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1.
G Ital Med Lav Ergon ; 31(2): 227-9, 2009.
Artigo em Italiano | MEDLINE | ID: mdl-19827292

RESUMO

Every year in the EU about 800 drivers die in road accidents. In Italy the average is around 200 deaths per year. Based on this context the Occupational Medicine Department (OMD) of Bergamo Hospital has sponsored a new project dedicated to the healthcare and safety of all employees of road haulage in the province of Bergamo. Furthermore the collaboration between UMD and the Clinical Psychology Department of the hospital has allowed the fulfillment of another project aiming to evaluate the personality profile of around 80 drivers employed in the road haulage sector". The aims of the projects is to identify and to point out dangerous situations of significant psychological vulnerability; to know the current situation and to discriminate stress factors from protective ones; to make companies more aware of prevention activities; to inform the drivers about their companies' policy in order to grant safety in their job. The psychological tools used were: half open interview and Personality Inventory MMPI2. The population was selected randomly from volunteers. Now we know the results in 33 tested drivers. So far seven cases have been classified as psychological vulnerable and stress and protective factors have been identified. Results underline the relevance of an integrated approach able to take care of the employees and involving the companies in the prevention programs.


Assuntos
Acidentes de Trânsito/prevenção & controle , Condução de Veículo/psicologia , Transtornos Mentais/prevenção & controle , Medicina do Trabalho/organização & administração , Vigilância da População/métodos , Meios de Transporte , Acidentes de Trabalho/prevenção & controle , Hospitais Públicos/organização & administração , Humanos , Entrevista Psicológica , Itália , Inventário de Personalidade , Fatores de Risco , Segurança , Inquéritos e Questionários , Tolerância ao Trabalho Programado
2.
Leukemia ; 31(8): 1727-1734, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28008174

RESUMO

In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m2 and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.


Assuntos
Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Talidomida/análogos & derivados , Administração Oral , Adulto , Idoso , Ensaios Clínicos Fase III como Assunto , Humanos , Lenalidomida , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Terapia de Salvação , Talidomida/uso terapêutico , Transplante Autólogo
4.
Clin Ter ; 157(3): 237-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16900850

RESUMO

The "Stiff person syndrome"(SPS) is a rare dysimmune chronic neurological disorder, sometimes paraneoplastic, characterized by progressive stiffness, painful persistent or spasmodic muscle contractions, mostly involving spine and lower extremities. In 60 to 90 percent of cases, non-paraneoplastic forms are associated to the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies in the cerebrospinal fluid and in the serum, while anti-amphiphysin antibodies are frequently associated to paraneoplastic types. The relevant treatment consists of three basic approaches: increase in the inhibitory processes in charge of muscle activity control, re-modulation of the immune response, removal of any associated neoplasia. Indications regarding the efficacy of high-dose intravenous immunoglobulin (IVIG) also in this dysimmune pathology are on the increase. We described an unusual case of autoimmune SPS associated with an exclusively motor left peroneal nerve neuropathy, with conduction block, treated with high-dose intravenous immunoglobulin (IVIG), oral cyclosporine, sodium valproate, baclofen and diazepam.


Assuntos
Condução Nervosa , Neuropatias Fibulares/complicações , Rigidez Muscular Espasmódica/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Neuropatias Fibulares/tratamento farmacológico , Neuropatias Fibulares/fisiopatologia , Rigidez Muscular Espasmódica/fisiopatologia
5.
Oncogene ; 35(7): 887-96, 2016 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25961924

RESUMO

Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family, cooperates with ErbB receptor family signaling in breast cancer. It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK. The concomitant overexpression of hMENA and HER2 in breast cancer patients is indicative of a worse prognosis. hMENA is expressed along with alternatively expressed isoforms, hMENA(11a) and hMENAΔv6 with opposite functions. A novel role for the epithelial-associated hMENA(11a) isoform in sustaining HER3 activation and pro-survival pathways in HER2-overexpressing breast cancer cells has been identified by reverse phase protein array and validated in vivo in a series of breast cancer tissues. As HER3 activation is crucial in mechanisms of cell resistance to PI3K inhibitors, we explored whether hMENA(11a) is involved in these resistance mechanisms. The specific hMENA(11a) depletion switched off the HER3-related pathway activated by PI3K inhibitors and impaired the nuclear accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors, whereas PI3K inhibitors activated hMENA(11a) phosphorylation and affected its localization. At the functional level, we found that hMENA(11a) sustains cell proliferation and survival in response to PI3K inhibitor treatment, whereas hMENA(11a) silencing increases molecules involved in cancer cell apoptosis. As shown in three-dimensional cultures, hMENA(11a) contributes to resistance to PI3K inhibition because its depletion drastically reduced cell viability upon treatment with PI3K inhibitor BEZ235. Altogether, these results indicate that hMENA(11a) in HER2-overexpressing breast cancer cells sustains HER3/AKT axis activation and contributes to HER3-mediated resistance mechanisms to PI3K inhibitors. Thus, hMENA(11a) expression can be proposed as a marker of HER3 activation and resistance to PI3K inhibition therapies, to select patients who may benefit from these combined targeted treatments. hMENA(11a) activity could represent a new target for antiproliferative therapies in breast cancer.


Assuntos
Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas dos Microfilamentos/metabolismo , Receptor ErbB-3/genética , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Eletroforese em Gel Bidimensional , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Proteínas dos Microfilamentos/genética , Inibidores de Fosfoinositídeo-3 Quinase , Isoformas de Proteínas , Inibidores de Proteínas Quinases/farmacologia , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Receptor ErbB-2/genética , Transfecção
6.
Leukemia ; 30(6): 1320-6, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26898189

RESUMO

This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Mieloma Múltiplo/mortalidade , Prednisona/administração & dosagem , Taxa de Sobrevida
7.
Oncogene ; 14(17): 2005-13, 1997 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9160879

RESUMO

We have generated a transgenic mouse model for astrocytoma by expressing the v-src kinase under control of the glial fibrillary acidic protein (GFAP) gene regulatory elements in astrocytes. Abnormal astrogliosis was observed in all transgenic animals already at 2 weeks postnatally, frequently followed by the development of dysplastic changes. Later, small proliferative foci arose, and overt astrocytoma developed in the brain and spinal cord in 14.4% of mice after a follow up time of 65 weeks. While early lesions were histologically consistent with low-grade astrocytoma, at later stages most tumors were highly mitotic and frankly malignant. Vascular endothelial growth factor (VEGF) was expressed by tumor cells already at early stages, suggesting induction by v-src, and it was most pronounced in pseudopalisading cells surrounding necrotic areas, implying additional upregulation by hypoxia. In larger lesions, mitotic activity and expression of flk-1, the cognate receptor of VEGF were induced in endothelial cells. Therefore, end-stage tumors mimicked the morphological and molecular characteristics of human glioblastoma multiforme. Time course and stochastic nature of the process indicate that v-src did not suffice for malignant transformation, and that astrocytomas were the result of a multistep process necessitating co-operation of additional genetic events.


Assuntos
Astrocitoma/genética , Neoplasias do Sistema Nervoso Central/genética , Genes Virais , Genes src , Proteína Glial Fibrilar Ácida/genética , Glioblastoma/genética , Proteína Oncogênica pp60(v-src)/fisiologia , Proteínas Recombinantes de Fusão/toxicidade , Animais , Astrocitoma/patologia , Hipóxia Celular , Neoplasias do Sistema Nervoso Central/patologia , Progressão da Doença , Fatores de Crescimento Endotelial/biossíntese , Fatores de Crescimento Endotelial/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Regulação Viral da Expressão Gênica , Glioblastoma/etiologia , Glioblastoma/patologia , Gliose/etiologia , Gliose/genética , Gliose/patologia , Linfocinas/biossíntese , Linfocinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Nus , Camundongos Transgênicos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Receptores Proteína Tirosina Quinases/biossíntese , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento/biossíntese , Receptores de Fatores de Crescimento/genética , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão/genética , Transgenes , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
8.
J Mol Biol ; 283(2): 395-407, 1998 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-9769213

RESUMO

The beta-sandwich structure of immunoglobulin variable domains is characterized by a typical kink in the first strand, which allows the first part of the strand to hydrogen bond to the outer beta-sheet (away from the VH-VL interface) and the second part to the inner beta-sheet. This kink differs in length and sequence between the Vkappa, Vlambda and VH domains and yet is involved in several almost perfectly conserved interactions with framework residues. We have used the selectively infective phage (SIP) system to select the optimal kink region from several defined libraries, using an anti-hemagglutinin single-chain Fv (scFv) fragment as a model system. Both for the kink with the Vkappa domain length and that with the Vlambda length, a sequence distribution was selected that coincides remarkably well with the sequence distribution of natural antibodies. The selected scFv fragments were purified and characterized, and thermodynamic stability was found to be the prime factor responsible for selection. These data show that the SIP technology can be used for optimizing protein structural features by evolutionary approaches.


Assuntos
Bacteriófagos/fisiologia , Cadeias kappa de Imunoglobulina/química , Bacteriófagos/genética , Evolução Molecular Direcionada , Escherichia coli/virologia , Cadeias kappa de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/isolamento & purificação , Modelos Moleculares , Conformação Proteica , Desnaturação Proteica/efeitos dos fármacos , Seleção Genética , Ureia/farmacologia
9.
J Mol Biol ; 268(3): 607-18, 1997 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-9171284

RESUMO

Selectively-infective phage (SIP) is a novel methodology for the in vivo selection of interacting protein-ligand pairs. It consists of two components, (1) a phage particle made non-infective by replacing its N-terminal domains of geneIII protein (gIIIp) with a ligand-binding protein, and (2) an "adapter" molecule in which the ligand is linked to those N-terminal domains of gIIIp which are missing from the phage particle. Infectivity is restored when the displayed protein binds to the ligand and thereby attaches the missing N-terminal domains of gIIIp to the phage particle. Phage propagation is thus strictly dependent on the protein-ligand interaction. We have shown that the insertion of beta-lactamase into different positions of gIIIp, mimicking the insertion of a protein-ligand pair, led to highly infective phage particles. Any phages lacking the first N-terminal domain were not infective at all. In contrast, those lacking only the second N-terminal domain showed low infectivity irrespective of the presence or absence of the F-pilus on the recipient cell, which could be enhanced by addition of calcium. An anti-fluorescein scFv antibody and its antigen fluorescein were examined as a protein-ligand model system for SIP experiments. Adapter molecules, synthesized by chemical coupling of fluorescein to the purified N-terminal domains, were mixed with non-infective anti-fluorescein scFv-displaying phages. Infection events were strictly dependent on fluorescein being coupled to the N-terminal domains and showed a strong dependence on the adapter concentration. Up to 10(6) antigen-specific events could be obtained from 10(10) input phages, compared to only one antigen-independent event. Since no separation of binders and non-binders is necessary, SIP is promising as a rapid procedure to select for high affinity interactions.


Assuntos
Inovirus , Ligantes , Biblioteca de Peptídeos , Proteínas/metabolismo , Cloreto de Cálcio/farmacologia , Proteínas do Capsídeo , Proteínas de Ligação a DNA/genética , Escherichia coli/virologia , Fluoresceína , Fluoresceínas , Vetores Genéticos/genética , Fragmentos de Imunoglobulinas/genética , Fragmentos de Imunoglobulinas/metabolismo , Inovirus/genética , Inovirus/patogenicidade , Cloreto de Magnésio/farmacologia , Ligação Proteica , Proteínas/genética , Proteínas Virais de Fusão/genética , beta-Lactamases/genética
10.
J Mol Biol ; 238(5): 649-54, 1994 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-8182740

RESUMO

Mammalian ferritins are 24-meric proteins composed of variable proportions of H and L-subunits. The L-chain, in contrast to the H-chain, lacks detectable ferroxidase activity, and its role in ferritin iron incorporation is unclear. In this study, apoferritins were subjected to iron loading with large iron increments to favour spontaneous iron hydrolysis. The homopolymers of the wild-type H-chain, and of a mutant H-chain with an inactivated ferroxidase centre, formed massive protein aggregates, while the L-chain homopolymers remained mostly soluble. The difference between H and L-ferritins was not related to the rate of iron oxidation or to the presence of preformed iron cores. Heteropolymers were constructed in vitro by co-renaturing different proportions of the H-chain with the L-chain or mutant H-chain with an inactivated ferroxidase centre. After loading with high iron increments, protein aggregation of the heteropolymers was reduced when the L-chain content was above 70 to 80%, either in combination with the wild-type H-chain or with the inactivated mutant H-chain. Under acidic conditions (pH 5.5, 1000 Fe atoms per molecule) the heteropolymers with about 20% H and 80% L-chains incorporated three to fourfold more iron into soluble 24-mers than the homopolymers. The data indicate that ferritins with more than 18 L-chains per molecule have the capacity to lower non-specific iron hydrolysis in bulk solution. This property is possibly due to a specific attraction of the incoming oxidized iron into the cavity and may be related to an effect of the L-chain on the cavity microenvironment. It is concluded that under high iron increments the ferritins with high L:H-chain ratios are the most efficient in incorporating iron, and this goes some way to explain why iron storage tissues contain L-rich isoferritins.


Assuntos
Ferritinas/química , Ferro/metabolismo , Ceruloplasmina , Ferritinas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Oxirredução , Polímeros/química , Polímeros/metabolismo , Proteínas Recombinantes/química , Solubilidade
11.
Vasa ; 34(1): 53-6, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15786940

RESUMO

Thrombocytosis is either caused by a reactive process (secondary thrombocytosis) or by a clonal bone marrow disorder The latter category includes essential thrombocythemia with bleedings and thrombotic complications as major causes of illness and death in this patients. We describe a 43-year-old man with a 6 months history of acroparesthesia in his toes. Half a year after onset of these symptoms, he noticed a bluish discoloration of digit V of his left foot. On first presentation physical examination revealed a bluish discoloration of all toes and a cold and blue digit V of the left foot. Peripheral pulses were all palpable, normal ankle systolic pressure measurements and normal pulse volume recordings except for digit V of the left foot were found. Laboratory tests revealed thrombocytosis of 800000/microliter. On treatment with acetylsalicylacid, prostanoids intravenously and low molecular weight heparin, the patient became asymptomatic and pulse volume recording of digit V was normalized. After exclusion of cardial or vascular sources of embolism by utrasonography bone marrow aspirate and biopsy supported the diagnosis of essential thrombocythemia.


Assuntos
Arteriopatias Oclusivas/etiologia , Parestesia/etiologia , Trombocitemia Essencial/diagnóstico , Dedos do Pé/irrigação sanguínea , Dedos do Pé/inervação , Adulto , Arteriopatias Oclusivas/diagnóstico , Biópsia , Medula Óssea/patologia , Diagnóstico Diferencial , Humanos , Isquemia/diagnóstico , Isquemia/etiologia , Masculino , Parestesia/diagnóstico
12.
FEBS Lett ; 377(2): 227-31, 1995 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-8543056

RESUMO

We have developed a chloramphenicol resistant derivative of fd phage with which cognate pairs of antibodies and antigens can be selected. The phage genome encodes a fusion of single-chain antibody to the C-terminal domain of gIIIp, rendering the phage non-infective. The antigen fused to the N-terminal domains of gIIIp is encoded in the same phage genome. Antigen and antibody fusion interact with each other in the periplasm of the phage-producing cell, restoring infectivity. This system has a very low background and will allow simultaneous randomisation of antibody and antigen.


Assuntos
Complexo Antígeno-Anticorpo/imunologia , Proteínas de Ligação a DNA/imunologia , Inovirus/genética , Proteínas Virais de Fusão , Proteínas Virais/imunologia , Sequência de Aminoácidos , Complexo Antígeno-Anticorpo/genética , Proteínas do Capsídeo , Cloranfenicol , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Vetores Genéticos , Genoma Viral , Fragmentos de Imunoglobulinas/genética , Fragmentos de Imunoglobulinas/imunologia , Inovirus/imunologia , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
13.
J Cancer Res Clin Oncol ; 124(3-4): 191-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9619746

RESUMO

Biochemical modulation is one of the most interesting fields in cancer chemotherapy. Interferon-alpha (IFNalpha) is a cytokine that is able to influence the pharmacodynamics of 5-fluorouracil (5FU) through a number of mechanisms. With the aim of confirming some data emerging from the literature, we initiated a multicentric randomized study comparing the combination of 5FU and IFNalpha-2a with 5FU alone in the treatment of advanced or metastatic colon cancer. A group of 205 colon cancer patients (104 in the 5FU arm and 101 in the 5FU + IFNapha-2a arm) were included in the final intention-to-treat analysis. Rectal cancers were not considered eligible. All patients had measurable disease, were aged 75 years or less, had a Karnofsky index of at least 60 and had good bone marrow, renal, liver and cardiac functions. No previous chemo-immunotherapy was allowed. The treatment was 750 mg/m2 5FU (4 h i.v. infusion) on days 1 5 and then i.v. bolus weekly, starting from day 12, with or without IFNalpha-2a given s.c. three times weekly (starting dose 3 x 10(6) IU rising to 9 x 10(6) IU, if tolerated). Patients were treated until progression or, if responsive, for a maximum of 48 weeks and then observed for a period of 2 years. The primary end-point of the study was objective clinical response (OR); secondary parameters were time to progression, overall survival, and time to death after progression. WHO criteria were used for both clinical response and toxicity measurements. Dose reduction was planned a priori in the event of significant toxicity due to 5FU, IFNalpha-2a or both. Association between primary and secondary end-points and treatment was studied by univariate and multivariate analysis. Altogether, 47 patients achieved a documented response. A 25% OR was observed in the combination arm while a 21% OR was seen in the 5FU arm; this difference is not statistically significant (P = 0.6). Patients with a small tumour burden (below 5 cm2) showed a higher probability of response in both arms. Patients in the experimental arm had a higher but not statistically significant cumulative progression-free probability. Median survival was 47.1 weeks overall, while it was 43.7 and 48.5 weeks in the control and experimental arms, respectively. The combination was clearly more toxic than 5FU alone, leukopenia being the most frequent side-effect in the experimental arm and nausea and vomiting in the control arm. In conclusion these results are quite disappointing and 5FU + IFNalpha-2a can not be considered a standard treatment for advanced colon cancer.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes
14.
Artigo em Inglês | MEDLINE | ID: mdl-12324240

RESUMO

The term conjugated linoleic acid (CLA) refers to a collection of positional and geometrical isomers of octadeca- dienoic acid with conjugated double bonds. CLA has been shown to possess several beneficial activities in different experimental models, however, out of 28 isomers only two, c9, t11 and t10, c12 have been thus far demonstrated to be biologically active. The discovery that it can be elongated and desaturated as a regular fatty acid in human and animal tissues brought a new possibility that its activity may be related to its properties as a peculiar unsaturated fatty acid. In fact, CLA is able to be incorporated in lipid classes as oleic acid, accumulating in those tissues rich in neutral lipids; to be metabolized as linoleic acid and so influencing linoleic acid desaturation and elongation; and to be beta oxidized in peroxisomes which may account for, through activation of PPARs, its ability to increase free retinol levels and influence gene expression. These activities are amplified where CLA accumulates more such as mammary and adipose tissues and may explain its peculiar beneficial properties, at relative low dietary concentrations, in these tissues. Furthermore, it has been demonstrated that CLA can be endogenously formed by delta 9 desaturation of vaccenic acid (t11 18:1) thus forming the isomer c9, t11. Either endogenously formed or through dietary intake, CLA showed to be metabolized in the same way and to exert the same biological properties. We may conclude that a regular intake of CLA, or/and vaccenic acid as its precursor, should work as an excellent preventive agent by modulating lipid metabolism in target tissues thus conferring protection against the attack of insults of different type.


Assuntos
Ácidos Linoleicos/farmacologia , Metabolismo dos Lipídeos , Vitamina A/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Gorduras na Dieta/metabolismo , Gorduras na Dieta/farmacologia , Humanos , Ácidos Linoleicos/química , Ácidos Linoleicos/metabolismo , Ácidos Oleicos/metabolismo
15.
Dig Liver Dis ; 34(8): 547-52, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12502210

RESUMO

AIMS: To evaluate whether health-related quality of life in adult coeliac disease is related to: 1) adhesion to gluten-free diet; 2) manifestation of clinical features; and 3) associated diseases. PATIENTS AND METHODS: A total of 68 coeliac patients (54 female and 14 male) aged between 18 and 74 years, on gluten-free diet for at least two years were studied. The subjective health status was measured by means of the Short Form 36 Health Survey. A series of 136 subjects, matched according to sex, age and ethnic group, were evaluated as control group. RESULTS: Patients obtained worse scores with respect to healthy controls at all domains of Short Form 36 Health Survey (p<0.05); compliers showed better results than non-compliers. The lowest scores were obtained in patients with more than six symptoms, mostly in non-compliers, the highest in compliers with less than six symptoms. Patients with two or more associated diseases presented significantly worse scores than patients with only one associated disease. CONCLUSIONS: The importance of gluten-free diet in clinical management of coeliac disease is confirmed by results of the present study; moreover, the results seem to indicate that a complex interplay of factors should be taken into account in evaluating health-related quality of life in adult coeliac disease. Accordingly, our data show that health-related quality of life of coeliac patients is impaired not only by poor compliance but also by different negative factors such as severity of illness (in terms of number of symptoms) at diagnosis and comorbidity.


Assuntos
Doença Celíaca/fisiopatologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Doença Celíaca/complicações , Doença Celíaca/dietoterapia , Feminino , Glutens , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente
16.
Clin Rheumatol ; 21(4): 335-8, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12189467

RESUMO

A 58-year-old man developed psoriatic arthritis and, after 6 months, persistent watery diarrhoea. Biopsies from the colorectal mucosa showed thickened subepithelial collagen consistent with collagenous colitis. There also was an inflammatory cell infiltration (mainly lymphocytes and monocytes) in the chorion. These findings and the parallel course of articular and bowel complaints suggest a clinicopathologic correlation between arthritis and colic involvement.


Assuntos
Artrite Psoriásica/complicações , Colite/complicações , Colágeno/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/metabolismo , Artrite Psoriásica/patologia , Artrografia , Colite/metabolismo , Colite/patologia , Quimioterapia Combinada , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestrutura , Articulações/patologia , Cetoprofeno/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Microscopia Eletrônica , Pessoa de Meia-Idade , Sulfassalazina/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
J Exp Clin Cancer Res ; 22(3): 371-8, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14582693

RESUMO

Hemigastrectomy for benign disease and Helicobacter pylori infection are risk conditions for the development of gastric cancer. Aim of the study was to compare gastric histology and precursor lesions of malignancy in these two conditions. The hemigastrectomy group included 351 consecutively endoscoped subjects operated for gastroduodenal benign disease. Six to ten biopsy specimens were routinely taken from the residual gastric mucosa. The intact stomach group included 2097 consecutively endoscoped symptomatic subjects, who did not receive eradication therapy against H. pylori. The histological findings were classified as normal mucosa (NM), chronic non atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS). One thousand and three intact stomachs were H. pylori negative, and 1094 showed H. pylori colonization. The age over fifty was a significant risk factor for the occurrence of IM (OR 2.52, P < or = 0.001) and DYS (OR 3.46, P < or = 0.001), while Hp-positivity was a risk factor for CNAG (OR 1.81, P < or = 0.001) and CAG (OR 3.88, P < or = 0.001). Gastroresection was associated to higher risk for CNAG (OR 1.53, P < or = 0.001) and DYS (OR 4.31, P < or = 0.001) and to a lower risk of CAG (OR 0.49, P < or = 0.001). Both in males and females the risk for CNAG was significantly higher in Hp-positive (males OR 1.92, P=0.000; females OR 1.70, P=0.000) and gastrectomized subjects (males OR 2.06, P=0.000; females OR 2.43, P=0.000). Gastrectomized males, furthermore, showed an increased risk for DYS (OR 5.82, P=0.000). The aged Hp-negative and Hp-positive subjects evidenced a significant risk for IM (respectively OR's 3.42, P=0.000 and 4.85, P=0.000); the risk for DYS was significant in aged Hp-negative subjects (OR 4.09 P < or = 0.020). The Hp-positive individuals evidenced a significant risk for metaplastic mucosal changes (OR 38.17, P=0.000). Subjects aged over forty at the time of surgery and those with a longer postoperative follow up endoscopy presented an increased risk for CNAG of the residual mucosa (respectively OR's 2.75, P=0.000 and 5.25, P=0.000). CNAG and IM were the most frequently observed mucosal lesions both in subjects operated for duodenal and gastric ulcer (respectively OR's 4.02, P=0.000 and 3.00, P=0.000). Our data support that hemigastrectomy for benign disease and H. pylori infection may induce an increased incidence for histological precursor lesions for gastric malignancy and suggest that carcinogenesis in a resected stomach may be different from that in the intact stomach.


Assuntos
Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrite/complicações , Gastrite/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/microbiologia , Prevalência , Neoplasias Gástricas/epidemiologia
18.
Braz J Med Biol Res ; 36(6): 781-6, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12792708

RESUMO

The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF) of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK) levels and magnetic resonance imaging (MRI) were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5 /s; range of motion from 40 to 110 of knee flexion). The isometric torque of the quadriceps (knee at 90 flexion) decreased 52% immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63%) and VMO (66%) and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL, respectively) and recovered one day later. Serum CK levels increased by 109% on the 2nd day and were still increased by 32% on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals.


Assuntos
Traumatismos em Atletas/fisiopatologia , Exercício Físico , Articulação do Joelho/fisiopatologia , Músculo Esquelético/lesões , Adulto , Feminino , Humanos , Músculo Esquelético/fisiopatologia
19.
Hepatogastroenterology ; 47(32): 455-60, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10791212

RESUMO

BACKGROUND/AIMS: In alcohol abusers an alteration of responses to psychometric tests has been reported, even when clinical symptoms of hepatic encephalopathy (HE) are absent. Our research was intended to individualize a simple psychometric test, easy enough to be performed also at the patient's home, able to reveal an impending encephalopathy and, consequently, to facilitate earlier treatment. METHODOLOGY: Twenty-six consecutive male alcoholics were engaged and, after informed consent, the following schedule was applied: administration of a psychometric test, followed by a drawing of blood for the determination of many blood parameters. After 15 days of treatment to detoxicate patients, psychometric tests and blood examinations were repeated. RESULTS: The results confirmed that common blood examinations are not useful to monitor brain damage in chronic alcoholism, that a psychometric test is able to demonstrate a therapeutic improvement and that a positive and significant correlation has been observed between BBCA/AAA ratio and WAIS Score. CONCLUSIONS: These preliminary results suggest that it is possible to suspect dangerous biochemical changes by means of a simple psychometric test.


Assuntos
Encefalopatia Hepática/diagnóstico , Cirrose Hepática Alcoólica/diagnóstico , Escalas de Wechsler/estatística & dados numéricos , Adulto , Encefalopatia Hepática/psicologia , Humanos , Cirrose Hepática Alcoólica/psicologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Psicometria , Fatores de Risco , Sensibilidade e Especificidade
20.
DNA Seq ; 11(6): 507-14, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11696977

RESUMO

Screening of a Thermus thermophilus genomic library led to the identification of a homologue of the ylmE gene. ylmE is highly conserved in widely divergent organisms from prokaryotes to mammals, suggesting an important, albeit currently unknown, cellular function. The 633 bp gene has a GC content of 69.2% overall and 90% in the third nucleotide position, while the gene product is predicted to be a soluble cytoplasmic protein of 23,441 Da. It belongs to a family of conserved proteins of unknown function and exhibits amino acid identities ranging from 45% to 28% to the Aquifex aeolicus and Saccharomyces cerevisiae family members, respectively. We speculate that the gene product may be involved in a cellular stress response in T. thermophilus.


Assuntos
Proteínas de Bactérias/genética , Thermus thermophilus/genética , Sequência de Aminoácidos , Sequência de Bases , Sequência Conservada , DNA Bacteriano , Genes Bacterianos , Humanos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos
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