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1.
Eur Rev Med Pharmacol Sci ; 23(16): 7163-7182, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31486519

RESUMO

Vaccinations are the most effective preventive methods against infectious diseases and represent one of the most relevant successes of medicine. Vaccine development is constantly evolving; therefore, the number of vaccine candidates is progressively increasing. However, most of new potential vaccines are characterized by a lower immunogenicity, with the inability to stimulate powerful and long-lasting immune responses. Hence, to get modern and effective vaccines, we need adjuvants and innovative delivery systems that increase their immunogenicity. The use of nanotechnology in vaccinology is providing the opportunity to contrast these difficulties and develop effective vaccines. Particularly, nanoparticles used as vehicles of vaccine components, are able to increase the host's immune responses and, due to their size, to reach specific cellular districts. To date, a certain number of nanovaccines has been approved for human health and many are studied in clinical or pre-clinical trials. There are several types of nanoparticles considered as possible delivers of vaccine antigens. These nanoparticles-based synthetic delivery systems, in the size range of 20-200 nm, protect antigen from degradation, enhance its presentation and facilitate its uptake by professional antigen-presenting cells. Virus-like particles, self-assembled proteins, micelles, liposomes, inorganic nanoparticles, and polymers are the most studied of these systems. In this review, we provide a general overview of different types, methods of synthesis, characterizations, properties and applications of nanoparticles in vaccine production.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/química , Vacinas/química , Animais , Humanos , Tamanho da Partícula , Vacinas/síntese química
2.
Immunobiology ; 223(3): 264-268, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29055566

RESUMO

BACKGROUND: Elevated IL-6 levels have been associated with both autoimmune diseases and treated HIV-seropositive (HIV+) subjects. However, few data on classic and trans-signaling IL-6 in autoimmune thyroid diseases and HIV+ subjects developing autoimmune disorders are currently available. MATERIALS AND METHODS: A total of 102 patients were included in the study. They were subdivided into two groups. Group A consisted in 51 HIV+ patients, who were followed-up for a period of five years in search of possible occurrence of autoimmune diseases. Ten of them, treated with antiretroviral therapy (ART), developed an autoimmune disorder, namely Hashimoto's thyroiditis, and psoriasis. Group B consisted in 51 patients affected by Hashimoto's thyroiditis (HT). Serum levels of the free form of IL-6 were analyzed by ELISA in all patients and for HIV+ patients at the beginning of the follow-up, before initiation of ART. RESULTS: Mean serum levels of IL-6 were similar in Group A and in Group B. In Group B, IL-6 levels showed a 5.8% increase compared with assay minimum detectable dose corresponding to 1% of full serum IL-6 level. However, serum levels of free IL-6 were increased in those HIV+ patients who developed autoimmune disorders (5.8±2.8pg/ml) and in these patients, the highest levels of free IL-6 correlated with age and CD4 cellular counts. CONCLUSIONS: The present study indicates a correlation between serum free IL-6 levels and the occurrence of autoimmune disease in HIV+ population, treated with ART during a long-term follow-up. The increased levels of serum free IL-6 were observed before ART treatment was initiated, indicating that IL-6 measurement in such patients may represent an early predictor of development of autoimmune disease.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Doença de Hashimoto/imunologia , Interleucina-6/sangue , Psoríase/imunologia , Adulto , Fatores Etários , Antirretrovirais/uso terapêutico , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Seguimentos , Infecções por HIV/epidemiologia , Doença de Hashimoto/epidemiologia , Humanos , Itália/epidemiologia , Contagem de Linfócitos , Masculino , Prognóstico , Psoríase/epidemiologia
3.
Histol Histopathol ; 32(4): 371-377, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27411919

RESUMO

BACKGROUND: P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. METHODS: By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). RESULTS: In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. CONCLUSIONS: We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Papiloma Invertido/patologia , Papiloma/patologia , Proteína Supressora de Tumor p53/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Papiloma/metabolismo , Papiloma Invertido/metabolismo , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética
4.
J Endocrinol Invest ; 38(11): 1175-82, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25935255

RESUMO

PURPOSE: p53, which is encoded by the tumor suppressor gene TP53, plays a crucial role in the regulation of mechanisms of cell cycle arrest and apoptosis. Some SNPs of TP53, involving a different apoptotic ability of p53, have been associated with increased susceptibility to develop autoimmune diseases as well as cancer. We investigated the genotypic distribution of TP53 exon 4 SNPs in a cohort of Caucasian patients affected by Hashimoto's thyroiditis (HT). METHODS: Peripheral blood for DNA extraction was collected from 109 Caucasian unrelated subjects, 79 HT patients and 30 healthy controls. SNPs analysis was carried out by amplification and sequencing of exon 4 TP53. RESULTS: For the Pro72Arg (rs 1042522) SNP we found these rates in HT patients: 11.4% wild-type C/C (Pro72Pro), 24.0% heterozygous G/C (Pro72Arg), 64.6% homozygous G/G (Arg72Arg). The corresponding rates in healthy controls were 10, 46.7 and 43.3%, respectively. Thus, significantly different were G/C heterozygosity (24.0 vs 46.7 %, p = 0.039) and G/G homozygosity (64.6 vs 43.3%, p = 0.042). These differences were also confirmed when comparing our study population to published Caucasian control groups. The other described SNPs (Pro34Pro rs 11575998, Pro36Pro rs1800370, Pro47Ser rs1800371, and Arg110Leu rs 11540654) were absent or very rare in our study population. CONCLUSIONS: Our preliminary data, the first on a Caucasian population, indicate an increased prevalence of the homozygous genotype Arg/Arg and a decreased prevalence of heterozygous genotype Arg/Pro of rs 1042522 in HT patients compared to controls, suggesting that such SNP may contribute to confer susceptibility to HT.


Assuntos
Doença de Hashimoto/genética , Proteína Supressora de Tumor p53/genética , Adulto , Éxons/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética
5.
Phys Rev Lett ; 110(2): 020404, 2013 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-23383879

RESUMO

Using the Wigner representation, compatibly with the uncertainty principle, we formulate a quantum maximum entropy principle for the fractional exclusion statistics. By considering anyonic systems satisfying fractional exclusion statistic, all the results available in the literature are generalized in terms of both the kind of statistics and a nonlocal description for excluson gases. Gradient quantum corrections are explicitly given at different levels of degeneracy and classical results are recovered when ℏ→0.

6.
J Exp Bot ; 63(1): 471-88, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21976770

RESUMO

The genetic basis of stem cell specification in somatic embryogenesis and organogenesis is still obscure. SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) genes are involved in embryogenesis and organogenesis in numerous species. In vitro culture of Cyclamen persicum immature ovules provides a system for investigating stem cell formation and maintenance, because lines forming either organs or embryos or callus without organs/embryos are available for the same cultivar and plant growth regulator conditions. The present aim was to exploit this property of cyclamen cultures to understand the role of SERK(s) in stem cell formation and maintenance in somatic embryogenesis and organogenesis in vitro, in comparison with expression in planta. CpSERK1 and CpSERK2 were isolated from embryogenic callus. CpSERK1 and CpSERK2 levels by RT-PCR showed that expression is high in embryogenic, moderate in organogenic, and null in recalcitrant calli. in situ hybridizations showed that the expression of both genes started in clumps of pluripotent stem cells, from which both pre-embryogenic aggregates and organ meristemoids derived, and continued in their trans-amplifying, meristem-like, derivatives. Expression declined in organ meristemoids, in parallel with a partial loss of meristematization. In mature somatic embryos, and in shoot and root primordia, CpSERK1 and CpSERK2 were expressed in meristems, and similar patterns occurred in zygotic embryo and primary meristems in planta. The results point to SERK1 and SERK2 as markers of pluripotency in cyclamen. It is proposed that the high expression of these genes in the trans-amplifying derivatives of the stem cells maintains a pluripotent condition leading to totipotency and, consequently, somatic embryogenesis.


Assuntos
Cyclamen/genética , Marcadores Genéticos , Proteínas de Plantas/genética , Proteínas Quinases/genética , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas Quinases/química , Reação em Cadeia da Polimerase em Tempo Real , Homologia de Sequência de Aminoácidos
7.
Histol Histopathol ; 27(1): 113-21, 2012 01.
Artigo em Inglês | MEDLINE | ID: mdl-22127603

RESUMO

OBJECTIVE: Upon binding with HGF, the thyrosine-kinase receptor c-met induces cell growth, scattering and morphogenic effects via the trasducers STAT3 and phosphorylated-STAT3, PI3K/Akt, Rho. HGF, c-met and STAT3 are expressed with very high frequency in papillary thyroid carcinomas (PTC), suggesting a role in PTC. Herein we first investigate the simultaneous expression of HGF, c-met, STAT3, phosphor-STAT3, PI3K, Akt and Rho in thyroid nodules. DESIGN AND METHODS: Using immunohistochemistry, we studied: 30 colloid nodules (CN), 18 hyperplastic nodules (HN), 20 follicular adenomas (FA), 15 oncocytic adenomas (OA), 20 PTC, 16 follicular carcinomas (FTC) and 6 anaplastic carcinomas (ATC). RESULTS: All 7 proteins were expressed in 15% of FA (with HGF, PI3K and Rho stromal reactivity) and 25% of PTC, and the combination HGF/c-met/STAT3/ pSTAT3/PI3K was expressed by all PTC, each protein being expressed by tumor cells. In contrast, 13/16 FTC (81%) exhibited immunoreactivity for PI3K (both epithelial and stromal), and 100% of ATC was PI3K+ (both epithelial and stromal) and Rho+ (epithelial). Epithelial expression of PI3K correlated with the clinical behavior of histotypes and, within FTC, the proportion of PI3K+ cells correlated with both the clinical and pathological stage (r=0.95; p<0.001). As for the shared epithelial expression of PI3K, this concerned approximately one-fourth of tumor cells in FTC and ATC vs one-thirtieth in PTC. CONCLUSIONS: Our data may have practical implications for the targeted medical therapy of thyroid cancer arising from the follicular epithelium.


Assuntos
Adenoma/química , Fator de Crescimento de Hepatócito/análise , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-met/análise , Neoplasias da Glândula Tireoide/química , Nódulo da Glândula Tireoide/química , Adenocarcinoma Folicular , Adenoma/patologia , Carcinoma , Carcinoma Papilar , Células Epiteliais/química , Humanos , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinase/análise , Fosforilação , Proteínas Proto-Oncogênicas c-akt/análise , Fator de Transcrição STAT3/análise , Células Estromais/química , Câncer Papilífero da Tireoide , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Proteínas rho de Ligação ao GTP/análise
8.
Eplasty ; 11: e48, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22140594

RESUMO

OBJECTIVE: Early studies of plastic surgery patient triage using telemedicine are descriptive and deal with feasibility rather than accuracy. The inpatient study arm compares on-site wound-evaluation accuracy with remotely viewed digital images. The outpatient arm prospectively compares on-site and remote diagnosis, management, and outcomes in a busy, urban, reconstructive-surgery clinic. The concurrent 6 patient case studies illustrate significant systems improvement by using remote consultation. METHODS: A total of 43 inpatients and 100 consecutive outpatients were evaluated by on-site and remote surgeons as performed in previous arms with digital-camera and store and forward technology. Consent was obtained from all patients participating. Agreements regarding diagnosis (skin lesion, hand injury, wound type, and scar character) and management (healing problem, emergent evaluation, antibiotics, and hospitalization) were calculated. RESULTS: In the first study arm, on-site and remote agreement (46%-86% for wound description and 65%-81% for management) generally matched agreement among on-site surgeons (68%-100% and 84%-89%). Moreover, when on-site agreement was low (68% for edema), agreement between on-site and remote surgeons was also low (57%). Remote evaluation was least sensitive detecting wound drainage (46%). On-site surgeons opted for more treatment, often prescribing antibiotics and admitting the patient. The second teleconsult arm provides further evidence of accuracy, overall agreement of 32%, sensitivity 48.55%, specificity 96.92%, positive predictive value 49.26%, negative predictive value 96.83%, and P < .001 regarding diagnosis (skin lesion, hand injury, wound type, wound problem, and scar character). Patient transfer, postoperative monitoring, and outcomes via electronic image transfer, as well as cost-benefit analysis of this clinic-based study, are presented. CONCLUSIONS: eConsultation renders similar outcomes to standard, on-site examination in a selected group of plastic surgery patients. Remote evaluation may assist triage decisions, thereby decreasing emergency room throughput time and office-visit frequency, supplementing satellite facility consultation by plastic surgeons, and providing real-time postoperative assessments, thereby improving quality and reducing costs.

9.
Tissue Cell ; 43(5): 304-10, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21764094

RESUMO

Sperm of Armadillidium peraccae have been examined with cytochemical and immunocytochemical methods for fluorescence and electron microscopic visualization of cytoskeleton components. Sperm incubation in an antibody anti-ß-tubulin shows only the presence of two centrioles located in the cytoplasmic region above the nucleus; no other microtubules are present in the sperm head. Instead, fluorescence microscopy of sperm incubated in FITC-phalloidin allowed to detect the presence of a large amount of F-actin in the apical region of the sperm head. The incubation of ultrathin sections of sperm embedded in Lowicryl K4M with a phalloidin-gold complex allowed a more precise localization of F-actin in the amorphous part of the acrosome and in the cytoplasmic region between acrosome and nucleus; F-actin is also present in the thin cytoplasmic layer between plasma membrane and nuclear envelope at the apical portion of the nucleus. Although the sperm was always found completely devoid of motility, the discovery of the presence of an actin cytoskeleton leads us to hypothesize a possible acquisition of motility by the sperm at the time of its interaction with the female gamete. Such a hypothesis is supported by what is known for ostracods whose aflagellate sperm implement a type of amoeboid movement only at the time of their interaction with the female gamete.


Assuntos
Actinas/metabolismo , Isópodes/metabolismo , Cabeça do Espermatozoide/metabolismo , Espermatogônias/metabolismo , Animais , Centríolos/metabolismo , Citoplasma/metabolismo , Feminino , Isópodes/anatomia & histologia , Masculino , Microscopia Eletrônica , Microscopia de Fluorescência , Sensibilidade e Especificidade , Cabeça do Espermatozoide/ultraestrutura , Motilidade dos Espermatozoides , Cauda do Espermatozoide/metabolismo , Espermatogônias/ultraestrutura , Coloração e Rotulagem/métodos
10.
G Chir ; 32(3): 135-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21453593

RESUMO

Pancreas is frequently site of isolated metastasis, approximately in the 40% of cases in patient with previous history of malignant neoplasia, more frequently from renal cell carcinoma. The melanoma metastasis can also interest the pancreas in case of disseminated disease (50% of the cases); more rarely the pancreas is site of isolated metastases from melanoma. The treatment of the pancreatic metastases from melanoma is controversial: the therapeutic choices are few and the role of surgery is not well defined. If the metastasis are confined to the pancreas, the surgical treatment can be useful for better long time survival. We report a rare case of melanoma with pancreatic isolated metastasi in a patient with a previous melanotic metastasis to the inguinal lymph nodes without evidence of primitive tumor.


Assuntos
Melanoma/secundário , Neoplasias Pancreáticas/secundário , Neoplasias Cutâneas/patologia , Adulto , Feminino , Humanos
11.
Phys Rev E Stat Nonlin Soft Matter Phys ; 84(6 Pt 1): 061147, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22304080

RESUMO

By introducing a quantum entropy functional of the reduced density matrix, the principle of quantum maximum entropy is asserted as fundamental principle of quantum statistical mechanics. Accordingly, we develop a comprehensive theoretical formalism to construct rigorously a closed quantum hydrodynamic transport within a Wigner function approach. The theoretical formalism is formulated in both thermodynamic equilibrium and nonequilibrium conditions, and the quantum contributions are obtained by only assuming that the Lagrange multipliers can be expanded in powers of h(2). In particular, by using an arbitrary number of moments, we prove that (1) on a macroscopic scale all nonlocal effects, compatible with the uncertainty principle, are imputable to high-order spatial derivatives, both of the numerical density n and of the effective temperature T; (2) the results available from the literature in the framework of both a quantum Boltzmann gas and a degenerate quantum Fermi gas are recovered as a particular case; (3) the statistics for the quantum Fermi and Bose gases at different levels of degeneracy are explicitly incorporated; (4) a set of relevant applications admitting exact analytical equations are explicitly given and discussed; (5) the quantum maximum entropy principle keeps full validity in the classical limit, when h → 0.

12.
Eur J Histochem ; 54(2): e24, 2010 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-20558345

RESUMO

Hepatocyte growth factor (HGF) exerts proliferative activities in thyrocytes upon binding to its tyrosine kinase receptor c-met and is also expressed in benign thyroid nodules as well as in Hashimoto's thyroiditis (HT). The simultaneous expression of HGF/c-met and three trasducers of tyrosine kinase receptors (STAT3, PI3K, RHO) in both the nodular and extranodular tissues were studied by immunohistochemistry in 50 benign thyroid nodules (NGs), 25 of which associated with HT. The ligand/tyrosine kinase receptor pair HGF/c-met and the two trasducers PI3K and RHO were expressed in NGs, regardless of association with HT, with a higher positive cases percentage in HT-associated NGs compared to not HT-associated NGs (25/25 or 100% vs 7/25 or 28%; P<0.001). HGF, PI3K and RHO expression was only stromal (fibroblasts and endothelial cells), in all 32 reactive NGs, while c-met localization was consistently epithelial (thyrocyes). Immunoreactions for HGF, c-met, PI3K and RHO were also apparent in the extra-nodular tissue of HT specimens, where HGF and PI3K were expressed not only in stromal cells but also in thyrocyes along with the c-met. Finally, a positive correlation was observed between the proportion of HGF, c-met, PI3K follicular cells and the grade of lymphoid aggregates in HT. In conclusion, HGF, c-met, PI3K are much more frequently and highly expressed in HT compared to NGs, and among all NGs in those present in the context of HT. A paracrine effect of HFG/c-met on nodule development, based on the prevalent stromal expression, may be suggested along with a major role of HGF/c-met and PI3K in HT. Finally, the expression of such molecules in HT may be regulated by lymphoid infiltrate.


Assuntos
Doença de Hashimoto/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Fator de Transcrição STAT3/metabolismo , Quinases Associadas a rho/metabolismo , Doença de Hashimoto/patologia , Humanos , Imuno-Histoquímica , Ligantes , Nódulo da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/patologia
13.
Phys Rev E Stat Nonlin Soft Matter Phys ; 81(2 Pt 1): 021119, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20365542

RESUMO

By introducing a functional of the reduced density matrix, we generalize the definition of a quantum entropy which incorporates the indistinguishability principle of a system of identical particles. With the present definition, the principle of quantum maximum entropy permits us to solve the closure problem for a quantum hydrodynamic set of balance equations corresponding to an arbitrary number of moments in the framework of extended thermodynamics. The determination of the reduced Wigner function for equilibrium and nonequilibrium conditions is found to become possible only by assuming that the Lagrange multipliers can be expanded in powers of variant Planck's over 2pi(2). Quantum contributions are expressed in powers of variant Planck's over 2pi(2) while classical results are recovered in the limit variant Planck's over 2pi-->0 .

14.
J Endocrinol Invest ; 32(5): 465-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19468262

RESUMO

BACKGROUND: Some growth factors and cytokines are known to cooperate with TSH in thyroid nodular growth, but few data are available on their circulating levels in Hashimoto's thyroiditis (HT). AIM: To evaluate in HT patients whether thyroid nodules are associated with variations in serum levels of hepatocyte growth factor (HGF) and interleukin-6 (IL-6). SUBJECTS AND METHODS: Serum levels of HGF and IL-6 were measured by enzyme-linked immunosorbent assay in 176 euthyroid subjects, subdivided into 4 groups: A) HT patients with nodular goiter (no.=42); B) non-goitrous HT patients (no.=36); C) non-HT patients with nodular goiter (no.=48), and D) healthy subjects without thyroid disease (no.=50). RESULTS: The highest concentrations of serumHGF were found in patients with nodular goiter, irrespective of the presence of associated HT (groups A and C). Nevertheless, in group A serum HGF levels were significantly higher than in group C (860.8+/-333.6 pg/ml vs 691.5+/-156 pg/ml, p<0.01). Moreover, though serum HGF levels in group B (578.3+/-217 pg/ml) were lower than in group A, they were significantly higher than in healthy controls (group D, 512.7+/-170.4 pg/ml, p<0.001). Serum IL-6 levels were similar in the two HT groups (A and B), and increased with respect to groups C and D. CONCLUSIONS: Serum HGF is increased in HT, especially associated to thyroid nodules, as compared with healthy non-goitrous individuals.


Assuntos
Bócio Nodular/sangue , Bócio Nodular/complicações , Doença de Hashimoto/sangue , Doença de Hashimoto/complicações , Fator de Crescimento de Hepatócito/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Saúde , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Panminerva Med ; 50(3): 221-6, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18927526

RESUMO

AIM: Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels. METHODS: The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant). RESULTS: Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration. CONCLUSION: DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.


Assuntos
Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Precursores de Proteínas/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Protrombina , Regulação para Cima , Vitamina K/sangue , Vitamina K 1/administração & dosagem , Deficiência de Vitamina K/sangue , alfa-Fetoproteínas/metabolismo
16.
J Pathol ; 215(1): 87-96, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18306168

RESUMO

The mechanisms of follicular thyroid carcinoma (FTC) transformation and progression are not well understood. Previously, we detected LOH at 7q21 in all FTCs examined, indicating that loss of genetic material in that region is a common trait in these lesions. To analyse the effects of LOH on gene expression, we performed an analysis of the mRNA expression levels of six different genes, located at 7q21.1-7q21.3. A total of 23 lesions, including eight follicular hyperplasias (FHs), eight follicular adenomas (FAs), two FTCs and five papillary thyroid carcinomas (PTCs) were analysed. The Frizzled-1 (FZD-1) gene, located at 7q21.13, showed the lowest levels of mRNA expression. Down-regulation of FZD-1 expression was also confirmed in an independent series of 69 follicular neoplastic lesions compared to 25 PTCs, analysed by quantitative RT-PCR. In vitro studies showed that FZD-1 expression was also markedly reduced at both protein and mRNA levels in three FTC-derived cell lines (FRO, WRO and FTC-133), while it was normal in the three PTC-derived cell lines (Ca300, Ca301 and K1) examined. We demonstrated that over-expression of FZD-1 in 3 FTC-derived cells decreased invasiveness and proliferation rate, indicating a possible pathogenetic role. In addition, FZD-1 RNA interference in the PTC-derived cell line K1 increased invasiveness. Our data indicated that FZD-1 is involved in growth of follicular tumours and may be considered as a novel marker of this type of tumour.


Assuntos
Adenocarcinoma Folicular/genética , Receptores Frizzled/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Folicular/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Linhagem Celular Tumoral , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Perda de Heterozigosidade , Invasividade Neoplásica/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
17.
Eur J Histochem ; 51(3): 193-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17921114

RESUMO

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease frequently associated with hyperplastic nodules (HN)s. Hepatocyte growth factor (HGF) is expressed in benign thyroid nodules and over-expressed in malignant thyroid nodules, particularly in papillary thyroid carcinomas. To elucidate the role of HGF in the development of HNs in association with HT we evaluated, by immunohistochemistry, the expression of HGF in both nodular and extranodular tissues, obtained from 30 HTs and 15 goiter samples. Six normal thyroid glands were used as controls. All normal control tissue samples exhibited no evidence of HGF immunoreaction. HNs showed weak to moderate HGF immunoreaction, which was located exclusively in the cytoplasm of stromal cells (fibroblasts and endothelial cells). However, the percentage of positive cases was higher in HNs arisen in the context of HT, compared to HNs not associated with HT (30/30 or 100% vs 4/15 or 40%; p<0.001). HGF immunoreactivity was also detected in all extranodular tissues from HT specimens (30/30 or 100%), but we found some significant differences. In fact, while in HNs observed in the context of HT lesions HGF was expressed only in stromal cells, in the extranodular tissues from the same thyroid gland affected by HT it was also detected in the cytoplasm of the epithelial follicular cells. Furthermore, HTs showed a much higher HGF staining grade in the extranodular tissue compared to HNs. Finally, a clear positive correlation was observed in HT between the proportion of HGF expressing follicular cells and the grade of lymphoid aggregates of the thyroid gland. In conclusion, HGF is much more frequently and highly expressed in thyroid tissue with HT, compared to goiter. In HT glands HGF can be detected in both follicular thyroid cells and stromal cells, while in HNs, either from goiters or associated with HT, its expression is restricted only to the stromal cells. These data indicate that HGF may play a role in cell proliferation processes occurring in thyroid glands affected by HT, probably under the regulation of the lymphoid infiltrate.


Assuntos
Bócio Nodular/metabolismo , Doença de Hashimoto/metabolismo , Fator de Crescimento de Hepatócito/biossíntese , Feminino , Bócio Nodular/patologia , Doença de Hashimoto/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia
18.
G Chir ; 28(6-7): 286-91, 2007.
Artigo em Italiano | MEDLINE | ID: mdl-17626775

RESUMO

The authors, reporting on their experience, confirm as the incidence of the hepatic hydatidosis and the complications related to this pathology today are very meaningful. They specify that the objectives to be pursued are: elimination of the parasite, prevention or treatment of the complications, prevention of the development of a new infestation. They dwell therefore upon the various techniques, both conservative and radical, that marked the history of the hepatic hydatidosis surgery, and they conclude affirming that the procedures of eradication of the parasite and the pericystectomy, in particular in laparotomic way, also represents the ideal treatment in consideration of the a little encouraging results of the medical therapy.


Assuntos
Equinococose Hepática/cirurgia , Humanos
19.
Neurology ; 68(18): 1474-80, 2007 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-17470749

RESUMO

OBJECTIVE: To relate clinical characteristics associated with acute transverse myelitis (ATM) in children with functional outcomes at follow-up. METHODS: We identified 47 patients for whom ATM occurred under the age of 18 years. Chart analysis, clinical evaluation, and administration of functional measures were completed. RESULTS: The age at onset clustered between ages 0 to 2 and 5 to 17. Febrile illness had occurred in 47% and vaccination in 28%. Major disability at the nadir of the clinical course was noted. Eighty-nine percent were unable to walk, required assisted ventilation, or both. At a median of 3.2 years after acute illness, 43% were unable to walk 30 ft and 21% required a walker or other support, 68% experienced urinary urgency, 50% required bladder catheterization, 54% were troubled by persistent dysesthesias, and 75% had numbness. Factors associated with a better functional outcome included older age at time of diagnosis, shorter time to diagnosis, lower sensory and anatomic levels of spinal injury, absence of T1 hypointensity on spinal MRI obtained during the acute period, lack of white blood cells in the CSF, and fewer affected spinal cord segments. Neither rapid progression to maximum impairment in less than 1 day nor any antecedent illness, immunization, or trauma was associated with a worse outcome. CONCLUSION: Persisting disability was present in many children with acute transverse myelitis. Urinary problems and sensory symptoms were the most common issues. Age at onset below 3 years was associated with worse functional outcomes.


Assuntos
Mielite Transversa/epidemiologia , Mielite Transversa/fisiopatologia , Medula Espinal/fisiopatologia , Vacinação/efeitos adversos , Viroses/epidemiologia , Viroses/fisiopatologia , Doença Aguda , Adolescente , Distribuição por Idade , Idade de Início , Criança , Pré-Escolar , Comorbidade , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mielite Transversa/diagnóstico , Paralisia/epidemiologia , Prognóstico , Estudos Retrospectivos , Transtornos de Sensação/epidemiologia , Distribuição por Sexo , Medula Espinal/imunologia , Medula Espinal/patologia , Bexiga Urinaria Neurogênica/epidemiologia
20.
G Chir ; 28(1-2): 39-49, 2007.
Artigo em Italiano | MEDLINE | ID: mdl-17313732

RESUMO

A retrospective review on 22 patients with gastric mesenchymal tumors, who underwent surgical treatment in the period 1974-2003, is presented. The aim of the study was to review our cases in the light of the new pathologic and immunohistochemical definitions and to analyse the value of clinical signs, diagnostic methods and principles of surgical technique. The Authors conclude that no specific clinical signs have been detected. Endoscopy plays a very important diagnostic role and CT-scan is the most sensible technique in the evaluation of location, size, invasion of adjacent organs and metastasis. The aim of treatment must be the complete resection of the tumor and the prognostic prediction on the basis of histologic findings is quite difficult.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Mesenquimoma/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Masculino , Mesenquimoma/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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