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2.
Alzheimers Dement ; 16(1): 60-70, 2020 01.
Article in English | MEDLINE | ID: mdl-31914226

ABSTRACT

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.


Subject(s)
Frontotemporal Dementia , Genetic Predisposition to Disease , Mutation/genetics , Neuropsychological Tests/statistics & numerical data , Age Factors , Aged , Brain/pathology , C9orf72 Protein/genetics , Female , Frontotemporal Dementia/classification , Frontotemporal Dementia/genetics , Humans , Male , Middle Aged , North America , Progranulins/genetics , tau Proteins/genetics
3.
Eur Rev Med Pharmacol Sci ; 22(18): 5874-5891, 2018 09.
Article in English | MEDLINE | ID: mdl-30280768

ABSTRACT

OBJECTIVE: Renal Cell Carcinoma (RCC) is the most common malignancy in adult kidneys. The American Cancer Society estimated 62,700 new cases and 14,240 deaths in 2018. Although early detection has improved in recent years, the treatment remains a challenge and reliable biomarkers for poor outcomes become necessary for the prevention of metastases and improve the quality of patients' life during and after treatment. Then, the current status of the search for new RCC biomarkers was discussed, as well as the latest discoveries in the RCC risk and metastatic treatment were discussed in this review. MATERIALS AND METHODS: Extensive research was carried out in the online databases and full-free text articles published in the last 5 years, or more when convenient, were evaluated. Articles were included that addressed the proposed theme and were published in the English language. RESULTS: The present state of knowledge on biomarkers for RCC carcinogenesis and progression is still much to be understood about RCC risk factors and molecular pathways resulting in metastatic progression. Newest RCC target therapies were discussed, mainly in relation to immunological therapy, and vaccines that have been tested in numerous trials with different cancer types. CONCLUSIONS: The development of targeted therapies has revolutionized the treatment of advanced and metastatic cancers or non-responder patients. Combined therapy between classical chemotherapy and adjuvant immunotherapies has been modifying the cancer patients prognosis and bringing the hope of a cure in many cases.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Clinical Trials as Topic , Disease Progression , Gene Expression Regulation, Neoplastic/drug effects , Humans , Kidney Neoplasms/drug therapy , Neoplasm Metastasis
4.
Clin Obes ; 7(1): 11-21, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28028931

ABSTRACT

Obesity tracks from childhood to adulthood most strongly of all cardiometabolic risk factors. To determine relationship of body mass index (BMI) and waist circumference (WC) with cardiometabolic risk (dyslipidemia, hyperglycemia and elevated blood pressure) in a large U.S. population ages 12-19 and demographic subgroups. Pooled 1999-2014 National Health and Nutrition Examination Survey data were analyzed (N = 23 438). In addition to standard cutoffs of BMI and WC, risk levels were identified for each laboratory variable: HDL-cholesterol, LDL-cholesterol, triglycerides, total cholesterol (category = lipids); fasting glucose, glycated haemoglobin (category = glucose); systolic/diastolic pressures (category =blood pressure). Within each category, being high-risk on any of the variables was high-risk; being borderline-risk on any, without being high-risk on any, was borderline-risk. Obesity severity was strongly associated with increased cardiometabolic risk, with prevalence of borderline-risk greater than high-risk. Anthropometric indicators in males and Hispanics, versus females and Whites/Blacks, respectively, had stronger associations with cardiometabolic risks. BMI and WC performed well for identifying adolescents with at least one borderline-risk or high-risk level measure for lipids, glucose and blood pressure; relationship strength varying by gender and race/ethnicity. Thus, to prevent or better manage clinical diseases of adolescents with elevated BMI and/or WC, all recommended laboratory tests are warranted.


Subject(s)
Cardiovascular Diseases/epidemiology , Dyslipidemias/epidemiology , Hyperglycemia/epidemiology , Hypertension/epidemiology , Pediatric Obesity/epidemiology , Adolescent , Blood Glucose , Body Mass Index , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Child , Cholesterol, HDL/blood , Dyslipidemias/etiology , Dyslipidemias/physiopathology , Female , Humans , Hyperglycemia/etiology , Hyperglycemia/physiopathology , Hypertension/etiology , Hypertension/physiopathology , Male , Nutrition Surveys , Odds Ratio , Pediatric Obesity/complications , Pediatric Obesity/physiopathology , Prevalence , Risk Assessment , Risk Factors , Triglycerides/blood , United States/epidemiology , Waist Circumference , Young Adult
5.
Oncogene ; 35(31): 4091-101, 2016 08 04.
Article in English | MEDLINE | ID: mdl-26686094

ABSTRACT

Solar ultraviolet (UV) light is a major etiological factor in skin carcinogenesis, with solar UV-stimulated signal transduction inducing pathological changes and skin damage. The primary sensor of solar UV-induced cellular signaling has not been identified. We use an experimental system of solar simulated light (SSL) to mimic solar UV and we demonstrate that Fyn is a primary redox sensor involved in SSL-induced signal transduction. Reactive oxygen species (ROS) generated by SSL exposure directly oxidize Cys488 of Fyn, resulting in increased Fyn kinase activity. Fyn oxidation was increased in mouse skin after SSL exposure and Fyn-knockout mice formed larger and more tumors compared with Fyn wild-type mice when exposed to SSL for an extended period of time. Murine embryonic fibroblasts (MEFs) lacking Fyn and cells in which Fyn expression was knocked down were resistant to SSL-induced apoptosis. Furthermore, cells expressing mutant Fyn (C448A) were resistant to SSL-induced apoptosis. These findings suggest that Fyn acts as a regulatory nexus between solar UV, ROS and signal transduction during skin carcinogenesis.


Subject(s)
Neoplasms, Radiation-Induced/etiology , Proto-Oncogene Proteins c-fyn/physiology , Signal Transduction/radiation effects , Skin Neoplasms/etiology , Animals , Apoptosis , Cells, Cultured , Mice , Mice, Hairless , Protein Kinase C-delta/physiology , Reactive Oxygen Species/metabolism , Ultraviolet Rays
6.
J Physiol ; 593(19): 4319-39, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-26136181

ABSTRACT

KEY POINTS: The superficial spinal dorsal horn contains a heterogeneous population of neurons that process sensory inputs. Information on the properties of excitatory interneurons in this region is limited. As calretinin is a protein thought to be restricted to an excitatory population in this region, the aim of this study was to characterize calretinin-expressing neurons. Most calretinin cells (85%) exhibited large A-type potassium currents and delayed firing action potential discharge, and received strong excitatory synaptic input, whereas the remainder exhibited hyperpolarization-activated cation currents and low threshold T-type calcium currents, and tonic- or initial bursting firing patterns, and received weak excitatory synaptic input. These respective features are consistent with properties of excitatory and inhibitory interneuron populations in this region of the spinal cord. Our findings have resolved a previously unidentified population of inhibitory interneurons. Furthermore, the contrasting excitability patterns of excitatory and inhibitory calretinin-expressing neurons suggest that they play distinct roles in spinal sensory processing circuits. ABSTRACT: Neurons in the superficial dorsal horn (SDH) of the spinal cord play an important role in nociceptive, thermal, itch and light touch sensations. Excitatory interneurons comprise ∼65% of all SDH neurons but surprisingly few studies have investigated their role in spinal sensory processing. Here we use a transgenic mouse to study putative excitatory SDH neurons that express the calcium binding protein calretinin (CR). Our immunocytochemical, morphological and electrophysiological analysis identified two distinct populations of CR-expressing neurons, which we termed 'Typical' and 'Atypical'. Typical CR-expressing neurons comprised ∼85% of the population and exhibited characteristic excitatory interneuron properties including delayed firing discharge, large rapid A-type potassium currents, and central, radial or vertical cell morphologies. Atypical neurons exhibited properties consistent with inhibitory interneurons, including tonic firing or initial bursting discharge, Ih currents, and islet cell morphology. Although both Typical and Atypical CR-expressing neurons responded to noxious peripheral stimulation, the excitatory drive onto Typical CR-expressing neurons was much stronger. Furthermore, Atypical CR-expressing cells comprise at least two functionally distinct subpopulations based on their responsiveness to noxious peripheral stimulation and neurochemical profile. Together our data suggest CR expression is not restricted to excitatory neurons in the SDH. Under normal conditions, the contribution of 'Typical' excitatory CR-expressing neurons to overall SDH excitability may be limited by the presence of A-type potassium currents, which limit the effectiveness of their strong excitatory input. Their contribution may, however, be increased in pathological situations where A-type potassium currents are decreased. By contrast, 'Atypical' inhibitory neurons with their excitable phenotype but weak excitatory input may be more easily recruited during increased peripheral stimulation.


Subject(s)
Calbindin 2/physiology , Posterior Horn Cells/physiology , Animals , Calbindin 2/genetics , Calbindin 2/metabolism , Female , Male , Membrane Potentials , Mice , Mice, Inbred C57BL , Mice, Transgenic , Pain/physiopathology , Posterior Horn Cells/metabolism
7.
Eur Cell Mater ; 23: 222-36, 2012 Apr 05.
Article in English | MEDLINE | ID: mdl-22481226

ABSTRACT

This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.


Subject(s)
Cartilage Diseases/pathology , Cartilage, Articular/cytology , Chondrocytes/cytology , Tissue Engineering/methods , Animals , Cartilage Diseases/metabolism , Cartilage Diseases/surgery , Cartilage, Articular/growth & development , Cartilage, Articular/metabolism , Cells, Cultured , Chondrocytes/metabolism , Chondrocytes/transplantation , Collagen Type I/metabolism , Collagen Type II/metabolism , Durapatite/chemistry , Female , Goats , Hyaluronic Acid/chemistry , Time Factors , Tissue Scaffolds/chemistry , Tissue Transplantation/methods , Transplantation, Autologous , Wound Healing
8.
Article in English | MEDLINE | ID: mdl-22511611

ABSTRACT

Multiple studies have demonstrated increased rates of osteopenia and osteoporosis in HIV-infected patients but there have been no published studies on current screening practices. We conducted a retrospective chart review of 2924 patients attending an urban HIV clinic. Thirty patients (1%) had dual-energy x-ray absorptiometry (DXA) scans. Patients undergoing DXA scans were more likely to be older, women, and have nondetectable HIV viral load and CD4 count ≥200. The most frequently cited indications for screening were perimenopausal or postmenopausal status and HIV infection. Of the patients screened, 96% had osteopenia or osteoporosis with a median T-score of -1.9 and a median of 3.8 osteoporosis risk factors in addition to HIV.  Of the 20 practitioners in the clinic, only 7 had patients with screening DXA scans. DXA scans are underutilized in the HIV population given the high rate of osteopenia and osteoporosis detected in this study.


Subject(s)
Absorptiometry, Photon/statistics & numerical data , HIV Infections/complications , Osteoporosis/diagnosis , Adult , Aged , Alcohol Drinking , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Female , HIV Infections/drug therapy , Humans , Male , Middle Aged , Osteoporosis/complications , Perimenopause , Postmenopause , Practice Guidelines as Topic , Practice Patterns, Physicians' , Retrospective Studies , Risk Factors , Smoking
9.
Obes Rev ; 13(3): 214-33, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22070186

ABSTRACT

Schools are an attractive and popular setting for implementing interventions for children. There is a growing body of empirical research exploring the efficacy of school-based obesity prevention programs. While there have been several reviews on the topic, findings remain mixed. To examine the quality of evidence and compare the findings from existing systematic reviews and meta-analyses of school-based programs in the prevention and control of childhood obesity. This paper systematically appraises the methodology and conclusions of literature reviews examining the effectiveness of school-based obesity interventions published in English in peer-reviewed journals between January 1990 and October 2010. Eight reviews were examined, three meta-analyses and five systematic reviews. All of the reviews recognized that studies were heterogeneous in design, participants, intervention and outcomes. Intervention components in the school setting associated with a significant reduction of weight in children included long-term interventions with combined diet and physical activity and a family component. Several reviews also found gender differences in response to interventions. Of the eight reviews, five were deemed of high quality and yet limited evidence was found on which to base recommendations. As no single intervention will fit all schools and populations, further high-quality research needs to focus on identifying specific program characteristics predictive of success.


Subject(s)
Diet/standards , Exercise/physiology , Health Behavior , Obesity/prevention & control , Students/statistics & numerical data , Adolescent , Body Mass Index , Child , Child Welfare , Child, Preschool , Family Relations , Female , Humans , Male , Obesity/epidemiology , Randomized Controlled Trials as Topic , Schools/statistics & numerical data , Sex Factors , Students/psychology
10.
Am J Alzheimers Dis Other Demen ; 26(6): 477-83, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22021861

ABSTRACT

This study utilized a community-based, participatory research model between the Association for Frontotemporal Degeneration (AFTD) and the Education Core of the Indiana Alzheimer Disease Center. A total of 30 caregivers of persons with frontotemporal dementia (FTD) participated in 6 focus groups in 3 cities. The majority of participants were spouses of the person with FTD and had been providing care for an average of 6 years. Transcript analysis revealed 7 prominent themes: willingness to participate, when/how the issue of brain donation is raised, who initiates discussion about brain donation, who is involved in decisions about brain donation, motivation for participating in brain donation, lack of effective communication, and barriers to research participation. Caregivers demonstrated a strong desire to participate in research and contribute to advancing knowledge. The lack of effective communication between the clinicians and caregivers was a barrier to developing positive rapport, detrimentally impacting research participation.


Subject(s)
Brain , Caregivers/psychology , Frontotemporal Dementia/psychology , Patient Participation/psychology , Tissue Donors/psychology , Adult , Aged , Aged, 80 and over , Autopsy , Child of Impaired Parents/psychology , Community-Institutional Relations , Female , Focus Groups , Humans , Male , Middle Aged , Patient Selection , Spouse Abuse/psychology , Tissue Banks
11.
Food Chem ; 126(4): 1771-8, 2011 Jun 15.
Article in English | MEDLINE | ID: mdl-25213956

ABSTRACT

The retention and speciation of selenium in flour and bread was determined following experimental applications of selenium fertilisers to a high-yielding UK wheat crop. Flour and bread were produced using standard commercial practices. Total selenium was measured using inductively coupled plasma-mass spectrometry (ICP-MS) and the profile of selenium species in the flour and bread were determined using high performance liquid chromatography (HPLC) ICP-MS. The selenium concentration of flour ranged from 30ng/g in white flour and 35ng/g in wholemeal flour from untreated plots up to >1800ng/g in white and >2200ng/g in wholemeal flour processed from grain treated with selenium (as selenate) at the highest application rate of 100g/ha. The relationship between the amount of selenium applied to the crop and the amount of selenium in flour and bread was approximately linear, indicating minimal loss of Se during grain processing and bread production. On average, application of selenium at 10g/ha increased total selenium in white and wholemeal bread by 155 and 185ng/g, respectively, equivalent to 6.4 and 7.1µg selenium per average slice of white and wholemeal bread, respectively. Selenomethionine accounted for 65-87% of total extractable selenium species in Se-enriched flour and bread; selenocysteine, Se-methylselenocysteine selenite and selenate were also detected. Controlled agronomic biofortification of wheat crops for flour and bread production could provide an appropriate strategy to increase the intake of bioavailable selenium.

12.
Osteoarthritis Cartilage ; 18(8): 1067-76, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20434576

ABSTRACT

OBJECTIVE: To characterize the post-expansion cartilage-forming capacity of chondrocytes harvested from detached fragments of osteochondral lesions (OCLs) of ankle joints (Damaged Ankle Cartilage Fragments, DACF), with normal ankle cartilage (NAC) as control. DESIGN: DACF were obtained from six patients (mean age: 35 years) with symptomatic OCLs of the talus, while NAC were from 10 autopsies (mean age: 55 years). Isolated chondrocytes were expanded for two passages and then cultured in pellets for 14 days or onto HYAFF-11 meshes (FAB, Italy) for up to 28 days. Resulting tissues were assessed histologically, biochemically [glycosaminoglycan (GAG), DNA and type II collagen (CII)] and biomechanically. RESULTS: As compared to NAC, DACF contained significantly lower amounts of DNA (3.0-fold), GAG (5.3-fold) and CII (1.5-fold) and higher amounts of type I collagen (6.2-fold). Following 14 days of culture in pellets, DACF-chondrocytes generated tissues less intensely stained for Safranin-O and CII, with significantly lower GAG contents (2.8-fold). After 28 days of culture onto HYAFF((R))-11, tissues generated by DACF-chondrocytes were less intensely stained for Safranin-O and CII, contained significantly lower amounts of GAG (1.9-fold) and CII (1.4-fold) and had lower equilibrium (1.7-fold) and dynamic pulsatile modulus (3.3-fold) than NAC-chondrocytes. CONCLUSION: We demonstrated that DACF-chondrocytes have inferior cartilage-forming capacity as compared to NAC-chondrocytes, possibly resulting from environmental changes associated with trauma/disease. The study opens some reservations on the use of DACF-derived cells for the repair of ankle cartilage defects, especially in the context of tissue engineering-based approaches.


Subject(s)
Chondrocytes/metabolism , Chondrogenesis/physiology , Tissue Engineering/methods , Adult , Ankle Joint , Cartilage, Articular/metabolism , Cell Differentiation , Cells, Cultured , Female , Humans , Male , Talus
13.
Gene Ther ; 17(6): 779-89, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20220780

ABSTRACT

Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was performed to test whether an abbreviated ex vivo protocol using vector-laden, coagulated bone marrow aspirates for gene delivery to cartilage defects may be feasible for clinical application. Ovine autologous bone marrow was transduced with adenoviral vectors containing cDNA for green fluorescent protein or transforming growth factor (TGF)-beta1. The marrow was allowed to clot forming a gene plug and implanted into partial-thickness defects created on the medial condyle. At 6 months, the quality of articular cartilage repair was evaluated using histological, biochemical and biomechanical parameters. Assessment of repair showed that the groups treated with constructs transplantation contained more cartilage-like tissue than untreated controls. Improved cartilage repair was observed in groups treated with unmodified bone marrow plugs and Ad.TGF-beta1-transduced plugs, but the repaired tissue from TGF-treated defects showed significantly higher amounts of collagen II (P<0.001). The results confirmed that the proposed method is fairly straightforward technique for application in clinical settings. Genetically modified bone marrow clots are sufficient to facilitate articular cartilage repair of partial-thickness defects in vivo. Further studies should focus on selection of transgene combinations that promote more natural healing.


Subject(s)
Cartilage, Articular/injuries , Gene Transfer Techniques , Genetic Therapy/methods , Transforming Growth Factor beta1/genetics , Adenoviridae/genetics , Animals , Bone Marrow Cells/physiology , Bone Marrow Transplantation , Genetic Vectors , Sheep , Transduction, Genetic , Wound Healing
14.
Osteoarthritis Cartilage ; 17(4): 489-96, 2009 Apr.
Article in English | MEDLINE | ID: mdl-18980848

ABSTRACT

OBJECTIVE: As compared to knee chondrocytes (KC), talar chondrocytes (TC) have superior synthetic activity and increased resistance to catabolic stimuli. We investigated whether these properties are maintained after TC are isolated and expanded in vitro. METHODS: Human TC and KC from 10 cadavers were expanded in monolayer and then cultured in pellets for 3 and 14 days or in hyaluronan meshes (Hyaff-11) for 14 and 28 days. Resulting tissues were assessed biochemically, histologically, biomechanically and by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The proteoglycan and collagen synthesis rates in the pellets were also measured following exposure to Interleukin-1 beta (IL-1 beta). RESULTS: After 14 days of pellet culture, TC and KC expressed similar levels of type I collagen (CI) and type II collagen (CII) mRNA and the resulting tissues contained comparable amounts of glycosaminoglycans (GAG) and displayed similar staining intensities for CII. Also proteoglycan and collagen synthesis were similar in TC and KC pellets, and dropped to a comparable extent in response to IL-1 beta. Following 14 days of culture in Hyaff-11, TC and KC generated tissues with similar amounts of GAG and CI and CII. After 28 days, KC deposited significantly larger fractions of GAG and CII than TC, although the trend was not reflected in the measured biomechanical properties. CONCLUSION: After isolation from their original matrices and culture expansion, TC and KC displayed similar biosynthetic activities, even in the presence of catabolic stimuli. These in vitro data suggest a possible equivalence of TC and KC as autologous cell sources for the repair of talar cartilage lesions.


Subject(s)
Ankle Joint/cytology , Cartilage, Articular/cytology , Chondrocytes/cytology , Knee Joint/cytology , Adult , Aged , Ankle Joint/metabolism , Cartilage, Articular/drug effects , Cartilage, Articular/metabolism , Cell Proliferation , Cells, Cultured , Chondrocytes/drug effects , Chondrocytes/metabolism , Chondrogenesis/physiology , Collagen/biosynthesis , Collagen/genetics , Glycosaminoglycans/metabolism , Humans , Interleukin-1beta/pharmacology , Knee Joint/metabolism , Middle Aged , Proteoglycans/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction/methods , Stress, Mechanical
15.
Arthritis Rheum ; 58(1): 197-208, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18163475

ABSTRACT

OBJECTIVE: To determine whether engineered cartilage generated by nasal chondrocytes (ECN) is responsive to different regimens of loading associated with joint kinematics and previously shown to be stimulatory of engineered cartilage generated by articular chondrocytes (ECA). METHODS: Human nasal and articular chondrocytes, harvested from 5 individuals, were expanded and cultured for 2 weeks into porous polymeric scaffolds. The resulting ECN and ECA were then maintained under static conditions or exposed to the following loading regimens: regimen 1, single application of cyclic deformation for 30 minutes; regimen 2, intermittent application of cyclic deformation for a total of 10 days, followed by static culture for 2 weeks; regimen 3, application of surface motion for a total of 10 days. RESULTS: Prior to loading, ECN constructs contained significantly higher amounts of glycosaminoglycan (GAG) and type II collagen compared with ECA constructs. ECN responded to regimen 1 by increasing collagen and proteoglycan synthesis, to regimen 2 by increasing the accumulation of GAG and type II collagen as well as the dynamic modulus, and to regimen 3 by increasing the expression of superficial zone protein, at the messenger RNA level and the protein level, as well as the release of hyaluronan. ECA constructs were overall less responsive to all loading regimens, likely due to the lower extracellular matrix content. CONCLUSION: Human ECN is responsive to physical forces resembling joint loading and can up-regulate molecules typically involved in joint lubrication. These findings should prompt future in vivo studies exploring the possibility of using nasal chondrocytes as a cell source for articular cartilage repair.


Subject(s)
Chondrocytes/cytology , Chondrocytes/physiology , Tissue Engineering , Weight-Bearing/physiology , Adult , Cartilage, Articular/cytology , Cartilage, Articular/physiology , Collagen Type II/physiology , Culture Media , Gene Expression/physiology , Glucuronosyltransferase/genetics , Humans , Hyaluronan Synthases , Middle Aged , Nose/cytology , Proteoglycans/genetics , Proteoglycans/physiology , RNA, Messenger/metabolism , Stress, Mechanical , Surface Properties
16.
Tissue Eng ; 13(2): 271-80, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17504061

ABSTRACT

The aim of this investigation was to determine the effect of growth factor treatment on ovine meniscal chondrocyte (OMC) proliferation in vitro and on the production of matrix proteins by OMCs grown within a polyglycolic acid (PGA) scaffold. Analysis of 72-h monolayer cultures using the mean transit time (MTT) assay revealed a greater increase in OMC numbers in the presence of platelet-derived growth factor (PDGF)-AB, PDGF-BB, insulin-like growth factor (IGF)-I, transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) than in untreated controls. In contrast, IGF-II and bone morphogenetic protein-2 had no effect on OMC proliferation at the concentrations tested. The growth factors that elicited the greatest proliferative response (PDGF-AB, PDGF-BB, TGF-beta1, and IGF-I) were subsequently tested for their ability to enhance OMC proliferation and differentiation within PGA scaffolds. Biochemical analysis revealed less glycosaminoglycan (GAG) production in the presence of all growth factors tested compared to untreated control samples. In contrast, all of the growth factors increased collagen type I production by OMCs within the scaffolds at day 20, and all except PDGF-BB resulted in an increase at day 39, when compared to appropriate control samples. With the exception of IGF-I, none of the growth factors tested had any significant effect on collagen type II production. Histological staining of sections from OMC-PGA scaffolds did not reveal any difference in GAG or collagen production between the treatment groups. However, immunohistochemical analysis demonstrated an increase in collagen type I expression and a decrease in collagen type II at day 39 in all growth factortreated constructs, concomitant with a high infiltration of cells. This suggests that PDGF-AB, PDGF-BB, TGF-beta1, and IGF-1 may be useful in future tissue engineering studies for promoting meniscal cell proliferation and differentiation within scaffolds.


Subject(s)
Chondrocytes/cytology , Chondrocytes/physiology , Intercellular Signaling Peptides and Proteins/administration & dosage , Lactic Acid/chemistry , Menisci, Tibial/cytology , Menisci, Tibial/physiology , Polyglycolic Acid/chemistry , Polymers/chemistry , Tissue Engineering/methods , Animals , Cattle , Cell Culture Techniques/methods , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Chondrocytes/drug effects , Drug Combinations , Menisci, Tibial/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer
17.
J Environ Qual ; 35(4): 982-91, 2006.
Article in English | MEDLINE | ID: mdl-16738382

ABSTRACT

Addition of anaerobically digested sewage sludge (biosolids) to soil may improve conditions for phytoremediation of petroleum hydrocarbons (PHCs) through improved soil chemical, biological, and physical properties. A 32-wk greenhouse study investigated three rates of biosolids addition (0, 13.34, and 26.68 g oven-dry biosolids kg(-1) oven-dry soil) and the presence or absence of smooth brome (Bromus inermis Leyss. cv. Carlton) plants on the removal of diesel (3.5 g kg(-1) oven-dry soil) in an industrial, sandy loam soil. Diesel PHCs were divided into two fractions based on equivalent normal straight-chain boiling point ranges (F2: nC10-nC16; F3: nC16-nC34). The addition of biosolids did not increase the extent of PHC degradation but did result in significantly greater first-order decay constants compared to unamended controls. Overall, the presence of plants did not increase the rate or extent of PHC degradation, relative to that observed in unamended, non-vegetated soils. Vegetation was, however, an important factor within the biosolids-amended soils as was observed by a greater extent of PHC degradation. Some of this decrease was attributed to plant-induced removal of biosolids components that were contributing to the F3 fraction. Overall, the low-amendment rate (13.34 g oven-dry biosolids kg(-1) oven-dry soil) was considered to be the most effective treatment because it produced the greatest overall PHC degradation rate (0.226 wk(-1) for total PHCs) and resulted in the greatest recovery of biosolids-derived N by smooth brome (26.6%).


Subject(s)
Hydrocarbons/isolation & purification , Sewage/analysis , Soil Microbiology , Soil Pollutants/isolation & purification , Agriculture , Biodegradation, Environmental , Biomass , Fertilizers , Hydrocarbons/metabolism , Industry , Nitrogen/metabolism , Sewage/chemistry , Soil Pollutants/metabolism
18.
Ann Rheum Dis ; 65(2): 184-90, 2006 Feb.
Article in English | MEDLINE | ID: mdl-15975972

ABSTRACT

BACKGROUND: The synergistic degradation of cartilage by oncostatin M (OSM) in combination with either interleukin 1 (IL1) or tumour necrosis factor alpha (TNFalpha) has been previously demonstrated using bovine nasal cartilage (BNC). OBJECTIVES: (a) To investigate if human nasal cartilage (HNC) responds in the same way as BNC to these cytokine combinations, particularly in collagen degradation. (b) To compare the response of human nasal and articular cartilages. METHODS: Collagen release was assessed by measuring the hydroxyproline content of culture supernatants and proteoglycan release by the dimethylmethylene blue assay. Matrix metalloproteinase (MMP)-1, MMP-13, and tissue inhibitor of metalloproteinase 1 release were measured by specific enzyme linked immunosorbent assays (ELISAs), and collagenolytic activity was measured by a bioassay using radiolabelled collagen. RESULTS: OSM in combination with either IL1 or TNFalpha acted synergistically to induce collagenolysis from HNC, with a maximum of 79% collagen release. This degradation strongly correlated with MMP-1 and MMP-13 levels and collagenolytic activity. CONCLUSION: Collagen release from human cartilage is marked and implicates both MMP-1 and MMP-13 in the synergistic degradation of human cartilage by OSM in combination with either IL1 or TNFalpha. HNC responds in the same way as BNC, thus validating the bovine cartilage degradation assay as a model relevant to human disease.


Subject(s)
Collagen/metabolism , Collagenases/metabolism , Cytokines/pharmacology , Interleukin-1/pharmacology , Nasal Septum/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Adult , Animals , Biological Assay/methods , Biomarkers/analysis , Cattle , Collagenases/analysis , Drug Synergism , Enzyme-Linked Immunosorbent Assay/methods , Humans , Matrix Metalloproteinase 1/analysis , Matrix Metalloproteinase 13 , Middle Aged , Models, Animal , Nasal Septum/metabolism , Oncostatin M , Stimulation, Chemical , Tissue Culture Techniques , Tissue Inhibitor of Metalloproteinase-1/analysis
19.
J Nutr ; 132(9): 2574-9, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12221211

ABSTRACT

Both postprandial hyperglycemia and insulin resistance (IR) have implications for the development of cardiovascular disease. The present study was designed to examine differences in postprandial glycemia and insulin sensitivity among young adults of different ethnic origins. Lean, healthy subjects (n = 60) from five ethnic groups [20 European Caucasians, 10 Chinese, 10 South East (SE) Asians, 10 Asian Indians and 10 Arabic Caucasians] were matched for age, body mass index, waist circumference, birth weight and current diet. A 75-g white bread carbohydrate challenge was fed to assess postprandial glycemia and insulinemia. Insulin sensitivity was assessed in three groups by the euglycemic-hyperinsulinemic clamp and in all subjects by homeostasis model assessment (HOMA) modeling. Postprandial hyperglycemia (incremental area under the curve) and insulin sensitivity (M-value) both showed a twofold variation among the groups (P < 0.001) and were significantly related to each other (R(2) = 56%, P < 0.001). Young SE Asians had the highest postprandial glycemia and lowest insulin sensitivity, whereas European and Arabic Caucasian subjects were the most insulin sensitive and carbohydrate tolerant. These findings suggest that IR is evident even in lean, young adults of some ethnic groups and is associated with significant increases in postprandial glycemia and insulinemia in response to a realistic carbohydrate load.


Subject(s)
Hyperglycemia/ethnology , Insulin/blood , Postprandial Period/genetics , Adolescent , Adult , Arabs/genetics , Asia, Southeastern/ethnology , Asian People/genetics , Australia , Bread , China/ethnology , Dietary Carbohydrates/administration & dosage , Europe/ethnology , Female , Glucose Clamp Technique , Homeostasis , Humans , Hyperglycemia/genetics , India/ethnology , Male , Models, Biological , White People/genetics
20.
Analyst ; 126(7): 1118-21, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11478646

ABSTRACT

The ability to determine the calcium carbonate polymorphic ratio of calcite, aragonite and vaterite in a mixture is important for a variety of applications, particularly the fields of biomineralisation and crystal engineering. Raman spectroscopy and powder X-ray diffraction were used to quantitatively determine the polymorphic composition of both binary and tertiary mixtures of calcium carbonate. It was found that the quantitative detection limits of powder X-ray diffraction were superior to both Raman and infrared spectroscopy.


Subject(s)
Calcium Carbonate/chemistry , Spectrophotometry, Infrared , X-Ray Diffraction/methods
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