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1.
Knee Surg Sports Traumatol Arthrosc ; 30(2): 500-506, 2022 Feb.
Article in English | MEDLINE | ID: mdl-32748231

ABSTRACT

BACKGROUND: This study aims to evaluate the clinical and radiological outcomes of a modified technique of Kinematically Aligned Total Knee Arthroplasty (KA TKA) using a cruciate sacrificing (CS) medially stabilised prosthesis at a minimum 24-months follow-up. METHODS: 59 patients with a varus HKA angle who underwent a TKA from May, 2016 to April, 2017 were retrospectively enrolled. Radiological and clinical evaluations were assessed after 40 days, 6 months and at a minimum follow-up of 24 months. Long leg standing X-rays were performed pre-operatively and the Hip-Knee-Ankle (HKA) angle, the mechanical Lateral Distal Femoral Angle (mLDFA), the mechanical Medial Proximal Tibial Angle (mMPTA) and the Knee Joint Line Obliquity Angle (KJLOA) were analysed. At a minimum follow-up of 24 months, the patients were evaluated subjectively based on the Western Ontario and McMaster Universities Osteoarthritis Index Score (WOMAC) and the Oxford Knee Score (OKS). The post-operative range of motion (ROM) was measured. To reduce flexion instability, an original technique was used, with more posterior positioning of the femoral component, called the "virtuous mistake". Results were compared to the data reported in the literature in patients treated with standard kinematic alignment (KA) technique. RESULTS: No difference was found between the mean pre-operative and post-operative angles regarding mLDFA (p value = 0.410) and mMTPA (p value = 0.242). A difference of 0.8° in HKA angle between males and females was found, with more varus results in males. At a minimum follow-up of 24 months, the WOMAC was 87 (SD 4.3), the OKS was 41 (SD 2.4), and the flexion was 124°, which was similar to the data reported in literature with standard KA. There were not any cases of aseptic failures. CONCLUSIONS: The modified KA TKA surgical technique proposed in this study can achieve good clinical results at minimum 24 months of follow-up, reproducing accurately native mLDFA and mMPTA. LEVEL OF EVIDENCE: Level III, therapeutic study.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Osteoarthritis, Knee , Arthroplasty, Replacement, Knee/methods , Biomechanical Phenomena , Female , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Male , Osteoarthritis, Knee/surgery , Range of Motion, Articular , Retrospective Studies
2.
Sci Rep ; 11(1): 6139, 2021 03 17.
Article in English | MEDLINE | ID: mdl-33731775

ABSTRACT

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.


Subject(s)
Biomarkers , Diagnostic Self Evaluation , Health Status , Self Report , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Biomarkers/urine , Female , Humans , Male , Middle Aged , Young Adult
3.
Orthopade ; 50(3): 173-178, 2021 Mar.
Article in German | MEDLINE | ID: mdl-32812069

ABSTRACT

BACKGROUND: Kinematic alignment (KA) total knee arthroplasty (TKA) has proven to be a viable alternative to mechanical alignment (MA) TKA. Like any technique, its validity has to encounter challenges. Two of these are flexion contracture and large deformities of the knee. FLEXION CONTRACTURE: Flexion contracture is commonly treated with posterior capsular release. Often, however, this technique is not sufficient. Many surgeons accustomed to MA techniques and guided by traditional femoral instruments manage the problem by proximalizing the distal femoral cut. However, this has proven to be a surgical mistake that often leads to mid-flex knee instability. KA rules limit this mistake but leave the problem of flexion contracture. In these cases, the surgeon acts on the tibia distalizing the cut and, so as not to create instability in flexion, decreasing the slope. The technique is effective to obtain full extension but often leaves instability at 90° of knee flexion. To avoid this, it is useful to use the so-called "virtuous mistake" strategy, which strictly follows the KA guidelines but undercuts the posterior femoral condyles by 2 mm. DEFORMITIES: Another problem that often limits the use of KA is large deformities. It is necessary to distinguish whether they are intra or extra-articular. In the first case, it is possible to decide whether to use the pure KA technique or to restrict the indication at the level of the tibial cut. In the latter, extraarticular osteotomies or combined procedures (osteotomy plus KA) have to be performed.


Subject(s)
Arthroplasty, Replacement, Knee , Contracture , Knee Prosthesis , Biomechanical Phenomena , Contracture/surgery , Femur/surgery , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Range of Motion, Articular , Tibia/surgery
4.
J Trace Elem Med Biol ; 55: 58-63, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31345366

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. OBJECTIVES: The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. METHODS AND RESULTS: 84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1ß concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. CONCLUSION: Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.


Subject(s)
Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/pharmacology , Copper/blood , Homeostasis/drug effects , Zinc/blood , Aged , Alzheimer Disease/blood , Alzheimer Disease/enzymology , Alzheimer Disease/metabolism , Cholinesterase Inhibitors/administration & dosage , Copper/metabolism , Female , Humans , Inflammation/drug therapy , Inflammation/metabolism , Linear Models , Male , Zinc/metabolism
5.
Diabetes Res Clin Pract ; 144: 102-110, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30142362

ABSTRACT

AIMS: ZnT8 Arg325Trp polymorphism has been associated with type 2 diabetes (T2DM) susceptibility. The Arg-325 risk variant shows accelerated zinc (Zn) transport kinetic and reduced glucose-stimulated insulin secretion in pancreatic cells. However, it remains unexplored the role of Znt8 polymorphism in the regulation of Zn homeostasis and inflammatory response in peripheral blood mononuclear cells (PBMCs) from T2DM patients. METHODS AND RESULTS: A total of 556 healthy controls and 413 T2DM patients were genotyped for ZnT8 Arg325Trp polymorphism confirming the association of Arg-325 variant with an increased T2DM risk (OR = 1.35 95% C.I: 1.10-1.66; p = 0.0044). Moreover, PBMCs from Arg/Arg T2DM subjects showed increased intracellular free Zn, higher gene expression of Metallothioneins, Znt1, Znt8, Zip2 genes, and reduced Znt4 and Znt7. Higher release of IL-1α, IL-1ß, IFN-γ, IL-12p70 and TNF-α and a reduced IL-10 secretion after lipopolysaccharide (LPS) stimulation were observed in PBMCs from Arg/Arg T2DM carriers as compared to subjects with the Trp variant. CONCLUSIONS: Our data provide evidence of a substantial different Zn homeostasis regulation between Znt8 Arg-325 and Trp-325 carriers in PBMCs from T2DM patients. Moreover, Znt8 Arg-325 risk variant shows an enhanced inflammatory response upon LPS stimulation that might aggravate insulin resistance and the progression of diabetes cardiovascular complications.


Subject(s)
Carrier Proteins/metabolism , Cytokines/metabolism , Diabetes Mellitus, Type 2/metabolism , Leukocytes, Mononuclear/metabolism , Polymorphism, Genetic , Zinc Transporter 8/genetics , Zinc/metabolism , Aged , Aged, 80 and over , Carrier Proteins/genetics , Case-Control Studies , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Female , Genotype , Humans , Male , Middle Aged
6.
Aging Clin Exp Res ; 29(3): 353-360, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27106901

ABSTRACT

BACKGROUND: Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward. AIMS: To describe the study protocol and methods of "My Mind Project: the effect of cognitive training for elderly" (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild-moderate Alzheimer's disease, mild cognitive impairment and normal cognitive functioning. METHODS: The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION: The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline. CONCLUSION: The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.


Subject(s)
Alzheimer Disease/therapy , Cognitive Dysfunction/therapy , Aged , Alzheimer Disease/psychology , Clinical Protocols , Cognitive Dysfunction/psychology , Humans , Italy , Memory , Prospective Studies
7.
Eur J Nutr ; 56(8): 2457-2466, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27459881

ABSTRACT

PURPOSE: Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal. METHODS: We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis. RESULTS: Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, RANTES and Zn intake after adjustment for multiple confounders. HSP70 +1267 AA genotype was an independent factor associated with Zn plasma concentrations. Cu/Zn ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels. CONCLUSIONS: Our findings show the most important independent determinants of plasma Zn concentration and Cu/Zn ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.


Subject(s)
Aging , Biomarkers/blood , Copper/blood , Zinc/blood , Aged , Aged, 80 and over , Chemokine CCL5/genetics , Chemokine CCL5/metabolism , Cohort Studies , Copper/administration & dosage , Diet , Diet, Mediterranean , Europe , Female , Genotyping Techniques , Homeostasis , Humans , Inflammation/blood , Inflammation/physiopathology , Male , Nutritional Status , Serum Albumin/metabolism , Zinc/administration & dosage
9.
Biogerontology ; 15(1): 65-79, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24243066

ABSTRACT

Proinflammatory cytokines and heat shock proteins play relevant roles in the pathogenesis of inflammatory diseases. We investigated whether Hsp70 1267 A/G and TNF-α -308 G/A polymorphisms are associated with proinflammatory mediators, zinc status and laboratory parameters in 1,078 healthy elderly from ZincAge study. Hsp70 1267 A/G genotype and allele distribution were similar among various European countries, while a TNF-α genetic heterogeneity was observed between the Northern and the Southern European populations, with a major frequency of the -308 A variant in France, Germany and Poland. We used linear regression models to test additive, dominant or recessive associations of each SNP with proinflammatory mediators, laboratory parameters, metallothioneins and zinc status. Hsp70 1267 A/G SNP, but not TNF-α -308 G/A SNP, influences TNF-α and IL-6 plasma levels under additive, dominant and recessive models (for TNF-α only). An association between Hsp70 1267 A/G SNP and zinc plasma levels was observed in the dominant model. In particular, G allele carriers showed increased circulating pro-inflammatory cytokines and zinc. Moreover, both these SNPs affect creatinine levels suggesting a possible influence on renal function. In conclusion, Hsp70 1267 A/G SNP is associated with pro-inflammatory cytokine production in healthy elderly and might represent a possible determinant of individual susceptibility to inflammatory diseases.


Subject(s)
Aging/metabolism , Cytokines/blood , HSP70 Heat-Shock Proteins/genetics , Inflammation/blood , Polymorphism, Single Nucleotide/genetics , Tumor Necrosis Factor-alpha/genetics , Zinc/metabolism , Aged , Aged, 80 and over , Aging/genetics , C-Reactive Protein/metabolism , Europe , Female , Gene Frequency/genetics , Genotype , Homeostasis/physiology , Humans , Inflammation/genetics , Male , Metallothionein/metabolism , Middle Aged
10.
J Nutr Health Aging ; 14(7): 515-22, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20818464

ABSTRACT

OBJECTIVES: To identify the relationship among cognitive status, psychological conditions, anthropometric measurements and life-style in a sample of elderly Italian men and women. METHODS: Three hundred and six volunteers for ZINCAGE Project recruited. The sample was made up of healthy older adults living in the Marche Region aged 65 and over. All elderly were given a complete medical, anthropometric assessment, and psycho-social evaluation. RESULTS: Overall, the participants perceived themselves to be in very good or good (22%) or fair (69%) health; only 9% reported a poor health status. The 46% of the sample fell within the normal body mass index (BMI) range, though 38% were overweight, 12% were obese, and only 4% were underweight. In both sexes, BMI significantly decreased with age (p<0.001). BMI was positively associated with performing sedentary activities (r=0.188; p<0.001). Levels of both sedentary (r=0.221; p<0.001) and non-sedentary (r=0.258; p<0.001) leisure activities were positively associated with education level (p<0.05). It was found that lower scores of physical activity were associated to higher scores of Geriatric Depression Scale (r=-0.425; p<0.01), lower scores of Mini Mental State Examination (r=0.266; p<0.001) and higher score of Perceived Stress Scale (r=-0.131; p<0.05). CONCLUSION: Men and women lead different lifestyles and have a different psychological status, with advancing age consequently stressing the need for healthy lifestyle programmes particularly in the case of overweight and obese elderly people.


Subject(s)
Body Mass Index , Cognition , Depression , Health Status , Life Style , Overweight/psychology , Stress, Psychological , Age Factors , Aged , Aged, 80 and over , Educational Status , Exercise/psychology , Female , Geriatric Assessment , Humans , Italy/epidemiology , Leisure Activities , Male , Mental Health , Motor Activity , Overweight/epidemiology , Sedentary Behavior , Self Concept , Sex Factors , Thinness/epidemiology , Thinness/psychology
11.
Proc Nutr Soc ; 69(3): 290-9, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20579408

ABSTRACT

Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. The nutritional factor, zinc, may remodel these changes with subsequent healthy ageing, because zinc improves the inflammatory/immune response as shown by in vitro and in vivo studies. The intracellular zinc homeostasis is regulated by buffering metallothioneins (MT) and zinc transporters (ZnT and ZIP families) that mediate the intracellular zinc signalling assigning to zinc a role of 'second messenger'. In ageing, the intracellular zinc homeostasis is altered, because high MT are unable to release zinc and some zinc transporters deputed to zinc influx (ZIP family) are defective leading to low intracellular zinc content for the immune efficiency. Physiological zinc supplementation in the elderly improves these functions. However, the choice of old subjects for zinc supplementation has to be performed in relation to the specific genetic background of MT and IL-6, because the latter is involved both in MTmRNA and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (C-carriers) in the IL-6-174G/C locus display high IL-6, low intracellular zinc content, impaired innate immunity and enhanced MT. Old subjects carrying GC and CC genotypes (C+carriers) display satisfactory intracellular zinc content, adequate innate immunity and are more prone to reach longevity. Zinc supplementation in old C-carriers restores natural killer cell cytotoxicity and zinc status. The genetic variations of the IL-6-174G/C locus when associated with those of the MT1A+647A/C locus are useful tools for the choice of old people for zinc supplementation.


Subject(s)
Aging/immunology , Carrier Proteins/immunology , Genetic Variation/immunology , Immunity/physiology , Metallothionein/immunology , Zinc/immunology , Aged , Carrier Proteins/metabolism , Dietary Supplements , Humans , Interleukin-6/genetics , Interleukin-6/metabolism , Metallothionein/genetics , Metallothionein/metabolism , Zinc/metabolism
12.
Article in English | MEDLINE | ID: mdl-19964348

ABSTRACT

In spite of advancement in biomaterials and biomechanics, in development of new osteo-integrative materials and coatings, and in macro- micro- component design, a non negligible fraction of the implanted prosthesis fails before the expected lifetime. A prospective observational clinical study has been conducted to define and apply a set of experimental techniques to in-deep assess the failure of joint prosthesis. Microbiological, histological and micro-structural techniques were implemented to specifically address phenomena occurring at the tissue-implant interface. Results obtained from 27 cases of prosthetic joint failure are discussed in terms of sensitivity and specificity. A procedural flow-chart is finally proposed for the assessment of joint prosthesis failure.


Subject(s)
Arthroplasty, Replacement/methods , Biomechanical Phenomena , Joint Prosthesis , Prosthesis Failure , Adult , Aged , Aged, 80 and over , Biocompatible Materials/chemistry , Female , Humans , Joints/pathology , Male , Materials Testing , Microbiological Techniques , Middle Aged , Prospective Studies , Prosthesis Design , Research Design
13.
Curr Pharm Des ; 14(26): 2719-32, 2008.
Article in English | MEDLINE | ID: mdl-18991691

ABSTRACT

Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Some nutritional factors (zinc, niacin, selenium) may remodel these changes leading to a possible escaping of diseases, with the consequence of healthy ageing, because they are involved in improving immune functions, metabolic homeostasis and antioxidant defence. Experiments performed "in vitro" (human lymphocytes exposed to endotoxins) and "in vivo" (old mice or young mice with low zinc dietary intake) show that zinc is important for immune efficiency (both innate and adaptive), metabolic homeostasis (energy utilization and hormone turnover) and antioxidant activity (SOD enzyme). Niacin is a precursor of NAD+, the substrate for the activity of DNA repair enzyme PARP-1 and, consequently, may contribute to maintaining genomic stability. Selenium provokes zinc release by Metallothioneins (MT), via reduction of glutathione peroxidase. This fact is crucial in ageing because high MT may be unable to release zinc with subsequent low intracellular free zinc ion availability for immune efficiency, metabolic harmony and antioxidant activity. Taking into account the existence of zinc transporters (ZnT and ZIP family) for cellular zinc efflux and influx, respectively, the association between zinc transporters and MT is crucial in maintaining satisfactory intracellular zinc homeostasis in ageing. Improved immune performance, metabolic homeostasis, antioxidant defence occur in elderly after physiological zinc supplementation, which also induces prolonged survival in old, nude and neonatal thymectomized mice. The association "zinc plus selenium" improves humoral immunity in old subjects after influenza vaccination. The association "zinc plus niacin" in elderly is actually in progress.


Subject(s)
Niacin/pharmacology , Selenium/pharmacology , Zinc/pharmacology , Age Factors , Aged , Aging/physiology , Animals , Antioxidants/metabolism , Dietary Supplements , Homeostasis/drug effects , Humans , Immune System/drug effects , Immune System/physiology , Longevity/drug effects , Longevity/physiology , Metallothionein/metabolism , Mice
14.
J Biol Regul Homeost Agents ; 22(1): 83-91, 2008.
Article in English | MEDLINE | ID: mdl-18394321

ABSTRACT

The aim of this study is to investigate whether subjective well-being in patients under treatment with typical (ATPs) and atypical antipsychotic (ATPsA) compounds can be compared with the improvement of psychopathological state and to verify if both variables correlate to adherence to treatment. We assessed 106 consecutive patients receiving ATPs or ATPsA in the University Psychiatric Ward of L?Aquila, according to DSM-IV diagnosis of Schizophrenia and Bipolar Disorder. Psychopathological state was assessed by Brief Psychiatric Rating Scale-4.0 version (BPRS), adherence to treatment and subjective well-being was assessed by Drug Attitude Inventory (DAI-10) and Subjective Well-being under Neuroleptics (SWN), respectively. BPRS and DAI-10 were administered on admission (T0) and at the end of recovery (T1). The subjects enrolled in this study were divided into 2 groups according to ATP prescribed. We observed an improvement of BPRS and SWN total scores in each group, and increasing scores in DAI-10, from admission to discharge, both in total samples and in each group. There were statistical differences between the patients receiving ATPs and those receving ATPsA regardindg the SWN total score and its different dimensions. This study emphasizes that patients receiving ATPsA show better subjective response compared with patients undergoing ATP treatment, although the adherence to pharmacotherapy and clinical improvement do not differ between the groups.


Subject(s)
Antipsychotic Agents/therapeutic use , Personality Inventory , Psychotic Disorders/drug therapy , Adult , Age of Onset , Antidepressive Agents, Second-Generation/pharmacology , Antidepressive Agents, Second-Generation/therapeutic use , Antipsychotic Agents/pharmacology , Attitude to Health , Female , Humans , Length of Stay , Male , Middle Aged , Psychotic Disorders/physiopathology , Psychotic Disorders/psychology , Self Concept , Social Behavior
15.
Exp Gerontol ; 43(5): 423-32, 2008 May.
Article in English | MEDLINE | ID: mdl-18316168

ABSTRACT

Decreased zinc ion availability in ageing is associated with altered immune response. One of the main regulators of zinc availability is metallothionein. Metallothionein induction is under the control of interleukin-6, a pro-inflammatory cytokine whose production is associated with poor ageing. The production of interleukin-6 is controlled, in part, by variability in the -174 nucleotide position. Under conditions of chronic inflammation, such as in ageing, zinc release by metallothionein is limited and may reduce zinc availability. Understanding the precise nature of the interactions between interleukin-6 and metallothioneins will aid in identifying individuals who are at risk of zinc deficiency. In the current study, we used gene arrays to investigate the effects of in vitro zinc supplementation on gene expression in elderly donors with described interleukin-6 and metallothionein 1a polymorphisms. Ingenuity Pathway Analysis identified several zinc-responsive genetic networks uniquely regulated only in elderly individuals with the pro-inflammatory interleukin-6 polymorphism. These include zinc-dependent decreased transcription of pro-inflammatory cytokines and alterations in metabolic regulatory pathways. The genomic effects of zinc increased in significance in the presence of the metallothionein 1a +647 C/A transition, suggesting that the interleukin-6 and metallothionein 1a genes act in a concerted manner to control zinc-regulated gene expression.


Subject(s)
Aging/genetics , Interleukin-6/genetics , Metallothionein/genetics , Polymorphism, Single Nucleotide/genetics , Zinc/physiology , Aged , Female , Gene Expression , Homeostasis , Humans , Male , Metallothionein/metabolism , Protein Array Analysis , RNA/metabolism , Reverse Transcriptase Polymerase Chain Reaction
16.
Mol Genet Metab ; 94(1): 98-104, 2008 May.
Article in English | MEDLINE | ID: mdl-18249147

ABSTRACT

Diabetes mellitus is a chronic disease characterized by an overproduction of reactive oxygen species, which perturbs zinc metabolism and promotes the onset of cardiovascular disease (CVD) in diabetic patients. Metallothioneins (MT) are cysteine-rich metal-binding proteins which, by means of their antioxidant and zinc-buffering properties, might prevent the development of diabetic cardiovascular complications. A recent investigation shows that a polymorphism (+647 A/C) in the human MT-1A gene, affects the intracellular zinc ion release (iZnR) from the proteins and is associated with longevity in Italian population. The aim of the present study is to assess the involvement of +647 A/C and +1245 A/G MT1A polymorphisms with the susceptibility to type 2 diabetes (DM2) and cardiovascular complications. The study included 694 old individuals: 242 old healthy controls, 217 DM2 patients without clinical evidence of CVD (DNC) and 235 diabetic patients with diagnosis of CVD (DCVD). +647 A/C MT1A polymorphism, but not the second SNP, was associated with DM2. C allele carriers were more prevalent in DNC and DCVD patients than in control group (OR=1.37, p=0.034; OR=1.54, p=0.002, respectively). C+ carriers was associated with higher glycemia and glycosylated hemoglobin in DCVD patients, but not in DNC or control subjects. No differences in plasma zinc, but a modulation of MT levels and iZnR in PBMCs were observed in DCVD cohort when related to +647 A/C MT1A polymorphism. In summary, this work provides novel evidence on the association of the +647 A/C MT1A polymorphism with DM2. Moreover, C+ carriers in DCVD patients presented a worse glycemic control, a reduced iZnR and a higher MT levels, suggesting a possible role of MT in diabetic cardiovascular complications.


Subject(s)
Cardiovascular Diseases/genetics , Diabetes Complications/genetics , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Metallothionein/genetics , Polymorphism, Single Nucleotide , Aged , Cardiovascular Diseases/complications , Diabetes Mellitus, Type 2/complications , Female , Flow Cytometry , Humans , Male , Middle Aged , Zinc/blood , Zinc/metabolism
17.
Exp Gerontol ; 43(5): 445-51, 2008 May.
Article in English | MEDLINE | ID: mdl-18078731

ABSTRACT

A large body of experimental research indicates that oxidative stress contributes to the processes related to aging and age-related diseases. Trace elements, particularly zinc (Zn), are essential components of the endogenous enzymatic antioxidant defenses. The aim of this study was to determine the activity of three main antioxidant enzymes in plasma [i.e. superoxide dismutase (pSOD), catalase (CAT), glutathione peroxidase (GPx)] and of SOD in erythrocyte (eSOD) in a group of 1108 healthy elderly subjects from different European countries. The same enzymatic activities were evaluated in a subgroup of 108 subjects before and after Zn supplementation. We observed that eSOD activity increased with age, whereas plasma Zn decreased. Moreover, we found that women showed higher eSOD activity and lower plasma Zn compared to men. There were no age and gender-related differences in the activities of pSOD, CAT and GPx. After Zn supplementation, the activities of Zn-dependent enzymes (pSOD and eSOD), as well as plasma Zn concentration, were significantly higher than before supplementation. These results were not influenced by age, gender, plasma Zn variations (Delta Zn) and geographic area. These data suggest the potential beneficial effects of Zn supplementation on Zn-dependent antioxidant enzymes in healthy elderly subjects.


Subject(s)
Aging/metabolism , Oxidoreductases/drug effects , Trace Elements/pharmacology , Zinc/pharmacology , Aged , Aged, 80 and over , Catalase/drug effects , Catalase/metabolism , Dietary Supplements , Erythrocytes/enzymology , Female , Glutathione Peroxidase/drug effects , Glutathione Peroxidase/metabolism , Humans , Male , Middle Aged , Oxidative Stress/drug effects , Oxidoreductases/metabolism , Sex Characteristics , Superoxide Dismutase/drug effects , Superoxide Dismutase/metabolism , Trace Elements/administration & dosage , Zinc/administration & dosage , Zinc/deficiency
18.
Rejuvenation Res ; 10(4): 603-20, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17985944

ABSTRACT

Mild zinc deficiency, which is prevalent in vegetarians, diseased individuals, and the general aging population, depresses immunity and increases risk of disease in later life. However, human zinc intervention trials have produced conflicting results, perhaps because many of these trials included young or zinc-sufficient subjects. Since heterogeneity of the adult population may impact on response to dietary zinc, nutrigenomic approaches aimed at understanding the impact of zinc on modulation of gene and protein activities may aid in identifying subsets of the population-in particular the aging population-with increased risk of zinc deficiency who might receive benefit from a dietary zinc intervention and in this way may influence the success of the intervention. In the current study we used nutrigenomic approaches to investigate the impact of age on zinc-regulated gene expression in peripheral blood mononuclear cells. Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA) identified several genetic networks and functional canonical pathways which appeared responsive to zinc that were differentially regulated in young and elderly individuals. These include tryptophan metabolism, eicosanoid signaling, p38 mitogen-activated protein kinase (MAPK) signaling, integrin signaling, purine metabolism, G-protein-coupled receptor signaling, and most significantly, peroxisome proliferator-activated receptor (PPAR) signaling. These data suggest that age impacts strongly on the transcriptional effects of zinc and provides evidence to support the hypothesis that young and elderly individuals may respond differentially to zinc intervention.


Subject(s)
Gene Expression Regulation/drug effects , Leukocytes, Mononuclear/drug effects , Zinc/pharmacology , Adult , Age Factors , Aged , Female , Humans , Leukocytes, Mononuclear/metabolism , Male , Metallothionein/genetics , Metallothionein/physiology , Middle Aged , NF-kappa B/genetics , NF-kappa B/physiology , Oligonucleotide Array Sequence Analysis , PPAR alpha/genetics , PPAR alpha/physiology , Signal Transduction
20.
Arch Gerontol Geriatr ; 44 Suppl 1: 259-69, 2007.
Article in English | MEDLINE | ID: mdl-17317461

ABSTRACT

The study of the interactions among biological factors and psychosocial conditions is a very innovative field, because data are lacking in the scientific literature. Among biological aspects, zinc is an essential element in the elderly, especially in relation to one of the proteins, such as albumin, involved in zinc transport into the cells. In this study, the aim is the assessment of the interrelationship between albumin value (used as an index of the body zinc status) and some psychosocial dimensions in elderly Italian sample recruited for ZINCAGE project, supported by the European Commission in the "Sixth Framework Programme". Some tests and questionnaires were administered to older people included in the trial: the "life-style questionnaire"; the mini mental state examination (MMSE); the geriatric depression scale (GDS-15 items). On the basis of the Senieur Protocol for gerontological studies, a sample of 291 Italian healthy old subjects has been recruited in Central Italy and divided into 3 age groups: (a) 125 subjects aged from 65 to 74 years, (b) 89 subjects aged from 75 to 84 years, (c) 77 subjects aged >or=85 years (classified like successful old people). No cognitive impairment assessed by MMSE was observed in 67.5% of the sample; 64.0% had GDS score less than 5, indicating no depression, whereas the prevalence of biological albumin deficiency (<3.5 g/dl) found in Italian old people was 21.0%. Sixty one percent of subjects with albumin deficiency displayed higher values of GDS (>or=5). These preliminary results showed an interrelationship among serum albumin value and psychosocial aspects in Italian old population, suggesting that low albumin values may be involved in impaired psychological dimensions.


Subject(s)
Aging/physiology , Albumins/deficiency , Cognition Disorders/epidemiology , Depressive Disorder, Major/epidemiology , Zinc/deficiency , Aged , Aged, 80 and over , Aging/psychology , Cognition Disorders/diagnosis , Depressive Disorder, Major/diagnosis , Female , Humans , Italy , Male , Neuropsychological Tests , Psychology , Severity of Illness Index , Surveys and Questionnaires
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