DCT
L-dopachrome tautomerase precursor (EC 5.3.3.12) (DCT) (DT) (L-dopachrome Delta-isomerase) (Tyrosinase-related protein 2) (TRP-2) (TRP2) [TYRP2]
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Elderly people thought to have an allergy to beta-lactams (BLs) may tolerate the drugs in subsequent exposures due to initial false labeling of allergies, the spontaneous loss of sensitivity to BLs over time or age-related decline in sensitization. As a result, they may be treated with less appropriate antibiotics, causing more side effects and entailing increased costs for health systems. The aim of this investigation was to assess whether patients in the third and fourth age with previously confirmed allergies to BLs had lost sensitization and could tolerate these antibiotics. Patients allergic to BLs were divided into group A (aged 60-79 years) and B (aged ≥80 years). Clinical history, skin testing, drug challenge tests (DCT) and evaluation of resensitization were used to classify participants as showing immediate reactions, non-immediate reactions, or tolerance. We compared clinical entities, drugs involved, and final outcome by age group. Of 1362 cases evaluated, 565 underwent an allergological study. The skin was the most common organ involved. Anaphylaxis and side chain reactions were more frequent in group A (p<0.01), as were positive DCT. Classical benzylpenicillin determinants (benzylpenicilloyl and/or minor determinant mixture) were more frequent triggers in group B (p< 0.01). Resensitization after challenge occurred in very few participants. The risk for allergy to BLs decreases with age and a history of anaphylaxis by BLs is a predictor of positive results in skin tests (ST). Both immunoglobin E (IgE) and T-cell-mediated responses can disappear in elderly people, who can develop tolerance to these antibiotics. These results are of clinical relevance to patients who need to be treated with antibiotics from this family.
Keywords
- aging
- beta-lactams
- cephalosporins
- cross-reactivity
- diagnosis
- drug allergy
- immunosenescence
Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM). We studied the expression of special AT-rich sequence binding protein 1 (SATB1) and phosphatase and tensin homologue (PTEN) in the kidneys of diabetic rats during ageing. Male Sprague Dawley rats were injected with 55 mg/kg streptozotocin (STZ) (DM group) or with citrate buffer (control group). Kidneys were collected after 2 weeks, 6 months and 12 months, and were analysed in three different kidney structures: glomeruli, proximal (PCT) and distal convoluted tubules (DCT). Sections were stained immunohistochemically, using SATB1 and PTEN. Significant differences in marker expression were observed after 2 weeks, with higher SATB1 expression and lower PTEN expression in diabetic rats. PTEN was more highly expressed in controls after 6 and 12 months. After 12 months, there was higher SATB1 expression in diabetic rats. In the glomeruli, control rats had higher PTEN expression, whereas diabetic rats had higher SATB1 expression, after 12 months. PTEN expression increased from 2 weeks to 12 months in both the PCT and DCT of control rats. SATB1 was expressed exclusively in the PCT of diabetic rats after 2 weeks, and its expression in the DCT was higher in controls. After 6 months, both the PCT and DCT showed higher SATB1 expression in diabetic rats. The major changes in expression of SATB1 and PTEN occur after 2 weeks of DM onset, particularly in the PCT, implying an early onset of pathophysiological changes in diabetic kidneys, which would normally occur with ageing. These findings help to contribute to our understanding of changes associated with DN and guide towards possible appropriate treatment modalities.
MeSH Terms
- Aging
- Animals
- Diabetes Mellitus, Experimental
- Diabetes Mellitus, Type 1
- Diabetic Nephropathies
- Gene Expression Regulation
- Homeodomain Proteins
- Kidney Glomerulus
- Male
- PTEN Phosphohydrolase
- Rats
- Rats, Sprague-Dawley
The National Acoustic Laboratories Dynamic Conversations Test (NAL-DCT) is a new test of speech comprehension that incorporates a realistic environment and dynamic speech materials that capture certain features of everyday conversations. The goal of this study was to assess the suitability of the test for studying the consequences of hearing loss and amplification in older listeners. Unaided and aided comprehension scores were measured for single-, two- and three-talker passages, along with unaided and aided sentence recall. To characterise the relevant cognitive abilities of the group, measures of short-term working memory, verbal information-processing speed and reading comprehension speed were collected. Participants were 41 older listeners with varying degrees of hearing loss. Performance on both the NAL-DCT and the sentence test was strongly driven by hearing loss, but performance on the NAL-DCT was additionally related to a composite cognitive deficit score. Benefits of amplification were measurable but influenced by individual test SNRs. The NAL-DCT is sensitive to the same factors as a traditional sentence recall test, but in addition is sensitive to the cognitive factors required for speech processing. The test shows promise as a tool for research concerned with real-world listening.
MeSH Terms
- Acoustic Stimulation
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Audiometry, Speech
- Cognition
- Comprehension
- Correction of Hearing Impairment
- Female
- Hearing
- Hearing Aids
- Hearing Loss, Sensorineural
- Humans
- Male
- Middle Aged
- Noise
- Perceptual Masking
- Persons With Hearing Impairments
- Predictive Value of Tests
- Reproducibility of Results
- Severity of Illness Index
- Speech Intelligibility
- Speech Perception
Keywords
- Speech comprehension
- hearing aids
- hearing loss
- realistic tests
Metabolic dysfunction is associated with aging and results in age-associated chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and stroke. Hence, there has been a focus on increasing energy expenditure in aged populations to protect them from age-associated diseases. Dihydrocapsiate (DCT) is a compound that belongs to the capsinoid family. Capsinoids are capsaicin analogs that are found in nonpungent peppers and increase whole body energy expenditure. However, their effect on energy expenditure has been reported only in young populations, and to date the effectiveness of DCT in increasing energy expenditure in aged populations has not been investigated. In this study, we investigated whether DCT supplementation in aged mice improves age-associated impairments. We obtained 5-wk-old and 1-yr-old male C57BL/6J mice and randomly assigned the aged mice to two groups, resulting in a total of three groups: [i]1[/i]) young mice, [i]2[/i]) old mice, and [i]3[/i]) old mice supplemented with 0.3% DCT. After 12 wk of supplementation, blood and tissue samples were collected and analyzed. DCT significantly suppressed age-associated fat accumulation, adipocyte hypertrophy, and liver steatosis. In addition, the DCT treatment dramatically suppressed age-associated increases in hepatic inflammation, immune cell infiltration, and oxidative stress. DCT exerted these suppression effects by increasing energy expenditure linked to upregulation of both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that DCT efficiently improves age-associated impairments, including liver steatosis and inflammation, in part by increasing energy expenditure via activation of the fat oxidation pathway in skeletal muscle.
MeSH Terms
- Adipocytes
- Aging
- Animals
- Capsaicin
- Energy Metabolism
- Fatty Acids
- Fatty Liver
- Lipid Metabolism
- Liver
- Male
- Mice
- Mice, Inbred C57BL
- Muscle, Skeletal
- Oxidation-Reduction
- Oxidative Stress
Keywords
- aging
- dihydrocapsiate
- fat oxidation
- inflammation
- liver steatosis
Ocular blood flow imbalance and the loss of autoregulation are widely believed to be important factors in the pathogenesis of glaucoma. The purpose of this study was to investigate the impact of morphometric and functional changes on ocular pulse amplitude (OPA) in normal tension glaucoma (NTG), primary open-angle glaucoma (POAG), pseudoexfoliation-glaucoma (PEX) and ocular hypertension (OHT). This prospective study included 172 patients with manifest glaucoma and OHT. All patients were examined with dynamic contour tonometry (DCT), Goldmann applanation tonometry (GAT), Heidelberg retina tomography II (HRT), and Octopus visual field analysis (program 30II). In order to identify potential determinants of OPA, a generalised linear model (GLM) analysis was defined. As effect sizes, we included gender as a factor and intraocular pressure (measured by DCT [IOP]), optic disc area, cup area, mean deviation (MD), central corneal thickness (CCT), cup-disc ratio (CDR), and patient age as covariates. Mean OPA was lower in patients with NTG than in other groups. In the generalised linear model in the entire population, a larger OPA was associated with a larger IOP and female gender. In the NTG group, we did not identify effect sizes, whereas, in the OHT group, IOP (measured with DCT) and MD, in the POAG group IOP (measured with DCT) and gender and in the PEX group MD and gender showed a positive effect on OPA. In this study, we showed that in the NTG group neither demographic nor morphological or functional factors affected OPA. However, in the OHT and POAG groups, OPA was influenced by IOP (measured with DCT), in the OHT and PEX group by MD and in the POAG and PEX groups by gender.
MeSH Terms
- Aged
- Aging
- Blood Pressure
- Computer Simulation
- Female
- Glaucoma
- Humans
- Intraocular Pressure
- Male
- Models, Cardiovascular
- Ocular Hypertension
- Pulsatile Flow
- Sex Characteristics
- Tonometry, Ocular
Mitochondria are highly dynamic and semi-autonomous organelles, essential for many fundamental cellular processes, including energy production, metabolite synthesis and calcium homeostasis, among others. Alterations in mitochondrial activity not only influence individual cell function but also, through non-cell autonomous mechanisms, whole body metabolism, healthspan and lifespan. Energy homeostasis is orchestrated by the complex interplay between mitochondrial biogenesis and mitochondria-selective autophagy (mitophagy). However, the cellular and molecular pathways that coordinate these 2 opposing processes remained obscure. In our recent study, we demonstrate that DCT-1, the Caenorhabditis elegans homolog of the mammalian BNIP3 and BNIP3L/NIX, is a key mediator of mitophagy, and functions in the same genetic pathway with PINK-1 and PDR-1 (the nematode homologs of PINK1 and Parkin respectively) to promote longevity and prevent cell damage under stress conditions. Interestingly, accumulation of damaged mitochondria activates SKN-1 (SKiNhead-1), the nematode homolog of NRF2, which in turn initiates a compensatory retrograde signaling response that impinges on both mitochondrial biogenesis and removal. In this commentary, we discuss the implications of these new findings in the context of innate immunity and aging. Unraveling the regulatory network that governs the crosstalk between mitochondrial biogenesis and mitophagy will enhance our understanding of the molecular mechanisms that link aberrant energy metabolism to aging and disease.
Keywords
- aging
- autophagy
- homeostasis
- innate immunity
- mitochondria
- mitophagy
- stress
To investigate the effect of aging on ocular parameters, including intraocular pressure (IOP), measured with different tonometry methods in healthy young (HY) and healthy elderly (HE) subjects and to study the effect of corneal parameters on tonometry methods. In this prospective, cross-sectional study, fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79) were included. IOP was measured with four tonometry methods in a standardized order: ocular response analyser (ORA), dynamic contour tonometry (DCT), applanation resonance tonometry (ART) and Goldmann applanation tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), anterior chamber volume (ACV), corneal hysteresis (CH) and corneal resistance factor (CRF). The mean IOP (HY/HE; mmHg ± standard deviation (SD)) was 12.2 ± 2.2/14.1 ± 3.5 with GAT. IOP was significantly higher (difference ± standard error) in HE compared to HY measured with an ORA ( 3.1 mmHg ± 0.6), GAT ( 1.9 ± 0.6) and DCT ( 1.6 ± 0.6). No significant difference was found in IOP measured with ART. CH and ACV were significantly lower in HE compared to HY. There was no difference between the groups in CCT, CC, AL or CRF. No tonometry method was dependant on CCT or CC. IOP measured with an ORA and via DCT and GAT was higher in HE compared to HY Swedish subjects, while IOP measured with ART did not differ between the groups. In these homogeneous groups, tonometry methods were independent of CCT and CC.
MeSH Terms
- Adult
- Aged
- Aging
- Anterior Chamber
- Axial Length, Eye
- Cornea
- Corneal Pachymetry
- Cross-Sectional Studies
- Female
- Healthy Volunteers
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Prospective Studies
- Tonometry, Ocular
- Young Adult
Keywords
- Age dependency
- Applanation resonance tonometry
- Central corneal thickness
- Corneal curvature
- Dynamic contour tonometry
- Intraocular pressure
- Ocular response analyser
Maintenance of mitochondrial function and energy homeostasis requires both generation of newly synthesized and elimination of dysfunctional mitochondria. Impaired mitochondrial function and excessive mitochondrial content are major characteristics of aging and several human pathophysiological conditions, highlighting the pivotal role of the coordination between mitochondrial biogenesis and mitophagy. However, the cellular and molecular underpinnings of mitochondrial mass homeostasis remain obscure. In our recent study, we demonstrate that DCT-1, the Caenorhabditis elegans homolog of mammalian BNIP3 and BNIP3L/NIX, is a key mediator of mitophagy promoting longevity under stress. DCT-1 acts downstream of the PINK-1-PDR-1/Parkin pathway and is ubiquitinated upon mitophagy-inducing conditions to mediate the removal of damaged mitochondria. Accumulation of damaged mitochondria triggers SKN-1 activation, which initiates a bipartite retrograde signaling pathway stimulating the coordinated induction of both mitochondrial biogenesis and mitophagy genes. Taken together, our results unravel a homeostatic feedback loop that allows cells to adjust their mitochondrial population in response to environmental and intracellular cues. Age-dependent decline of mitophagy both inhibits removal of dysfunctional or superfluous mitochondria and impairs mitochondrial biogenesis resulting in progressive mitochondrial accretion and consequently, deterioration of cell function.
MeSH Terms
- Aging
- Animals
- Autophagy
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Carrier Proteins
- DNA-Binding Proteins
- Homeostasis
- Longevity
- Membrane Proteins
- Mitochondria
- Mitophagy
- Signal Transduction
- Transcription Factors
Keywords
- Caenorhabditis elegans
- aging
- autophagy
- homeostasis
- mitochondria
- mitophagy
- stress
Impaired mitochondrial maintenance in disparate cell types is a shared hallmark of many human pathologies and ageing. How mitochondrial biogenesis coordinates with the removal of damaged or superfluous mitochondria to maintain cellular homeostasis is not well understood. Here we show that mitophagy, a selective type of autophagy targeting mitochondria for degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content and longevity in Caenorhabditis elegans. We find that DCT-1 is a key mediator of mitophagy and longevity assurance under conditions of stress in C. elegans. Impairment of mitophagy compromises stress resistance and triggers mitochondrial retrograde signalling through the SKN-1 transcription factor that regulates both mitochondrial biogenesis genes and mitophagy by enhancing DCT-1 expression. Our findings reveal a homeostatic feedback loop that integrates metabolic signals to coordinate the biogenesis and turnover of mitochondria. Uncoupling of these two processes during ageing contributes to overproliferation of damaged mitochondria and decline of cellular function.
MeSH Terms
- Aging
- Animals
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Carrier Proteins
- DNA-Binding Proteins
- Homeostasis
- Insulin
- Insulin-Like Growth Factor I
- Longevity
- Membrane Proteins
- Mitochondria
- Mitophagy
- Signal Transduction
- Stress, Physiological
- Transcription Factors
A defect in Klotho gene expression in the mouse results in a syndrome that resembles rapid human aging. In this study, we investigated the detailed distribution and the time of the first appearance of Klotho in developing and adult mouse kidney. Kidneys from 16-(F16), 18-(F18) and 20-day-old (F20) fetuses, 1- (P1), 4- (P4), 7- (P7), 14- (P14), and 21-day-old (P21) pups and adults were processed for immunohistochemistry and immunoblot analyses. In the developing mouse kidney, Klotho immunoreactivity was initially observed in a few cells of the connecting tubules (CNT) of 18-day-old fetus (F) and in the medullary collecting duct (MCD) and distal nephron of the F16 developing kidney. In F20, Klotho immunoreactivity was increased in CNT and additionally observed in the outer portion of MCD and tip of the renal papilla. During the first 3 weeks after birth, Klotho-positive cells gradually disappeared from the MCD due to apoptosis, but remained in the CNT and cortical collecting ducts (CCD). In the adult mouse, the Klotho protein was expressed only in a few cells of the CNT and CCD in cortical area. Also, Klotho immunoreactivity was observed in the aquaporin 2-positive CNT, CCD, and NaCl co-transporter-positive distal convoluted tubule (DCT) cells and type B and nonA-nonB intercalated cells of CNT, DCT, and CCD. Collectively, our data indicate that immunolocalization of Klotho is closely correlated with proliferation in the intercalated cells of CNT and CCD from aging, and may be involved in the regulation of tubular proliferation.
MeSH Terms
- Aging
- Animals
- Aquaporin 2
- Cell Proliferation
- Gene Expression Regulation
- Glucuronidase
- Humans
- Kidney Cortex
- Kidney Tubules, Collecting
- Mice
To evaluate the relationships between Reichert Ocular Response Analyzer (ORA) parameters corneal hysteresis (CH) and corneal response factor (CRF) and ocular dimensions, age and intraocular pressure. Two hundred and twelve eyes of 212 participants with no ocular pathology had CH and CRF measured with the ORA. Intraocular pressure (IOP) was measured with the Dynamic Contour tonometer and central corneal thickness (CCT) was also evaluated. Partial least squares linear regression (PLSLR) analyses were performed to examine the relationships between each response variable, CH and CRF, and the predictor variables age, corneal curvature (CC), axial length (AL), CCT and IOP. CH was positively associated with CCT and negatively associated with age (scaled coefficients: CCT 0.62, p < 0.0001; age -0.55, p <0.0001; r2 = 0.25). CRF was positively associated with CCT and DCT IOP and negatively associated with age and AL (scaled coefficients: CCT 0.89, p < 0.0001; DCT IOP 0.46, p < 0.01; age - 0.60, p < 0.0001; AL -0.37, p < 0.01; r2 = 0.43). There was no significant association between CC and CH or CRF. The study suggests that age and CCT are strongly associated with CH and CRF, and that the latter is also influenced by AL and IOP. However, the variables studied could explain only 25% and 43% of the measured variation in CH and CRF, respectively, suggesting other factors also affect the values of these measurements.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Axial Length, Eye
- Biomechanical Phenomena
- Cornea
- Cross-Sectional Studies
- Female
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Models, Biological
- Prospective Studies
- Regression Analysis
- Tonometry, Ocular
- Young Adult
Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.
MeSH Terms
- Aging
- Animals
- Carrier Proteins
- Cilia
- DNA
- Gene Expression Regulation
- Kidney Diseases
- Kidney Tubules, Distal
- Mechanistic Target of Rapamycin Complex 1
- Mice
- Mice, Knockout
- Multiprotein Complexes
- Proteins
- Rapamycin-Insensitive Companion of mTOR Protein
- Signal Transduction
- TOR Serine-Threonine Kinases
- Trans-Activators
- Transcription Factors
- Tuberous Sclerosis Complex 1 Protein
- Tumor Suppressor Proteins
The Pascal Dynamic Contour Tonometer (DCT) is an ophthalmic investigational device which directly calculates the dynamic pulsatile fluctuations in intraocular pressure (IOP) using a piezoelectric pressure sensor embedded in the devices tip. The aim of this study was to compare IOP results obtained with Goldmann applanation tonometer (GAT), and their correlation with central corneal thickness (CCT) in patients of various age groups. We studied 37 patients (17 male and 20 female), divided into three age groups: younger than 40 years; 40-60 years old, and older than 60 years. In the first and second group there were patients rarely and in the third mostly diagnosed and medicamentously compensated glaucoma. In topical anaesthesia, first we measured CCT, with ultrasound pachimeter, then IOP with DCT and GAT. Statistically significant difference between measurements of IOP with the DCT and GAT appeared in all groups: I mean diff. -1.71 /- 1.27 mm; p < 0.0001; II mean diff. -1.19 /- 1.06 mm; p < 0.0001; III mean diff. -1.69 /- 1.67 mm; p < 0.0001. CCT was in indirect correlation with the values of IOP measured both with the DCT and GAT in the first and third, while it was in the direct correlation with these values in the second group. CCT had no influence on IOP measurements both with the DCT and GAT in none of the groups. The DCT cannot replace GAT, but it is a reliable device for the measurement of IOP particularly in corneal deformations (keratoconus, after corneal refractive surgery, corneal scars, etc.).
MeSH Terms
- Adult
- Aging
- Corneal Topography
- Female
- Glaucoma
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Tonometry, Ocular
Preconditioning sciatic nerve injury enhances axonal regeneration of ascending sensory neurons after spinal cord injury. A key question is whether direct injury of sensory nerves is necessary for the enhanced regeneration. The lumbar 5 ventral root transection (L5 VRT) model, a model of selective motor nerve injury, provides a useful tool to address this question. Here we examined the effects of a preconditioning L5 VRT on the regeneration after a subsequent dorsal column transection (DCT) in adult Sprague-Dawley rats. We found that L5 VRT 1 week before DCT increased the number of Fast Blue (FB)-labeled neurons in the L5 dorsal root ganglia (DRG) and promoted sprouting/regenerating axons to grow into the glial scar. L5 VRT also induced a dramatic upregulation of expression of brain-derived neurotrophic factor (BDNF) in the preconditioned DRG and in the injured spinal cord. Moreover, almost all of the FB-labeled sprouting/regenerating neurons expressed BDNF, and approximately 55% of these neurons were surrounded by p75 neurotrophin receptor-positive glial cells. This combined injury led to an increase in the number of BDNF- and TrkB-immunoreactive nerve fibers in the dorsal column caudal to the lesion site. Taken together, these findings demonstrate that L5 VRT promotes sprouting/regeneration of ascending sensory neurons, indicating that sensory axotomy may not be essential for the plasticity of injured dorsal column axons. Thus, the sensory neurons could be preprimed in the regenerative milieu of Wallerian degeneration and neuroinflammation, which might alter the expression of neurotrophic factors and their receptors, facilitating sprouting/regeneration of ascending sensory neurons.
MeSH Terms
- Aging
- Animals
- Axons
- Brain-Derived Neurotrophic Factor
- Disease Models, Animal
- Female
- Ganglia, Spinal
- Nerve Regeneration
- Nerve Tissue Proteins
- Neuroglia
- Neuronal Plasticity
- Rats
- Rats, Sprague-Dawley
- Receptor, trkB
- Receptors, Growth Factor
- Receptors, Nerve Growth Factor
- Sensory Receptor Cells
- Spinal Cord Injuries
- Spinal Nerve Roots
- Time Factors
To examine the relationship between office-hour changes in IOP, measured with the Goldmann applanation tonometer (GAT) and dynamic contour tonometer (DCT), and the corneal characteristics central corneal thickness (CCT) and corneal hysteresis (CH). Sixty-two eyes of 62 untreated normal subjects and patients with untreated glaucoma had IOP measurements performed with the GAT (mm Hg) and DCT (mm Hg) over an 8-hour period at 2-hour intervals beginning at 9 AM. CCT (micrometers) was measured using a noncontact optical low-coherence reflectometry (OLCR) pachymeter, and CH (mm Hg) was measured with an ocular response analyzer (ORA). The associations between IOP measurements and corneal characteristics for each patient over the measurement period were assessed by using multilevel modeling. GAT and DCT IOP and CCT changed significantly during office hours (ANOVA; GAT: F = 19.9, P < 0.001; DCT: F = 4.6, P = 0.001; CCT: F = 16.4; P < 0.001). No significant changes were observed in CH (ANOVA; F = 1.8, P = 0.13). Multilevel modeling analysis of the interrelationships between CCT, CH, and age on IOP measurements revealed that both CCT and CH changes were significantly associated with GAT IOP changes (GAT IOP/CCT slope, 0.04 mm Hg/microm; 95% confidence intervals [CIs], 0.02-0.06; GAT IOP/CH slope, 0.20 mm Hg/mm Hg; 95% CI, 0.01-0.39). CCT, but not CH, changes were significantly associated with DCT IOP changes (DCT IOP/CCT slope, 0.03 mm Hg/microm; 95% CI, 0.00-0.05). However, although the association between CCT and GAT IOP was relatively uniform between subjects, association between CCT and DCT IOP showed greater intersubject variability. Age had no effect on the diurnal variation of IOP measured with either device. Measured IOP and corneal characteristics covary during office hours. Changes in CCT and CH are associated with changes in GAT IOP and, less consistently, with DCT IOP. The data suggest that variations in corneal characteristics explain a small proportion of the change in IOP measurements made with the GAT during office hours.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Circadian Rhythm
- Cornea
- Female
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Optic Nerve Diseases
- Tonometry, Ocular
To compare the difference between 2 methods of measuring the intraocular pressure (IOP), namely, Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) and to study the relationship with the corneal parameters in patients with no glaucoma signs. One hundred and eighteen eyes of 118 healthy subjects from 20 to 77 years of age underwent IOP measurements with DCT and GAT, central corneal thickness, and corneal volume measurements with Pentacam Scheimpflug camera. Pentacam examination has been performed first, then DCT and, after 10 minutes, GAT measurements. The measurements with GAT ranged between 11 and 22 mm Hg (m=15.49 /-2.43 mm Hg), the measurements with DCT ranged between 10.5 and 25.1 mm Hg (m=17.59 /-2.9 mm Hg). DCT showed a statistically significant (P<0.0001) higher IOP measurement compared with GAT. A relation between differences in IOP with central corneal thickness and corneal volume was found, whereas no relation was found with corneal radius and age. Our results show a discrete correlation between GAT and DCT measurements, but DCT showed slightly higher values of IOP. If DCT should be considered the gold standard, higher values of IOP could still be considered normal. These 2 devices cannot to be used interchangeably.
MeSH Terms
- Adult
- Aged
- Aging
- Cornea
- Humans
- Intraocular Pressure
- Middle Aged
- Photography
- Prospective Studies
- Reproducibility of Results
- Tonometry, Ocular
The purpose of the study was to examine the effect of central corneal thickness (CCT), corneal curvature, astigmatism, axial length (AL), and age on measurements with the Pascal Dynamic Contour Tonometer (DCT). In a prospective clinical trial 75 eyes of 75 patients undergoing phacoemulsification were examined. Before phacoemulsification, the anterior chamber was cannulated at the temporal corneal limbus. In a closed system the IOP was directly set to 15, 20, or 35 mm Hg with a manometric water column. IOP measurements taken by DCT were compared to intracameral measurements with a precision reference pressure sensor. Measurements from 60 patients were suitable for statistical analysis. At IOP of 15 mm Hg, the mean difference between IOP measured by DCT and intracameral IOP was -0.02 /- 1.32 mm Hg; at 20 mm Hg it was -0.2 /- 1.44 mm Hg and at 35 mm Hg, -0.84 /- 1.90 mm Hg. The concordance coefficient according to Lin was 0.9763, showing good agreement between DCT- and intracamerally measured IOP. There was a statistically significant correlation between the difference in IOP measured by DCT minus intracameral IOP and CCT (P = 0.0291, R2 = 0.00012). All other parameters had no statistically significant effect on the difference between DCT and intracameral IOP (corneal curvature, P = 0.6094, R2 = 0.00367; age, P = 0.9198, R2 = 0.000003; astigmatism, P = 0.1564, R2 = 0.08497; and axial length, P = 0.9484, R2 = 0.00008). Measurements with the DCT showed good concordance with intracameral IOP. CCT exerted a statistically significant but clinically irrelevant effect on measurements with the DCT.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Anterior Chamber
- Astigmatism
- Catheterization
- Cornea
- Female
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Ocular Hypertension
- Phacoemulsification
- Prospective Studies
- Reproducibility of Results
- Tonometry, Ocular
To assess the agreement in the measurement of intraocular pressure obtained by dynamic contour tonometer (DCT) and noncontact tonometer (NCT) in patients with glaucoma and ocular hypertension, to investigate the effect of corneal thickness on pressure readings by both instruments, and to assess the reproducibility of dynamic contour tonometer. NCT and DCT measurements were made on 104 eyes of 104 patients with primary open-angle glaucoma (n=75) or ocular hypertension (n=29), and agreement was assessed by means of Bland-Altman plots. The effect of corneal thickness on both tonometers was assessed by linear regression analysis. Interobserver and intraobserver variations for dynamic contour tonometer were assessed in 41 eyes of 41 patients. The mean difference /-SD (95% limits of agreement) between NCT and DCT was -0.80 /-2.98 (-6.6 to 5.1) mm Hg (P=0.009) and no relation between NCT/DCT differences and average was found. The intraocular pressure readings obtained by noncontact tonometer depended on central corneal thickness (P<0.001, adjusted r(2)=0.301). However, dynamic contour tonometer readings showed no effect of corneal thickness (P=0.388, adjusted r(2)=-0.002). The coefficient of repeatability for DCT was 0.92 (95% CI 0.85-0.96, P=0.001). In subjects with primary open-angle glaucoma and ocular hypertension, NCT and DCT readings are not interchangeable. DCT measurements, unlike NCT measurements, did not depend on corneal thickness.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cornea
- Epidemiologic Methods
- Female
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Observer Variation
- Ocular Hypertension
- Tonometry, Ocular
To compare intraocular pressure (IOP) measurements taken with Pascal dynamic contour tonometry (DCT), the TonoPen and the Goldmann applanation tonometry (GAT). The influence of central corneal thickness (CCT) on IOP measurements taken with Pascal DCT and the TonoPen was evaluated. One eye in each of 101 consecutive patients with primary open-angle glaucoma (POAG) underwent ultrasonic CCT measurement and IOP evaluation with GAT, Pascal DCT and the TonoPen in random order. The agreement between results from Pascal DCT and the TonoPen and those of GAT was assessed using the Bland-Altman method. The deviation of Pascal DCT and TonoPen readings from GAT values, corrected for CCT, was calculated and correlated to CCT using a linear regression model. The mean of the differences in IOP measurements was 3.2 /- 2.4 mmHg for Pascal DCT minus GAT readings and 0.5 /- 4.5 mmHg for TonoPen minus GAT readings. The 95% confidence interval of differences in IOP measurements was higher between TonoPen and GAT readings (- 6 to 7 mmHg) than between Pascal and GAT readings (0.1-6.8 mmHg). Pascal DCT significantly overestimated IOP compared with GAT, especially for higher IOP readings. Bland-Altman scatterplots showed reasonable inter-method agreement between Pascal DCT and GAT measurements, and poor agreement between TonoPen and GAT measurements. The deviations of Pascal DCT and TonoPen readings from the corrected GAT values were both highly correlated with CCT values (linear regression analysis, p < 0.0001). The mean change in measured IOP for a 10-microm increase in CCT was 0.48 mmHg for Pascal DCT and 0.74 mmHg for the TonoPen. Agreement with GAT measurements was higher for Pascal DCT than for TonoPen readings; however, Pascal DCT significantly overestimated IOP values compared with GAT. Measurements of IOP obtained with both Pascal DCT and the TonoPen appeared to be influenced by CCT, and this influence appeared to be greater for the latter.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cornea
- Female
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Prospective Studies
- Reproducibility of Results
- Tonometry, Ocular
- Ultrasonography
- Visual Acuity
To establish the effects of central corneal thickness (CCT) on intraocular pressure (IOP) measured with a prototype Pascal dynamic contour tonometer (DCT), to evaluate the effect of CCT and age on the agreement between IOP measured with the Pascal DCT and Goldmann applanation tonometer (GAT), and to compare the interobserver and intraobserver variation of the DCT with the GAT. GAT and DCT IOP measurements were made on 130 eyes of 130 patients and agreement was assessed by means of Bland-Altman plots. The effect of CCT and age on GAT/DCT IOP differences was assessed by linear regression analysis. Interobserver and intraobserver variations for GAT and DCT were assessed in 100 eyes of 100 patients. The mean difference (95% limits of agreement) between GAT and DCT was -0.7 (-6.3 to 4.9) mm Hg. GAT/DCT IOP differences increased with thicker CCT (slope 0.017 mm Hg/microm, 95% CI 0.004 to 0.03, r2 = 0.05, p = 0.01), and with greater age, slope 0.05 mm Hg/year (95% CI 0.012 to 0.084, r2 = 0.05, p = 0.01). The intraobserver variability of GAT and DCT was 1.7 mm Hg and 3.2 mm Hg, respectively. The interobserver variability was (mean difference (95% limits of agreement)) 0.4 (-3.5 to 4.2) mm Hg for GAT and 0.2 (-4.9 to 5.3) mm Hg for DCT. GAT is significantly more affected than DCT by both CCT and subject age. The effect of age suggests an age related corneal biomechanical change that may induce measurement error additional to that of CCT. The prototype DCT has greater measurement variability than the GAT.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cornea
- Female
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Observer Variation
- Ocular Hypertension
- Reproducibility of Results
- Tonometry, Ocular
We determined the reliability and validity of a cancellation test of symbols (Symbol Cancellation Test [[[SCT]]]), designed to assess visual selective attention deficits in the elderly, on 34 Alzheimer's disease (AD) patients from Bari University Hospital Center, Bari, Italy, and 232 nondemented elderly subjects, aged 68 to 87 years, from the second prevalence survey (1995 through 1996) of the Italian Longitudinal Study on Aging (Casamassima, Bari, Italy). To assess convergent and discriminant validity, the Digit Cancellation Test (DCT), Mini-Mental State Examination (MMSE), and Babcock Story Recall Test (BSRT) were administered. Finally, discriminant accuracy of SCT between AD patients and nondemented elderly subjects was assessed. Inter-rater and test-retest reliability for P1 and P2 was excellent for both AD patients and the normal population, with a high degree of internal consistency. The SCT was significantly correlated with the DCT (0.67), MMSE (0.60), and BSRT (0.33). The classification accuracies of overall performance on the SCT for subjects with and without AD were 0.62 and 0.91, respectively. The SCT is a valid and reliable test to assess selective attention in elderly subjects, in whom dementing illness must be diagnosed and clinically distinct from age-related cognitive decline.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Attention
- Cohort Studies
- Diagnosis, Differential
- Educational Status
- Female
- Humans
- Italy
- Longitudinal Studies
- Male
- Pattern Recognition, Visual
- Psychiatric Status Rating Scales
- Reproducibility of Results
- Sex Factors
To study the relationships between dietary macronutrient intakes and age-related changes in cognitive functions. We investigated these associations in the prevalence survey (1992 through 1993) of the Italian Longitudinal Study on Aging (ILSA). The population-based sample of 5,632 subjects of the ILSA, age 65 to 84 years, was identified from the electoral rolls of eight Italian municipalities. In this study, standardized test batteries assessing global cognitive functions (Mini-Mental State Examination [MMSE]), selective attention (Digit Cancellation Test [[[DCT]]]), and episodic memory (Babcock Story Recall Test), and a semi-quantitative food frequency questionnaire evaluating macronutrient energy intakes, were performed on 278 nondemented elderly subjects from the randomized cohort of Casamassima, Bari (n = 704). There was an inverse relationship between monounsaturated fatty acids (MUFAs) energy intake and cognitive decline (MMSE < 24). The effect of education on the odds of having a MMSE score <24 decreased exponentially with the increase of MUFA intakes (over 2,400 kJ; odds ratio, 0.69). Moreover, a significant inverse association was observed between MUFA intakes and DCT score (odds ratio, 0.99). No association was found between nutritional variables and episodic memory. In an elderly population of Southern Italy with a typical Mediterranean diet, high MUFA intakes appeared to be protective against age-related cognitive decline. Prospective clinical trials are needed to evaluate the impact of specific dietary macronutrient intakes on the age-related changes of cognitive functions.
MeSH Terms
- Age Distribution
- Aged
- Aged, 80 and over
- Aging
- Cognition Disorders
- Fatty Acids, Monounsaturated
- Female
- Humans
- Longitudinal Studies
- Male
- Nutritional Status
- Sex Distribution
During the past several years, sites of expression of ion transport proteins in tubules from adult kidneys have been described and correlated with functional properties. Less information is available concerning sites of expression during tubule morphogenesis, although such expression patterns may be crucial to renal development. In the current studies, patterns of renal axial differentiation were defined by mapping the expression of sodium transport pathways during nephrogenesis in the rat. Combined in situ hybridization and immunohistochemistry were used to localize the Na-Pi cotransporter type 2 (NaPi2), the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), the thiazide-sensitive Na-Cl cotransporter (NCC), the Na/Ca exchanger (NaCa), the epithelial sodium channel (rENaC), and 11beta-hydroxysteroid dehydrogenase (11HSD). The onset of expression of these proteins began in post-S-shape stages. NKCC2 was initially expressed at the macula densa region and later extended into the nascent ascending limb of the loop of Henle (TAL), whereas differentiation of the proximal tubular part of the loop of Henle showed a comparatively retarded onset when probed for NaPi2. The NCC was initially found at the distal end of the nascent distal convoluted tubule (DCT) and later extended toward the junction with the TAL. After a period of changing proportions, subsegmentation of the DCT into a proximal part expressing NCC alone and a distal part expressing NCC together with NaCa was evident. Strong coexpression of rENaC and 11HSD was observed in early nascent connecting tubule (CNT) and collecting ducts and later also in the distal portion of the DCT. Ontogeny of the expression of NCC, NaCa, 11HSD, and rENaC in the late distal convolutions indicates a heterogenous origin of the CNT. These data present a detailed analysis of the relations between the anatomic differentiation of the developing renal tubule and the expression of tubular transport proteins.
MeSH Terms
- 11-beta-Hydroxysteroid Dehydrogenases
- Aging
- Animals
- Animals, Newborn
- Carrier Proteins
- Epithelial Sodium Channels
- Hydroxysteroid Dehydrogenases
- Nephrons
- Rats
- Rats, Sprague-Dawley
- Sodium
- Sodium Channels
- Sodium-Calcium Exchanger
- Sodium-Phosphate Cotransporter Proteins
- Sodium-Phosphate Cotransporter Proteins, Type II
- Sodium-Potassium-Chloride Symporters
- Symporters
The intralysosomal proteinases cathepsins B and L were measured in microdissected segments of rat nephron. Z-Arg-Arg-NMec served as the substrate for cathepsin B and Z-Phe-Arg-NMec for cathepsin B and L together. Individual S1, S2, and S3 segments of proximal tubules, TDL, MTAL, CTAL, DCT, CCD, and OMCD were dissected from young female rats weighing 130 /- 11 g with low protein excretion (0.68 /- 0.1 mg/24 h), from older female rats weighing 289 /- 9 g with protein excretion of 10 /- 6.3 mg/24 h, from older male rats weighing 404 /- 11 g with protein excretion of 22 /- 6 mg/24 h, from female rats weighing 198 /- 10 g with albumin-induced proteinuria (411 /- 134 mg/24 h), and from female rats weighing 203 /- 11 g with low protein excretion (2.7 /- 0.4 mg/24 h). The distributions of cathepsin activities along the nephron were similar. In all five groups, S1 and S2 segments had enzyme activities three times higher than in all remaining segments. In S2 and S3, enzyme activities were two to three times higher in proteinuric animals. These findings suggest that in proteinuric animals the increase in the protein load delivered to the proximal tubules selectively stimulated cathepsin activities in the S2 and S3 segments, presumably because of an increase in protein uptake, and that cathepsins B and L participate in lysosomal digestion of protein reabsorbed from the glomerular filtrate via endocytosis.
MeSH Terms
- Aging
- Animals
- Cathepsin B
- Cathepsin L
- Cathepsins
- Coumarins
- Cysteine Endopeptidases
- Endopeptidases
- Female
- Hydrogen-Ion Concentration
- In Vitro Techniques
- Kinetics
- Male
- Nephrons
- Protease Inhibitors
- Proteinuria
- Rats
- Rats, Inbred Strains
- Reference Values
- Serum Albumin, Bovine
- Sex Characteristics
- Time Factors