Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 121
Filter
1.
Rev Mal Respir ; 41(3): 248-256, 2024 Mar.
Article in French | MEDLINE | ID: mdl-38320877

ABSTRACT

INTRODUCTION: Respiratory diseases represent a major public health issue and impact both quality of life and life expectancy of the patients. STATE OF ART: Several interventions used in respiratory physiotherapy have been shown to reduce dyspnoea, improve quality of life and reduce hospitalisation in many respiratory diseases. However, respiratory physiotherapy remains poorly known to the medical community and may be under-prescribed. PERSPECTIVES: In order to improve the interdisciplinarity around the patient with respiratory impairment, we describe the interests and prescription modalities of liberal respiratory physiotherapy. In the context of respiratory physiotherapy acts, the precision of drafting prescription directly conditions the means implemented by the physiotherapist regarding care provided to the patient. CONCLUSION: The increased knowledge of prescribers, both concerning the prescription methods and the precise content of the rehabilitation sessions is one of the keys to their success.


Subject(s)
Quality of Life , Respiratory Tract Diseases , Humans , Physical Therapy Modalities , Prescriptions , Private Practice , Respiratory Tract Diseases/therapy
2.
Br J Haematol ; 204(5): 1752-1756, 2024 May.
Article in English | MEDLINE | ID: mdl-38176400

ABSTRACT

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.


Subject(s)
Cell-Free Nucleic Acids , Lymphoma, T-Cell, Peripheral , Humans , Lymphoma, T-Cell, Peripheral/mortality , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/blood , Lymphoma, T-Cell, Peripheral/genetics , Male , Female , Middle Aged , Aged , Cell-Free Nucleic Acids/blood , Prognosis , Adult , Biomarkers, Tumor/blood , Prospective Studies , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
3.
Exp Mol Pathol ; 134: 104874, 2023 12.
Article in English | MEDLINE | ID: mdl-37775022

ABSTRACT

An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far. To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers. These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.


Subject(s)
COVID-19 , Induced Pluripotent Stem Cells , Humans , SARS-CoV-2 , Dopaminergic Neurons , Dopamine , RNA, Messenger
4.
Rev. Fac. Odontol. (B.Aires) ; 33(75): 15-22, jul.-dic. 2018. ilus
Article in Spanish | LILACS | ID: biblio-999406

ABSTRACT

La extrusión dentaria o erupción forzada es una opción de tratamiento con enormes ventajas cuando nos vemos obligados a tratar fracturas corono-radiculares. Se define como el movimiento en dirección coronal a través de la aplicación de fuerzas ligeras y continuas para provocar cambios en los tejidos blandos y hueso. La extrusión dental forzada amplía las alternativas en cuanto a la rehabilitación futura del paciente, ya que se puede optar por la restauración periférica total con anclaje del resto radicular, o bien por la exodoncia posterior a la extrusión, con la consecuente mejoría de las condiciones del tejido óseo para una posterior rehabilitación implanto-asistida. Presentación de caso clínico, pieza dentaria 2.2 con fractura corono-radicular en la cual se realizó tratamiento de erupción forzada y rehabilitación protésica (AU)


Extrusion or forced eruption es a treatment option with enormous advantages when we are forced to treat crown-root fractures. It is defined as the movement in the coronal direction through the application of light and continuous forces to cause changes in the soft tissues and bone. Forced dental extrusion expands the alternatives regarding the future rehabilitation of the patient, since it is possible to choose either total peripheral restoration with anchoring of the radicular rest of the post-extrusion extraction, with the consequent improvement of bone tissue conditions for subsequent implant-assissted rehabilitation. Presentation of a case report: tooth 2.2 with a crown-root fracture in which forced eruption and prosthetic rehabilitation were performed (AU)


Subject(s)
Humans , Female , Adult , Tooth Fractures/therapy , Tooth Root/injuries , Tooth Crown/injuries , Orthodontic Extrusion , Dental Prosthesis, Implant-Supported , Dental Restoration, Permanent
5.
Rev. bras. plantas med ; 18(1,supl.1): 341-348, 2016. tab, graf
Article in Portuguese | LILACS | ID: lil-782984

ABSTRACT

RESUMO Tivemos como objetivo avaliar o efeito da infusão de Cunila microcephala Benth sobre a atividade da enzima acetilcolinesterase (AChE) e marcadores de estresse oxidativo em eritrócitos de agricultores. Foram utilizadas amostras provenientes de 16 trabalhadores rurais expostos a pesticidas agrícolas pelo período mínimo de 5 anos e um grupo controle constituído de 16 indivíduos não expostos a agrotóxicos. As hemácias dos agricultores e o grupo A foram expostos “in vitro” à solução salina (NaCl 0,9%). Os demais grupos foram expostos à infusão de poejo nas concentrações de 0; 5; 10; 25 e 50 g/L (Grupos B; C; D e E, respectivamente). Em seguida, foram realizadas as determinações da atividade da AChE e dos níveis de substâncias reativas ao ácido tiobarbitúrico (TBARS), proteínas carboniladas (PCs) e glutationa reduzida (GSH). Os resultados mostram que a infusão de poejo 50g/L, aumenta a atividade da enzima AChE e os níveis de GSH. Contudo, os níveis de TBARS e PCs diminuíram após o tratamento com a infusão de poejo 25 e 50 g/L. A infusão de poejo, na concentração de 50 g/L, é capaz de reverter, “in vitro” a inibição da atividade da AChE que ocorre pela exposição a pesticidas, e ainda demonstra um importante potencial antioxidante, tendo em vista que diminuiu danos lipídicos e proteicos e ainda, estimulou a produção do principal antioxidante não enzimático endógeno.


ABSTRACT Evaluating the effect of infusion Cunila microcephala Benth on acetylcholinesterase activity (AChE) enzyme and on biomarkers of oxidative stress in farmers erythrocytes. We used samples from 16 rural workers exposed to pesticides for a minimum of five years, and a control group composed of 16 individuals not exposed to pesticides. The erythrocytes of farmers and from group A were exposed “in vitro” the saline solution (NaCl 0,9%). The other groups were exposed to the infusion of “poejo” at concentrations of 0; 5; 10; 25 and 50 g/L (Groups B, C, D and E, respectively). Then, it was realized the analitical determinations of AChE activity and TBARS, PCs and GSH levels. The results showed that “poejo” infusion 50g/L, increased the AChE activity and GSH levels. However, the TBARS e PCs levels decreased after the treatment with “poejo” infusion 25 e 50 g/L. The “poejo” infusion 50 g/L is able to revert “in vitro” the inhibition of AChE activity that occurs by exposure to pesticides and also demonstrates an important antioxidant potential, given that decreased lipid and protein damage and also it stimulated the production of the main non-enzymatic antioxidant endogenous.


Subject(s)
Humans , Acetylcholinesterase/pharmacology , In Vitro Techniques/instrumentation , Biomarkers/analysis , Oxidative Stress , Lamiaceae/classification , Pesticides , Erythrocytes/classification , Farmers/classification
6.
Ann Oncol ; 26(1): 167-172, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25344361

ABSTRACT

BACKGROUND: In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. RESULTS: From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded. CONCLUSIONS: The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasms, Germ Cell and Embryonal/drug therapy , Testicular Neoplasms/drug therapy , Adult , Bleomycin/administration & dosage , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Disease-Free Survival , Drug Combinations , Etoposide/administration & dosage , Female , Hematopoietic Stem Cell Transplantation , Humans , Male , Neoplasms, Germ Cell and Embryonal/mortality , Testicular Neoplasms/mortality , Young Adult
7.
Bone Marrow Transplant ; 49(4): 485-91, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24442244

ABSTRACT

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Doxorubicin/administration & dosage , Female , Hematopoietic Stem Cell Mobilization/methods , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Melphalan/administration & dosage , Middle Aged , Prednisone/administration & dosage , Prospective Studies , Rituximab , Transplantation, Autologous , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Vincristine/administration & dosage
8.
Curr Opin Biotechnol ; 24 Suppl 1: S6-13, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23797042

ABSTRACT

Biotechnology uses substances, materials or extracts derived from living cells, employing 22 million Europeans in a € 1.5 Tn endeavour, being the premier global economic growth opportunity this century. Significant advances have been made in red biotechnology using pharmaceutically and medically relevant applications, green biotechnology developing agricultural and environmental tools and white biotechnology serving industrial scale uses, frequently as process feedstocks. Red biotechnology has delivered dramatic improvements in controlling human disease, from antibiotics to overcome bacterial infections to anti-HIV/AIDS pharmaceuticals such as azidothymidine (AZT), anti-malarial compounds and novel vaccines saving millions of lives. Green biotechnology has dramatically increased food production through Agrobacterium and biolistic genetic modifications for the development of 'Golden Rice', pathogen resistant crops expressing crystal toxin genes, drought resistance and cold tolerance to extend growth range. The burgeoning area of white biotechnology has delivered bio-plastics, low temperature enzyme detergents and a host of feedstock materials for industrial processes such as modified starches, without which our everyday lives would be much more complex. Biotechnological applications can bridge these categories, by modifying energy crops properties, or analysing circulating nucleic acid elements, bringing benefits for all, through increased food production, supporting climate change adaptation and the low carbon economy, or novel diagnostics impacting on personalized medicine and genetic disease. Cross-cutting technologies such as PCR, novel sequencing tools, bioinformatics, transcriptomics and epigenetics are in the vanguard of biotechnological progress leading to an ever-increasing breadth of applications. Biotechnology will deliver solutions to unimagined problems, providing food security, health and well-being to mankind for centuries to come.


Subject(s)
Biotechnology/trends , Agriculture/trends , Animals , Antimalarials , Biofuels , Biotechnology/economics , Carbohydrates , Climate Change , Droughts , Environment , Epigenomics , Food Supply/methods , Humans , Plastics , Proteins/metabolism
10.
Curr Opin Biotechnol ; 22 Suppl 1: S7-14, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21680172

ABSTRACT

The European Biotechnology Congress 2011 held under the auspices of the European Biotechnology Thematic Network Association (EBTNA) in conjunction with the Turkish Medical Genetics Association brings together a broad spectrum of biotechnologists from around the world. The subsequent abstracts indicate the manner in which biotechnology has permeated all aspects of research from the basic sciences through to small and medium enterprises and major industries. The brief statements before the presentation of the abstracts aim to introduce not only Biotechnology in general and its importance around the world, but also the European Biotechnology Thematic Network Association and its aims especially within the framework of education and ethics in biotechnology.


Subject(s)
Biotechnology/education , Biotechnology/ethics , Biotechnology/trends , Biotechnology/economics , Congresses as Topic , Europe , Humans , Industry , Public-Private Sector Partnerships , Research , Universities
13.
Arch Biochem Biophys ; 478(1): 52-8, 2008 Oct 01.
Article in English | MEDLINE | ID: mdl-18682246

ABSTRACT

Intranuclear lipid metabolism modifications in relation to cell proliferation and/or apoptosis were demonstrated in hepatocytes. The aim of this study was to establish whether nuclear lipid metabolites influence cell function in different experimental models using a rat thyroid cell line (FRTL-5) treated with UV-C radiation. After UV-C irradiation cells proliferate and undergo apoptosis in the presence of thyrotropin, are quiescent and resistant to radiation-induced apoptosis in its absence and finally are proapoptotic for nutrition withdrawal. In nuclei purified from proliferating cells, irradiation stimulates neutral-sphingomyelinase activity and inhibits sphingomyelin-synthase, phosphatidylcholine-specific phospholipase C and phosphatidylinositol-specific phospholipase C activity with a consequent increase in the ceramide/diacylglycerol ratio. This effect is marked in proapoptotic cell nuclei and low in quiescent cell nuclei. In conclusion, UV-C radiation induces apoptosis, modifying nuclear lipid metabolism in relation to the physiological state of cells.


Subject(s)
Apoptosis , Ceramides/metabolism , Diglycerides/metabolism , Animals , Cell Line , Cell Nucleus/metabolism , Lipid Metabolism , Lipids/chemistry , Models, Biological , Rats , Thyroid Gland/metabolism , Thyrotropin/metabolism , Transferases (Other Substituted Phosphate Groups)/metabolism , Type C Phospholipases/metabolism , Ultraviolet Rays
14.
Leukemia ; 21(8): 1802-11, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17554382

ABSTRACT

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell/therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Peripheral Blood Stem Cell Transplantation , Adolescent , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Disease-Free Survival , Etoposide/administration & dosage , Feasibility Studies , Female , Humans , Male , Melphalan/administration & dosage , Middle Aged , Mitoxantrone/administration & dosage , Prospective Studies , Rituximab , Transplantation, Autologous , Treatment Outcome
15.
Int J Immunopathol Pharmacol ; 19(4): 879-88, 2006.
Article in English | MEDLINE | ID: mdl-17166408

ABSTRACT

Antiphospholipid antibodies are generally associated with Antiphospholipid Syndrome, which can occur as a primary disorder or may be secondary to connective tissue disease or tumour. The presence of antiphospholipid antibodies in patients with tumour disease is responsible for thrombotic complications. In a population of 53 tumor patients with positive carcinoembryonic antigen CEA, carbohydrate antigen CA19.9, CA125 and CA15.3 markers, IgM and IgG anticardiolipin and antiphosphatidylinositol were detected by solid-phase immunoassays. Our results show that moderate or high levels of antiphospholipid antibodies are present in a great number of patients with CEA and CA19.9 markers, suggesting a specific association with gastroenteric tumors. By testing for antiphosphatidylinositol antibodies, many patients not evidenced by the standard anticardiolipin assay were found to be antiphospholipid-positive. The analysis of antiphosphatidylinositol antibodies as a diagnostic tool in gastroenteric cancer to highlight patients with the risk of thromboembolic complications is discussed.


Subject(s)
Antibodies, Antiphospholipid/blood , Neoplasms/blood , Aged , Female , Humans , Immunoassay , Male , Middle Aged
16.
Int J Immunopathol Pharmacol ; 19(2): 331-7, 2006.
Article in English | MEDLINE | ID: mdl-16831300

ABSTRACT

A decrease in cholesterol blood level, not due to a decrease synthesis by the liver, has been observed in patients suffering from tumors. In this work cholesterol blood was evaluated in patients affected by monoclonal gammopathy who were not subjected to any treatment. The blood of 25 patients were analyzed for protein and lipid content. Patients were divided according to the gamma protein content into three groups, and it was demonstrated that the group with high levels of gamma proteins presented a strong decrease in blood cholesterol and phospholipids. In these patients the presence of antibodies against phospholipids by using cardiolipin and phosphatidylinositol as antigens has also been demonstrated. The antibodies were rare in patients with a low content of gamma proteins and normal level of lipids, but the frequency was more than 80% in patients with low blood lipid levels.


Subject(s)
Antibodies, Antiphospholipid/immunology , Cholesterol/blood , Paraproteinemias/blood , Paraproteinemias/immunology , Phospholipids/blood , Aged , Cardiolipins/immunology , Cholesterol Esters/blood , Female , Humans , Immunoglobulin A/analysis , Immunoglobulin A/immunology , Male , Middle Aged , Phosphatidylinositols/immunology , Phospholipids/immunology
17.
Biol Cell ; 96(8): 657-67, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15519699

ABSTRACT

The presence of phospholipids as a component of chromatin is now well documented and many enzymes such as sphingomyelinase, sphingomyelin-synthase, reverse sphingomyelin-synthase and phosphatidylcholine-dependent phospholipase C have been described and characterised. Other lipids were demonstrated inside the nucleus especially plasmalogens and cholesterol. The chromatin phospholipids, comprising 10% of that present in the nucleus, show a different metabolism with respect to those present in either microsomes or in nuclear membranes; they increase also during the DNA duplication as shown during both liver regeneration and cell maturation. They appear localised near newly synthesized RNA in decondensed chromatin. Digestion of chromatin with RNase, but not with DNase, causes a loss of phospholipids. The composition of the chromatin phospholipid fraction shows an enrichment in sphingomyelin and phosphatidylserine. In this review the behaviour of single lipids in relation to cell proliferation, cell differentiation and apoptosis is described. Sphingomyelin, the lipid most represented in chromatin with respect to microsomes and nuclear membranes, is localised near to newly synthesized RNA, its presence appearing to protect RNA from RNase digestion. This effect is reversed by sphingomyelinase which digests sphingomyelin and, as a consequence, RNA may be hydrolysed. The amount of sphingomyelin is restored by sphingomyelin-synthase. Sphingomyelin increases during the differentiation process and apoptosis. An increase of sphingomyelinase with consequent decrease in sphingomyelin is observed at the beginning of S-phase of the cell cycle. A possible role in stabilising the DNA double helix is indicated. Phosphatidylserine behaves similarly during differentiation and appears to stimulate both RNA and DNA polymerases. Phosphatidylcholine is implicated in cell proliferation through the activation of intranuclear phosphatidylcholine-dependent phospholipase C and diacylglycerol production. The increase in diacylglycerol stimulates phosphatidylcholine synthesis through the major pathway from cytidyltriphosphate. An inhibition of phosphatidylcholine synthesis is responsible for the initiation of apoptosis. The presence of reverse sphingomyelin-synthase favours the formation of phosphatidylcholine, the donor of phosphorylcholine, from sphingomyelin. Little information has been reported for phospatidylethanolamine, but phosphtidylinositol appears to influence cell differentiation and proliferation. This last effect is due to the action of two enzymes: PI-PLCss1 having a role in the onset of DNA synthesis and PC-PLCgamma1 acting in G2 transit. Phosphoinositides also may have an important role: in membrane-stripped nuclei isolated from mitogen stimulated cells a decrease in PIP and PIP2 followed by an increase in diacylglycerol and a translocation of protein kinase C inside the nucleus is observed. On the other hand, overexpression of the enzyme inositol polysphosphate-1-phosphatase reduced DNA synthesis by 50%. Nevertheless, an enhanced rate of phosphorylation has been demonstrated in cells induced to differentiate. These molecules probably favour RNA transcription, counteracting the inhibition of H1 on RNA polymerase II. Plasmalogens were demonstrated in the nucleus and their increase favours the increased activity of phosphatidylcholine-dependent phospholipase C when DNA synthesis starts. Moreover, two forms of cholesterol has been described in chromatin: one, a less soluble sphingomyelin-linked form and a free fraction. Cholesterol increases during liver regeneration, first as a linked fraction and then, when DNA synthesis starts, as a free fraction. The changes of these components have been summarised in relation to cell function in order to give an overview of their possible roles in the different phases of cell duplication and their influence on cell differentiation and during apoptosis. Finally, the relevance of these molecules as intranuclear signals is discussed and future directions are indicated in clarifying pathological process such as tumour cell transformation and the possibility in finding new therapeutic tools.


Subject(s)
Intranuclear Space/metabolism , Lipids/physiology , Animals , Apoptosis/physiology , Cell Differentiation/physiology , Cell Nucleus/metabolism , Cell Proliferation , Cholesterol/metabolism , Cholesterol/physiology , Chromatin/chemistry , Chromatin/metabolism , Humans , Lipid Metabolism , Lipids/analysis , Phospholipids/metabolism , Phospholipids/physiology , Plasmalogens/metabolism , Plasmalogens/physiology , RNA/metabolism , Sphingomyelins/metabolism , Sphingomyelins/physiology
18.
Cell Biochem Funct ; 21(3): 211-5, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12910472

ABSTRACT

After the first histochemical demonstration by Chayen and Gahan of the presence of phospholipids and especially of sphingomyelin in chromatin, this became the object of long debate and of contradictory results. The general conclusion was that the presence of phospholipids may due to contamination during the isolation of chromatin. More recently the existence of a phospholipid chromatin fraction was confirmed by demonstrating that isolated hepatocyte nuclei, labelled by saturated and unsaturated radioiodination method, showed the presence of radioactivity only in the membrane and not in the isolated chromatin. The phospholipid composition showed an enrichment in sphingomyelin which increased during hepatocyte maturation or erythroleukemic cell differentiation induced by DMSO. A decrease in sphingomyelin was observed at the beginning of the S-phase in regenerating liver or in cultured proliferating cells. These changes were due to the presence of sphingomyelinase and sphingomyelin synthase in the chromatin, the activity of which paralleled the variation in sphingomyelin content. The sphingomyelin was co-localized with RNA as shown by biochemical and electron microscopy methods. Using bromo-uridine it was demonstrated that labelled RNA and sphingomyelin were present in actively transcribing nuclear regions. Isolated nuclear complexes after DNase and RNase digestion contained not only protein, but also RNA and sphingomyelin. After hydrolysis of sphingomyelin the RNAse-resistant RNA becomes RNAse sensitive. It can therefore be concluded that sphingomyelin and the related enzymes are present in the chromatin; sphingomyelin may have a role in RNA transcription protecting RNA by RNAse digestion before its transfer to the cytoplasm.


Subject(s)
Chromatin/metabolism , Sphingomyelins/metabolism , Animals , Apoptosis/physiology , Cell Differentiation/physiology , Cell Division/physiology , Phospholipids/analysis , RNA/metabolism , Rats , Ribonucleases/metabolism , Sphingomyelin Phosphodiesterase/analysis , Sphingomyelin Phosphodiesterase/metabolism , Sphingomyelins/analysis , Transferases (Other Substituted Phosphate Groups)/analysis , Transferases (Other Substituted Phosphate Groups)/metabolism
19.
J Cell Physiol ; 196(2): 354-61, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12811829

ABSTRACT

It has been shown that neutral-sphingomyelinase and sphingomyelin-synthase activities are present in chromatin and they modify the sphingomyelin (SM) content. The activity of the first enzyme is stimulated and the second inhibited, when the hepatocytes enter into the S-phase after partial hepatectomy, thus suggesting that ceramide may have a pivotal role in cell proliferation. An opposite function was attributed to ceramide in hepatocytes which undergo apoptosis after lobular ligature. In order to clarify this point, a model was developed in which the same liver cells undergo proliferation followed by induced apoptosis. To this purpose, the rats were treated for 7 days with ciprofibrate and then left without treatment for 4 days. During the treatment, the peroxisome enzyme markers increase their activity and the number of proliferating cells increases, reaching a maximum after 3 days of treatment, as shown by the number of cells positive for the proliferating cell nuclear antigen. At the same time, the chromatin sphingomyelinase activity reaches the maximum, while a similar increase is not found in the cytoplasm or in the isolated nuclei. On the contrary, SM-synthase activity is depressed in chromatin, but not in the nuclei in which a peak is shown after 3 days of ciprofibrate treatment. After drug withdrawal, the hepatocytes undergo apoptosis as confirmed by the increase of Bax and tissue transglutaminase (tTGase) expression; the chromatin SM increases as a consequence of an increase of SM-synthase activity. It can be hypothesised that chromatin SM may have a role in cell duplication by influencing the chromatin structure stability.


Subject(s)
Apoptosis/physiology , Chromatin/metabolism , Clofibric Acid/analogs & derivatives , Clofibric Acid/pharmacology , Sphingomyelins/physiology , Animals , Cell Division/physiology , Enzyme Activation , Fibric Acids , Liver/anatomy & histology , Liver/drug effects , Liver/growth & development , Liver/physiology , Male , Organ Size/drug effects , Phosphatidylcholines/metabolism , Rats , Rats, Wistar , Sphingomyelin Phosphodiesterase/metabolism
20.
Int J Immunopathol Pharmacol ; 16(1): 61-6, 2003.
Article in English | MEDLINE | ID: mdl-12578733

ABSTRACT

Antiphospholipid antibodies are a heterogeneous group of immunoglobulins with specificity for a number of phospholipids, phospholipid-binding proteins and phospholipid-protein complexes. The association between antiphospholipid antibodies and a variety of pathologic disorders, such as arterial and venous thrombosis and recurrent pregnancy loss is recognized as Antiphospholipid Syndrome. The immunoassay currently used to detect antiphospholipid antibodies is the anticardiolipin test. Anticardiolipin antibodies are believed to be polyspecific antibodies that cross-react with all the anionic phospholipids. Therefore, testing only for anticardiolipin antibodies does not always permit detection of all antiphospholipid antibodies, specially when only IgG are evaluated. In a selected population of 74 idiopathic and secondary deep venous thrombosis patients, IgG anticardiolipin, antiphosphatidylinositol and antiphosphatidylserine antibodies were detected by solid-phase immunoassays. Our results show that by testing for each antiphospholipid family, many patients, not evidenced by the standard anticardiolipin assay, were found to be antiphospholipid-positive. The anticardiolipin positive patients have always low, moderate or high levels of antiphospholipid antibodies, suggesting that the antiphospholipid positivity is predictive of anticardiolipin positivity. It should be noted that the patients with only antiphosphatidylinositol positive antibody have a story of nervous system pathology. The meaning of these results is at present under discussion.


Subject(s)
Antibodies, Antiphospholipid/blood , Phosphatidylinositols/immunology , Venous Thrombosis/blood , Adolescent , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Phosphatidylinositols/blood , Venous Thrombosis/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...