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3.
Nutrients ; 14(19)2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36235800

ABSTRACT

In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation.


Subject(s)
Fractures, Bone , Osteoporosis , Vitamin D Deficiency , Adult , Dietary Supplements/adverse effects , Fractures, Bone/drug therapy , Fractures, Bone/prevention & control , Humans , Minerals/therapeutic use , Osteoporosis/drug therapy , Osteoporosis/etiology , Osteoporosis/prevention & control , Vitamin D , Vitamins/therapeutic use
4.
Acta Haematol ; 144(3): 302-307, 2021.
Article in English | MEDLINE | ID: mdl-32906140

ABSTRACT

Hypercalcemia is a significant feature of patients with active multiple myeloma (MM) with extensive bone disease. Among the causes of non-neoplastic hypercalcemia, primary hyperparathyroidism (PHPT) is one of the most common, leading to osteoporosis and bone fractures. Interestingly, some preclinical data indicate that high secretion of parathyroid hormone (PTH) may have a negative impact on bone disease and MM progression. However, concomitant diagnosis of MM and PHPT has rarely been described. Here, we present 4 cases of patients with active MM and hypercalcemia with high or inappropriately normal PTH levels. Interestingly, CD138+ cells from these 4 MM patients lack PTH receptor 1 and PTH-related peptide expressions, indicating that PTH could have a paracrine rather than a direct pro-tumoral effect. Moreover, these cases suggest that the concomitant diagnosis of MM and PHTP may not be so rare and should be considered for the clinical management of MM patients with hypercalcemia.


Subject(s)
Hyperparathyroidism, Primary/diagnosis , Multiple Myeloma/diagnosis , Aged , Antineoplastic Agents/therapeutic use , Female , Humans , Hyperparathyroidism, Primary/complications , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Parathyroid Hormone/blood , Parathyroid Hormone-Related Protein/metabolism , Receptor, Parathyroid Hormone, Type 1/metabolism , Syndecan-1/metabolism
5.
Article in English | MEDLINE | ID: mdl-30113605

ABSTRACT

The purpose of this study was to evaluate the survival of 525 composite indirect restorations in premolars and molars after a follow-up of 20 years. For each patient, the following variables were recorded and analyzed: age, sex, smoking status, presence of plaque according to O'Leary index, and presence of bruxism. For each restoration, the following variables were collected: restoration class, tooth type (premolar or molar), and restoration material. Mean 20-year survival rate of composite restorations was 57%, ranging from 44% to 75%. The Kaplan-Meier method demonstrated a probability of survival at 10 years of 80% and 90%. Surviving restorations kept their clinical characteristics extremely well, as assessed on the basis of the United States Public Health Service criteria. The results of this study demonstrate the efficacy of indirect composite restorations, confirming their reliability as a posterior prosthetic clinical option.


Subject(s)
Composite Resins/therapeutic use , Dental Restoration, Permanent/methods , Bicuspid/surgery , Dental Restoration Failure , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Molar/surgery , Retrospective Studies
7.
J Bone Miner Metab ; 35(5): 562-570, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27830385

ABSTRACT

The aim of this study was to determine the incidence of atypical femoral fractures (AFFs) seen in a large emergency department in Italy. It was a retrospective study of all men and women aged 40 years or older admitted to the Emergency Department of Parma University Hospital for a femoral fracture. Cases were identified in the hospital database with use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 820 or 821 or text strings. All the radiographic images of fractures not clearly identified as proximal or condylar were retrieved and evaluated by three independent reviewers. Fractures were considered as atypical if all three reviewers agreed on at least four of five major features defined by the 2013 American Society for Bone and Mineral Research criteria. In the 7-year period (2007-2013), with a total follow-up of 1,383,154 patient-years, we found 22 AFFs in 21 patients, accounting for 7.1% of low-trauma subtrochanteric/femoral shaft fractures and 0.6% of all femoral fractures. The incidence was very low (1.6 in 100,000 patient-years in both sexes combined). In contrast, the incidence of classic fractures of the proximal end of the femur was at least two orders of magnitude higher (typical/atypical rate ratio 152). Bisphosphonate use was reported in 13 patients (62%; mean treatment duration 9 years; range 5-14 years). Among 286 patients with typical subtrochanteric/femoral shaft fractures, 20 were being treated with bisphosphonate (7%; odds ratio 22; 95% confidence interval 8-58; p < 0.001). This study confirms the very low incidence of AFFs in the largest Italian cohort of patients to date. Even though the risk is higher in patients treated with bisphosphonates, AFFs are very rare, and typical femoral fractures are at least 100-fold more frequent.

8.
PLoS One ; 11(3): e0151965, 2016.
Article in English | MEDLINE | ID: mdl-26990192

ABSTRACT

Human cytomegalovirus (HCMV) imprints the immune system after primary infection, however its effect during chronic infection still needs to be deciphered. In this study we report the variation of blood cell count along with anti-HCMV IgG and T cell responses to pp-65 and IE-1 antigens, that occurred after an interval of five years in a cohort of 25 seropositive healthy adults. We found increased anti-viral IgG antibody responses and intracellular interferon-gamma secreting CD8+ T cell responses to pp-65: a result consistent with memory inflation. With the only exception of shortage in naive CD8+ T cells most memory T cell subsets as well as total CD8+ T cells, T cells, lymphocytes, monocytes and leukocytes had increased. By contrast, none of the cell types tested were found to have increased in 14 subjects stably seronegative. Rather, in addition to a shortage in naive CD8+ T cells, also memory T cell subsets and most other cell types decreased, either in a statistically significant or non-significant manner. The trend of T cell pool representation with regard to CD4/CD8 ratio was in the opposing directions depending on HCMV serology. Globally, this study demonstrates different dynamic changes of most blood cell types depending on presence or absence of HCMV infection. Therefore, HCMV plays a continual role in modulating homeostasis of blood T cells and a broader expanding effect on other cell populations of lymphoid and myeloid origin.


Subject(s)
Cytomegalovirus Infections/immunology , Antibodies, Viral/blood , Blood Cell Count , CD4-Positive T-Lymphocytes/physiology , CD8-Positive T-Lymphocytes/physiology , Chronic Disease , Cytomegalovirus/immunology , Homeostasis , Humans , Immunologic Memory , Lymphocyte Activation , T-Lymphocytes/physiology
9.
Adv Orthop ; 2014: 397059, 2014.
Article in English | MEDLINE | ID: mdl-25298896

ABSTRACT

This study was aimed at investigating the prevalence of hyponatremia in patients with intracapsular femoral neck fracture. All records containing clinical and laboratory information of patients admitted with femoral neck fractures to the Academic Hospital of Parma (Italy) during the year 2013 were retrieved from the hospital database. The control population consisted of subjects admitted to the outpatient phlebotomy center during the same period. The final population consisted of 543 patients with femoral neck fractures and 700 outpatients. The category of elderly subjects (i.e., ≥65 years) included 491 patients and 380 controls. In both the entire population and elderly subjects, serum sodium was lower in patients than in controls (138 versus 139 mmol/L, P < 0.001). The prevalence of hyponatremia was also higher in cases than in controls, both in the entire population (19.5 versus 10.4%, P < 0.001) and in elderly subjects (20.8 versus 11.8%, P < 0.001). The odds ratio of hyponatremia for femoral neck fracture was 2.08 in the entire study population and 1.95 in those aged 65 years and older. In conclusion, we found that hyponatremia is significantly associated with femoral neck fracture. Serum sodium should hence be regularly assessed and hyponatremia eventually corrected.

10.
Age (Dordr) ; 36(4): 9694, 2014.
Article in English | MEDLINE | ID: mdl-25086618

ABSTRACT

In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1ß, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (ß ± SE = -0.11 ± 0.03, p = <0.0001) and log (hsCRP) (ß ± SE = -0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (ß ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (ß ± SE = -0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (ß ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (ß ± SE = -0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.


Subject(s)
Aging/blood , C-Reactive Protein/metabolism , Cytokines/blood , Inflammation/blood , Osteoporosis/blood , Vitamin D/analogs & derivatives , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , Female , Humans , Incidence , Inflammation/epidemiology , Italy/epidemiology , Male , Middle Aged , Osteoporosis/epidemiology , Vitamin D/blood , Young Adult
11.
Age (Dordr) ; 36(2): 625-40, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24318918

ABSTRACT

Alterations in the circulating CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, are pronounced in older adults. However, homeostatic forces that dictate such changes remain incompletely understood. This observational cross-sectional study explored the basis for variability of CD8+ T cell number and composition of its main subsets: naïve, central memory and effector memory T cells, in 131 cytomegalovirus (CMV) seropositive subjects aged over 60 years. We found great heterogeneity of CD8+ T cell numbers, which was mainly due to variability of the CD8 + CD28- T cell subset regardless of age. Analysis, by multiple regression, of distinct factors revealed that age was a predictor for the loss in absolute number of naïve T cells, but was not associated with changes in central or effector memory CD8+ T cell subsets. By contrast, the size of CD8+ T cells specific to pp65 and IE-1 antigens of CMV, predicted CD28 - CD8+ T cell, antigen-experienced CD8+ T cell, and even total CD8+ T cell numbers, but not naïve CD8+ T cell loss. These results indicate a clear dichotomy between the homeostasis of naïve and antigen-experienced subsets of CD8+ T cells which are independently affected, in human later life, by age and antigen-specific responses to CMV, respectively.


Subject(s)
Aging/immunology , Antigens, Viral/immunology , CD8-Positive T-Lymphocytes/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus/immunology , Homeostasis/immunology , Immunologic Memory/immunology , Aged , Aged, 80 and over , Antibodies, Viral/immunology , Cross-Sectional Studies , Female , Flow Cytometry , Follow-Up Studies , Humans , Lymphocyte Activation , Male , Middle Aged , Phenotype
12.
J Transl Med ; 11: 248, 2013 Oct 07.
Article in English | MEDLINE | ID: mdl-24099643

ABSTRACT

BACKGROUND: The role of body composition (lean mass and fat mass) on urine chemistries and bone quality is still debated. Our aim was therefore to determine the effect of lean mass and fat mass on urine composition and bone mineral density (BMD) in a cohort of healthy females. MATERIALS AND METHODS: 78 female volunteers (mean age 46 ± 6 years) were enrolled at the Stone Clinic of Parma University Hospital and subdued to 24-hour urine collection for lithogenic risk profile, DEXA, and 3-day dietary diary. We defined two mathematical indexes derived from body composition measurement (index of lean mass-ILM, and index of fat mass-IFM) and the cohort was split using the median value of each index, obtaining groups differing only for lean or fat mass. We then analyzed differences in urine composition, dietary intakes and BMD. RESULTS: The women with high values of ILM had significantly higher excretion of creatinine (991 ± 194 vs 1138 ± 191 mg/day, p = 0.001), potassium (47 ± 13 vs 60 ± 18 mEq/day, p < 0.001), phosphorus (520 ± 174 vs 665 ± 186 mg/day, p < 0.001), magnesium (66 ± 20 vs 85 ± 26 mg/day, p < 0.001), citrate (620 ± 178 vs 807 ± 323 mg/day, p = 0.002) and oxalate (21 ± 7 vs 27 ± 11 mg/day, p = 0.015) and a significantly better BMD values in limbs than other women with low values of ILM. The women with high values of IFM had similar urine composition to other women with low values of IFM, but significantly better BMD in axial sites. No differences in dietary habits were found in both analyses. CONCLUSIONS: Lean mass seems to significantly influence urine composition both in terms of lithogenesis promoters and inhibitors, while fat mass does not. Lean mass influences bone quality only in limb skeleton, while fat mass influences bone quality only in axial sites.


Subject(s)
Adiposity , Bone Density , Health , Urinary Calculi/epidemiology , Urinary Calculi/physiopathology , Diet , Discriminant Analysis , Female , Humans , Italy/epidemiology , Middle Aged , Reproducibility of Results , Risk Factors
13.
J Am Med Dir Assoc ; 14(7): 507-12, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23582341

ABSTRACT

OBJECTIVE: To identify the mean values and percentiles for ASMM (appendicular skeletal muscle mass) and the prevalence of sarcopenia, in terms of muscle mass reduction, using different cutoffs in a European population. DESIGN: A retrospective analysis on the dataset from a multicenter study on apparently healthy Italian adults conducted between 1999 and 2002. A significant muscle mass loss, necessary to diagnose sarcopenia, was defined in 3 different ways: (1) by subtracting 2 SDs from the mean ASMM index (ASMMI) of a young adult population (20-39 year-olds), as in the Rosetta study and the NHANES survey; (2) by calculating the 15th percentile of the distribution of our young population, corresponding to about 1 SD below the mean ASMMI; (3) by calculating the 20th percentile of the distribution of the ASMMI (as in the Health ABC study) of an elderly population. SETTING: Five centers for the diagnosis and treatment of osteoporosis in various parts of the country (Padova, Verona, Parma, Roma, Napoli). PARTICIPANTS: Participants were 1535 volunteers (1208 women and 327 men) aged 20 to 80 years, drawn from among staff members, university students, lay people contacted by word of mouth, and patients presenting spontaneously for osteoporosis screening. MEASUREMENTS: Body weight and height were measured for all participants. Body composition was assessed by DEXA, and the ASMMI was calculated as the ASMM divided by body height in meters squared. RESULTS: Both men's and women's lean mass in the arms and ASMM were highest in the young group and became lower in older age. In men, the ASMMI dropped gradually from age 20 to 29 to age 60 to 69, then remained stable in the oldest group. In women, the ASMMI gradually increased from age 20 to 29 to age 60 to 69, then dropped among the 70- to 80-year-olds. Based on the 15th percentile of the ASMMI for our young adult reference population, the cutoffs for sarcopenia were 7.59 kg/m(2) in men and 5.47 kg/m(2) in women; if the 20th percentile of the ASMMI in our elderly subjects (>65 years) was considered, the cutoffs were 7.64 kg/m(2) in men and 5.78 kg/m(2) in women. Applying the different diagnostic criteria to the those older than 65, the prevalence of sarcopenia ranged from 0% to about 20% in both genders. CONCLUSION: The 15th percentile (or 1 SD below the mean) of the ASMMI of our young adults, and the 20th percentile of this index for an elderly reference population proved more effective in identifying cases of sarcopenia than subtracting 2 SD from the mean ASMMI of a young adult population.


Subject(s)
Absorptiometry, Photon , Body Composition , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Adult , Aged , Aged, 80 and over , Aging , Analysis of Variance , Female , Humans , Italy , Male , Middle Aged , Prevalence , Reference Values , Retrospective Studies , Sex Characteristics , Young Adult
14.
Ann Nutr Metab ; 61(2): 151-9, 2012.
Article in English | MEDLINE | ID: mdl-23037332

ABSTRACT

BACKGROUND AND AIMS: Global fat mass distribution seems to correlate with different levels of cardio-metabolic risk; centrally distributed fat carries a high risk of cardiovascular disease, while lower limb adiposity may have a protective effect against insulin resistance. Reference data regarding body composition have already been published for the Italian population; the aim of this study was to add reference values for trunk and lower limb fat mass, and their ratio (TLR), developing percentile distributions for age brackets between 20 and 80 years. METHODS: A retrospective analysis of a multicenter, cross-sectional study was conducted and 1,570 healthy Italian adults (1,241 females and 329 males) were selected. The regional fat mass, measured by dual-energy X-ray absorptiometry total body scan, was analyzed and the TLR was calculated. RESULTS: In both genders we observed higher trunk fat mass values in older subjects against a smaller difference in BMI values. The leg fat mass was higher in old men, while it was similar in women at different ages. The TLR values in older subjects doubled those of younger subjects in both genders (62% in males and 71% in females). CONCLUSIONS: The identified ranges for trunk, leg fat mass, and TLR may be used as reference values to describe the global fat mass distribution in healthy individuals and to identify states of altered body fat distribution.


Subject(s)
Absorptiometry, Photon/methods , Lower Extremity/diagnostic imaging , Obesity/epidemiology , Torso/diagnostic imaging , Adiposity/physiology , Adult , Aged , Aged, 80 and over , Body Fat Distribution , Body Height , Body Mass Index , Body Weight , Cross-Sectional Studies , Female , Humans , Insulin Resistance , Italy/epidemiology , Leg/diagnostic imaging , Male , Middle Aged , Prevalence , Reference Values , Retrospective Studies , White People , Young Adult
15.
Clin Nutr ; 31(4): 506-11, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22342050

ABSTRACT

BACKGROUND & AIMS: To establish reference values for limb composition, fat-free mass (FFM) and fat mass (FM) in Italian adults for gender-specific age brackets 20-80 years old and to assess age-related regional changes in body composition. METHODS: A multicenter, retrospective study was conducted on 1571 healthy subjects, 1240 women and 331 men. Regional FFM and FM were measured by dual-energy X-ray absorptiometry. FM was expressed as % of limb weight. RESULTS: FFM in men diminished with age in both arms and legs, with reference ranges (25th -75th percentile) of 3.8-4.6 kg and 10.4-12.2 kg, respectively for 20-29 year-olds, and 3.1-3.9 kg and 8.2-10.4 kg for 70-79 year-olds. Women's arm FFM remained stable with aging (reference values 1.7-2.2 kg), decreasing in their legs (6.2-7.2 kg for 20-29 year-olds, 5.5-6.5 kg for 70-79 year-olds). Limb FM% increased with age in both genders: the reference values were 9-15% (arms) and 12-21% (legs) for 20-29 year-old men, and 19-26% and 19-29%, respectively, for 70-79 year-olds; for women's arms, they were 25-36% for 20-29 year-olds and 36-48% for 70-79 year-olds, while their leg FM remained the same with aging, i.e. 32-40%. CONCLUSIONS: These data complete the published reference values for whole body composition, enabling physiological or pathological changes in limb composition to be identified in Caucasian populations living in the Mediterranean area.


Subject(s)
Absorptiometry, Photon/methods , Adipose Tissue/diagnostic imaging , Aging , Leg/diagnostic imaging , Muscle, Skeletal/diagnostic imaging , Adult , Aged , Aged, 80 and over , Body Composition , Body Weight , Female , Humans , Italy , Leg/anatomy & histology , Male , Middle Aged , Reference Values , Retrospective Studies , White People , Young Adult
16.
Acta Biomed ; 83(2): 122-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-23393920

ABSTRACT

Humeral shaft fractures may occur as a result of arm wrestling. We discuss the biomechanics of this rare injury mechanism. Using Strength of materials concepts, Computerized Tomography and Bone Density Scans we studied the biomechanical and anatomical conditions that predispose to this particular fracture. An unfavorable ratio between inner-outer diameter and a low bone mineral concentration in the distal third of humerus compared to other sections of bone were seen as critical aspects. The biomechanical study observed the primary importance of these factors to explain the typical shape and location of this fracture. These results indicate that each arm wrestler should be conscious of the risks of practicing this activity. (www.actabiomedica.it).


Subject(s)
Humeral Fractures/etiology , Humeral Fractures/physiopathology , Wrestling/injuries , Adult , Arm , Biomechanical Phenomena , Cadaver , Humans , Humeral Fractures/diagnostic imaging , Male , Radiography
17.
J Biomed Mater Res A ; 95(3): 682-90, 2010 Dec 01.
Article in English | MEDLINE | ID: mdl-20725985

ABSTRACT

It is known that the roughness of titanium surfaces affects cell proliferation and differentiation. However, the mechanisms mediating the cellular responses to surface topography are only partially understood. The present study investigated whether Wnt canonical signaling, an important pathway in determining cell fate, is modulated by surface roughness. This study analyzed the behavior of the murine C2C12 mesenchymal cell line on polished or acid-etched, sand-blasted (SLA) commercially pure titanium. When we transfected cells with Wnt3a or wild-type ß-catenin and a reporter construct, we found that stimulation of Wnt canonical signaling was enhanced in cells on SLA surfaces. Moreover, more ß-catenin translocated to the nucleus in cells on SLA surfaces after stimulation with Wnt3a as evidenced by immunofluorescence. However, when cells were transfected with constitutively active S33Y ß-catenin mutant, no difference was observed between the groups. Higher levels of transcripts of Wnt target genes were detected in C2C12 cells cultured on SLA surfaces following transfection with Wnt3a, but the expression of a gene regulating ß-catenin degradation, Axin 2, was reduced on SLA surfaces. Inhibition of ß-catenin mediated transcription by dnTCF in murine osteoblastic MC3T3 cells, reversed the effects of topography on cell differentiation. Taken together, these results show that surface roughness modulates the responsiveness of mesenchymal cells to Wnt3a, that this requires the control of ß-catenin degradation, and that the control of ß-catenin signaling by surface topography is accountable for at least part of the effects of surface on cell differentiation.


Subject(s)
Mesenchymal Stem Cells/physiology , Signal Transduction/physiology , Wnt Proteins/metabolism , beta Catenin/metabolism , Animals , Axin Protein , Cell Culture Techniques , Cell Differentiation/physiology , Cell Line , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Mesenchymal Stem Cells/cytology , Mice , Osteocalcin/metabolism , Surface Properties , Titanium/chemistry , Titanium/metabolism , Wnt Proteins/genetics , beta Catenin/genetics
18.
J Am Geriatr Soc ; 58(8): 1489-95, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20646099

ABSTRACT

OBJECTIVES: To compare the effects on parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. DESIGN: Randomized-controlled trial with 6-month follow-up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Sixty community-dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. INTERVENTION: Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D(3) group) or cholecalciferol 1,000 IU/day (daily D(3) group). MEASUREMENTS: Serum PTH, 25(OH)D, calcium, bone-specific alkaline phosphatase, ß-C-terminal telopeptide of type I collagen, phosphate, 24-hour urinary calcium excretion. RESULTS: The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D<20 ng/mL)], and 36 subjects (60%) had severe deficiency (<10 ng/mL), with no difference between the groups (severe deficiency: intermittent D(3) group, n=18; daily D(3) group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase ± standard deviation of 25(OH)D at 6 months was higher in the intermittent D(3) group (22.7±11.8 ng/mL) than in the daily D(3) group (13.7±6.7 ng/mL, P<.001), with a higher proportion of participants in the intermittent D(3) group reaching desirable serum concentration of 25(OH)D≥30 ng/mL (55% in the intermittent D(3) group vs 20% in the daily D(3) group, P<.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. CONCLUSION: Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher-dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet-higher doses will be required for adequate vitamin D repletion.


Subject(s)
Cholecalciferol/administration & dosage , Hyperparathyroidism, Secondary/drug therapy , Vitamin D Deficiency/drug therapy , Vitamins/administration & dosage , Aged , Alkaline Phosphatase/metabolism , Biomarkers/metabolism , Calcium/blood , Calcium/urine , Collagen Type I/metabolism , Dose-Response Relationship, Drug , Female , Humans , Parathyroid Hormone/blood , Peptides/metabolism , Phosphates/blood , Vitamin D/analogs & derivatives , Vitamin D/blood
19.
J Immunol ; 184(6): 3242-9, 2010 Mar 15.
Article in English | MEDLINE | ID: mdl-20173031

ABSTRACT

Human aging is characterized by expanded and altered adaptive immune responses to human CMV (HCMV). It is unclear whether this expansion has its origins in age-related homeostatic disturbances or viral reactivation, whether anti-CMV immune surveillance may still be effective, and what are the consequences of this expanded immune response for health and longevity. We conducted an observational cross-sectional study in groups of HCMV-seropositive subjects aged >or=65 y of variable health status to compare the intensity of Ab responses against HCMV with those against EBV and with CD4(+) and CD8(+) T cell proinflammatory effector responses directed to HCMV-derived pp65 and immediate-early protein 1 synthetic peptides. Ab responses to HCMV, but not to EBV, and anti-HCMV CD4(+), but not CD8(+), T cell responses were more intense in elderly subjects aged >or=85 y in poor health and were inversely correlated with markers of functional activity and cognitive function. Therefore, humoral and CD4(+) T cell anti-HCMV responses were specifically intensified in advanced aging associated with comorbidity and cognitive and functional impairments. Such a distinctive pattern of adaptive immunity indicates that immune responses targeting the extracellular phase of HCMV are increased in these elderly subjects and could represent an indirect effect of localized and undetectable HCMV reactivation. This study demonstrates that the oldest subjects in poor health with physical and mental impairment express intense functional immune responses to extracellular HCMV and suggests that they may be at risk for direct pathogenic effects by HCMV reactivation as well as indirect pathogenic effects linked to proinflammatory anti-HCMV effector responses.


Subject(s)
Adaptive Immunity , Cognition Disorders/immunology , Cognition Disorders/psychology , Cytomegalovirus/immunology , Extracellular Space/immunology , Extracellular Space/virology , Aged , Aged, 80 and over , Antibodies, Viral/biosynthesis , Brief Psychiatric Rating Scale , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/virology , Cognition Disorders/epidemiology , Comorbidity , Cross-Sectional Studies , Epitopes, T-Lymphocyte/immunology , Female , Humans , Immediate-Early Proteins/chemical synthesis , Immediate-Early Proteins/immunology , Inflammation Mediators/physiology , Male , Phosphoproteins/chemical synthesis , Phosphoproteins/immunology , Viral Matrix Proteins/chemical synthesis , Viral Matrix Proteins/immunology , Virus Activation/immunology
20.
Clin Nutr ; 27(1): 87-94, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18206273

ABSTRACT

BACKGROUND & AIMS: To establish reference values for fat-free mass (FFM), the FFM index (FFMI), fat mass (FM) and the FM index (FMI) in an Italian adult population, developing percentile distribution curves for age brackets between 20 and 80 years. METHODS: A multicenter, retrospective study was conducted on a sample of 1866 healthy Italian adults, 1435 females and 431 males. FFM and FM were measured by dual-energy X-ray absorptiometry. FFMI and FMI were calculated as the ratio of FFM and FM to height squared. RESULTS: The reference range for the FFMI (25-75th percentile) was similar in all age groups, i.e. 18.7-21 kg/m(2) in men and 14.9-17.2 kg/m(2) in women. In both genders, FM, the FMI and FM as a percentage of body weight (FM%) increased with age. The reference values for FM% in the two age brackets 20-29 and 60-69 were, respectively, 13-20% and 22.5-29.3% for men and 26.1-34.9%, 32.5-39.6% for women. CONCLUSIONS: These body composition ranges can be used by clinicians and nutritionists as reference values for a Caucasian population in the Mediterranean area when evaluating body composition variations occurring in aging, malnutrition and chronic diseases.


Subject(s)
Absorptiometry, Photon/methods , Adipose Tissue/diagnostic imaging , Body Composition , Muscle, Skeletal/diagnostic imaging , Absorptiometry, Photon/standards , Adipose Tissue/anatomy & histology , Adipose Tissue/physiology , Adult , Aged , Aged, 80 and over , Aging/physiology , Female , Humans , Italy , Male , Middle Aged , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Reference Values , Retrospective Studies
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