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1.
Waste Manag ; 144: 336-348, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35429871

ABSTRACT

Air pollution control residues (APCr) are hazardous materials generated from municipal solid waste incineration and require appropriate management. This life cycle assessment (LCA) study investigates the environmental impacts of current and alternative management options, considering the possibility of a cascading management of APCr, where one treatment technology is followed by another. In total, 14 base case scenarios and 30 sensitivity scenarios were evaluated. The effects of APCr composition, leaching, time horizon, and uncertainties were investigated. The APCr management options with the lowest environmental impacts and the smallest uncertainties were i) backfilling of underground salt mines and ii) neutralization treatment followed by backfilling (Langøya, Norway). These options were followed by iii) scenarios that included Zn extraction, iv) cement stabilization of fresh APCr followed by landfilling and v) production of cement aggregates made from carbonated APCr followed by their utilization in construction works. Recovery of salts from APCr required further performance optimizations before being environmentally competitive with other options. Long-term leaching emissions of Zn, Cr and As were among the largest contributors to toxicity-related impacts, emphasizing the need for management strategies that minimize their leaching. The investigated scenarios demonstrate that increased "processing" and cascading utilization of the residues, contribute with increased uncertainty of the results compared to landfilling and may not necessarily lead to decreased environmental impacts. LCA studies of APCr management should address the full management chain, rather than just the first treatment. Overall, the results of this study were found robust, also considering potential changes in the surrounding energy system.


Subject(s)
Incineration , Refuse Disposal , Animals , Conservation of Natural Resources , Life Cycle Stages , Solid Waste/analysis , Technology
2.
J Intern Med ; 287(6): 592-608, 2020 06.
Article in English | MEDLINE | ID: mdl-32463135

ABSTRACT

Mitochondrial medicine is a field that expanded exponentially in the last 30 years. Individually rare, mitochondrial diseases as a whole are probably the most frequent genetic disorder in adults. The complexity of their genotype-phenotype correlation, in terms of penetrance and clinical expressivity, natural history and diagnostic algorithm derives from the dual genetic determination. In fact, in addition to the about 1.500 genes encoding mitochondrial proteins that reside in the nuclear genome (nDNA), we have the 13 proteins encoded by the mitochondrial genome (mtDNA), for which 22 specific tRNAs and 2 rRNAs are also needed. Thus, besides Mendelian genetics, we need to consider all peculiarities of how mtDNA is inherited, maintained and expressed to fully understand the pathogenic mechanisms of these disorders. Yet, from the initial restriction to the narrow field of oxidative phosphorylation dysfunction, the landscape of mitochondrial functions impinging on cellular homeostasis, driving life and death, is impressively enlarged. Finally, from the clinical standpoint, starting from the neuromuscular field, where brain and skeletal muscle were the primary targets of mitochondrial dysfunction as energy-dependent tissues, after three decades virtually any subspecialty of medicine is now involved. We will summarize the key clinical pictures and pathogenic mechanisms of mitochondrial diseases in adults.


Subject(s)
Mitochondrial Diseases/genetics , Adult , DNA Repair/genetics , DNA, Mitochondrial/genetics , Genome, Mitochondrial/genetics , Humans , MELAS Syndrome/diagnosis , MELAS Syndrome/genetics , Mitochondria/genetics , Mitochondria/metabolism , Mitochondrial Diseases/diagnosis , Mutation/genetics
3.
Waste Manag ; 83: 113-122, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30514457

ABSTRACT

In Denmark, increasing amounts of woody biomass are being used for the production of renewable energy, resulting in more wood ashes being generated. While these materials have been mainly landfilled, wood ashes may also be utilised for fertilizing and liming purposes on top of soils. Pre-treatments involving hardening or granulation may be carried out prior to soil application. In this study, two Danish wood ash samples were hardened and/or granulated. Lab-hardening induced rapid changes in the shape of the acid neutralisation capacity curve of the ashes. Up-flow column tests, assuming local equilibrium conditions, were employed to investigate the leaching from pre-treated ashes. Granules and loose ashes demonstrated similar leaching behaviours, indicating that similar geochemical processes were governing their leaching. In comparison with untreated fresh ashes, the hardened ashes demonstrated reduced leaching of Ca, Ba, Pb and Zn with concentration levels generally below or close to the analytical limits of quantification; to the contrary, the leaching of As, P, Sb, Si, V and Mg was enhanced in the hardened ashes. The release of alkalinity was reduced by hardening. In general, all granules were barely breakable by finger-pinching and they could withstand one month of continuous leaching, preserving their overall shape. The solubility of phosphorous in neutral ammonium citrate indicated that about 30-51% of the total P content in the ash samples was released, suggesting that the ashes could be potentially valuable as P-fertiliser if applied onto soil.


Subject(s)
Coal Ash , Incineration , Biomass , Denmark , Soil
4.
Injury ; 49 Suppl 4: S2-S8, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30526947

ABSTRACT

This case report describes the management and therapeutic solution for the treatment of subtrochanteric non-union in a patient with hip arthrodesis. Two techniques can be used in the treatment of these non-unions: a closed intramedullary nailing or an open technique with plate, preferably carried out together with cortical bone graft. The surgical technique varies depending on the fixation method used for the initial treatment of the fracture and on the characteristics of the non-union. We report an unusual case of a patient who started her long clinical history more than 40 years ago with a septic arthritis of the hip healed in arthrodesis. 35 years later, after having undergone various surgeries, she fractured the proximal femur, which had to be operated seven times before reaching healing. Satisfactory outcomes were finally obtained. Arthrodesis proved to be the main cause of failed healing and of the recurrent non-union.


Subject(s)
Arthrodesis/adverse effects , Bone Transplantation/methods , Femoral Fractures/surgery , Fracture Healing/physiology , Fractures, Ununited/surgery , Hip Fractures/surgery , Reoperation/statistics & numerical data , Bone Nails , Bone Plates , Female , Femoral Fractures/diagnostic imaging , Femoral Fractures/pathology , Fracture Fixation, Intramedullary , Fractures, Ununited/diagnostic imaging , Fractures, Ununited/pathology , Hip Fractures/diagnostic imaging , Hip Fractures/pathology , Humans , Middle Aged , Reoperation/adverse effects , Time Factors , Treatment Outcome
5.
Waste Manag ; 74: 373-383, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29246665

ABSTRACT

With increasing amounts of woody biomass being combusted for energy purposes worldwide, more wood ash is being generated and needs management. As an alternative to landfilling, residues may be utilised for liming and fertilising purposes on forest soils. Comprehensive evaluations of long-term leaching from these residues are needed in order to assess potential environmental impacts associated with their utilisation. Two Danish wood ash samples, one fly ash and one mixed ash (a combination of fly ash and bottom ash), were evaluated in long-term percolation column tests (up to L/S ∼2000 L/kg), in order to quantify the release of major, minor and trace metal(loid)s. While columns of three different lengths were used, the leaching of individual elements could be described as a function of the L/S ratio - irrespective of the column length. At L/S 1000 L/kg, the cumulative releases of K, S, Na, Ca and Rb were at 40-100% of their respective solid contents, followed by Ba, Cr, Sb, Sr and V at 15-40% and Al, Mg, Zn, Cd, Co, Fe, Pb, Tl, Mn and P at < 5%. Speciation calculations indicated that (i) the observed concentrations of Ca, Mg, Al, Ba, Si and sulphate from both ash types could be described through the dissolution/precipitation of a limited set of minerals and that (ii) leaching of silicates should be included in long-term assessment of alkalinity release from wood ashes. Non-equilibrium conditions were indicated by flow interruptions. However, the presence of non-equilibrium did not have significant effect on the calculated cumulative releases at high L/S ratios. Based on the assessment of cumulative releases at L/S 10 L/kg and L/S 1000 L/kg it is concluded that low L/S-based data may not provide sufficient background for prediction of long-term release from wood ash, in particular for Ba, Cr, Sb and V, and less critically also for As, Cd, Cu, Mo and Ni.


Subject(s)
Coal Ash , Trace Elements/chemistry , Biomass , Incineration , Soil
6.
Musculoskelet Surg ; 101(Suppl 2): 105-112, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29052035

ABSTRACT

AIM: The aim of this study was to evaluate nonunion causes of surgically treated humeral shaft fractures in two different trauma centers. METHODS: A total of 327 cases of humeral shaft fractures were treated in 11 years in two trauma centers. We retrospectively reviewed in detail some factors in order to understand the reasons for nonunion: (1) fracture type, according to the AO classification, (2) grade of open fracture, according to Gustilo-Anderson, (3) timing, (4) reduction and (5) fixation. RESULTS: We observed 19 nonunions, 10 women and 9 men, with an average age of 57 years. Fractures were 1 A1 case, 2 A2 cases, 4 B2 cases, 6 B3 cases, 2 C1 cases, 1 C2 case and 3 C3 cases. Three cases had a simple fracture with two fragments; all the other were comminuted. Fifteen cases were closed, four open. The major criticalities observed were fracture comminution, exposure, unstable fixation and bone resorption. All 19 patients with nonunion underwent surgical fixation with compression plate and frozen cortical bone graft. A 4.5 LCP plate was used in 17 cases. The remaining 2 cases had an anatomical site-specific proximal humeral 3.5-mm LCP plate (Synthes, Paoli, PA, USA). In 17 patients, the nonunion healed: 15 cases treated with a 4.5 straight plate, and 2 cases with an anatomical site-specific proximal humeral 3.5 mm LCP plate, at a mean of 5 months. In 2 cases, consolidation was not reached. CONCLUSIONS: We believe that humeral diaphyseal fractures should be treated surgically to avoid many complications. Our retrospective analysis indicates that factors that lead to a fixation failure are fracture comminution, open fracture, unstable fixation. The 19 nonunions treated with compression plating and frozen bone graft demonstrated consolidation in almost 90% of the cases.


Subject(s)
Fracture Healing , Fractures, Comminuted/surgery , Fractures, Ununited/etiology , Humeral Fractures/surgery , Trauma Centers/statistics & numerical data , Adult , Aged , Aged, 80 and over , Bone Plates , Bone Resorption , Bone Transplantation , Female , Fracture Fixation/methods , Fractures, Closed/surgery , Fractures, Open/surgery , Fractures, Ununited/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Treatment Failure , Young Adult
7.
Waste Manag ; 70: 127-138, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28947146

ABSTRACT

In Denmark, increasing amounts of wood ashes are generated from biomass combustion for energy production. The utilisation of ashes on top of forest soil for liming purposes has been proposed asan alternative to landfilling. Danish wood ash samples were collected and characterised with respect to chemical composition, mineralogy and leaching properties (batch leaching at L/S 2 and 10L/kg, and pH-dependent leaching at 10L/kg). Large variations in the ash liming properties were observed (ANC7.5: 1.8-6.4meqH+/g), indicating that similar soil application dosages may result in different liming effects. High contents of Ca, Si, P, K and Mg were observed in all samples, while the highest contents of S and N were found in fly ashes and mixed ashes (combination of fly and bottom ashes). Similarly, the highest contents of some trace metals, e.g. Cd, Mo and Se, were observed for fly ash. Releases of major, minor and trace elements were affected significantly by pH: high releases of PO43-, Mg, Zn, Cu and Cd were found for acidic conditions relevant to forest soils, while the highest releases of Mo and Cr were observed in alkaline conditions. Mineral phases were selected based on XRD analyses and the existing literature, and they were applied as inputs for the geochemical modelling of pH-dependent leaching. Mineral dissolution was found adequate for a wide range of major elements and nutrients, while the description of trace elements could be done only for parts of the pH-range. Content and leaching of PAHs were observed below detection limits. The source-term release of Ca, K, Mg, Mn, and P in acidic conditions relevant to forest soils was higher than ten years of atmospheric deposition, in contrast to the relatively low release of Al, Fe and Na. The potential release of Cd was found to be the most critical element compared with soil quality criteria, whereas the maximum theoretical loads of Ba, Cd, Cr, Sr, Mo, Ni, Pb, Sb, Se, Sn and V were relatively low.


Subject(s)
Incineration/methods , Waste Products/analysis , Biomass , Denmark , Forests , Hydrogen-Ion Concentration , Metals/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Soil/chemistry , Soil Pollutants/analysis , Trace Elements/analysis
8.
Musculoskelet Surg ; 100(Suppl 1): 97-104, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27521146

ABSTRACT

PURPOSE: Distal-third diaphyseal fractures of the humerus are often hard to treat due to location and pattern of the fractures, radial nerve injury, and quality of bone and age of patients. The aim of this retrospective study is to propose the best approach and the best surgical technique according to the pattern of extra-articular fracture of the distal humerus. METHODS: We have treated 37 fractures of the distal humerus between January 2010 and July 2015 classified according to the AO classification. There were 2 open fractures. We treated all fractures with open reduction and internal fixation with plates and screws. In 20 cases, we performed a posterior midline triceps-splitting approach, with patients in prone decubitus position; in 2 cases, the triceps-splitting approach with the patients in supine decubitus position; in 3 cases, the olecranon osteotomy approach in prone decubitus position; and in 12 cases, the lateral approach in supine decubitus position. RESULTS: Thirty cases had a medium follow-up of 6 months. We observe 2 post-operative radial nerve palsies healed in 5 months and 2 cases of non-union. The average time to union of remaining cases was 16 weeks (range 12-24). Elbow motility was complete in 25 cases, in 4 cases there was an extension loss of 5°, and in one case there was an extension loss of 10°. CONCLUSIONS: The use of plates allows an anatomical fracture reduction, a better control of alignment of humerus and, with a rigid fixation, an early elbow mobilization. The best approach and the best surgical technique depend on the pattern of the fracture of distal humerus.


Subject(s)
Bone Plates , Bone Screws , Fracture Fixation, Internal , Humeral Fractures/surgery , Radial Nerve/injuries , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
9.
Musculoskelet Surg ; 100(1): 1-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26667625

ABSTRACT

PURPOSE: The incidence of trochanteric fractures has increased significantly during the last few decades, especially in elderly patients with osteoporosis. The dynamic/sliding hip screw and the cephalomedullary nail are the most commonly used fixation methods to treat trochanteric fractures. The improvements in the Gamma Nail System (GNS) associated with a correct surgical technique reduced the postoperative orthopedic complications. The purpose of this study was to compare the results of the different Gamma Nails. METHODS: The present study is a retrospective analysis of 2144 patients treated with GNS between January 1997 and December 2011 for trochanteric fractures, classified according to AO classification method. The patients were divided into three groups according to the nailing system: 525 were treated with Standard Gamma Nail (SGN), 422 with Trochanteric Gamma Nail (TGN) and 1197 with Gamma3 Nail. RESULTS: The overall incidence of intra-operative complications was 1.21 %; the incidence of intra-operative complications for each group was 1.71 % for SGN group, 0.47 % for TGN group and 1.25 % for Gamma3 Nail group. The overall incidence of postoperative complications was 5.48 %, and the incidence for each group was 10.73 % for SGN group, 9.92 % for TGN group and 2.92 % for Gamma3 Nail group. CONCLUSION: The GNS is a safe device with a low rate of intra-operative complications. The evolution of this nail system reduces postoperative complications, thus improving the results at follow-up and confirming that the Gamma3 Nail is a safe and predictable device to fix trochanteric fracture.


Subject(s)
Bone Nails , Fracture Fixation, Intramedullary/methods , Hip Fractures/surgery , Bone Screws , Humans , Retrospective Studies
10.
Cell Death Dis ; 6: e2021, 2015 Dec 17.
Article in English | MEDLINE | ID: mdl-26673666

ABSTRACT

Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke.


Subject(s)
DNA, Mitochondrial/genetics , Optic Atrophy, Hereditary, Leber/etiology , Reactive Oxygen Species/metabolism , Smoking/adverse effects , Smoking/genetics , DNA, Mitochondrial/metabolism , Female , Humans , Male , Optic Atrophy, Hereditary, Leber/genetics , Optic Atrophy, Hereditary, Leber/metabolism , Optic Atrophy, Hereditary, Leber/pathology , Oxidative Phosphorylation , Smoking/metabolism , Smoking/pathology
11.
Curr Mol Med ; 14(8): 985-992, 2014.
Article in English | MEDLINE | ID: mdl-25323873

ABSTRACT

Over two decades have elapsed since the first mtDNA point mutation was associated with Leber's hereditary optic neuropathy (LHON) in 1988. We have subsequently witnessed a substantial understanding of the molecular basis of hereditary optic neuropathies, as well as of their clinical features and pathogenic mechanisms. It became clear that the large majority of genetic optic neuropathies have a primary or an indirect involvement of mitochondrial functions, justifying the definition of "mitochondrial optic neuropathies". Despite this progress many unsolved features remain to be understood, such as incomplete penetrance and variable clinical expressivity in LHON and dominant optic atrophy (DOA), gender prevalence in LHON, and complex gene/environment interactions in both LHON and DOA. The most recent advancement in our understanding of the molecular basis of mitochondrial optic neuropathies is the topic of this review. In particular, we analyze the role that mitochondrial biogenesis may play in the compensatory mechanisms that underlie incomplete penetrance and clinical expressivity, a scenario relevant for the possible design of future therapeutic approaches.

12.
J Orthop Traumatol ; 15(3): 181-7, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24671489

ABSTRACT

BACKGROUND: Posterior wall fracture is the most common acetabular fracture. Comminuted fractures with an impacted segment represent a subtype of this injury. The subchondral bone of the articular zone is compressed and causes a bone defect. The impacted fragment should be isolated, mobilized, and then reduced. A bone graft should be used to fill the gap. The other fragments are fixed following the reduction of the impacted segment. MATERIALS AND METHODS: Ten patients with comminuted fractures and impacted segments with bone defects were enrolled in our study, from January 2010 to July 2012. Autogenous bone grafts from the greater trochanter were used to fill the gap in all patients. The reduction was achieved through the insertion of the graft above the impacted fracture, and plate fixation was performed subsequently. Merle d'Aubigne and Postel scoring, modified by Matta, was applied to evaluate the patients during follow-up. The mean follow-up was 12 months. RESULTS: The clinical results included one "excellent", four "very good", four "good" and one "poor". Pain in the zone of graft harvesting was not detected in any patient. Femoral head necrosis was observed in one case. No other severe complications were detected. CONCLUSIONS: Using an autogenous bone graft to fill the bone defect supplies excellent mechanical stability without any severe complications at the donor site. This surgical technique seems to be effective and safe in treating a comminuted fracture of the posterior wall in association with an impacted segment. LEVEL OF EVIDENCE: Level IV.


Subject(s)
Acetabulum/injuries , Bone Transplantation , Femur/transplantation , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Fractures, Comminuted/surgery , Adult , Aged , Aged, 80 and over , Bone Plates , Female , Fractures, Comminuted/complications , Hip Dislocation/complications , Hip Dislocation/surgery , Humans , Male , Middle Aged , Treatment Outcome
13.
Injury ; 45(2): 444-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24183393

ABSTRACT

INTRODUCTION: Multifocal humeral fractures are extremely rare. These may affect the neck and the shaft, the shaft alone, or the diaphysis and the distal humerus. There is no classification of these fractures in the literature. MATERIALS AND METHODS: From 2004 to 2010, 717 patients with humeral fracture were treated surgically at our department. Thirty-five patients presented with an associated fracture of the proximal and diaphyseal humerus: synthesis was performed with plate and screws in 34 patients, and the remaining patient had an open fracture that was treated with an external fixator. RESULTS: Mean follow-up was 3 years and 3 months. A classification is proposed in which type A fractures are those affecting the proximal and the humeral shaft, type B the diaphysis alone, and type C the diaphysis in association with the distal humerus. Type A fractures are then divided into three subgroups: A-I, undisplaced fracture of the proximal humerus and displaced shaft fracture; A-II: displaced fracture of the proximal and humeral shaft; and A-III: multifragmentary fracture affecting the proximal humerus and extending to the diaphysis. DISCUSSION: Multifocal humeral fractures are very rare and little described in the literature, both for classification and treatment. The AO classification describes bifocal fracture of the humeral diaphysis, type B and C. The classification suggested in this article mainly concerns fractures involving the proximal and humeral shaft. CONCLUSIONS: A simple classification of multifocal fractures is suggested to help the surgeon choose the most suitable type of synthesis for surgical treatment.


Subject(s)
Diaphyses/surgery , External Fixators , Fracture Fixation, Intramedullary , Humeral Fractures/surgery , Humerus/surgery , Radial Nerve/injuries , Radial Neuropathy/surgery , Bone Plates , Diaphyses/physiopathology , Equipment Design , Female , Follow-Up Studies , Fracture Healing , Humans , Humeral Fractures/classification , Humeral Fractures/physiopathology , Humerus/physiopathology , Male , Practice Guidelines as Topic , Radial Neuropathy/physiopathology , Range of Motion, Articular , Recovery of Function
14.
Cell Death Dis ; 4: e663, 2013 Jun 13.
Article in English | MEDLINE | ID: mdl-23764844

ABSTRACT

Mitochondrial biogenesis is an orchestrated process that presides to the regulation of the organelles homeostasis within a cell. We show that γ-rays, at doses commonly used in the radiation therapy for cancer treatment, induce an increase in mitochondrial mass and function, in response to a genotoxic stress that pushes cells into senescence, in the presence of a functional p53. Although the main effector of the response to γ-rays is the p53-p21 axis, we demonstrated that mitochondrial biogenesis is only indirectly regulated by p53, whose activation triggers a murine double minute 2 (MDM2)-mediated hypoxia-inducible factor 1α (HIF1α) degradation, leading to the release of peroxisome-proliferator activated receptor gamma co-activator 1ß inhibition by HIF1α, thus promoting mitochondrial biogenesis. Mimicking hypoxia by HIF1α stabilization, in fact, blunts the mitochondrial response to γ-rays as well as the induction of p21-mediated cell senescence, indicating prevalence of the hypoxic over the genotoxic response. Finally, we also show in vivo that post-radiotherapy mitochondrial DNA copy number increase well correlates with lack of HIF1α increase in the tissue, concluding this may be a useful molecular tool to infer the trigger of a hypoxic response during radiotherapy, which may lead to failure of activation of cell senescence.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mitochondria/radiation effects , Mitochondrial Turnover , Tumor Suppressor Protein p53/metabolism , Base Sequence , Binding Sites , Carrier Proteins/metabolism , Cell Shape , Cellular Senescence , DNA Copy Number Variations , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Gene Expression Regulation , Genome, Mitochondrial , HCT116 Cells , Humans , Mitochondria/metabolism , Molecular Sequence Data , Mutation, Missense , Promoter Regions, Genetic , Protein Stability , Proteolysis , Proto-Oncogene Proteins c-mdm2/metabolism , RNA-Binding Proteins , Response Elements , Tumor Suppressor Protein p53/genetics
15.
Acta Radiol ; 54(7): 749-56, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23550187

ABSTRACT

BACKGROUND: The main causes of renal artery stenosis (RAS) are atherosclerosis and fibromuscular dysplasia. Despite contrast-enhanced magnetic resonance angiography (CE-MRA) being a safe and reliable method for diagnosis of RAS especially in young individuals, recently it has been possible to adopt innovative technologies that do not require paramagnetic contrast agents. PURPOSE: To assess the accuracy of steady-state free-precession (SSFP) non-contrast-enhanced magnetic resonance angiography (NC-MRA) by using a 1.5 T MR scanner for the detection of renal artery stenosis, in comparison with breath-hold CE-MRA as the reference standard. MATERIAL AND METHODS: Sixty-three patients (33 men, 30 women) with suspected renovascular hypertension (RVHT) were examined by a 1.5T MR scanner; NC-MRA with an electrocardiography (ECG)-gated SSFP sequence was performed in 58.7% (37/63) of patients; in 41.3% (26/63) of patients a respiratory trigger was used in addition to cardiac gating. CE-MRA, with a three-dimensional gradient echo (3D-GRE) T1-weighted sequence, was performed in all patients within the same session. Maximum intensity projection (MIP) image quality, number of renal arteries, and the presence of stenosis were assessed by two observers (independently for NC-MRA and together for CE-MRA). The agreement between NC-MRA and CE-MRA as well as the inter-observer reproducibility were calculated with Bland-Altman plots. RESULTS: MIP image quality was considered better for NC-MRA. NC-MRA identified 143 of 144 (99.3%) arteries detected by CE-MRA (an accessory artery was not identified). Fourteen stenoses were detected by CE-MRA (11 atherosclerotic, 3 dysplastic) with four of 14 (28.5%) significant stenosis. Bland-Altman plot demonstrated an excellent concordance between NC-MRA and CE-MRA; particularly, the reader A evaluated correctly all investigated arteries, while over-estimation of two stenoses occurred for reader B. Regarding NC-MRA, inter-observer agreement was excellent. CONCLUSION: NC-MRA is a valid alternative to CE-MRA for the assessment of renal arteries.


Subject(s)
Magnetic Resonance Angiography/methods , Renal Artery Obstruction/diagnosis , Renal Artery , Adult , Aged , Aged, 80 and over , Cardiac-Gated Imaging Techniques , Contrast Media , Female , Humans , Hypertension, Renovascular/complications , Imaging, Three-Dimensional , Male , Middle Aged , Organometallic Compounds , Renal Artery Obstruction/etiology , Reproducibility of Results , Sensitivity and Specificity
16.
J Enzyme Inhib Med Chem ; 28(2): 289-93, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22299577

ABSTRACT

4-Sulfamoyl-N-(3-morpholinopropyl)benzamide (I-1), N-(3-morpholinopropyl)benzene-1,4-disulfonamide (I-2) and N-(4-diethylaminoethoxybenzyl)benzene-1,4-bis(sulfonamide (I-3), were prepared and assayed as inhibitors of four carbonic anhydrase (CA) isoenzymes hCA I, hCA II, hCA IV and hCA XII. These compounds exhibited nanomolar half maximal inhibitory concentration (IC(50)) ranging from 58 to 740 nmol/L. All three aromatic sulfonamides show different activities for the isoenzymes studied with lowest affinity against isoenzyme hCA XII.


Subject(s)
Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrases/metabolism , Sulfonamides/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrases/isolation & purification , Dose-Response Relationship, Drug , Humans , Molecular Structure , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/isolation & purification , Protein Isoforms/metabolism , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry
17.
Nutr Metab Cardiovasc Dis ; 23(8): 771-5, 2013 Aug.
Article in English | MEDLINE | ID: mdl-22770750

ABSTRACT

AIM: The study was aimed to evaluate the influence of gender on left ventricular (LV) remodeling in metabolic syndrome (MetS). METHODS AND RESULTS: We enrolled 200 subjects without diabetes or overt cardiovascular diseases, never treated with anti-hypertensive drugs or statins: 60 men and 40 women with MetS matched by age, gender and 24 h systolic and diastolic blood pressure (BP) with 60 men and 40 women without MetS. The patients underwent blood tests, 24 h our BP monitoring, LV echocardiographic examination. LV mass indexed by eight(2.7) was significantly greater in men and women with MetS than without MetS. Compared with women without MetS, women with MetS had significantly higher posterior wall thickness and relative wall thickness, greater prevalence of LV concentric remodeling/hypertrophy and lower indices of LV diastolic function, whereas all these parameters were not significantly different between men with and without MetS. MetS was an independent predictor of relative wall thickness and LV mass index in women, but not in men. CONCLUSION: The impact of MetS on LV remodeling is significantly influenced by gender: the effects of MetS are more pronounced in women, with development of LV concentric hypertrophy/remodeling and preclinical diastolic dysfunction.


Subject(s)
Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/physiopathology , Metabolic Syndrome/physiopathology , Ventricular Remodeling/physiology , Adult , Anthropometry , Blood Pressure , Case-Control Studies , Diabetes Mellitus , Echocardiography , Female , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Male , Metabolic Syndrome/diagnosis , Middle Aged , Prevalence , Sex Factors , Ventricular Function, Left/physiology
19.
J Hum Hypertens ; 26(10): 570-6, 2012 Oct.
Article in English | MEDLINE | ID: mdl-21918540

ABSTRACT

The high cardiovascular risk of HIV infected (HIV+) patients is still partly unexplained. We aimed to evaluate if HIV infection and highly active antiretroviral therapy (HAART) are linked per se to left ventricular (LV) remodelling, independently of blood pressure (BP) values. We enrolled 4 groups of patients matched by gender, age, body mass index and smoking habit: 30 HIV+ hypertensives, 30 HIV+ normotensives, 30 not-infected (HIV-) hypertensives and 30 HIV- normotensives. HIV+ patients were on chronic HAART. Hypertension was newly diagnosed (≤6 months) and never treated. Each patient underwent blood tests, 24-h BP monitoring and LV echocardiogram. The 4 groups had similar fasting glucose and cholesterol; triglycerides, HOMA index and prevalence of metabolic syndrome were higher in the HIV+ groups. Despite similar 24-h BP values, HIV+ hypertensives had greater LV mass and higher prevalence of preclinical diastolic dysfunction than HIV- hypertensives. Compared to HIV- normotensives, HIV+ normotensives had similar 24-h BP values, but greater LV mass and lower LV diastolic indices, similar to HIV- hypertensives, whose 24-h BP values were higher. Asymptomatic HIV infection and chronic HAART are associated with myocardial hypertrophy and preclinical diastolic dysfunction, independently of BP values.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/physiopathology , Hypertension/complications , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Function, Left/physiology , Ventricular Remodeling , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Case-Control Studies , Echocardiography , Female , HIV Infections/complications , HIV Infections/drug therapy , Humans , Hypertension/diagnostic imaging , Male , Metabolic Syndrome
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