS-independent activation of Drosophila SOD1 (dSOD1). Yet SOD1 activity was not detectable in Ccs(n)(29)(E) flies, due largely to a striking loss of SOD1 protein. In contrast, human SOD1 expressed in CCS-null flies is robustly active and rescues the deficits in adult life span and sensitivity to oxidative stress. The dependence of dSOD1 on CCS was also observed in a yeast expression system where the dSOD1 polypeptide exhibited unusual instability in CCS-null (ccs1Delta) yeast. The residual dSOD1 polypeptide in ccs1Delta yeast was nevertheless active, consistent with CCS-independent activation. Stability of dSOD1 in ccs1Delta cells was readily restored by expression of either yeast or Drosophila CCS, and this required copper insertion into the enzyme. The yeast expression system also revealed some species specificity for CCS. Yeast SOD1 exhibits preference for yeast CCS over Drosophila CCS, whereas dSOD1 is fully activated with either CCS molecule. Such variation in mechanisms of copper activation of SOD1 could reflect evolutionary responses to unique oxygen and/or copper environments faced by divergent species.
MeSH Terms
- Animals
- Animals, Genetically Modified
- Drosophila Proteins
- Drosophila melanogaster
- Enzyme Stability
- Evolution, Molecular
- Gene Expression
- Humans
- Longevity
- Molecular Chaperones
- Oxidative Stress
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins
- Species Specificity
- Superoxide Dismutase
- Superoxide Dismutase-1
Experimental and clinical investigations suggest that blockade of Na( )/H( ) exchange (NHE) with cariporide provides functional protection during ischemia and reperfusion in mature hearts. The benefit on aged human myocardium is unknown. Therefore, the impact of cardiac aging on cardio-protection by cariporide after prolonged ischemia was studied in isolated myocardium of adult (<or=55 years), old (56-69 years), and very old (>or=70 years) patients with coronary artery disease. Isolated atrial trabeculae were subjected to 30 min of simulated ischemia with and without cariporide, and early post-ischemic contractile recovery was determined. During the reoxygenation period, trabeculae of adults, but not those of old or very old patients, improved after treatment with cariporide. After 90 min of reoxygenation, cariporide-treated adult trabeculae developed 41 /-5% of their pre-ischemic force (non-treated control group, 27 /-5%; P<0.05), and old trabeculae recovered to 41 /-7% (control, 25 /-6%), whereas very old trabeculae recovered to only 26 /-2% (control, 28 /-6%). Trabeculae of all patients <70 years with CCS stage I-II angina pectoris recovered well (45 /-6%; control, 22 /-5%; P<0.01), which was in contrast to patients with CCS stage III (34 /-4%; control, 31 /-5%). Subsequent immunoblot analyses indicated no concomitant alterations in the myocardial NHE1 protein level depending on age. In very old myocardium, higher levels of active p38MAPK in atrial trabeculae after ischemia pointed at an increased cellular stress, which was even more pronounced after post-ischemic reperfusion. In summary, cariporide is protective against ischemia-reperfusion injury in mature human hearts but has no benefit on the post-ischemic functional recovery of the aging myocardium.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Anti-Arrhythmia Agents
- Cardiotonic Agents
- Cation Transport Proteins
- Drug Evaluation, Preclinical
- Guanidines
- Heart
- Heart Atria
- Humans
- Ischemic Preconditioning, Myocardial
- Middle Aged
- Myocardial Contraction
- Myocardial Reperfusion Injury
- Organ Culture Techniques
- Sodium-Hydrogen Exchanger 1
- Sodium-Hydrogen Exchangers
- Sulfones
To alleviate traffic congestion in Central London, the Mayor introduced the Congestion Charging Scheme (CCS) in February 2003. We modelled the impact of the CCS on levels of traffic pollutants, life expectancy and socioeconomic inequalities. Annual average NO(2) and PM(10) were modelled using an emission-dispersion model. We assumed the meteorology and vehicle fleet remained constant during the pre- and post-CCS periods to isolate changes due to traffic flow. Air pollution concentrations were linked to small area socioeconomic, population and mortality data. Associated changes in life expectancy were predicted using life table analysis and exposure-response coefficients from the literature. Before the introduction of the CCS, annual average NO(2) was 39.9 microg/m(3) and PM(10) was 26.2 microg/m(3) across Greater London. Concentrations were 54.7 microg/m(3) for NO(2) and 30.3 microg/m(3) for PM(10) among census wards within or adjacent to the charging zone. Absolute and relative reductions in concentrations following the introduction of the CCS were greater among charging zone wards compared to remaining wards. Predicted benefits in the charging zone wards were 183 years of life per 100,000 population compared to 18 years among the remaining wards. In London overall, 1888 years of life were gained. More deprived areas had higher air pollution concentrations; these areas also experienced greater air pollution reductions and mortality benefits compared to the least deprived areas. The CCS, a localised scheme targeting traffic congestion, appears to have modest benefit on air pollution levels and associated life expectancy. Greater reductions in air pollution in more deprived areas are likely to make a small contribution to reducing socioeconomic inequalities in air pollution impacts.
MeSH Terms
- Air Pollutants
- Air Pollution
- Automobiles
- Environmental Exposure
- Environmental Health
- Humans
- Life Expectancy
- London
- Nitrogen Dioxide
- Particulate Matter
- Socioeconomic Factors
- Urban Health
- Vehicle Emissions
Cellular and functional changes secondary to aging could impair myocardial tolerance to ischemia and affect the heart's response to ischemic preconditioning. We investigated the impact of cardiac aging on preconditioning in right atrial trabeculae of adult patients (< or = 55 years) and senescent patients (> or = 70 years) with coronary artery disease. Specimens were subjected to 30 minutes of simulated ischemia (hypoxic substrate-free superfusion) with and without 5 minutes of ischemic pretreatment. Postischemic contractile recovery was measured and expressed as percentage of base line force values. During the reoxygenation period, trabeculae of adult patients but not those of senescent patients improved after ischemic preconditioning. After 40 minutes of reoxygenation, preconditioned adult trabeculae developed 57% /- 5% of their preischemic force (nonpreconditioned control 44% /- 5%, p < 0.01), senescent trabeculae recovered to 44% /- 4% (control 45% /- 3%). Especially myocardium from adult patients with Canadian Cardiovascular Society (CCS) stage III angina pectoris treated with ACE inhibitors recovered well (70% /- 7%; control 50% /- 8%, p < 0.01), contrasting with trabeculae from patients with CCS stage II angina (44% /- 5%; control 40% /- 10%). Ischemia-inducible Hsp70 (human heat shock protein) was additionally measured after reoxygenation. Total Hsp70 mRNA was elevated in preconditioned myocardium along with its contractile recovery (r = 0.33, p = 0.07). Because the control transcription, analyzing 18S rRNA and beta-actin, was reduced by ischemia but recovered in preconditioned trabeculae, relative Hsp70 mRNA was not altered. Our data indicate that ischemic preconditioning has no beneficial effect on the postischemic functional recovery of senescent human myocardium.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Base Sequence
- Coronary Disease
- Culture Techniques
- Elasticity
- Female
- Heart Arrest, Induced
- Humans
- Ischemic Preconditioning, Myocardial
- Male
- Middle Aged
- Molecular Sequence Data
- Myocardial Contraction
- Myocardial Reperfusion
- Myocardial Reperfusion Injury
- Myocardium
- Probability
- RNA, Messenger
- Reference Values
- Reverse Transcriptase Polymerase Chain Reaction
- Risk Assessment
Copper-mediated oxidative damage is proposed to play a critical role in the pathogenesis of Cu/Zn superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (FALS). We tested this hypothesis by ablating the gene encoding the copper chaperone for SOD1 (CCS) in a series of FALS-linked SOD1 mutant mice. Metabolic 64Cu labeling in SOD1-mutant mice lacking the CCS showed that the incorporation of copper into mutant SOD1 was significantly diminished in the absence of CCS. Motor neurons in CCS-/- mice showed increased rate of death after facial nerve axotomy, a response documented for SOD1-/- mice. Thus, CCS is necessary for the efficient incorporation of copper into SOD1 in motor neurons. Although the absence of CCS led to a significant reduction in the amount of copper-loaded mutant SOD1, however, it did not modify the onset and progression of motor neuron disease in SOD1-mutant mice. Hence, CCS-dependent copper loading of mutant SOD1 plays no role in the pathogenesis of motor neuron disease in these mouse models.
MeSH Terms
- Amyotrophic Lateral Sclerosis
- Animals
- Axotomy
- Copper
- Humans
- Life Expectancy
- Mice
- Mice, Knockout
- Molecular Chaperones
- Motor Neuron Disease
- Motor Neurons
- Mutation
- Spinal Cord
- Superoxide Dismutase
- Superoxide Dismutase-1
- Survival Rate
- Tissue Extracts
{{medline-entry |title=Comparison of physical quality and composition of eggs from historic strains of single comb White Leghorn chickens. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10230915 |abstract=The effect of long-term genetic selection on physical quality and composition of eggs was determined by analyzing eggs acquired from Agriculture Canada: Ottawa Control Strain 5 (CS5) from a 1950 base population, 7 (CS7) from a 1958 population and 10 (CS10) from a 1972 population. Eggs from the H