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Protein ecdysoneless homolog (Human suppressor of GCR two) (hSGT1)

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Outcome of Descemet Membrane Endothelial Keratoplasty Using Corneas from Donors ≥80 Years of Age.

The purpose of this study was to investigate whether corneas from donors ≥80 years old are suitable for Descemet membrane endothelial keratoplasty (DMEK). Retrospective, comparative, interventional case series. Records of 1,765 consecutive DMEKs were reviewed and matched with corresponding donor tissue data. Older donors (≥80 years of age) were compared to younger donors (<80 years). Outcome measurements in DMEK recipients included best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), central corneal thickness (CCT) at 3 and 6 months and at 1, 2, and 3 years' follow-up and re-bubbling rates. Of 1,748 DMEKs, 284 (16.2%) were performed with older donor lamellae (mean donor age, 83.96 ± 3.19 years; range, 80-94 years) and 1,464 (83.7%) with younger donor tissue (mean donor age, 65.27 ± 9.57 years; range, 17-79). BSCVA results were comparable for all postoperative time points. CCT results for younger donors were more favorable in the early postoperative course (P < 0.001 at 6 months; and P < 0.001 at 1 year), whereas mid-term results were comparable in both groups. ECD values were significantly higher in donors <80 years of age preoperatively and during the first 2 postoperative years (P ≤ 0.024). Overall re-bubbling rates were comparable in both groups. Older donors, ≥80 to 94 years of age, seem to produce comparable mid-term functional results following DMEK surgery compared to younger donors. The use of corneas from donors aged ≥80 for DMEK surgery may therefore be a promising approach to counteract global donor shortage.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Cell Count
  • Cornea
  • Descemet Stripping Endothelial Keratoplasty
  • Donor Selection
  • Endothelium, Corneal
  • Female
  • Fuchs' Endothelial Dystrophy
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tissue Donors
  • Treatment Outcome
  • Visual Acuity
  • Young Adult


Relationship Between the Dose Administered, Target Tissue Dose, and Toxicity Level After Acute Oral Exposure to Bifenthrin and Tefluthrin in Young Adult Rats.

Most pyrethroid insecticides (PYRs) share a similar primary target site in mammals. However, the potency estimates of the lethal and sublethal effects of these compounds differ up to 103-fold. The aim of this study was to evaluate the relationship between the dose administered, the target tissue dose, and the effect of 2 highly toxic PYRs, tefluthrin (TEF; 0.1-9 mg/kg) and bifenthrin (BIF; 0.5-12 mg/kg), by using the oral route, a corn oil vehicle (1 ml/kg) and subcutaneous temperature (Tsc) monitoring assays in adult rats. The Tsc was determined at 30-min intervals for 5 h (TEF) or 4.5 h (BIF) after dosing. Rats were sacrificed at 6 h after dosing, and BIF and TEF concentrations were determined in blood (Bd), liver (Lv), and cerebellum (Cb) by using a GC-ECD system. The minimal effective dose of BIF (3 mg/kg) affecting Tsc was similar to that found in prior studies using other testing paradigms. Regarding TEF, a very steep relationship between the dose administered and toxicity was observed, with a near-threshold to low-effective range for Tsc at 0.1-6 mg/kg, and a near lethal syndrome at ≥ 7.5 mg/kg. At 6-7.5 mg/kg TEF, the Cb/Bd and Cb/Lv concentration ratios were both > 1. Conversely, for BIF, the Cb concentration was barely over the Bd concentration and the Cb/Lv concentration ratio remained < 1. Our results and previous findings call for more comprehensive consideration to establish the relevance of the distribution into target tissues and the tissue dosimetry for health risks through the exposure to PYRs in humans.

MeSH Terms

  • Administration, Oral
  • Aging
  • Animals
  • Body Temperature
  • Cerebellum
  • Cyclopropanes
  • Dose-Response Relationship, Drug
  • Hydrocarbons, Fluorinated
  • Liver
  • Male
  • Pyrethrins
  • Rats
  • Rats, Wistar
  • Tissue Distribution
  • Toxicokinetics

Keywords

  • acute effects
  • bifenthrin
  • body temperature
  • disposition
  • rat
  • tefluthrin


The occurrence and dynamics of polychlorinated hydrocarbons in roe deer ([i]Capreolus capreolus[/i]) in South-western Slovakia.

The goal of this study was to determined polychlorinated biphenyls (PCBs) and organochlorine pesticides in the depot fat of roe deer ([i]Capreolus capreolus[/i]) coming from south-western Slovakia. The mutual correlations of the organic pollutants were analyzed. The study included dichlorodiphenyltrichloroethane (DDT), hexachlorobenzen (HCB), alpha-hexachlorocyclohexane and beta-hexachlorocyclohexane (α   β-HCH), gamma-hexachlorocyclohexane (γ-HCH), and polychlorinated biphenyls (PCB-delor). The gas chromatograph with an electron capture detector ECD was used for analysis. The accumulations of organic pollutant in depot fat of roe deer were in following order: DDT > PCB-delor > α   β-HCH > HCB > γ-HCH. Among all pollutants, DDT was accumulated significantly in the highest level in the samples. The significantly higher content of DDT, HCB, α   β-HCH, and γ-HCH was detected in the adult animals when compared to the juveniles. Some strong positive correlations among pollutants, between HCB and DDT, α   β-HCH and HCB, α   β-HCH and HCB, between γ-HCH and other pollutants, and between PCB-delor and γ-HCH were found. Game animals are a part of human food chain and monitoring of the environment pollution by PCBs and other organic pollutants are worthy to study.

MeSH Terms

  • Adipose Tissue
  • Aging
  • Animals
  • Deer
  • Environmental Monitoring
  • Environmental Pollutants
  • Female
  • Humans
  • Hydrocarbons, Chlorinated
  • Male
  • Pesticides
  • Polychlorinated Biphenyls
  • Sex Factors
  • Slovakia

Keywords

  • Slovakia
  • depot fat
  • organic pollution
  • polychlorinated hydrocarbon
  • roe deer


Corneal thickness, endothelial cell density, and morphological and morphometric features of corneal endothelial cells in goats.

OBJECTIVE To determine corneal thickness (CT), endothelial cell density (ECD), and morphological and morphometric features of caprine eyes and to assess effects of aging on these variables. SAMPLE 27 healthy eyes of 19 Murciano-Granadina goats. PROCEDURES Goats were classified into 2 age groups (kids, 14 months old [14 eyes]; and adults, 7 to 10 years old [13 eyes]). The ECD and CT were calculated in the central cornea and 4 peripheral quadrants. Mean cell area (MCA), pleomorphism (percentage of hexagonal cells), and polymegathism were evaluated in the central cornea. RESULTS Median values for kids were determined for ECD (3,831 cells/mm ; inter-quartile [25th to 75th percentile] range [IQR], 3,669 to 4,011 cells/mm ), CT (608 μm; IQR, 573 to 655 μm), MCA (255 μm ; IQR, 243 to 272 μm ), pleomorphism (80.53%; IQR, 78.83% to 83.30%), and polymegathism (19; IQR, 18 to 22). Median values for adults were determined for ECD (2,101 cells/mm ; IQR, 1,966 to 2,251 cells/mm ), CT (706 μm; IQR, 670 to 730 μm), MCA (466 μm ; IQR, 425 to 507 μm ), pleomorphism (67.80%; IQR, 65.50% to 70.00%), and polymegathism (21; IQR, 15 to 26). Values differed significantly between the 2 groups for all variables, except polymegathism. For both groups, the dorsal and temporal quadrants were the thickest and thinnest, respectively. Ventral ECD was the lowest for both groups. CONCLUSIONS AND CLINICAL RELEVANCE ECD decreased with age, whereas MCA, pleomorphism, and CT increased. Moreover, differences among regions of the cornea indicated that the central cornea should not be considered as representative of the entire cornea.

MeSH Terms

  • Aging
  • Animals
  • Cell Count
  • Cornea
  • Endothelial Cells
  • Endothelium, Corneal
  • Goats
  • Reference Values


Endothelial cell density and characterization of corneal endothelial cells in the Tawny Owl (Strix aluco) using specular microscopy.

To determine endothelial cell density (ECD) and morphology and morphometry of corneal endothelial cells in the tawny owl (Strix aluco), as well as to report the effects of aging on these parameters. Twenty tawny owls were included in the study and classified into 2 groups according to their age: fledglings (<1 year old) and adults (>1 year old). Central corneal endothelium was studied by means of noncontact specular microscopy (Specular Microscope SP-2000P; Topcon, Tokyo, Japan), and results for ECD (cells/mm ), mean cell area ((MCA (μm )), polymegathism (CV), and pleomorphism (% hexagonal cells) were obtained. Results are described by median, interquartile range (25th, 75th percentiles), and absolute range for ECD, MCA, pleomorphism, and polymegathism. In addition, inferential analyses by Mann-Whitney U test were also performed. A two-tailed Type I error of 5% was established. Results in fledglings were as follows: ECD = 2864 cells/mm , MCA = 348 μm , % hexagonal cells = 72.75%, and CV = 21. Results in adults were as follows: ECD = 2602 cells/mm , MCA = 384 μm , % hexagonal cells = 78.83%, and CV = 16. No significant differences in ECD and MCA were seen between the groups (P > .05), although there were significant differences in % hexagonal cells and CV (P < .05). Tawny owls present a uniform endothelium in cell size and shape, although ECD and MCA differ greatly from other bird species. Differences in ECD and MCA could not be found between fledglings and adults probably because of the youth of adult specimens, although there were differences in pleomorphism and polymegathism.

MeSH Terms

  • Aging
  • Animals
  • Cell Count
  • Endothelium, Corneal
  • Microscopy
  • Strigiformes

Keywords

  • bird
  • cornea
  • endothelium
  • pleomorphism
  • raptor
  • specular microscopy


An autopsy case report: Differences in radiological images correlate with histology in Erdheim-Chester disease.

p16 activation caused by oncogenic mutations may represent oncogene-induced senescence (OIS), a protective mechanism against oncogenic events. However, OIS can contribute to tumor development via tissue remodeling in some tumors. Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, is one such tumor. Its clinical and histological features vary, making it difficult to diagnose. Herein, we describe an autopsy of an ECD patient. The patient underwent radiological examinations, including F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT), bone scintigraphy and CT. A biopsy from the lesion with the highest FDG accumulation confirmed the presence of foamy macrophages, a diagnostic clue for ECD. Based on this finding and the clinical features, ECD was diagnosed. However, the patient died from heart dysfunction. After the autopsy, each radiologically different site showed various histological findings regarding the morphology of macrophages, fibrosis, inflammation, and p16 expression. OIS-induced histological progression can cause certain changes observed in radiological images. In addition, in order to evaluate the increase in glucose metabolism, which can affect FDG accumulation, the expression of glucose transporter 1 and hexokinase II was also analyzed. Summarizing the radio-histological correlation can help further both the understanding and diagnosis of ECD.

MeSH Terms

  • Aged
  • Autopsy
  • Erdheim-Chester Disease
  • Humans
  • Male
  • Positron Emission Tomography Computed Tomography
  • Tomography, Emission-Computed

Keywords

  • 18F-fluorodeoxyglucose-positron emission tomography/computed tomography
  • Erdheim-Chester disease
  • autopsy
  • bone scintigraphy
  • hexokinase II
  • non-Langerhans cell histiocytosis
  • oncogene-induced senescence
  • radio-histological correlation


Community-based trials of mobile solutions for the detection and management of cognitive decline.

This study focused on the development and usability evaluation of EnCare diagnostics (ECD) and the brain fit plan (BFP) in healthy older adults, cognitively impaired and physically impaired individuals. ECD is proposed as a novel solution to cognitive assessment based on colour selection. BFP is a novel solution to personalised cognitive stimulation. The study consisted of two trials designed to evaluate the usability of the apps. Trial 1 involved 11 healthy older adults and four older adults with physical impairments who undertook ECD and mini-mental state examination (MMSE) once per month for 4 months with only those with physical impairments also completing the BFP daily. Trial 2 involved eight older adults diagnosed with early stage dementia who completed MMSE and ECD once per month for 6 months. In Trial 1, 10 out of 11 participants enjoyed the trial and managed the usability of the app easily. A 75% drop out was observed in response to the BFP with issues of dexterity and lack of understanding on how to use the technology being the main reasons for lack of compliance. Four out of eight participants completed Trial 2 with most of the participants having no usability issues. This usability study demonstrated that ECD is highly acceptable in both healthy older adults and those with early stage dementia when given the shorter versions to accommodate their diagnosis. The BFP was not suited to this population of participants.


Keywords

  • EnCare diagnostics
  • brain
  • brain fit plan
  • cognition
  • cognitive assessment
  • colour selection
  • early stage dementia
  • geriatrics
  • health care
  • healthy older adults
  • minimental state examination
  • patient diagnosis


Evaluating age-related change in lip somatosensation using somatosensory evoked magnetic fields.

Somatosensory evoked fields (SEFs) to electrical stimulation on the right and left sides of the lower lip were measured using magnetoencephalography and compared in the bilateral hemispheres of 31 healthy normal young and 29 healthy normal elderly subjects to evaluate age-related change in lip somatosensation. The initial peak of the response around 13 ms, designated as N13m, and the second peak of the response, designated as P21m, were investigated. The N13m response, which was detected in 22 of 62 hemispheres in young adults and 37 of 58 hemispheres in elderly adults, showed significantly prolonged latency and increased equivalent current dipole (ECD) moment in the elderly adults. The P21m response, which was detected in 56 of 62 hemispheres in young adults and in 52 of 58 hemispheres in elderly adults, showed longer peak latency in the elderly adults. No significant difference was found in the ECD moment for P21m, which suggests that aging affected the SEFs of the lip somatosensation, but the effects of aging on N13m and P21m differed. Prolonged latency and increased ECD moment of N13m might result from decreased peripheral conduction and increased cortical excitation system associated with aging. Therefore, the initial response component might be an objective parameter for investigating change in lip function with age.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Cerebral Cortex
  • Electric Stimulation
  • Evoked Potentials, Somatosensory
  • Female
  • Humans
  • Lip
  • Male
  • Middle Aged


A novel method for examining corneal endothelial cell morphology in infants.

Previous studies have suggested that central corneal endothelial cell density (ECD) decreases from 6,100 cells/mm in neonates to 3,100 cells/mm in 10-year-olds. Currently data on ECD in young children as well as the trend for ECD decrease during childhood is sparse because of the difficulty of examination using existing clinic-based specular microscopes. We developed a novel method of imaging young children intraoperatively with the goal of beginning to establish age-specific normative data for ECD and hexagonality of cells (%HEX). Children were imaged using our novel technique under general anesthesia or awake in clinic using a child-friendly technique. A total of 58 children were recruited (mean age, 5.50; range, 0.44-10.36). Our cohort displayed a significant linear decrease in ECD with age (r = -0.56, P < 0.001). No correlation was found between %HEX and age (r = -0.10, P = 0.48).

MeSH Terms

  • Aging
  • Anesthesia, General
  • Cell Count
  • Cell Shape
  • Child
  • Child, Preschool
  • Diagnostic Techniques, Ophthalmological
  • Endothelium, Corneal
  • Female
  • Humans
  • Infant
  • Male
  • Microscopy
  • Pilot Projects
  • Prospective Studies
  • Reference Values


Analyses of Factors Affecting Endothelial Cell Density in an Eye Bank Corneal Donor Database.

To analyze the factors affecting central corneal endothelial cell density (ECD) in an eye bank corneal donor database. The Lion's Eye Institute corneal donor database consisting of 18,665 donors (34,234 corneas) aged 20 years or older was analyzed. In particular, differences in the ECD based on age, sex, race, prior ocular surgery, a history of systemic diseases, and smoking were investigated. Furthermore, risk factors for donor cell count inadequacy (defined here as ECD less than 2000/mm) were identified. ECD decreased with age. Regarding race, the average ECD of African American donors was higher than those of white or Hispanic donors. A history of diabetes mellitus (DM) and ocular surgery were associated with a lower ECD. Donor medical history of hypertension, glaucoma, depression, dementia, Parkinson disease, hyper- or hypothyroidism, or smoking did not seem to affect the ECD. The risk factors for donor cell count inadequacy, based on binary logistic regression analyses were advanced age [65-74 years yielded an odds ratio of 17.8; confidence interval (CI), 10.6-29.8; P < 0.001; and 75-99 years yielded an odds ratio of 24.6 (CI, 14.5-41.61; P < 0.001) when compared with 20-34 years], cataract surgery (odds ratio, 4.3; CI, 4.0-4.8; P < 0.001), and DM (odds ratio, 1.2; CI, 1.1-1.3; P = 0.001). Age, race, ocular surgery (cataract and refractive), and DM seem to significantly affect donor corneal ECD. Of these variables, age, a history of cataract surgery, and DM were found to be the greatest risk factors for inadequate donor cell density (less than 2000/mm).

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Brain Diseases
  • Cell Count
  • Cornea
  • Corneal Endothelial Cell Loss
  • Databases, Factual
  • Depressive Disorder
  • Diabetes Mellitus
  • Endothelium, Corneal
  • Eye Banks
  • Female
  • Humans
  • Hypertension
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Thyroid Diseases
  • Tissue Donors
  • Young Adult


Morphological Abnormalities of Schlemm's Canal in Primary Open-Angle Glaucoma From the Aspect of Aging.

To evaluate morphological abnormalities of Schlemm's canal (SC) among primary open-angle glaucoma (POAG) patients with a family history of POAG (group A), those without a family history of POAG (group B), and patients with normal-tension glaucoma (group C) from the aspect of aging. A total of 160 trabeculectomy specimens from 133 POAG patients were processed for light microscopy using immunohistochemical staining of thrombomodulin and transmission electron microscopy. The following parameters were statistically evaluated: SC length, the percentage of the thrombomodulin-negative area (PTNA) of SC, and the inner-wall SC endothelial cell density (SC-ECD/100 μm). No significant differences in age were observed among the three groups (group A: 56.71 ± 14.83; group B: 58.13 ± 18.13; group C: 56.61 ± 9.78). Length of SC in the group A patients (198.70 ± 81.65 μm, n = 70 eyes) was significantly shorter than in group B (250.30 ± 70.83 μm, n = 67 eyes), and group C (277.70 ± 65.52 μm, n = 23 eyes) patients. A positive correlation of patient age and SC length was observed in group B (r = 0.45, P = 0.0013), but SC length in group A tended to decrease with aging (r = -0.22, P = 0.07). No significant difference in SC was found between group A and B patients before age 50 years (P = 0.30). Correlations between patient age and increase of PTNA (r = 0.38, P = 0.0013) and patient age and decrease of SC-ECD (r = -0.53, P = 3.95 × 10(-6)) were observed only in the group B cases. Our findings suggest that SC in group A may easily collapse during middle age, while SC in group B remains open and SC endothelial cells drop out at around middle age.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Cell Count
  • Disease Progression
  • Endothelium
  • Female
  • Follow-Up Studies
  • Glaucoma, Open-Angle
  • Humans
  • Male
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Retrospective Studies
  • Trabecular Meshwork
  • Trabeculectomy
  • Young Adult


[TEMPORAL ORDER DETERIORATION AND CIRCADIAN DISRUPTION WITH AGE].

The present review summarizes the current knowledge of gradual deterioration of temporal order in aging humans and other mammals. An obvious consequence of age-dependent circadian disruption in complex mechanisms is extra-circadian dissemination (ECD) that can be observed in overt rhythmic functions. ECD is a variance transposition from circadian to ultradian and infradian frequencies accompanied by a loss of interdaily phase stability. Moreover, heterochronic changes in central and peripheral tissue-specific cellular mechanisms are involved in circadian desychronization. A multitude of internal factors accounts for cumulative clockwork misalignment. Age-related circadian disruption is a consequence of weaker rhythm generation and the loss of proper orchestration on molecular, tissue and systemic levels, disabling their circadian synchrony and resonance.

MeSH Terms

  • Aging
  • Animals
  • Circadian Rhythm
  • Humans


Age-Dependent Changes of the Temporal Order--Causes and Treatment.

This review summarizes current knowledge on deteriorations in temporal order with advanced age. Changes of the overt rhythms will be described but also their putative causes and possible treatments of the disturbances. In aging animals and humans, all rhythm characteristics change. The most prominent changes are a decrease of circadian amplitude, leading to an extra-circadian dissemination (ECD), and a diminished ability to synchronize with the periodic environment. ECD is a shift from circadian to ultradian and infradian frequencies, accompanied by the loss of day-to-day phase stability. Responsiveness to photic and non-photic cues is decreased. As a consequence, both internal and external temporal order are disturbed not only under steady-state conditions but and even more markedly after changes in the periodic environment or following stressful events. Many of the changes seem to occur within the suprachiasmatic nucleus (SCN), the central circadian pacemaker, itself. The number of functioning neurons decreases with advancing age as does the coupling between them. Accordingly, the SCN generates a weaker and less stable circadian signal, insufficient to entrain peripheral oscillators properly or to regulate body functions rhythmically. However, age-dependent disturbances in peripheral organs must also be considered. These changes may occur at different ages, thus causing further internal desynchronization. Several possibilities exist with regard to treating circadian disruptions or at least minimizing their consequences for health and fitness and preventing sleep disturbances. Benefits of bright light, melatonin and other chronobiotics, physical activity, social contacts and regular feeding schedules in preserving the temporal order of aged organisms are discussed.

MeSH Terms

  • Aging
  • Animals
  • Cardiovascular Physiological Phenomena
  • Cardiovascular System
  • Circadian Rhythm
  • Humans
  • Suprachiasmatic Nucleus


Pathogenesis of endothelial cell dysfunction in chronic kidney disease: a retrospective and what the future may hold.

Cardiovascular complications dominate the landscape of chronic kidney diseases (CKD). Endothelial cell dysfunction (ECD) is a well-known culprit of cardiovascular morbidity and it develops in CKD with remarkable frequency. This brief overview of ECD in CKD scans two decades of studies performed in my laboratory, from genetic analyses to proteomic and metabolomics screens. I provide a detailed description of findings related to the premature senescence of endothelial cells, cell transition from the endothelial to mesenchymal phenotype, and stages of development of ECD. Clinical utility of some of these findings is illustrated with data on laser-Doppler flowmetry and imaging in patients with CKD. Some currently available and emerging therapeutic options for the management of ECD are briefly presented.


Keywords

  • Endothelial-to-mesenchymal  transition
  • Metabolomics
  • Premature senescence proteomics
  • Stress-induced


Specular microscopy to determine corneal endothelial cell morphology and morphometry in chinchillas (Chinchilla lanigera) in vivo.

The purpose of this study was to measure cell density, average area, and morphology of corneal endothelium of chinchillas in different age groups. The corneal endothelium was studied with a contact specular microscope. Thirty chinchillas (Chinchilla lanigera) were evaluated, and 30 male chinchillas were divided into three groups of 10 chinchillas each, by age: Group 1 (2-4-month-old), Group 2 (48-month-old), and Group 3 (10 years of age). Data are presented as endothelial cell density (ECD), average cell area, and pleomorphism. Endothelial cell density decreases and an increase in endothelial cell area and pleomorphism were observed with age, in the corneas of normal chinchillas. For Group 1 chinchillas, the mean cell density was 3.423 cells per mm(2) . The mean ECD for Group 2 chinchillas was 2.650 cells per mm(2) . The mean ECD for Group 3 chinchillas was 2.124 cells per mm(2) . The average area for Group 1 chinchillas was 350.5 μm(2) . The average area for Group 2 chinchillas was 442.15 μm(2) . The average area for Group 3 chinchillas was 583.64 μm(2) . The pleomorphism for Group 1 was 70.05%. The pleomorphism for Group 2 was 65.18%, and the pleomorphism for Group 3 was 62.28%. The results suggested that chinchilla corneal endothelium undergoes age-related changes. Moreover, with advancing age, the mean cell area increased and cell density decreased.

MeSH Terms

  • Aging
  • Animals
  • Chinchilla
  • Endothelium, Corneal
  • Female
  • Male
  • Microscopy

Keywords

  • cornea
  • density
  • endothelium
  • pleomorphism
  • rodent


Oncogene-induced senescence as a new mechanism of disease: the paradigm of erdheim-chester disease.

Erdheim-Chester disease (ECD) is a rare form of systemic histiocytosis characterized by the diffuse infiltration of tissues by lipid-laden macrophages. As the clinical course and prognosis are highly influenced by site of disease involvement, ECD course ranges from asymptomatic to life threatening, with a reported global 5-year mortality of 30-40%. Whether ECD is an inflammatory or clonal disease in its nature has long been debated. The disease is characterized by a network of pro-inflammatory cyto/chemokines responsible for the recruitment and activation of histiocytes into ECD lesions, similarly to what reported in Langerhans cell histiocytosis (LCH). Growing evidence supports a central role of the oncogenic BRAF(V600E) mutation in histiocytosis pathogenesis, and suggests oncogene-induced senescence (OIS), a major protective mechanism against oncogenic events characterized by cell-cycle arrest and the induction of pro-inflammatory molecules, as the possible link between the oncogenic mutation and the observed inflammation. Indeed, ECD recapitulates in vivo the molecular events associated with OIS, i.e., cell-cycle arrest and a potent local inflammatory response. Accordingly, the infiltration of different tissues by macrophages and the inflammatory local and systemic effects observed in ECD likely represent a drawback of OIS. Therefore, these findings delineate a new conception of OIS as a new pathogenic mechanism intrinsically responsible for disease development.


Keywords

  • BRAF kinases
  • Erdheim–Chester disease
  • histiocytosis
  • inflammation
  • macrophages
  • oncogene-induced senescence


Comparison of endothelial cell density of organ cultured corneas with cornea donor study.

Determination of the endothelial cell density (ECD) by eye banks is paramount in donor cornea qualification. Unbiased measurement avoids wastage and grafts with an increased risk of premature failure. Internal calibration of the counting method is essential, but external validation would add an extra stage in the assessment of reliability. In this respect, data published by the multicenter Cornea Donor Study (CDS) in 2005 is a reference. The aim of the study was to compare ECD determined within a single eye bank, which uses calibrated image analysis software designed for transmitted light microscopy images of organ cultured corneas, with the CDS data determined on specular microscopy images of corneas stored at 4°C. ECD of consecutive corneas retrieved between 2005 and 2013 was determined after exposure to 0.9% NaCl. More than 300 ECs were counted on 3 fields of the central 8 mm. Endothelial cell boundaries were automatically drawn and verified by a skilled technician who performed all necessary corrections. Three thousand fifty-two corneas were analyzed, of which 48.5% donors were >75 years (CDS upper age limit). Between 10 and 75 years, the ECD varied according to donor age exactly in the same manner as in the CDS, but were consistently higher of 100 ± 25 cells per square millimeter (P < 0.001). ECD determined by a computer-aided method from transmitted light microscopy images compares favorably with the American CDS reference series. The slight systematic difference on either side of the Atlantic Ocean could be due to (1) differences in counting principles and/or (2) higher shrinkage of the cornea caused by stromal edema in organ culture.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aging
  • Cell Count
  • Child
  • Endothelium, Corneal
  • Eye Banks
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Organ Culture Techniques
  • Tissue Donors
  • Young Adult


Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: Specular Microscopy Ancillary Study.

To examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP). Multicenter, prospective, double-masked clinical trial. We included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥ 10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema). Corneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD). Endothelial cell density at 10 years. Among study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm(2) (interquartile range [IQR], 522-850 cells/mm(2)), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm(2) (IQR, 483-694 cells/mm(2); P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P<0.001) and larger donor tissue size (P<0.001). Forty-two of the 176 participants (24%) had an ECD of <500 cells/mm(2) at 10 years and only 24 (14%) had an ECD of >1000 cells/mm(2). Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aging
  • Cell Count
  • Child
  • Corneal Edema
  • Corneal Endothelial Cell Loss
  • Double-Blind Method
  • Endothelium, Corneal
  • Eye Banks
  • Female
  • Fuchs' Endothelial Dystrophy
  • Graft Survival
  • Humans
  • Keratoplasty, Penetrating
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prospective Studies
  • Risk Factors
  • Time Factors
  • Tissue Donors
  • Young Adult


Evaluation of grafted patients with donor corneas that today are more than 100 years old.

Life expectancy is increasing. When corneal donors become older and corneal-grafted patients live longer with their graft, the need for good-quality donor tissue becomes more crucial. The aim of the present investigation is to study grafted recipients with a donor cornea with a total tissue age of more than 100 years. One thousand consecutive donor records from the Danish Cornea Bank were initially reviewed. After applying different inclusion criteria, 35 recipients with corneal donor tissue of more than 100 years of age were invited for a follow-up visit. Visual acuity, corneal transparency and thickness, and intraocular pressure were measured. Corneal topography and endothelial photos were taken.   Seventeen of the invited patients attended the examination. The average age of the grafts at examination was 107 years old; the oldest being 118 years. Most grafts were still clear 23-35 years after transplantation, and almost one-fourth had best spectacle-corrected visual acuity (BSCVA) ≥ 0.50. Cell morphology showed irregularity in size and shape for both grafted and healthy corneas, but the alterations were more extensive in the grafted corneas. The average endothelial cell density (ECD) was 1360 mm(2) in the grafted corneas. Sixty per cent had ECD > 1000 cells/mm(2). No signs of decompensation were observed for those with <1000 cells. The average central corneal thickness of the grafts was 0.582 mm (SD = 0.067) compared with 0.494 mm (SD = 0.043) in the fellow cornea.   This study shows a trend of moderate long-term survival and quality for very old grafts despite low ECD. Most recipients had a clear transplant, and one-fifth had BSCVA of 0.80.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Cell Count
  • Cornea
  • Corneal Diseases
  • Corneal Pachymetry
  • Corneal Topography
  • Corneal Transplantation
  • Endothelium, Corneal
  • Eye Banks
  • Female
  • Graft Survival
  • Humans
  • Longevity
  • Male
  • Middle Aged
  • Tissue Donors
  • Tissue and Organ Procurement
  • Transplant Recipients
  • Visual Acuity

Keywords

  • cornea banking
  • cornea donation
  • corneal graft performance
  • follow-up study
  • tissue survival


Brain perfusion SPECT in the mouse: normal pattern according to gender and age.

Regional cerebral blood flow (rCBF) is a useful surrogate marker of neuronal activity and a parameter of primary interest in the diagnosis of many diseases. The increasing use of mouse models spawns the demand for in vivo measurement of rCBF in the mouse. Small animal SPECT provides excellent spatial resolution at adequate sensitivity and is therefore a promising tool for imaging the mouse brain. This study evaluates the feasibility of mouse brain perfusion SPECT and assesses the regional pattern of normal Tc-99m-HMPAO uptake and the impact of age and gender. Whole-brain kinetics was compared between Tc-99m-HMPAO and Tc-99m-ECD using rapid dynamic planar scans in 10 mice. Assessment of the regional uptake pattern was restricted to the more suitable tracer, HMPAO. Two HMPAO SPECTs were performed in 18 juvenile mice aged 7.5 ± 1.5weeks, and in the same animals at young adulthood, 19.1 ± 4.0 weeks (nanoSPECT/CTplus, general purpose mouse apertures: 1.2kcps/MBq, 0.7mm FWHM). The 3-D MRI Digital Atlas Database of an adult C57BL/6J mouse brain was used for region-of-interest (ROI) analysis. SPECT images were stereotactically normalized using SPM8 and a custom made, left-right symmetric HMPAO template in atlas space. For testing lateral asymmetry, each SPECT was left-right flipped prior to stereotactical normalization. Flipped and unflipped SPECTs were compared by paired testing. Peak brain uptake was similar for ECD and HMPAO: 1.8 ± 0.2 and 2.1 ± 0.6 %ID (p=0.357). Washout after the peak was much faster for ECD than for HMPAO: 24 ± 7min vs. 4.6 ± 1.7h (p=0.001). The general linear model for repeated measures with gender as an intersubject factor revealed an increase in relative HMPAO uptake with age in the neocortex (p=0.018) and the hippocampus (p=0.012). A decrease was detected in the midbrain (p=0.025). Lateral asymmetry, with HMPAO uptake larger in the left hemisphere, was detected primarily in the neocortex, both at juvenile age (asymmetry index AI=2.7 ± 1.7%, p=0.000) and at young adult age (AI=2.4 ± 1.7%, p=0.000). Gender had no effect on asymmetry. Voxel-wise testing confirmed the ROI-based findings. In conclusion, high-resolution HMPAO SPECT is a promising technique for measuring rCBF in preclinical research. It indicates lateral asymmetry of rCBF in the mouse brain as well as age-related changes during late maturation. ECD is not suitable as tracer for brain SPECT in the mouse because of its fast clearance from tissue indicating an interspecies difference in esterase activity between mice and humans.

MeSH Terms

  • Aging
  • Animals
  • Brain
  • Cerebrovascular Circulation
  • Cysteine
  • Female
  • Functional Laterality
  • Image Processing, Computer-Assisted
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organotechnetium Compounds
  • Perfusion
  • Radiopharmaceuticals
  • Sex Characteristics
  • Technetium Tc 99m Exametazime
  • Tomography, Emission-Computed, Single-Photon


Deficiency of catecholamine syntheses caused by downregulation of phosphorylation of tyrosine hydroxylase in the cerebral cortex of the senescence-accelerated mouse prone 10 strain with aging.

The purpose of this study was to elucidate the alteration of catecholamine metabolism and the contribution of catecholamines to the decline of learning and memory in the brain of the senescence-accelerated mouse prone 10 (SAMP10) with aging. Catecholamines and their metabolites in the cerebral cortex were measured by HPLC-ECD. The protein levels of tyrosine hydroxylase (TH) as well as TH phosphorylated at Ser19 or Ser40, dopamine-β-hydroxylase (DβH), and cAMP-dependent protein kinase (PKA) were determined by western blot analysis. Dopamine (DA) and norepinephrine (NE) levels in SAMP10 were significantly lower than those in control animals. However, no significant difference was observed in catecholamine metabolite levels between SAMP10 and control mice. The level of TH phosphorylation at Ser40 in SAMP10 was significantly lower than that in control mice, but no significant difference was observed in the levels of TH, TH phosphorylated at Ser19, or DβH. The amount of PKA, which regulates the phosphorylation of TH at Ser40, was significantly lower in SAMP10 than in control mice. The present study demonstrated that a decline in DA and NE concentrations was observed in the cerebral cortex of SAMP10 with aging, and this decrease of catecholamine levels was caused by impairment of their synthetic pathway. These impairments are considered to be caused by downregulation of TH phosphorylation at Ser40 as a result of PKA deficiency. The present study suggests that the decline of learning and memory abilities of SAMP10 is caused by a decrease in catecholamine synthesis in the cerebral cortex with aging.

MeSH Terms

  • Aging
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Cerebral Cortex
  • Cyclic AMP-Dependent Protein Kinases
  • Dopamine
  • Dopamine beta-Hydroxylase
  • Down-Regulation
  • Learning
  • Male
  • Memory
  • Mice
  • Mice, Inbred Strains
  • Norepinephrine
  • Phosphorylation
  • Tyrosine 3-Monooxygenase


Cerebral small vessel disease in aging and Alzheimer's disease: a comparative study using MRI and SPECT.

White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs). Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns. WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs. Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.

MeSH Terms

  • Aged
  • Aging
  • Alzheimer Disease
  • Brain
  • Cerebral Small Vessel Diseases
  • Cysteine
  • Female
  • Humans
  • Leukoaraiosis
  • Magnetic Resonance Imaging
  • Male
  • Nerve Fibers, Myelinated
  • Neuroimaging
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Tomography, Emission-Computed, Single-Photon


Use of specular microscopy to determine corneal endothelial cell morphology and morphometry in enucleated cat eyes.

The purpose of this study was to investigate the effect of age on endothelial morphology and morphometry in cats. The corneal endothelium was studied using a contact specular microscope. A total of 18 cats (Felis catus Linnaeus, 1758) were evaluated in this study. The subjects were divided into three groups of six cats each in function of age: G1 (1 to 3 months old), G2 (5 to 12 months old), and G3 (24 to 40 months old). The examination presented data as endothelial cell density (ECD), average cell area, corneal thickness, polymegathism, and pleomorphism. Results revealed ECD decrease in corneas of normal cats with age, as well as a corresponding increase in endothelial cell area and pleomorphism. The present work suggests that the endothelial parameters evaluated change with advancing age.

MeSH Terms

  • Aging
  • Animals
  • Cats
  • Cell Count
  • Cornea
  • Endothelium, Corneal
  • Female
  • Male
  • Microscopy


Two single descriptors of endothelial polymegethism and pleomorphism.

To compute two new quantitative parameters that directly reflect the level of polymegethism and pleomorphism using data provided by a non-contact specular microscope. We examined right eyes of 306 voluntaries (102 males, 204 females) whose ages ranged from 6 to 82 years (mean /- SD, 44 /- 22 years). Endothelial cell density (ECD), average cell size (ACS), standard error of cells surface (SEM), coefficient of variation in cell size (CV) and hexagonality index (HI) were obtained. In addition, two new indices of polymegethism (POLi) and pleomorphism (PLEi) were derived using weighted linear combinations of data obtained from instrument classification of endothelial cells based on the individual counts of cells by size and number of sides respectively, as provided by the instrument. Values of POLi and PLEi were compared between a group of diabetic patients and a group of age-matched controls. Average values of POLi and PLEi were 10.47 /- 3.94 and 8.36 /- 1.21 respectively. POLi and PLEi display high correlation with SEM (r = 0.911, r = 0.664), ECD (r = -0.997, r = -0.585), ACS (r = 0.997, r = 0.441), ACS (SD) (r = 0.883, r = 0.682), CV (r = 0.301, r = 0.712) and HI (r = -0.437, r = -0.991); all these correlations were highly significant (p < 0.001). POLi and PLEi also showed significant positive correlations with age (r = 0.765, p < 0.001 and r = 0.428, p < 0.001 respectively). POLi was significantly higher in a group of diabetic patients when compared with another group of age-matched controls (p = 0.001). Two single quantitative parameters of endothelial polymegethism and pleomorphism (POLi and PLEi respectively) have been derived from the data obtained with a commercial non-contact specular microscope. These parameters have been demonstrated to identify differences between the corneal endothelium of diabetic and non-diabetic patients.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Cell Count
  • Cell Shape
  • Cell Size
  • Child
  • Diabetes Complications
  • Endothelium, Corneal
  • Female
  • Humans
  • Male
  • Middle Aged
  • Young Adult


Maturation of somatosensory cortical processing from birth to adulthood revealed by magnetoencephalography.

To evaluate the maturation of tactile processing by recording somatosensory evoked magnetic fields (SEFs) from healthy human subjects. SEFs to tactile stimulation of the left index finger were measured from the contralateral somatosensory cortex with magnetoencephalography (MEG) in five age groups: newborns, 6- and 12-18-month-olds, 1.6-6-year-olds, and adults. The waveforms of the measured signals and equivalent current dipoles (ECDs) were analyzed in awake and sleep states in order to separate the effects of age and vigilance state on SEFs. There was an orderly, systematic change in the measured and ECD source waveforms of the initial cortical responses with age. The broad U-shaped response in newborns (M60) shifted to a W-shaped response with emergence of a notch by 6 months of age. The adult-type response with M30 and M50 components was present by 2 years. The ECDs of M60 and M30 were oriented anteriorly and that of M50 posteriorly. These maturational changes were independent of vigilance state. The most significant maturation of short latency cortical responses to tactile stimulation takes place during the first 2 years of life. The maturational changes of somatosensory processing can noninvasively be evaluated with MEG already in infancy.

MeSH Terms

  • Adolescent
  • Adult
  • Age Factors
  • Aging
  • Brain Mapping
  • Child
  • Child, Preschool
  • Electric Stimulation
  • Electroencephalography
  • Evoked Potentials, Somatosensory
  • Female
  • Functional Laterality
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Magnetoencephalography
  • Male
  • Middle Aged
  • Physical Stimulation
  • Reaction Time
  • Sleep
  • Somatosensory Cortex
  • Time Factors
  • Wakefulness
  • Young Adult


Molecular evidence of senescence in corneal endothelial cells of senescence-accelerated mice.

To investigate senescent evidence in corneal endothelial cells (CECs) of the senescence-accelerated mouse (SAM), which is considered a suitable animal model for the further study of the senescent mechanism in CECs. Thirty-six male mice from a senescence resistant mouse strain (SAM R1) and a senescence-prone strain (SAM P8) at various ages (1, 6, and 12 months) were analyzed in this study. The endothelial cell density (ECD) and cell viability were detected using trypan blue and alizarin red dyes while the senescent cells were observed by senescence-associated beta-galactosidase (SA-beta-Gal; pH 6.0) staining. In addition, ultrastructure was observed using an electron microscope. The senescence-related genes (p16(INK4a), p19(ARF), p21(WAF1/CIP1), and p53) in the CECs were visualized via immunohistochemistry and were quantitatively detected using real-time polymerase chain reaction (PCR). Signal proteins of phospho-extracellular signal-regulated kinase 1/2 (p-ERK 1/2) were detected by western blot analysis. Our results indicated that the ECD values decreased with increasing age in both the SAM-R1 and SAM P8 series where the values in the older SAM p8 series decreased even lower than in the older SAM R1 series. The mean decreased rate was 2.276% per month in the SAM R1 and 2.755% per month in the SAM P8 series. In addition, changes in the senescence-like ultrastructure were observed in the CECs of both strains, and the increase in the positive staining of SA-beta-Gal was observed in both strains as well. It is worth noting that such changes were more significant in the SAM P8 strain. Immunohistochemical detection assays indicated the expression of p-ERK 1/2, p16(INK4a), p19(ARF), p21(WAF1/CIP1), and p53 (nuclear localization for each) in each age group analyzed. Furthermore, the results of real-time PCR studies showed an increase in the expression of p16(INK4a) mRNA as a function of age in the SAM R1 strain and in the early senescence stage of the SAM P8 strain in addition to an increase in the expression of p21(WAF1/CIP1) and p53 mRNA as a function of age in the SAM P8 strain (no significant increase was observed in the SAM R1 strain). Additional results from western blot analysis demonstrated an age-related increase in the quantity of the p-ERK 1/2 proteins in both strains. The SAM R1 and SAM P8 strains represent suitable models for the study of CEC senescence in vivo. In addition, the progression of cellular senescence in CECs occurs more quickly in the SAM P8 strain as opposed to the SAM R1 strain. Our results also indicate that the p16(INK4a) signaling pathway may play a key role in the early stages of senescence in CECs while the p53/p21(WAF1/CIP1) signaling pathway may exert its principle effect in the late stages of senescence in CECs. Further study is still required about the role of the mitogen-activated protein kinase (MAPK) signaling cascade in the process of senescence in CECs.

MeSH Terms

  • Aging
  • Animals
  • Blotting, Western
  • Cell Count
  • Cell Survival
  • Cellular Senescence
  • Descemet Membrane
  • Endothelial Cells
  • Endothelium, Corneal
  • Gene Expression Regulation
  • Immunohistochemistry
  • MAP Kinase Signaling System
  • Male
  • Mice
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • beta-Galactosidase


Renal transplantation in the elderly.

Elderly patients are increasingly being considered for kidney transplantation due to a global explosion of the aging population with end-stage renal disease (ESRD). However, mounting scarcity of available organs for transplant has led to a wider disparity between organ supply and demand. Consequently, the criteria for accepting kidneys for transplantation have been extended in an attempt to allow the use of organs from elderly donors or those with significant co-morbidities, so-called "expanded criteria donor" (ECD) kidneys. Excellent outcomes have been achieved from ECD kidneys with appropriate donor and recipient profiling and selection. With increasing recovery efforts directed at older donors, the concept of age-matching is becoming more accepted as a method of optimizing utilization of organs in elderly donors and recipients. Utilization of pulsatile perfusion has further improved ECD outcomes and helped the decision-making process for the UNOS (United Network for Organ Sharing) offer. However, age-related immune dysfunction and associated co-morbidities make the elderly transplant recipients ever more susceptible to complications associated with immunosuppressive agents. Consequently, the elderly population is at a higher risk to develop infections and malignancy in the post-transplant period notwithstanding improved transplant outcomes. Appropriate immunosuppressive agents and dosages should be selected to minimize adverse events while reducing the risk of acute rejections and maximizing patient and renal allograft survival.

MeSH Terms

  • Age Factors
  • Aged
  • Aging
  • Forecasting
  • Graft Rejection
  • Humans
  • Immunosuppression
  • Kidney Transplantation
  • Neoplasms
  • Risk Factors
  • Tissue Donors
  • Tissue and Organ Procurement
  • Treatment Outcome


Outcomes of kidney transplantation from older living donors to older recipients.

More than half the newly wait-listed patients for kidney transplantation in 2005 were older than 50 years, and 13% were older than 65 years. As waiting times for a deceased donor kidney increase, these older candidates are disadvantaged by rapidly deteriorating health, often resulting in death or removal from the wait list before transplantation. An observational cohort study was conducted using data from the Organ Procurement Transplant Network/United Network for Organ Sharing. All adult kidney-only transplantations performed in recipients 60 years and older from 1996 to 2005 were included. The recipient cohort was stratified into 4 groups based on donor source: older living donor (OLD: living donor age > 55 years), younger living donor (YLD: living donor age </= 55 years), standard criteria deceased donor (SCD), and expanded criteria deceased donor (ECD). Early posttransplantation outcomes, graft survival, patient survival, renal function 1 year posttransplantation, and relative risk of graft loss and patient death were compared. Of 23,754 kidney transplantations performed in recipients 60 years and older, 7,006 were living donor transplantations (1,133 were > 55 years [OLD] and 5,873 were <or= 55 years [YLD]), 12,197 from SCDs, and 4,551 from ECDs. Early posttransplantation outcomes were best in YLD transplantations, followed by SCD and OLD transplantations. OLD transplantations were associated with inferior 3-year graft survival rates (85.7%), but similar 3-year patient survival rates (88.4%) compared with YLD (3-year graft survival, 83.4%; patient survival, 87.4%) and had superior graft survival compared with all deceased donor options. Compared with OLD transplantations, ECD transplantations were associated with a greater risk of graft loss (hazard ratio, 2.36; 95% confidence interval, 1.18 to 4.74). Observational retrospective studies using registry data are subject to inherent limitations, including the possibility of selection bias. With superior graft and patient survival in recipients of transplants from OLDs compared with SCDs and ECDs, OLDs may be an important option for elderly transplantation candidates and should be considered for older patients with a willing and suitable older donor.

MeSH Terms

  • Acute Disease
  • Aged
  • Aging
  • Cohort Studies
  • Delayed Graft Function
  • Female
  • Graft Rejection
  • Graft Survival
  • Humans
  • Incidence
  • Kidney
  • Kidney Transplantation
  • Living Donors
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Postoperative Complications
  • Postoperative Period
  • Proportional Hazards Models
  • Renal Insufficiency
  • Survival Analysis
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome


DDT, DDE and DDD in human milk from South Africa.

Human breast milk samples (n=30) were collected from mothers within the age range of 19-40 years from Thohoyandou area, South Africa. DDT and its metabolites were extracted from the milk samples using diethyl ether. The crude extracts were subjected to column chromatography. The eluates were then evaporated on a stream of nitrogen up to 0.5 mL. One microliter of the cleaned extracts were injected into GC-ECD for selected organochlorine compounds. The sum total of DDT and its metabolites from each village ranged from not detectable for DMS, GNN and THN to 1,930 ng g(-1) fat wt for BDL while SigmaDDE ranged from 1.32 ng g(-1) fat wt for GNN to 2,570 ng g(-1) fat wt for TKD. SigmaDDD ranged from not detectable for GNN to 4,060 ng g(-1) fat wt for MNN. SigmaDDE was the most predominant followed by SigmaDDD and finally SigmaDDT. This was an indication of breakdown of the parent compound, DDT. Some villages namely, Lufule and Budeli, and Maniini and Makhuvha exhibited similar DDT occurrence of 89% in their areas. Other villages, DMS, TLM, and MND and TKD showed a similarity percentage of 82% while others showed similarities of 75% for GNN and MTT, 69% and 65% for MPG and THN respectively. A significant cluster of DDT and its metabolites between the infants' weight range of 2.5-3.9 kg/body wt was observed. Increase in lipid content was followed by a decrease in the sum DDT in the older mothers (27-30). The estimated daily intake varied from 260 to 4,696 ng/g, nd-10,551 ng/g and nd-4,237 ng/g for DDE, DDD and DDT respectively. These values are significantly (p<0.05) higher than the FAO/WHO acceptable daily intake (ADI) of 20 ng/g. The SigmaDDT was found to decrease with increasing age of the mothers. The observed high levels of DDE compared to DDT indicated chronic exposure of the mothers to DDT, which is metabolised to DDE and retained in the body.

MeSH Terms

  • Adult
  • Aging
  • Birth Weight
  • Chromatography, High Pressure Liquid
  • Chromatography, Ion Exchange
  • DDT
  • Dichlorodiphenyl Dichloroethylene
  • Dichlorodiphenyldichloroethane
  • Eating
  • Electrochemistry
  • Fats
  • Female
  • Humans
  • Indicators and Reagents
  • Insecticides
  • Milk, Human
  • Pesticide Residues
  • South Africa


Hormones in the field: evolutionary endocrinology of juvenile hormone and ecdysteroids in field populations of the wing-dimorphic cricket Gryllus firmus.

Virtually no published information exists on insect endocrine traits in natural populations, which limits our understanding of endocrine microevolution. We characterized the hemolymph titers of juvenile hormone (JH) and ecdysteroids (ECDs), two key insect hormones, in field-collected short-winged, flightless (SW) and long-winged, flight-capable (LW(f)) morphs of the cricket Gryllus firmus. The JH titer exhibited a dramatic circadian rhythm in the LW(f) morph but was temporally constant in the flightless SW morph. This pattern was consistent in each of three years; in young, middle-aged, and older G. firmus; and in three other cricket species. The ECD titer was considerably higher in SW than in LW(f) females but did not exhibit temporal variation in any morph and did not differ between male morphs. JH and ECD may control different aspects of the morph-specific trade-off between nocturnal dispersal and reproduction. Results confirm and extend laboratory studies on young female G. firmus; most, but not all, important aspects of morph-specific differences in JH and ECD titers can be extrapolated from field to laboratory environments and vice versa. Hormone titers in Gryllus are more complex than those proposed in evolutionary endocrine models. Directly measuring hormone titer variation remains a fundamentally important task of insect evolutionary endocrinology.

MeSH Terms

  • Aging
  • Animals
  • Biological Evolution
  • Circadian Rhythm
  • Ecdysteroids
  • Female
  • Gryllidae
  • Hemolymph
  • Juvenile Hormones
  • Male
  • Wings, Animal

{{medline-entry |title=Corneal endothelial morphologic features in cataract and clear lens in an Indian population. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17919447 |abstract=To compare the morphologic features of corneal endothelium in patients with cataract and clear lenses. A single, observational clinic-based case-control study. In this single, observational clinic-based case-control study at Iladevi Cataract