ADA
Adenosine deaminase (EC 3.5.4.4) (Adenosine aminohydrolase) [ADA1]
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Over 466 million people worldwide are diagnosed with hearing loss (HL). About 90% of HL cases are sensorineural HL (SNHL) with treatments limited to hearing aids and cochlear implants with no FDA-approved drugs. Intriguingly, ADA-deficient patients have been reported to have bilateral SNHL, however, its underlying cellular and molecular basis remain unknown. We report that Ada mice, phenocopying ADA-deficient humans, displayed SNHL. Ada mice cochlea with elevated adenosine caused substantial nerve fiber demyelination and mild hair cell loss. ADA enzyme therapy in these mice normalized cochlear adenosine levels, attenuated SNHL, and prevented demyelination. Additionally, ADA enzyme therapy rescued SNHL by restoring nerve fiber structure in Ada mice post two-week drug withdrawal. Moreover, elevated cochlear adenosine in untreated mice was associated with enhanced Adora2b gene expression. Preclinically, ADORA2B-specific antagonist treatment in Ada mice significantly improved HL, nerve fiber density, and myelin compaction. We also provided genetic evidence that ADORA2B is detrimental for age-related SNHL by impairing cochlear myelination in WT aged mice. Overall, understanding purinergic molecular signaling in SNHL in Ada mice allows us to further discover that ADORA2B is also a pathogenic factor underlying aged-related SNHL by impairing cochlear myelination and lowering cochlear adenosine levels or blocking ADORA2B signaling are effective therapies for SNHL.
Keywords
- ADA-deficiency
- adenosine deaminase deficiency
- aging
- myelin protein zero
- myelination
Adenosine is a neuromodulator that has been involved in aging and neurodegenerative diseases as Alzheimer's disease (AD). In the present work, we analyzed the possible modulation of purine metabolites, 5'nucleotidase (5'NT) and adenosine deaminase (ADA) activities, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its phosphorylated form during aging in the cerebral cortex. Three murine models were used: senescence-accelerated mouse-resistant 1 (SAMR1, normal senescence), senescence-accelerated mouse-prone 8 (SAMP8, a model of AD), and the wild-type C57BL/6J (model of aging) mice strains. Glutamate and excitatory amino acid transporter 2 (EAAT2) levels were also measured in these animals. HPLC, Western blotting, and enzymatic activity evaluation were performed to this aim. 5'-Nucleotidase (5'NT) activity was decreased at six months and recovered at 12 months in SAMP8 while opposite effects were observed in SAMR1 at the same age, and no changes in C57BL/6J mice. ADA activity significantly decreased from 3 to 12 months in the SAMR1 mice strain, while a significant decrease from 6 to 12 months was observed in the SAMP8 mice strain. Regarding purine metabolites, xanthine and guanosine levels were increased at six months in SAMR1 without significant differences in SAMP8 mice. In C57BL/6J mice, inosine and xanthine were increased, while adenosine decreased, from 4 to 24 months. The AMPK level was decreased at six months in SAMP8 without significant changes nor in SAMR1 or C57BL/6J strains. Glutamate and EAAT2 levels were also modulated during aging. Our data show a different modulation of adenosine metabolism participants in the cerebral cortex of these animal models. Interestingly, the main differences between SAMR1 and SAMP8 mice were found at six months of age, SAMP8 being the most affected strain. As SAMP8 is an AD model, results suggest that adenosinergic metabolism is involved in the neurodegeneration of AD.
Keywords
- adenosine metabolism
- aging
- animal models
- glutamate
- purinergic signaling
The ART program in low- and middle-income countries (LMIC) like India, follows a public health approach with a standardized regimen for all people living with HIV (PLHIV). Based on the evidence from high-income countries (HIC), the risk of an enhanced, and accentuated onset of premature-aging or age-related diseases has been observed in PLHIV. However, very limited data is available on residual inflammation and immune activation in the populations who are on first-generation anti-HIV drugs like zidovudine and lamivudine that have more toxic side effects. Therefore, the aim of the present study was to evaluate the levels of systemic inflammation and understand the risk of age-associated diseases in PLHIV on long-term suppressive ART using a large number of biomarkers of inflammation and immune activation. Blood samples were obtained from therapy naïve PLHIV (Pre-ART, [i]n[/i] = 43), PLHIV on ART for >5 years (ART, [i]n[/i] = 53), and HIV-negative healthy controls (HIVNC, [i]n[/i] = 41). Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, and telomere length. Several statistical tests were performed to compare the groups under study. Multivariate linear regression was used to investigate the associations. Despite a median duration of 8 years of successful ART, sCD14 ([i]p[/i] < 0.001) and sCD163 ([i]p[/i] = 0.04) levels continued to be significantly elevated in ART group as compared to HIVNC. Eleven inflammatory markers, including 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL, and TRANCE, were found to be significantly different ([i]p[/i] < 0.05) between the groups. Many of these markers are associated with age-related co-morbidities including cardiovascular disease, neurocognitive decline and some of these markers are being reported for the first time in the context of HIV-induced inflammation. Linear regression analysis showed a significant negative association between HIV-1-positivity and telomere length ([i]p[/i] < 0.0001). In ART-group CXCL1 ([i]p[/i] = 0.048) and TGF-α ([i]p[/i] = 0.026) showed a significant association with the increased telomere length and IL-10RA was significantly associated with decreased telomere length ([i]p[/i] = 0.042). This observation warrants further mechanistic studies to generate evidence to highlight the need for enhanced treatment monitoring and special interventions in HIV-infected individuals.
MeSH Terms
- Adult
- Aging
- Anti-HIV Agents
- Antiretroviral Therapy, Highly Active
- Biomarkers
- CD4 Lymphocyte Count
- Computational Biology
- Cross-Sectional Studies
- Disease Susceptibility
- Duration of Therapy
- Female
- HIV Infections
- Humans
- Inflammation
- Male
- Metabolome
- Metabolomics
- Middle Aged
- Proteomics
- Telomere Homeostasis
- Viral Load
Keywords
- HIV
- India
- LMIC (lower middle income country)
- inflammation markers
- long term antiretroviral therapy
Diabetic kidney disease (DKD) is an independent predictor of cardiovascular morbidity and mortality in type 1 diabetes (T1D). We aimed to explore clinical and biochemical factors, including the achievement of American Diabetes Association (ADA) recommended targets associated with DKD in people living with T1D for ≥50 years. This was a post hoc analysis of a cross-sectional study of 75 participants enrolled in the Canadian Study of Longevity in T1D. We explored diabetes-related complications, including neuropathy, retinopathy, cardiovascular disease, and DKD. Study participants were dichotomized based on the achievement of ADA recommended targets as the low-target group (achieving ≤4 targets, [i]n[/i] = 31) and high-target group (achieving >4 targets, [i]n[/i] = 44). The outcome of interest was DKD defined by estimated glomerular filtration rate (eGFR) values <60/mL/min/1.73 m and/or 24-h albumin excretion >30 mg. Multivariable logistic regression models were employed to estimate odds ratios (ORs) for DKD with 95% confidence intervals (CIs). Of the 75 participants with prolonged T1D duration (45% male, mean age 66 years), 25 participants had DKD and 50 did not. There was no statistical difference between the high- and low-target groups in terms of age and body mass index. eGFR was significantly higher and the prevalence of diabetic retinopathy was significantly lower in the high-target group. Older age at diagnosis of T1D and lower frequency component to high-frequency component ratio increased the odds of having DKD. In adults with prolonged T1D duration, older age at diagnosis and lower heart rate variability may be associated with DKD.
MeSH Terms
- Age Factors
- Aged
- Canada
- Cross-Sectional Studies
- Diabetes Mellitus, Type 1
- Diabetic Nephropathies
- Female
- Heart Rate
- Humans
- Longevity
- Male
- Middle Aged
- Prevalence
- Risk Factors
Keywords
- Type 1 diabetes
- diabetic kidney disease
- diabetic neuropathy
- diabetic retinopathy
In the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) VII trial, IDegLira (a combination of insulin degludec and liraglutide) was compared with insulin glargine U100 plus insulin aspart. Both treatment approaches achieved similar glycemic control, but there were differences in hypoglycemia, changes in body weight, and injection frequency. The aim of the present analysis was to assess the short-term cost effectiveness of IDegLira versus insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin in the U.S. A cost-utility model was developed to evaluate the clinical and economic outcomes associated with the 2 treatments over a 1-year time horizon, capturing the impact on quality of life of hypoglycemic events, body mass index, and injection frequency. Costs were captured from a healthcare payer perspective in 2017 U.S. dollars ($). IDegLira was associated with improved quality of life by 0.12 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. The key drivers of this difference were reduced injection frequency and hypoglycemic events avoided. IDegLira was associated with increased annual drug costs, but this was entirely offset by reduced needle costs and reduced costs of self-monitoring of blood glucose testing. IDegLira was associated with total annual cost savings of $743 per patient. IDegLira was found to improve quality-adjusted life expectancy and reduce costs when compared with insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes not achieving glycemic control on basal insulin in the U.S. ADA = American Diabetes Association; BMI = body mass index; CI = confidence interval; DUAL = Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes; GLP-1 = glucagon-like peptide-1; HbA1c = glycated hemoglobin; ICER = incremental cost-effectiveness ratio; IU = international units; QALY = quality-adjusted life year; SMBG = self-monitoring of blood glucose.
MeSH Terms
- Cost Savings
- Diabetes Mellitus, Type 2
- Drug Combinations
- Humans
- Hypoglycemic Agents
- Insulin Aspart
- Insulin Glargine
- Insulin, Long-Acting
- Life Expectancy
- Liraglutide
In recent years, modified glycemic targets have been defined for older adults with diabetes mellitus. In a sample of elderly patients, we have identified several inconsistencies between the real life applicability of glycated hemoglobin goals recommended by the American Diabetes Association and the American Geriatrics Society.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Biomarkers
- Blood Glucose
- Comorbidity
- Diabetes Mellitus, Type 2
- Drug Therapy, Combination
- Endocrinology
- Female
- Geriatrics
- Glycated Hemoglobin A
- Guideline Adherence
- Humans
- Hypoglycemic Agents
- Male
- Medical Overuse
- Practice Guidelines as Topic
- Practice Patterns, Physicians'
- Risk Factors
- Treatment Outcome
- United States
- Voluntary Health Agencies
Keywords
- Elderly
- HbA1c
- Hypoglycemia
- Overtreatment
ATP and adenosine, the main signaling molecules of purinergic system, are involved in toxicological effects induced by metals. The manganese (Mn) exposure induces several cellular changes, which could interfere with signaling pathways, such as the purinergic system. In this study, we evaluated the effects of exposure to manganese(II) chloride (MnCl ) during 96 h on nucleoside triphosphate diphosphohydrolase (NTPDase), ecto-5'-nucleotidase, and adenosine deaminase (ADA) activities, followed by analyzing the gene expression patterns of NTPDases (entpd1, entpd2a.1, entpd2a.2, entpd2-like, entpd3) and ADA (ADA , ADA , ADA , ADAasi, ADAL) families in zebrafish brain. In addition, the brain metabolism of nucleotides and nucleosides was evaluated after MnCl exposure. The results showed that MnCl exposure during 96 h inhibited the NTPDase (1.0 and 1.5 mM) and ecto-ADA (0.5, 1.0, and 1.5 mM) activities, further decreasing ADA2.1 expression at all MnCl concentrations analyzed. Purine metabolism was also altered by the action of MnCl . An increased amount of ADP appeared at all MnCl concentrations analyzed; however, AMP and adenosine levels are decreased at the concentrations of 1.0 and 1.5 mM MnCl , whereas decreased inosine (INO) levels were observed at all concentrations tested. The findings of this study demonstrated that MnCl may inhibit NTPDase and ecto-ADA activities, consequently modulating nucleotide and nucleoside levels, which may contribute for the toxicological effects induced by this metal.
MeSH Terms
- Adenosine Deaminase
- Aging
- Animals
- Antigens, CD
- Apyrase
- Brain
- Chlorides
- Female
- Male
- Manganese Compounds
- Nucleosides
- Nucleotides
- Zebrafish
Keywords
- Adenosine deaminase
- Manganese(II) chloride
- NTPDases
- Purinergic signaling
- Zebrafish
Autism is a neurodevelopmental disorder characterized by symptoms related to stereotyped movements, deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Evidence indicates an important role of extracellular ATP and adenosine as signaling molecules in autism. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering zebrafish is an animal model that may contribute towards to understanding the mechanisms that underlie social behavior, we investigated the purinergic signaling in a model of embryological exposure to valproic acid (VPA) that induces social interaction deficit in adult zebrafish. We demonstrated embryological exposure to VPA did not change ATP and ADP hydrolysis in zebrafish at 120 dpf, and the cytosolic (soluble) ADA activity was not altered. However, we observed an increase of AMP hydrolysis (12.5 %) whereas the ecto-ADA activity was decreased (19.2 %) in adult zebrafish submitted to embryological exposure to VPA. Quantitative reverse transcription PCR (RT-PCR) analysis showed changes on ntpd8, ADA 2.1, and A2a1 mRNA transcript levels. Brain ATP metabolism showed a rapid catabolism of ATP and ADP, whereas the extracellular metabolism of AMP and adenosine (ADO) occurred slowly. We demonstrated that embryological exposure to VPA altered biochemical and molecular parameters related to purinergic system in adult zebrafish. These findings indicate that the enzyme activities involved in the control of ATP and adenosine levels may be involved in the pathophysiological mechanisms of diseases related to the impairment of social interaction, such as autism.
MeSH Terms
- 5'-Nucleotidase
- Adenosine Deaminase
- Aging
- Animals
- Brain
- Cell Membrane
- Embryo, Nonmammalian
- Extracellular Space
- Gene Expression Regulation
- Hydrolysis
- Nucleotides
- Solubility
- Valproic Acid
- Zebrafish
Keywords
- Adenosine
- Adenosine deaminase
- Autism
- Ectonucleotidases
- Purinergic system
- Zebrafish
Access to the Internet is increasingly critical for health information retrieval, access to certain government benefits and services, connectivity to friends and family members, and an array of commercial and social services that directly affect health. Yet older adults, particularly those with disabilities, are at risk of being left behind in this growing age- and disability-based digital divide. The Americans with Disabilities Act (ADA) was designed to guarantee older adults and persons with disabilities equal access to employment, retail, and other places of public accommodation. Yet older Internet users sometimes face challenges when they try to access the Internet because of disabilities associated with age. Current legal interpretations of the ADA, however, do not consider the Internet to be an entity covered by law. In this article, we examine the current state of Internet accessibility protection in the United States through the lens of the ADA, sections 504 and 508 of the Rehabilitation Act, state laws and industry guidelines. We then compare U.S. rules to those of OECD (Organisation for Economic Co-Operation and Development) countries, notably in the European Union, Canada, Japan, Australia, and the Nordic countries. Our policy recommendations follow from our analyses of these laws and guidelines, and we conclude that the biggest challenge in bridging the age- and disability-based digital divide is the need to extend accessibility requirements to private, not just governmental, entities and organizations.
MeSH Terms
- Access to Information
- Aged
- Disabled Persons
- Geriatrics
- Health Services Accessibility
- Human Rights
- Humans
- Internet
- Public Policy
- United States
Keywords
- Disability
- Information Technology
- Law
- Public Policy
The aim of this study was to evaluate the effect of zinc supplementation on the ecto-adenosine deaminase activity (E-ADA), zinc seric levels and cytokines (TNF-α, IL-1, IL-6, and IL -10) on rats experimentally infected by Trypanosoma evansi. Four groups with 10 rats each were used as negative controls (groups A and B), while the animals from the groups C and D were infected intraperitoneally with 0.1 mL of cryopreserved blood containing 1.4 × 10(4) of trypanosomes. Animals of groups B and D received two doses of Zinc (Zn) at 5 mg kg(-1), subcutaneously, on the 2nd and 7th day post-infection (PI). Blood samples were collected on days 5 (n = 5) and 15 PI (n = 5). Zn supplementation was able to increase the rat's longevity and to reduce their parasitemia. It was observed that seric Zn levels were increased on infected animals under Zn supplementation. Animals that were infected and supplemented with Zn showed changes in E-ADA activity and in cytokine levels (P < 0.05). Zn supplementation of healthy animals (Group B), increased the E-ADA activity, as well as reduced the concentration of cytokines. Infected animals from groups C and D showed increased levels of cytokines. Finally, we observed that Zn supplementation led to a modulation on cytokine's level in rats infected by T. evansi, as well as in E-ADA activity.
MeSH Terms
- Adenosine Deaminase
- Animals
- Cytokines
- Disease Models, Animal
- Immunologic Factors
- Longevity
- Parasite Load
- Parasitemia
- Rats, Wistar
- Serum
- Survival Analysis
- Trypanosoma
- Trypanosomiasis
- Zinc
Keywords
- Adenosine deaminase
- Immune response
- Treatment
- Trypanosoma evansi
Extracellular adenosine, a key regulator of physiology and immune cell function that is found at elevated levels in neonatal blood, is generated by phosphohydrolysis of adenine nucleotides released from cells and catabolized by deamination to inosine. Generation of adenosine monophosphate (AMP) in blood is driven by cell-associated enzymes, whereas conversion of AMP to adenosine is largely mediated by soluble enzymes. The identities of the enzymes responsible for these activities in whole blood of neonates have been defined in this study and contrasted to adult blood. We demonstrate that soluble 5'-nucleotidase (5'-NT) and alkaline phosphatase (AP) mediate conversion of AMP to adenosine, whereas soluble adenosine deaminase (ADA) catabolizes adenosine to inosine. Newborn blood plasma demonstrates substantially higher adenosine-generating 5'-NT and AP activity and lower adenosine-metabolizing ADA activity than adult plasma. In addition to a role in soluble purine metabolism, abundant AP expressed on the surface of circulating neonatal neutrophils is the dominant AMPase on these cells. Plasma samples from infant observational cohorts reveal a relative plasma ADA deficiency at birth, followed by a gradual maturation of plasma ADA through infancy. The robust adenosine-generating capacity of neonates appears functionally relevant because supplementation with AMP inhibited whereas selective pharmacologic inhibition of 5'-NT enhanced Toll-like receptor-mediated TNF-α production in neonatal whole blood. Overall, we have characterized previously unrecognized age-dependent expression patterns of plasma purine-metabolizing enzymes that result in elevated plasma concentrations of anti-inflammatory adenosine in newborns. Targeted manipulation of purine-metabolizing enzymes may benefit this vulnerable population.
MeSH Terms
- 5'-Nucleotidase
- Adenosine
- Adenosine Deaminase
- Adult
- Aging
- Alkaline Phosphatase
- Female
- Gene Expression Regulation, Enzymologic
- Humans
- Infant, Newborn
- Inosine
- Male
Keywords
- ADP
- AMP
- ATP
- Adenosine
- Adenosine Receptor
- Immunology
- Infectious Diseases
- Innate Immunity
- Purine
- Purinergic Agonists
Clinical evaluation of immune reconstitution and health status during HIV-1 infection and anti-retroviral therapy (ART) is largely based on CD4 T cell counts and viral load, measures that fail to take into account the CD8 T cell subset, known to show features of accelerated aging in HIV disease. Here, we compare adenosine deaminase (ADA), glucose uptake receptor 1 (GLUT1), and leucine-rich repeat neuronal 3 (LRRN3) to CD38 expression and telomerase activity, two strong predictors of HIV disease progression. Our analysis revealed that reduced ADA, telomerase activity and LRRN3 gene expression were significantly associated with high CD38 and HLA-DR in CD8 T cells, with % ADA cells being the most robust predictor of CD8 T cell activation. Our results suggest that ADA, LRRN3 and telomerase activity in CD8 T cells may serve as novel, clinically relevant biomarkers of immune status in HIV-1 infection, specifically by demonstrating the degree to which CD8 T cells have progressed to the end stage of replicative senescence. Since chronological aging itself leads to the accumulation of senescent CD8 T cells, the prolonged survival and resultant increased age of the HIV population may synergize with the chronic immune activation to exacerbate both immune decline and age-associated pathologies. The identification and future validation of these new biomarkers may lead to fresh immune-based HIV treatments.
MeSH Terms
- Aging
- Base Sequence
- Biomarkers
- CD8-Positive T-Lymphocytes
- Cellular Senescence
- DNA Primers
- Flow Cytometry
- HIV Infections
- Humans
- Middle Aged
- Real-Time Polymerase Chain Reaction
Serum Adenosine deaminase (ADA) activity in normal healthy control subjects increases upto 30 years, remains steady between 31-60 years of age and shows a steep increase in the age group of 61-70 years. This was compared with serum aspartate transaminase (AST) and alanine transaminase (ALT) activity which also showed a gradual increase upto 40 years of age and decreased thereafter. The activities of serum ADA, AST and ALT increased in patients with hepatitis of all age groups compared to their respective controls. The degree of increase in the activities of the above enzymes in hepatitis, decreased with age. The present study also shows that while studying serum ADA activity in hepatitis for diagnostic purposes, the value obtained in a particular age group should be compared with normal range of values for the respective age group only.
Keywords
- ADA
- Aging
- Hepatitis
- Serum
Aging is a complex phenotype with multiple determinants but a strong genetic component significantly impacts on survival to extreme ages. The dysregulation of immune responses occurring with increasing age is believed to contribute to human morbidity and mortality. Conversely, some genetic determinants of successful aging might reside in those polymorphisms for the immune system genes regulating immune responses. Here we examined the main effects of single loci and multi-locus interactions to test the hypothesis that the adenosine deaminase (ADA) and tumor necrosis factor alpha (TNF-α) genes may influence human life-expectancy. ADA (22G>A, rs73598374) and TNF-α (-308G>A, rs1800629; -238G>A, rs361525) functional SNPs have been determined for 1071 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes: for men (women), the first class consists of individuals<66 years old (<73 years old), the second class of individuals 66-88 years old (73-91 years old), and the third class of individuals>88 years old (>91 years old). Single-locus analysis showed that only ADA 22G>A is significantly associated with human life-expectancy in males (comparison 1 (age class 2 vs. age class 1), O.R. 1.943, P=0.036; comparison 2 (age class 3 vs. age class 2), O.R. 0.320, P=0.0056). Age- and gender-specific patterns of epistasis between ADA and TNF-α were found using Generalized Multifactor Dimensionality Reduction (GMDR). In comparison 1, a significant two-loci interaction occurs in females between ADA 22G>A and TNF-α -238G>A (Sign Test P=0.011). In comparison 2, both two-loci and three-loci interaction are significant associated with increased life-expectancy over 88 years in males. In conclusion, we report that a combination of functional SNPs within ADA and TNF-α genes can influence life-expectancy in a gender-specific manner and that males and females follow different pathways to attain longevity.
MeSH Terms
- Adenosine Deaminase
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Base Sequence
- DNA Primers
- Epistasis, Genetic
- Female
- Humans
- Life Expectancy
- Male
- Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
- Tumor Necrosis Factor-alpha
- Young Adult
The changing social and economic conditions and the increase of the life span induced a progressive increase of the general prevalence of DMT2, particularly in the elderly population of the highly evoluted countries. Up to now 18 genetic loci have been identified, each of them consisting of several single nucleotide polymorphisms (SNPs). The evidence that the DMT2 is regulated by a high number of genes, demonstrate the pathogenetic complexity of this disease. The onset of diabetes mellitus (DM) in medium age is a consequence of the breakdown of the glycemic homeostasis in correlation with the genetic factors, such as the variants of the TCF7L2, obesity, etc., and the environmental factors, such as the life-style, the evolution of chronic-degenerative diseases, etc. In case of DM that onsets in old age we have to add the deterioration of the anti-aging defense mechanisms, characterized by the antagonistic action of the genes of longevity and aging. One can observe several clinical and therapeutic differences; therefore, the authors of this review propose the reinsertion of three forms into the DMT2 correlated with the age of onset and with the actual age of the subjects: the maturity onset diabetes (MOD), the maturity onset diabetes in elderly (MODE), and the senile diabetes (DS).
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Diabetes Mellitus, Type 2
- Female
- Humans
- Incidence
- Male
- Polymorphism, Single Nucleotide
- Prevalence
Aim of this study was to investigate whether the polymorphic ADA (Adenosine Deaminase, EC 3.5.4.4) gene, which determines the cellular level of adenosine and plays a crucial role in the regulation of the immune system and in the control of metabolic rates, is involved in longevity. 884 unrelated healthy individuals (age range 10-106 years, 400 males and 484 females) from central Italy were studied. ADA genotyping was performed by RFLP-PCR. Frequency distributions were compared using the chi-square test and a three-way contingency table analysis by a log linear model was applied to test independence between the variables. We found that ADA influences human life-span in a sex and age specific way. An increased frequency of ADA*2 carriers was found in males aged 80-85, and a decreased frequency in males over 85 (chi(2) = 13.93; df = 3; P = 0.003); significant differences among the age groups was not found in females. A strong interaction among age groups, ADA genotype and sex (G = 15.086; df = 3; P = 0.0017) was found. Males aged 80-85 could be protected from ischemic stroke by higher levels of adenosine (determined by the ADA*2 allele). The decrease of ADA*2 carriers in males over 85 may depend essentially on immunological factors; reduced levels of adenosine protect from asthma and other pulmonary diseases and lead to a reduced activation of inflammatory cells and pro-inflammatory cytokines production. Moreover, the low level of adenosine may potentiate the activity of NK and other cellular effectors against tumor cells. The negligible effect of ADA genetic polymorphism in females suggest a marginal influence of genetic factors in determining longevity in this sex, confirming previous reports.
MeSH Terms
- Adenosine Deaminase
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Child
- Female
- Genotype
- Humans
- Longevity
- Male
- Middle Aged
- Polymorphism, Genetic
- Sex Characteristics
- Young Adult
Adenosine is generated at sites of tissue injury where it serves to regulate inflammation and damage. Adenosine signaling has been implicated in the regulation of pulmonary inflammation and damage in diseases such as asthma and chronic obstructive pulmonary disease; however, the contribution of specific adenosine receptors to key immunoregulatory processes in these diseases is still unclear. Mice deficient in the purine catabolic enzyme adenosine deaminase (ADA) develop pulmonary inflammation and mucous metaplasia in association with adenosine elevations making them a useful model for assessing the contribution of specific adenosine receptors to adenosine-mediated pulmonary disease. Studies suggest that the A(2A) adenosine receptor (A(2A)R) functions to limit inflammation and promote tissue protection; however, the contribution of A(2A)R signaling has not been examined in the ADA-deficient model of adenosine-mediated lung inflammation. The purpose of the current study was to examine the contribution of A(2A)R signaling to the pulmonary phenotype seen in ADA-deficient mice. This was accomplished by generating ADA/A(2A)R double knockout mice. Genetic removal of the A(2A)R from ADA-deficient mice resulted in enhanced inflammation comprised largely of macrophages and neutrophils, mucin production in the bronchial airways, and angiogenesis, relative to that seen in the lungs of ADA-deficient mice with the A(2A)R. In addition, levels of the chemokines monocyte chemoattractant protein-1 and CXCL1 were elevated, whereas levels of cytokines such as TNF-alpha and IL-6 were not. There were no compensatory changes in the other adenosine receptors in the lungs of ADA/A(2A)R double knockout mice. These findings suggest that the A(2A)R plays a protective role in the ADA-deficient model of pulmonary inflammation.
MeSH Terms
- Adenosine Deaminase
- Animals
- Bronchoalveolar Lavage Fluid
- Cell Count
- Chemokines
- Gene Expression Regulation
- Inflammation Mediators
- Longevity
- Lung
- Mice
- Mice, Inbred Strains
- Mice, Knockout
- Mucins
- Mucus
- Neovascularization, Pathologic
- Pneumonia
- RNA, Messenger
- Receptor, Adenosine A2A
- Receptors, Interleukin-8B
- Trachea
It is the position of the American Dietetic Association (ADA) that the quality of life and nutritional status of older residents in long-term care facilities may be enhanced by liberalization of the diet prescription. The Association advocates the use of qualified dietetics professionals to assess and evaluate the need for medical nutrition therapy according to each person's individual medical condition, needs, desires, and rights. In 2003, ADA designated aging as its second "emerging" area. Nutrition care in long-term settings must meet two goals: maintenance of health and promotion of quality of life. The Nutrition Care Process includes assessment of nutritional status through development of an individualized nutrition intervention plan. Medical nutrition therapy must balance medical needs and individual desires and maintain quality of life. The recent paradigm shift from restrictive institutions to vibrant communities for older adults requires dietetics professionals to be open-minded when assessing risks vs benefits of therapeutic diets, especially for frail older adults. Food is an essential component of quality of life; an unacceptable or unpalatable diet can lead to poor food and fluid intake, resulting in weight loss and undernutrition and a spiral of negative health effects. Facilities are adopting new attitudes toward providing care. "Person-centered" or "resident-centered care" involves residents in decisions about schedules, menus, and dining locations. Allowing residents to participate in diet-related decisions can provide nutrient needs, allow alterations contingent on medical conditions, and simultaneously increase the desire to eat and enjoyment of food, thus decreasing the risks of weight loss, undernutrition, and other potential negative effects of poor nutrition and hydration.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Dietary Services
- Dietetics
- Geriatric Assessment
- Health Services for the Aged
- Humans
- Long-Term Care
- Needs Assessment
- Nutrition Assessment
- Nutrition Disorders
- Nutrition Therapy
- Nutritional Requirements
- Nutritional Status
- Patient-Centered Care
- Quality of Life
- Societies
- United States
To assess, by a house to house study, the prevalence of diabetes, impaired glucose tolerance (IGT) and their associated risk factors in Benghazi, Libya using 75 gram oral glucose tolerance test (OGTT) and ADA 1997 and WHO 1998 diagnostic criteria. A multistage cluster sampling was used to select the study population. A total of 314 men and 554 women underwent a standard 75 grams OGTT. The response rate was 77.7% for males and 89.2% for females. The overall prevalence of IGT was 8.5% (95% confidence interval (CI) 5.8 - 11.3) (men 8.6% 95% CI 7.7-9.6, women 8.5% 95% CI 5.0 -11.9), and that of diabetes was 14.1% (95% CI 10.9-17.1) (men 16.3% 95% CI 14.5-18.3 women 13.0% 95% CI 10.0 - 16.1). Diabetes was present in 19.4% (95% CI 15.4-20.5) (men 22.7% 95% CI 20.2-25.4, women 17.6% 95% CI 14.1-19.1) in 30-64 years age range. Prevalence of diabetes was slightly higher in urban than in rural areas (14.5% vs 13.5%). The prevalence of newly diagnosed diabetes in urban and rural areas were 3.6% and 7.3% respectively and that of known diabetes were 10.9% and 6.3% respectively. Associated risk factors with diabetes and IGT were age, family history of diabetes, hypertension, BMI, WHR and serum cholesterol. Diabetes is emerging as an important public health problem in Libya and should rank very high in the priority list of health planners.
MeSH Terms
- Adult
- Aging
- Body Constitution
- Body Mass Index
- Cholesterol
- Diabetes Complications
- Diabetes Mellitus
- Female
- Glucose Intolerance
- Humans
- Hypertension
- Libya
- Male
- Middle Aged
- Risk Factors
- Rural Population
- Urban Population
Using data on history of diabetes, fasting glucose (FG) and the oral glucose tolerance test (OGTT), the authors contrasted cardiovascular disease (CVD) risk factors (body mass index, blood pressure, lipids and glycated hemoglobin) in 3052 African-American and White adults aged 70-79 in mutually exclusive categories of diagnosed diabetes, undiagnosed diabetes defined by the American Diabetes Association (ADA), isolated post-challenge hyperglycemia (IPH; FG < 126 mg/dL and 2 h post-OGTT > or = 200 mg/dL), impaired fasting glucose (IFG; FG > or = 110 but < 126 mg/dL), and individuals who were non-diabetic by both ADA and World Health Organization (WHO) criteria (FG < 126 mg/dL and 2 h post-challenge glucose < 200 mg/dL). The prevalence of diagnosed diabetes, undiagnosed ADA diabetes and IPH were 15.2, 3.8 and 4.7%, respectively, with more diagnosed and undiagnosed ADA diabetes in African-Americans than Whites. Compared to mean glycated hemoglobin (HbA(1c)) among ADA/WHO non-diabetic individuals (6.0%), HbA(1c) was substantially higher in the diagnosed diabetes and undiagnosed ADA diabetes groups (8.0% and 7.7%), but not in the IPH group (6.3%). The diagnosed and undiagnosed ADA diabetic groups had worse CVD risk factor profiles than the ADA/WHO non-diabetic group. IPH subjects had elevated levels of some CVD risk factors, but differences were more modest than those for the diabetic groups. Among people with IPH, those who also had IFG had worse CVD profiles than those with IPH alone. Although the OGTT may identify additional adults with more CVD risk factors than normals, these differences appear to be clustered among those who also have IFG.
MeSH Terms
- African Americans
- African Continental Ancestry Group
- Aged
- Aging
- Body Composition
- Cohort Studies
- Diabetes Mellitus
- Epidemiologic Research Design
- European Continental Ancestry Group
- Female
- Glucose Tolerance Test
- Guidelines as Topic
- Humans
- Hyperglycemia
- Male
- Prevalence
- Societies, Medical
- United States
- World Health Organization
Adenosine is a signaling nucleoside that has been suggested to play a role in asthma in part through its ability to influence mediator release from mast cells. Adenosine levels are elevated in the lungs of asthmatics, further implicating this molecule in the regulation of lung inflammation and suggesting that animal models exhibiting endogenous increases in adenosine will be useful for the analysis of adenosine function. Adenosine deaminase (ADA) is a purine catabolic enzyme responsible for regulating the levels of adenosine in tissues and cells. ADA-deficient mice develop lung inflammation and damage reminiscent of that seen in asthma in association with elevated adenosine levels. In the current study, we investigated the status of mast cells in ADA-deficient lungs. ADA-deficient mice exhibited extensive lung mast cell degranulation concurrent with elevated adenosine levels. ADA enzyme therapy prevented the accumulation of lung adenosine as well as mast cell degranulation, suggesting that this process was dependent on elevated lung adenosine levels. Consistent with this, treatment of ADA-deficient mice with broad spectrum adenosine receptor antagonists attenuated degranulation by 30 to 40%, supporting the involvement of adenosine receptor signaling. Moreover, these studies demonstrate the ability of endogenously generated adenosine to influence lung mast cell degranulation in a receptor-mediated manner and establish ADA-deficient mice as a model system to investigate the specific adenosine receptor responses involved in the degranulation of lung mast cells.
MeSH Terms
- Adenosine
- Adenosine Deaminase
- Aging
- Animals
- Cell Count
- Cell Degranulation
- Cromolyn Sodium
- Immunohistochemistry
- Lung
- Mast Cells
- Mice
- Mice, Transgenic
- Receptors, Purinergic P1
- Tolonium Chloride
The American Diabetes Association (ADA) clinical practice recommendations have been widely promoted, but they lack a geriatric-specific approach to care. We aimed to determine the style of care that endocrinologists, general internists, and geriatricians provided to their elderly patients with diabetes and to what extent these medical professionals adhered to the ADA standards. We performed a retrospective cohort study of a stratified sample of 531 diabetic patients aged 65 years and older from the endocrinology, general internal medicine, and geriatrics clinics of an urban academic medical center. Patients of geriatricians were older, had higher comorbidity, and were more likely to be demented. The average number of diabetic complications was similar across the specialties, although patients of endocrinologists had higher prevalence of neuropathy and retinopathy compared with patients of geriatricians. Endocrinologists were more likely to use insulin, multiple types of insulin, and combined oral hypoglycemic and insulin therapies. Most patients had hemoglobin A1c measured, and average values were similarly high across specialties at 8.6%. Blood pressures were above 130/85 mm Hg in 85% of the patients. All specialties rarely measured urine microalbumin; geriatricians seldom performed fractionated cholesterol tests, and ophthalmology visits occurred in only half of the patients. Endocrinologists had the most aggressive, complex diabetes treatment regimens, although geriatricians had older patients with more dementia and lower prevalence of microvascular complications. Average hemoglobin A1c levels and blood pressures were higher than recommended among patients of all three specialties. Screening for diabetic complications and hyperlipidemia was lower than advised.
MeSH Terms
- Aged
- Cohort Studies
- Delivery of Health Care
- Dementia
- Diabetes Mellitus
- Endocrinology
- Female
- Geriatrics
- Glycated Hemoglobin A
- Health Care Costs
- Health Resources
- Humans
- Hypoglycemic Agents
- Insulin
- Internal Medicine
- Male
- Referral and Consultation
- Retrospective Studies
This article examines the ways in which the growing economic market for assistive technology (AT) may be analyzed in the context of effective implementation of the Americans with Disabilities Act (ADA). It summarizes the results of an ongoing study of patent data from the United States Patent and Trademark Office (PTO). The purpose of the study is to examine how the ADA is fostering innovation and economic opportunity for AT developers, manufacturers, and retailers. The findings suggest that evaluations of the ADA based on its perceived costs to society need to be balanced by the range of societal benefits accruing from the law, including those unanticipated economic benefits found in the present study.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Disabled Persons
- Humans
- Middle Aged
- Patents as Topic
- Self-Help Devices
- United States
The enzymatic fundamentals of lipid metabolism of equine have not been thoroughly investigated at this point in time. It is still unclear why ponies in contrast to horses may become hyperlipaemic when coming negative energy balance. In this study, the activities of the triglyceride-cleaving key enzymes of ponies are large bred horses were investigated in order to obtain insight into the aetiology of the syndrome. The objective of the study was to measure the activities of hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in ponies and horses in ex vivo in vitro assays. Norepinephrine (NE) stimulated pony adipocytes to release FFA in a linear fashion (4.57 /- 2.09 nmol FFA.10(5) cells-1.min-1). This was not observed in horses. Lipolysis was significantly higher in fat cells of ponies than in horses when adenosine deaminase (ADA) and NE were added (12.71 /- 3.12 vs. 1.96 /- 1.22 nmol FFA.10(5) cells-1.min-1). Relative inhibition of lipolysis by the action of insulin was comparable in adipocytes of horses and ponies. However, absolute FFA release in pony fat cells was as high as the maximal NE and ADA stimulated lipolysis in horse adipocytes. Postheparin plasma lipase activities in ponies and horses did not differ between the sub-species. This finding was supported by the results obtained from measurement of LPL activity in adipose and muscle tissue showing only a tendency of increased activities in pony explants when compared to horse tissue incubations. This study further supports the hypothesis that differences in regulation of TG release from fat stores rather than clearance of TG from plasma is causative for the development of hyperlipaemia in ponies. Abbreviations used: ADA, adenosine deaminase; BW, body weight; FFA, free fatty acid; HSL, hormone-sensitive lipase; HTGL, hepatic triglyceride lipase; LPL, lipoprotein lipase; NE, norepinephrine; SDS, sodium dodecyl sulfate; TG, triglyceride; VLDL, very low density lipoprotein.
MeSH Terms
- Adipocytes
- Aging
- Animals
- Female
- Horses
- Kinetics
- Lipase
- Lipolysis
- Male
- Muscle, Skeletal
Effect of alloxan induced diabetes on the activity of adenosine deaminase (ADA) was studied in the liver, spleen, stomach and small intestine of mice at two different postnatal ages (preweaned, 15-day and postweaned, 60-day). Alloxan significantly stimulates (133%) ADA activity in the liver of 15-day old mice, while it has no significant effect in the 60-day old animals. In contrast, ADA activity was moderately increased (25%) in spleen of both the ages. However, no significant influence of alloxan was observed on ADA activity of stomach at either age of mice. On the other hand, alloxan treatment increases (69%) intestinal ADA activity in 15-day old mice, with no significant change in 60-day old animals. Thus, alloxan diabetes increases ADA activity in an age- and tissue-specific manner. Stimulation of ADA activity in diabetic mice might play role in immune and other metabolic dysfunctions in diabetic conditions.
MeSH Terms
- Adenosine Deaminase
- Aging
- Alloxan
- Animals
- Diabetes Mellitus, Experimental
- Female
- Intestine, Small
- Liver
- Mice
- Mice, Inbred BALB C
- Organ Specificity
- Spleen
- Stomach
Adenosine deaminase (ADA; EC 3.5.4.4) deficiency in humans is an autosomal recessive genetic disorder that results in severe combined immunodeficiency disease. ADA-deficient mice generated by targeted gene disruption die perinatally, preventing postnatal analysis of ADA deficiency. We have recently rescued ADA-deficient fetuses from perinatal lethality by expression of an ADA minigene in the placentas of ADA-deficient fetuses, thus generating postnatal mice admissible to analysis of ADA deficiency. The minigene used also directed ADA expression to the forestomach postnatally, producing adult animals that lacked ADA enzymatic activity in all tissues outside the gastrointestinal tract. Mice with limited ADA expression exhibited profound disturbances in purine metabolism, including thymus-specific accumulations of deoxyadenosine and dATP, and inhibition of S-adenosylhomocysteine hydrolase in the thymus, spleen, and, to a lesser extent, the liver. Lymphopenia and mild immunodeficiency were associated with these tissue-specific metabolic disturbances. These mice represent the first genetic animal model for ADA deficiency and provide insight into the tissue-specific requirements of ADA.
MeSH Terms
- Adenosine Deaminase
- Adenosylhomocysteinase
- Aging
- Animals
- B-Lymphocytes
- Cells, Cultured
- Death
- Genotype
- Hydrolases
- Immunologic Deficiency Syndromes
- Lymphocyte Activation
- Mice
- Mice, Knockout
- Mice, Mutant Strains
- Nucleosides
- Nucleotides
- Organ Specificity
- Spleen
- T-Lymphocytes
We evaluated the age-related distribution of adenosine deaminase (ADA) and adenosine deaminase-complexing protein (CP) in rabbit kidney by immunohistochemical staining procedures. Paraffin- or resin-embedded tissue from rabbits < 1 week-4 years of age were stained by the peroxidase-anti-peroxidase (PAP) method for ADA and CP. With the exception of neonates, the qualitative staining pattern of each protein remained generally constant with age. In the cortex, distal tubules, blood vessels, histiocytes, and epithelial cells lining Bowman's capsule stained for ADA. Proximal tubules and glomeruli were positive for CP. In contrast to the segregated pattern in the cortex, staining for ADA and CP overlapped in the corticomedullary junction. ADA and CP co-localized on the brush border of tubule cells of the S3 segment. In the cytoplasm of these cells, staining for ADA was characterized by scattered punctuate deposits of peroxidase reaction product. In some instances these punctuate deposits also appeared to be positive for CP. In medulla, epithelial cells of the thin limb were positive for both ADA and CP, whereas papillary collecting ducts stained only for CP. These results document the age-related, tissue-specific expression and localization of ADA in renal tissue, features that probably reflect the crucial role played by the enzyme in adenosine/deoxyadenosine catabolism. In addition, colocalization of ADA and CP on the brush border of cells in the S3 segment of proximal tubules provides support for the hypothesis that one function of CP may be to position ADA on the plasma membrane of specific cell populations, further expanding the enzyme's utility in nucleoside metabolism.
MeSH Terms
- Adenosine Deaminase
- Aging
- Animals
- Animals, Newborn
- Female
- Glycoproteins
- Histological Techniques
- Isoenzymes
- Kidney
- Male
- Microscopy, Electron
- Rabbits
- Subcellular Fractions
The major objectives of the present study were to detect whether there are any differences in genetic blood markers distribution between the young and old Israeli population. We also investigated the question about the relationship between the genetic heterozygosity (H) and fluctuating asymmetry (FA) of an individual. The study sample consisted of 208 elderly people aged between 75 and 94 years old. Each individual was assessed for the same 18 anthropological traits, 8 of which were paired bilateral structures and 10 were size and mass measurements. Thirteen polymorphic gene markers were also taken from each individual. Most of the studied gene systems showed no inter-group (old sample vs 207 young individuals) differences. Significant differences were detected at ADA, ESD, GTP1 and FY loci. These differences were mainly due for the considerably lower frequency of the heterozygous individuals in elderly samples. Our working hypothesis at the next stage of the analysis were as follows: 1. Morphologically central phenotypes are more symmetric (processes lower FA) than morphologically extreme individuals. 2. There is a detectable negative correlation between the FA and individuals H. To study these questions we developed a multivariate measure of FA and morphological deviation of the individual from the population centroid. Yet, no reliable evidence in support of either of the two hypotheses were obtained.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Anthropometry
- Female
- Genetic Markers
- Genetics, Population
- Heterozygote
- Humans
- Israel
- Male
- Multivariate Analysis
- Phenotype
We have generated mice with a null mutation at the Ada locus, which encodes the purine catabolic enzyme adenosine deaminase (ADA, EC 3.5.4.4). ADA-deficient fetuses exhibited hepatocellular impairment and died perinatally. Their lymphoid tissues were not largely affected. Accumulation of ADA substrates was detectable in ADA-deficient conceptuses as early as 12.5 days postcoitum, dramatically increasing during late in utero development, and is the likely cause of liver damage and fetal death. The results presented here demonstrate that ADA is important for the homeostatic maintenance of purines in mice.
MeSH Terms
- Adenosine Deaminase
- Adenosine Triphosphate
- Aging
- Animals
- Deoxyadenine Nucleotides
- Female
- Genes, Lethal
- Genotype
- Gestational Age
- Hematopoietic Stem Cells
- Homeostasis
- Leukocytes
- Liver
- Mice
- Mice, Mutant Strains
- Mutagenesis
- Pregnancy
- Purines
- Restriction Mapping
The activities of two enzymes of purine metabolism, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP), were determined in spleen lymphocytes from mice of various ages. We found that in the older animals, which have depressed responses to concanavalin A and phytohemagglutinin, there is a decrease in the activity of PNP but normal activity of ADA. The decline of PNP activity was seen at 7.5 months of age and appears to be concurrent with a decline in T-cell function. These results suggest that a decrease in PNP activity may be a contributing factor in the immunodeficient state of the aged.
MeSH Terms
- Adenosine Deaminase
- Aging
- Animals
- Immunity, Cellular
- Mice
- Mitogens
- Nucleoside Deaminases
- Pentosyltransferases
- Purine-Nucleoside Phosphorylase
- Spleen
In this study we compare the phenotype and the enzyme content of T lymphocytes purified from tonsils and from circulating blood before and different times after in vitro activation with PHA. The phenotype was studied with the following panel of monoclonal antibodies for the presence of activation antigens: OKT9, OKT10, anti-Dr, and Tac antigen. The enzyme content was studied by estimation of the LDH isoenzyme distribution and the enzymes of the purine metabolism ADA and PNP. In addition, the in vitro responsiveness of the T lymphocytes from tonsils and blood to human recombinant interleukin 2, to the lectins PHA, Con A and PWM was also studied. The LDH isoenzyme pattern expressed as B:A ratio decreases progressively after in vitro activation of T lymphocytes. The B:A ratio is already significantly different as early as 12 hr after activation, at a time that OKT9 and Tac are already expressed, but before the expression of OKT10, HLA-Dr, and the onset of the DNA synthesis. Tonsillar T lymphocytes exhibit also a significantly lower B:A ratio, but the activation antigens are not detected on their surface, except for the Tac antigens by means of a sensitive protein A rosette assay. Tonsillar T lymphocytes have a better responsiveness to lectins and recombinant II-2 than the corresponding circulating T lymphocytes. Therefore we are in favor of the hypothesis that tonsillar T lymphocytes contain activated T lymphocytes.
MeSH Terms
- Adult
- Aging
- Child
- Humans
- Interleukin-2
- Isoenzymes
- Kinetics
- L-Lactate Dehydrogenase
- Lymphocyte Activation
- Mitogens
- Palatine Tonsil
- Recombinant Proteins
- T-Lymphocytes
An in vitro model of ADA deficiency is selectively toxic to cartilage from immature rabbits with a greater effect on growth plate than articular cartilage. The selective toxicity observed appears to be the consequence of ATP depletion. These results support the hypothesis that the chondro-osseous dysplasia observed in patients with ADA deficiency is caused by the disordered metabolism that results from the enzyme deficiency.
MeSH Terms
- Adenosine Deaminase
- Aging
- Animals
- Cartilage, Articular
- Disease Models, Animal
- Exostoses, Multiple Hereditary
- Growth Plate
- Nucleoside Deaminases
- Rabbits
Three catabolic enzymes, 5'-nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and one anabolic enzyme, myokinase (MK) involved in adenine nucleotide (AN) metabolism were studied in myocardium from 4 to 105 day old rats. The specific enzyme activities (nmoles/min/mg protein) at day 4 were 35.3 for 5'NT, 28.4 for ADA, 43.3 for PNP, and 5 X 10(3) for MK. At day 7, 5'NT, activities rose to 450%; PNP and ADA 150%; and MK 120%; of the day 4 level. The activities of the three catabolic enzymes were elevated for one or two weeks then declined rapidly. By day 34, they were slightly above the adult values. MK activity displayed a different time course. It continued to increase slowly with age after the initial surge. Compared to the adult heart, the total activities of these catabolic enzymes in the one- to three-week-old heart were 30% to 220% higher. This transient elevation in AN catabolic enzyme activities may be related to active DNA synthesis and cell proliferation occurred in the rat myocardium during the same period.
MeSH Terms
- 5'-Nucleotidase
- Adenine Nucleotides
- Adenosine Deaminase
- Adenylate Kinase
- Aging
- Animals
- Body Weight
- Heart
- Myocardium
- Nucleotidases
- Organ Size
- Purine-Nucleoside Phosphorylase
- Rats
- Rats, Inbred Strains
We studied purine metabolism in rheumatoid arthritis (RA), adenosine deaminase (ADA), 5'-nucleotidase (5'NU) and purine nucleoside phosphorylase (PNP) activities by measuring the circulating mononuclear cells of patients with RA and healthy controls. Patients had significantly lower levels of ADA and 5'NU but not of PNP than controls. The decreases could not be related to age, antiinflammatory therapy, decreased percentages of T cells or imbalance between major T cells subsets. Differences in cell maturation or traffic could account for our observation. Alternatively, abnormalities of purine metabolism are not definitely excluded in RA if the lower enzyme activity is not sufficient to perform the metabolic steps.
MeSH Terms
- 5'-Nucleotidase
- Adenosine Deaminase
- Adult
- Aged
- Aging
- Anti-Inflammatory Agents
- Arthritis, Rheumatoid
- Humans
- Middle Aged
- Nucleoside Deaminases
- Nucleotidases
- Pentosyltransferases
- Prednisolone
- Purine-Nucleoside Phosphorylase
- T-Lymphocytes
All ADA Plan IV programs were surveyed to determine whether geriatric nutrition was included in their curriculums. Of the 268 Plan IV programs, 66% responded. Less than one-fifth of the programs offered or planned to offer a specific geriatric nutrition course. An overview of geriatric nutrition occurred most frequently in a human nutrition course. A practicum/clinical experience or a course other than nutrition most frequently provided in-depth study, if such was available. Nursing homes and congregate meal sites were the primary locations for experiences with the geriatric population. Major activities with that age group included (a) taking diet histories, (b) making nutrition assessments, and (c) providing diet instruction. In some programs, didactic and experiential training with the geriatric population may not be adequate to prepare dietetic undergraduate students to meet the health care needs of that growing segment of society.
MeSH Terms
- Aged
- Dietetics
- Geriatrics
- Homes for the Aged
- Humans
- Nursing Homes
- Nutritional Sciences
Dietitians' attitudes and knowledge about aging are important because of the potential influence on quality and quantity of nutrition services provided to older adults. Four instruments were used to survey active members of The American Dietetic Association (ADA) in Michigan. The survey was mailed to 1,408 dietitians; 738 responded (52.4%). The responding dietitians were predominantly under 40, well educated, and female, which was consistent with the 1986 national census of ADA members. The results indicated that dietitians hold positive attitudes toward older adults in most areas. An exception was that a majority of the dietitians perceived older adults as resistant to treatment. Although dietitians' knowledge about aging generally was adequate, the questionnaire revealed that dietitians lacked knowledge in the areas of economic and health status; dietitians answered that older adults have a lower income and are sicker and more institutionalized than is in fact true. These are critical areas of deficiency in knowledge by dietitians, since food and nutrition issues often involve money and health. In the problem-solving section of the study, the dietitians usually focused on one specific environment or area of concern. Neither the full range of all possible environments for older adults nor the diversity of older adults' needs was usually considered. Continuing education as well as comprehensive undergraduate courses on aging would have a positive influence on Michigan dietitians' attitudes and knowledge about aging.
MeSH Terms
- Adult
- Aged
- Aging
- Attitude of Health Personnel
- Dietetics
- Female
- Humans
- Male
- Michigan
- Middle Aged
- Surveys and Questionnaires
This study examined the precision of central fiber growth in a subpopulation of dorsal root ganglion neurons in developing mouse spinal cord. Immunohistochemical techniques using a monospecific, polyclonal antiserum to mouse adenosine deaminase (ADA) were utilized to label a population of primary sensory afferents that have been found to exclusively innervate laminae I and II of the dorsal horn in adult mice. Initial growth of ADA-immunoreactive (ADA-IR) primary afferents occurred very early in development, embryonic day 10 (E10), a time coincident with the earliest settling time of dorsal root ganglion neurons. Adenosine deaminase immunoreactive primary afferents were observed throughout the cross-sectional area of the primordial dorsal funiculus (DF) as early as E10. Immunostained fibers remained quiescent in the DF during its growth and separation into the tract of Lissauer and dorsal column pathway. By E15, the two pathways had formed and ADA-IR fibers were observed exclusively in the tract of Lissauer. This segregation of fibers remained throughout development and reflected the adult pattern. Growth was reinitiated at E16 when the fibers advanced into the dorsal horn and proceeded directly to laminae I and II mimicking their adult distribution. Exuberant fiber growth was not detected throughout their development. These results strongly suggest that ADA-IR fibers exhibit precise fiber guidance to a preferred pathway, the tract of Lissauer, and accurate laminar innervation of the dorsal horn.
MeSH Terms
- Adenosine Deaminase
- Afferent Pathways
- Aging
- Animals
- Axons
- Female
- Gestational Age
- Immune Sera
- Immunoenzyme Techniques
- Immunohistochemistry
- Mice
- Mice, Inbred ICR
- Nerve Fibers
- Neurons, Afferent
- Spinal Cord