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1.
J Trace Elem Med Biol ; 55: 58-63, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345366

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored. OBJECTIVES: The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use. METHODS AND RESULTS: 84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1ß concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time. CONCLUSION: Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.


Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Cobre/sangue , Homeostase/efeitos dos fármacos , Zinco/sangue , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Inibidores da Colinesterase/administração & dosagem , Cobre/metabolismo , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Modelos Lineares , Masculino , Zinco/metabolismo
2.
Diabetes Res Clin Pract ; 144: 102-110, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30142362

RESUMO

AIMS: ZnT8 Arg325Trp polymorphism has been associated with type 2 diabetes (T2DM) susceptibility. The Arg-325 risk variant shows accelerated zinc (Zn) transport kinetic and reduced glucose-stimulated insulin secretion in pancreatic cells. However, it remains unexplored the role of Znt8 polymorphism in the regulation of Zn homeostasis and inflammatory response in peripheral blood mononuclear cells (PBMCs) from T2DM patients. METHODS AND RESULTS: A total of 556 healthy controls and 413 T2DM patients were genotyped for ZnT8 Arg325Trp polymorphism confirming the association of Arg-325 variant with an increased T2DM risk (OR = 1.35 95% C.I: 1.10-1.66; p = 0.0044). Moreover, PBMCs from Arg/Arg T2DM subjects showed increased intracellular free Zn, higher gene expression of Metallothioneins, Znt1, Znt8, Zip2 genes, and reduced Znt4 and Znt7. Higher release of IL-1α, IL-1ß, IFN-γ, IL-12p70 and TNF-α and a reduced IL-10 secretion after lipopolysaccharide (LPS) stimulation were observed in PBMCs from Arg/Arg T2DM carriers as compared to subjects with the Trp variant. CONCLUSIONS: Our data provide evidence of a substantial different Zn homeostasis regulation between Znt8 Arg-325 and Trp-325 carriers in PBMCs from T2DM patients. Moreover, Znt8 Arg-325 risk variant shows an enhanced inflammatory response upon LPS stimulation that might aggravate insulin resistance and the progression of diabetes cardiovascular complications.


Assuntos
Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Leucócitos Mononucleares/metabolismo , Polimorfismo Genético , Transportador 8 de Zinco/genética , Zinco/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/genética , Estudos de Casos e Controles , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
3.
RSC Adv ; 8(16): 8662-8670, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35539881

RESUMO

Physicochemical analysis was carried out to obtain the species distribution diagrams (SDDs) for the deposition of ZnO films as a function of OH- ion concentration ([OH-]) in the reaction solution. The study of SDDs predicts nucleation and ZnO film growth by means of the dominant species at a given pH value. To confirm this, a series of experiments were made varying the [OH-] in the reaction solution and keeping the others parameters constant. Structured zinc oxide (ZnO) films were obtained on glass substrates by microwave chemical bath deposition (MWCBD). Structural, optical and morphological ZnO film properties were investigated as a function of [OH-]. X-Ray diffraction technique (XRD) measurements show multiple diffraction peaks, indicating the polycrystalline nature of ZnO films. Scanning Electron Microscopy (SEM) images of ZnO structures showed morphological changes with the variation of [OH-]. The stoichiometry of the structures changed as the [OH-] was varied in solution. From Raman spectra, it was observed that the [OH-] of the reaction mixture strongly affects the crystal quality of ZnO structures. A reaction pathway for the synthesis of ZnO structures based on our results is proposed. Experimental results are consistent with the physical-chemical analysis.

4.
Int J Oral Maxillofac Surg ; 45(10): 1280-2, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27515851

RESUMO

The first case of an oral infection caused by Sphingomonas paucimobilis is reported. A 73-year-old man presented with a gingival ulcer with bone exposure affecting the attached gingiva in the anterior maxillary region. He reported pain during chewing and the presence of fever. Since the first case of S. paucimobilis infection was reported in 1977, involving a leg ulcer, the number of reports related to this organism has been increasing, indicating that the bacterium should be considered an emerging pathogen. It is possible that other non-classical pathogens of the oral cavity may be responsible for infectious lesions, which represents a diagnostic and therapeutic challenge.


Assuntos
Doenças da Gengiva/microbiologia , Infecções por Bactérias Gram-Negativas/complicações , Úlceras Orais/microbiologia , Sphingomonas , Idoso , Febre/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino
5.
Geobiology ; 14(4): 404-16, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27001345

RESUMO

Benthic foraminifera are single-celled eukaryotes that make a protective organic, agglutinated or calcareous test. Some agglutinated, single-chambered taxa, including Psammophaga Arnold, 1982, retain mineral particles in their cytoplasm, but the selective mechanism of accumulation is not clear. Here, we report the ability of a foraminiferal species to select and accumulate zircons and other heavy minerals in their cytoplasm. In particular, the use of Scanning Electron Microscope coupled with an Energy Dispersive X-ray microanalysis system (SEM-EDS) enabled a representative overview of the mineral diversity and showed that the analysed Psammophaga zirconia sp. nov. individuals contained dominantly crystals of zircon (51%), titanium oxides (27%), and ilmenite (11%) along with minor magnetite and other minerals. The studied specimens occur in the shallow central Adriatic Sea where the sediment has a content of zircon below 1% and of other heavy minerals below 4%. For that reason we hypothesize that: (i) P. zirconia may be able to chemically select minerals, specifically zircon and rutile; (ii) the chemical mechanism allowing the selection is based on electrostatic interaction, and it could work also for agglutinated foraminifera (whether for ingestion, like Xenophyophores, or incorporation in the test as in many other described taxa). In particular, this aptitude for high preferential uptake and differential ingestion or retention of zircon is reported here for the first time, together with the selection of other heavy minerals already described in members of the genus Psammophaga. They are generally counted among early foraminifera, constructing a morphologically simple test with a single chamber. Our molecular phylogenetic study confirms that P. zirconia is a new species, genetically distinctive from other Psammophaga, and occurs in the Adriatic as well as in the Black Sea.


Assuntos
Foraminíferos/química , Foraminíferos/classificação , Metais Pesados/análise , Zircônio/análise , Análise por Conglomerados , Citoplasma/química , DNA de Protozoário/química , DNA de Protozoário/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Foraminíferos/citologia , Genes de RNAr , Mar Mediterrâneo , Microscopia Eletrônica de Varredura , Minerais/análise , Filogenia , RNA de Protozoário/genética , RNA Ribossômico 18S/genética , Análise de Sequência de DNA , Espectrometria por Raios X
6.
Biogerontology ; 15(1): 65-79, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24243066

RESUMO

Proinflammatory cytokines and heat shock proteins play relevant roles in the pathogenesis of inflammatory diseases. We investigated whether Hsp70 1267 A/G and TNF-α -308 G/A polymorphisms are associated with proinflammatory mediators, zinc status and laboratory parameters in 1,078 healthy elderly from ZincAge study. Hsp70 1267 A/G genotype and allele distribution were similar among various European countries, while a TNF-α genetic heterogeneity was observed between the Northern and the Southern European populations, with a major frequency of the -308 A variant in France, Germany and Poland. We used linear regression models to test additive, dominant or recessive associations of each SNP with proinflammatory mediators, laboratory parameters, metallothioneins and zinc status. Hsp70 1267 A/G SNP, but not TNF-α -308 G/A SNP, influences TNF-α and IL-6 plasma levels under additive, dominant and recessive models (for TNF-α only). An association between Hsp70 1267 A/G SNP and zinc plasma levels was observed in the dominant model. In particular, G allele carriers showed increased circulating pro-inflammatory cytokines and zinc. Moreover, both these SNPs affect creatinine levels suggesting a possible influence on renal function. In conclusion, Hsp70 1267 A/G SNP is associated with pro-inflammatory cytokine production in healthy elderly and might represent a possible determinant of individual susceptibility to inflammatory diseases.


Assuntos
Envelhecimento/metabolismo , Citocinas/sangue , Proteínas de Choque Térmico HSP70/genética , Inflamação/sangue , Polimorfismo de Nucleotídeo Único/genética , Fator de Necrose Tumoral alfa/genética , Zinco/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Proteína C-Reativa/metabolismo , Europa (Continente) , Feminino , Frequência do Gene/genética , Genótipo , Homeostase/fisiologia , Humanos , Inflamação/genética , Masculino , Metalotioneína/metabolismo , Pessoa de Meia-Idade
7.
Int J Cardiol ; 164(1): 99-105, 2013 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-21737157

RESUMO

BACKGROUND: The functional characteristics of circulating angiogenic cells (CACs) are impaired in congestive heart failure (CHF) patients, suggesting that CAC dysfunction could contribute to CHF pathogenesis. However, the underlying mechanisms are only partly unraveled. No data are currently available regarding telomere/telomerase system in CACs of CHF patients. METHODS: CACs were obtained from 80 subjects: 40 healthy control subjects (CTR) [median age (IQR), 80 (76-85 yrs)] and 40 patients affected by post-ischemic cardiomyopathy CHF [median age (IQR), 82 (77-89)]. CAC and leukocyte telomere length, assessed as T/S ratio, and telomerase (TERT) activity were determined in all the enrolled subjects. Specificity and sensitivity of CAC and leukocyte T/S in discriminating between CHF and CTR were evaluated using Receiver Operator Characteristic (ROC) curve analysis and reported as AUC values. CD34+/VEGFR2+ number and pro-inflammatory cytokines plasma levels, such as IL-6 and TNF-α, were also measured. RESULTS: CAC T/S and TERT activity were significantly reduced in CHF patients compared to CTR subjects. In leukocytes, only a significant T/S reduction was observed. AUC values were higher for CAC T/S with respect to leukocyte T/S (AUC=0.89, and AUC=0.73, P<0.01, respectively). In multivariate analysis, leukocyte T/S, CAC T/S, CAC TERT activity and NT-proBNP levels were confirmed as parameters significantly associated with CHF. CD34+/VEGFR2+ number, IL-6 and TNF-α plasma levels were significantly increased in CHF patients. CONCLUSIONS: CACs from CHF patients are characterized by telomere/telomerase system impairment, providing new insight into the clinical relevance of CACs in CHF pathogenesis.


Assuntos
Células , Insuficiência Cardíaca/sangue , Neovascularização Fisiológica , Telomerase/fisiologia , Telômero/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
8.
J Mol Graph Model ; 26(7): 1082-90, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18023379

RESUMO

Peptidoglycan, a key constituent of bacterial cell walls, is currently the target of broad spectrum antibiotics and a new research field involves both design and synthesis of inhibitors of its biosynthesis. Most bacteria require either lysine, or its biosynthetic precursor, diaminopimelate (meso-DAP), as a component of the peptidoglycan layer of the cell wall. In this paper, molecular modelling studies were undertaken in order to shed light on the molecular basis of interaction between (2S,6S)-diaminopimelic acid (l,l-DAP) (1) with its target enzyme DAP-epimerase, since this is a key step in the lysine biosynthetic path leading to (2R,6S)-diaminopimelic acid (meso-DAP) (2). In particular, the docking of the ligand-enzyme complex was studied by means of MD simulations and DFT computations in order to ascertain the optimal structural requirements for the epimerization reaction. Molecular dynamics simulations clearly showed that the configuration of the distal carbon C6 of l,l-DAP is critical for complex formation since both amino and carboxylate groups are involved in Hbonding interactions with the active site residues. Furthermore, the interactions occurring between the functional groups bonded to the C2 and some residues of the binding cavity immobilize the ligand in a position appropriate for the epimerization reaction, i.e., exactly in the middle of the two catalytic residues Cys73 and Cys217 as confirmed by DFT quantum mechanical computation of the Michaelis complex. All this mechanistic information could be useful for the rational design of new potential antibiotic drugs effective as inhibitors of peptidoglycan biosynthesis.


Assuntos
Isomerases de Aminoácido/química , Proteínas de Bactérias/química , Simulação por Computador , Ácido Diaminopimélico/química , Modelos Moleculares , Isomerases de Aminoácido/antagonistas & inibidores , Isomerases de Aminoácido/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Domínio Catalítico , Ácido Diaminopimélico/metabolismo , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Ligação de Hidrogênio , Cinética , Estrutura Molecular , Ligação Proteica , Conformação Proteica , Especificidade por Substrato
9.
Amino Acids ; 34(2): 333-6, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17136507

RESUMO

The synthesis of an orthogonally protected constrained analogue of dipeptide DG (Asp-Gly) is reported exploiting alkylation of a chiral lactam. The versatility of this analogue was proven by removal of t-Boc protecting group, followed by coupling under homogeneous conditions with t-Boc-Arg(Z(2))-Gly, to give a conformationally restricted analogue of RGDG tetrapeptide.


Assuntos
Dipeptídeos/síntese química , Biomimética
10.
Clin Biochem ; 40(12): 887-92, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17512513

RESUMO

OBJECTIVES: A neuroinflammatory process, triggered by amyloid-beta (Abeta)-peptide, is thought to play a central role in the neurodegenerative process leading to Alzheimer's disease (AD). Abeta(25-35) retains the functionality of Abeta(42) and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) alpha1-antichymotrypsin (A1ACT) and alpha1-antitrypsin (A1AT) on fibrillar aggregation and cytotoxicity. DESIGN AND METHODS: Inhibitory concentrations of the ISPs were determined in an established human red blood cell lysis model of Abeta-cytotoxicity. For studies of Abeta-fibrillar aggregation CSF levels of A1ACT (0.041 microM)/A1AT (0.11 microM) were incubated with Congo Red dye 25 microM+Abeta(25-35) 10 microM noting the formation of visible aggregates and spectrophotometric changes over 24 h. RESULTS: A1ACT at CSF reported levels inhibited fibrillar aggregation and cytotoxicity while A1AT at CSF reported levels failed to cause a similar inhibition. CONCLUSIONS: A1ACT neutralizes fibrillar aggregation and cytotoxicity of Abeta-peptide more effectively than A1AT. Both proteins are known to be co-deposited with Abeta within senile plaques of AD brains.


Assuntos
Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , alfa 1-Antiquimotripsina/farmacologia , alfa 1-Antitripsina/farmacologia , Adulto , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/toxicidade , Morte Celular/efeitos dos fármacos , Vermelho Congo , Eritrócitos/efeitos dos fármacos , Humanos , Inflamação , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/toxicidade , Estrutura Quaternária de Proteína , Espectrofotometria
11.
Clin Biochem ; 38(12): 1112-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16183049

RESUMO

OBJECTIVES: The aim of this study was to investigate transthyretin (prealbumin) effects on Abeta25-35-induced cytotoxicity. DESIGN AND METHODS: In view of the well-recognized literature data demonstrating that Abeta25-35 fibrillar aggregates cause in vitro cytotoxicity to human red blood cells and apoptotic changes to SK-N-BE neuroblastoma cells in cultures (ultrastructural evidence), we tested transthyretin effects on these two experimental models. RESULTS: Incubation of Abeta25-35 with transthyretin (at transthyretin concentrations equal to CSF physiological levels) demonstrated both inhibition of red blood cells lysis and neutralization of SK-N-BE neuroblastoma cells ultrastructural apoptotic changes. Moreover, transthyretin was shown to be able to inhibit the formation of fibrillar macroaggregates of Abeta25-35. CONCLUSIONS: The findings imply that experimental systems investigating Abeta-induced cytotoxicity consider the protective interaction of transthyretin with Abeta; an interaction to be considered also in vivo in view of the fact that transthyretin immunoreactivity has been previously demonstrated in amyloid plaques of brains from Alzheimer's disease patients.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Eritrócitos/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Fragmentos de Peptídeos/antagonistas & inibidores , Pré-Albumina/farmacologia , Sequência de Aminoácidos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Vermelho Congo/química , Eletroforese em Gel de Poliacrilamida , Hemólise/efeitos dos fármacos , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , Neuroblastoma/patologia , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade , Pré-Albumina/análise , Sensibilidade e Especificidade , Espectrofotometria/métodos , Células Tumorais Cultivadas
12.
Eur Rev Med Pharmacol Sci ; 9(5 Suppl 1): 15-21, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16457125

RESUMO

BACKGROUND: Intragastric balloons have been proposed to induce weight loss in obese subjects. The consequences of the balloon on gastric physiology remain poorly studied. We studied the influence of an intragastric balloon on gastric emptying in obese patients. PATIENTS AND METHODS: 12 patients were included in the study, with BMI (mean +/- SD) of 38.51 +/- 4.32 kg/m2. The balloon was inserted under light anaesthesia and endoscopic control, inflated with 700 ml saline, and removed 6 months later. Body weight and gastric emptying (T1/2 and T lag) using 13C-octanoic acid breath test were monitored before balloon placement, during its permanence and 2 months after removal. RESULTS: Mean weight loss was: 6.2 +/- 2.3 kg after one month; 12.4 +/- 5.8 kg after 3 months; 14.4 +/- 6.6 kg after 6 months and 10.1 +/- 4.3 kg two months after BIB removal. Gastric emptying rates were significantly decreased in the first periods with balloon in place, and returned to pre-implantation values after balloon removal. T1/2 was: 87 +/- 32 min before BIB positioning, 181 +/- 91 min after 1 month, 145 +/- 99 min after 3 months, 104 +/- 50 min after 6 months and 90 +/- 43 min 2 months after removal. T lag was 36 +/- 18 min before BIB positioning, 102 +/- 82 min after 1 month, 77 +/- 53 min after 3 months, 59 +/- 28 min after 6 months and 40 +/- 21 min. 2 months after removal. CONCLUSIONS: BIB in obese patients seems to be a good help in following the hypo caloric diet, especially during the first three months when the gastric emptying is slower and the sense of repletion is higher. After this period gastric emptying starts to return to normal and the stomach adapts to BIB loosing efficacy in weight loss.


Assuntos
Balão Gástrico , Esvaziamento Gástrico/fisiologia , Obesidade/terapia , Adulto , Índice de Massa Corporal , Testes Respiratórios , Caprilatos/análise , Isótopos de Carbono , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia
13.
Dig Liver Dis ; 36(10): 671-6, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15506666

RESUMO

BACKGROUND: So far the reliability of the anti-guinea pig and anti-human tissue transglutaminase antibodies for the coeliac disease diagnosis has been evaluated in selected groups of patients. AIM: To compare the diagnostic accuracy of anti-human versus anti-guinea pig tissue transglutaminase in the coeliac disease screening of the general population. SUBJECTS: Two healthy Italian populations living in Marche region and in Western Sardinia. METHODS: Both anti-guinea pig and anti-human tissue transglutaminase were determined using an enzyme-linked immunosorbent assay-based commercially available kit (Eu-tTG, Eurospital, Trieste, Italy). RESULTS: During the period 1999-2001, 3541 subjects (1500 from "continental" Italy and 2041 from Sardinia) were screened for coeliac disease using both anti-guinea pig and anti-human tissue transglutaminase as first-level tests. Both these tests were negative in 3439/3541 sera, while 29 resulted positive for both of them and 73 showed discordant results. Overall, 50 intestinal biopsies were performed in 22, 21 and 7 subjects with positivity to both screening tests, to anti-guinea pig and to anti-human tissue transglutaminase alone, respectively. A coeliac disease diagnosis was made in 25 subjects giving an overall prevalence of 1:126 individuals. The anti-tissue transglutaminase specificity and sensitivity were 98 and 92% for guinea pig and 99.6 and 96% for human tissue transglutaminase, respectively. CONCLUSIONS: The anti-human tissue transglutaminase test should definitely replace the anti-guinea pig-derived one as first-level screening tool for identifying all subjects who need the second-level investigations (small intestinal biopsy).


Assuntos
Anticorpos/sangue , Doença Celíaca/diagnóstico , Transglutaminases/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doença Celíaca/sangue , Ensaio de Imunoadsorção Enzimática , Cobaias , Humanos , Itália , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Sensibilidade e Especificidade
14.
Biofactors ; 18(1-4): 299-305, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14695947

RESUMO

The aim of this study was to inquire the antioxidant status in plasma and lipoproteins isolated from normal subjects possessing different ApoE genotypes. For this purpose we investigated blood samples from 106 healthy blood donors: the distribution of ApoE alleles (E2/E2 = 0.9%, E2/E3 = 10.4%, E2/E4 = 2.8%, E3/E3 = 71.7%, E3/E4 = 12.3% and E4/E4 1.9% with 1, 11, 3, 76, 13, and 2 subjects respectively for each genotype) was in agreement with previous data. Almost no differences were found in the concentrations of both coenzyme Q10 (CoQ10) and vitamin E for the different genotypes. Concentration of CoQ10 in isolated lipoproteins was also similar, in the different genotypes, when referred to cholesterol; CoQ10 in LDL was higher for the E3/E3 subjects when referred to protein. Neither CoQ10 nor vitamin E correlated with paraoxonase (PON) activity or cholesteryl-ester hydroperoxides (CHP). Furthermore, there was no correlation between the same lipophilic antioxidants and CHP levels. The only E2 homozygous subject found had high levels of PON and low levels of CHP; the two E4/E4 subjects had low PON activity together with low levels of CHP.


Assuntos
Antioxidantes/análise , Apolipoproteínas E/genética , Ubiquinona/análogos & derivados , Ubiquinona/sangue , Alelos , Apolipoproteína E2 , Apolipoproteína E3 , Apolipoproteína E4 , Apolipoproteínas E/sangue , Arildialquilfosfatase/sangue , Doadores de Sangue , Ésteres do Colesterol/sangue , Coenzimas , Genótipo , Humanos , Peróxido de Hidrogênio/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Vitamina E/sangue
15.
Eur J Clin Invest ; 32(3): 158-62, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11895466

RESUMO

BACKGROUND: Data in the literature have not clarified whether type 2 diabetes mellitus affects homocysteine plasma levels. Different variables able to influence homocysteine could be the cause of these controversial findings. An important but neglected confounding factor is Helicobacter pylori, which has been demonstrated to be a cause of elevated levels of homocysteine and which is prevalent in the Caucasian population, ranging from 30 to 40% incidence. Starting from these findings we wanted to verify whether differences in homocysteine levels exist between a type 2 diabetic population and a control group, taking into account the presence/absence of Helicobacter pylori. DESIGN: The study was carried out on a group of uncomplicated and normotensive type 2 diabetic patients (n = 30, 55.7 +/- 9.7 years) and on a control group (n = 43, 51.2 +/- 11.3 years). On these subjects we evaluated: main parameters of glyco- and lipo-metabolic balance, presence of Helicobacter pylori by 13C Urea Breath Test, plasma homocysteine, vitamin B12, folate and genetic polymorphism of methylenetetrahydrofolate reductase. RESULTS: Evaluating the two groups as a whole, significant differences in homocysteine were found when considering Helicobacter pylori presence/absence (14.0 +/- 6.5 vs. 10.6 +/- 4.7 micromol L-1, respectively, P < 0.01) without differences of vitamins and the genetic polymorphism of methylenetetrahydrofolate reductase. The positive interaction found among Helicobacter pylori, diabetes and homocysteine (P = 0.03) taking into account all the other evaluated confounding factors, demonstrates that a significant difference in homocysteine plasma levels exists between diabetics and controls (Helicobacter pylori-negative: diabetics 12.5 +/- 5.6 micromol L-1, controls 9.4 +/- 3.8 micromol L-1; Helicobacter pylori-positive: diabetics 13.6 +/- 5.8 micromol L-1, controls 14.3 +/- 7.0 micromol L-1). CONCLUSIONS: Type 2 diabetes seems to induce per se higher levels of homocysteine, which appears to be one of the factors responsible for the increased risk of vascular damage.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Infecções por Helicobacter/sangue , Helicobacter pylori , Homocisteína/sangue , Adulto , Idoso , Diabetes Mellitus Tipo 2/genética , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Mutação Puntual
16.
Bioorg Med Chem ; 10(4): 1019-24, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11836110

RESUMO

MO theoretical calculations were used with the aim to investigate the electronic properties of a number of sulphonylureas 1-8 which are employed as antifeedants. Quantum chemical descriptors [electron density, molecular electrostatic potential (MEP), the topology of frontier orbitals and reactivity index] were determined for these compounds, aimed both to obtain a deeper insight in their mechanism of action and to correlate these properties with their activity as inhibitors of ALS synthase.


Assuntos
Herbicidas/química , Compostos de Sulfonilureia/química , Acetolactato Sintase/antagonistas & inibidores , Eletroquímica , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Compostos de Sulfonilureia/farmacologia
17.
Adv Ther ; 18(6): 261-71, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11841196

RESUMO

Systemic glucocorticosteroids have demonstrated efficacy in ulcerative colitis (UC) but cause undesired systemic side effects. Beclomethasone dipropionate (BDP) has potent topical activity and is extensively metabolized. This randomized double-blind study investigated an oral gastroresistant controlled-release preparation of BDP in 57 patients with mild to moderately severe extensive or left-sided UC. Patients were assigned to receive BDP 5 or 10 mg/d; a third group took a clinically inactive dose (1.6 g/d) of 5-aminosalicylic acid (5-ASA). Both BDP doses displayed excellent efficacy confirmed by results of endoscopy, biopsy, and clinical evaluation. Significant improvement from baseline occurred in most signs and symptoms of UC, particularly stool frequency, rectal bleeding, and mucus in the stool (P<.01). Tolerability was good in both BDP groups. Morning plasma cortisol levels decreased significantly from baseline with BDP 10 mg, but no significant changes in vital signs were observed at the end of treatment. Despite a small sample size and the open comparison with 5-ASA, this multicenter study showed the therapeutic equivalence of BDP 5 and 10 mg/d in alleviating clinical symptoms and improving endoscopic and biopsy scores in patients with mild to moderate UC. BDP 5 mg/d displayed better general tolerability and less reduction of plasma cortisol levels, however, and may be preferable to the higher dose in this indication.


Assuntos
Beclometasona/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Glucocorticoides/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Análise de Variância , Beclometasona/farmacologia , Colite Ulcerativa/patologia , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Glucocorticoides/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas
18.
J Pept Sci ; 7(12): 626-40, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11798019

RESUMO

Three linear Thr6-bradykinin analogues in which either one or both the two phenylalanine residues in the peptide sequence have been substituted by N-benzylglycine (BzlGly) and their head-to-tail cyclic analogues were synthesized and tested on an isolated rat duodenum preparation. The linear (BzlGly5,Thr6-BK, BzlGly8,Thr6-BK and BzlGly(5,8),Thr6-BK) and the cyclic (cyclo BzlGly5,Thr6-BK, cyclo BzlGly8,Thr6-BK and cyclo BzlGly(5,8),Thr6-BK) peptoid-like analogues were characterized by amino acid analysis, optical rotation, analytical HPLC and MALDI-TOF mass spectroscopy. The conformational features of both the linear and cyclic derivatives were investigated by FT-IR and CD measurements. Preliminary molecular mechanics calculations were also performed on some synthetic peptides. Pharmacological screening using the relaxation of the isolated rat duodenum preparation showed that incorporation of N-benzylglycine at positions 5 and/or 8 in the linear Thr6-BK causes a substantial decrease in potency. Comparable incorporation in cyclo Thr6-BK, at position 8, or 5 and 8, resulted in nearly inactive analogues. However, cyclo BzlGly5,Thr6-BK showed a potency which is of the same order of magnitude as for cyclo-BK and cyclo Thr6-BK.


Assuntos
Bradicinina/química , Bradicinina/síntese química , Glicina/análogos & derivados , Glicina/química , Fenilalanina/química , Treonina/química , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Biossíntese Peptídica , Peptídeos/química , Peptoides , Conformação Proteica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Proteins ; 40(1): 39-48, 2000 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10813829

RESUMO

The functions of N-acylethanolamines, minor constituents of mammalian cells, are poorly understood. It was suggested that NAEs might have some pharmacological actions and might serve as a cytoprotective response, whether mediated by physical interactions with membranes or enzymes or mediated by activation of cannabinoid receptors. Albumins are identified as the major transport proteins in blood plasma for many compounds including fatty acids, hormones, bilirubin, ions, and many drugs. Moreover, albumin has been used as a model protein in many areas, because of its multifunctional binding properties. Bovine (BSA) and human (HSA) serum albumin are similar in sequence and conformation, but differ for the number of tryptophan residues. This difference can be used to monitor unlike protein domains. Our data suggest that NOEA binds with high affinity to both albumins, modifying their conformational features. In both proteins, NOEA molecules are linked with higher affinity to hydrophobic sites near Trp-214 in HSA or Trp-212 in BSA. Moreover, fluorescence data support the hypothesis of the presence of other NOEA binding sites on BSA, likely affecting Trp-134 environment. The presence of similar binding sites is not measurable on HSA, because it lacks of the second Trp residue.


Assuntos
Etanolaminas/química , Albumina Sérica/química , Dicroísmo Circular , Fluorometria , Humanos , Modelos Moleculares , Conformação Proteica , Estrutura Terciária de Proteína , Soroalbumina Bovina/química , Triptofano/química
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