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1.
Eur J Paediatr Dent ; 24(3): 201-206, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37668462

RESUMO

AIM: In this study we present the new postoperative oro-myofunctional protocol following frenectomy by atmospheric plasma associated with a systemic postural approach, which determines functional recovery through body symmetry restoration based on the concepts of the French "Mezieres Method" and postural bench. METHODS: A total of 130 patients (76 female, 54 male) affected by ankyloglossia of class III/IV, according to Kotlow's Tongue Tie Classification have been treated with atmospheric plasma followed by oro-myofunctional therapy associated with a systemic postural approach. The overall change, improved/worsened speech, feeding, or sleep has been evaluated through the 10 points Parents Speech Satisfaction (PSS) Score after one week and two months. CONCLUSION: Based on the findings of the current investigation, myofunctional therapy in tongue-tie results in a consistent significant functional ameliorating of feeding capability, speech and sleeping of subject treated as reported with traditional oro-myofunctional therapy.


Assuntos
Anquiloglossia , Humanos , Feminino , Masculino , Terapia Miofuncional , Pais , Língua/cirurgia
2.
Sci Rep ; 11(1): 1340, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446684

RESUMO

Omega 3 polyunsaturated fatty acids (PUFAs) influence metabolism and thermogenesis in non-hibernators. How omega 3 PUFAs influence Arctic Ground Squirrels (AGS) during hibernation is unknown. Prior to hibernation we fed AGS chow composed of an omega 6:3 ratio approximately 1:1 (high in omega 3 PUFA, termed Balanced Diet), or an omega 6:3 ratio of 5:1 (Standard Rodent Chow), and measured the influence of diet on core body temperature (Tb), brown adipose tissue (BAT) mass, fatty acid profiles of BAT, white adipose tissue (WAT) and plasma as well as hypothalamic endocannabinoid and endocannabinoid-like bioactive fatty acid amides during hibernation. Results show feeding a diet high in omega 3 PUFAs, with a more balanced omega 6:3 ratio, increases AGS Tb in torpor. We found the diet-induced increase in Tb during torpor is most easily explained by an increase in the mass of BAT deposits of Balanced Diet AGS. The increase in BAT mass is associated with elevated levels of metabolites DHA and EPA in tissue and plasma suggesting that these omega 3 PUFAs may play a role in thermogenesis during torpor. While we did not observe diet-induced change in endocannabinoids, we do report altered hypothalamic levels of some endocannabinoids, and endocannabinoid-like compounds, during hibernation.


Assuntos
Tecido Adiposo Marrom/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Sciuridae/metabolismo , Termogênese/efeitos dos fármacos , Torpor/efeitos dos fármacos , Animais , Ácidos Graxos Ômega-3/metabolismo
3.
J Chem Phys ; 152(16): 164105, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32357781

RESUMO

TRAVIS ("Trajectory Analyzer and Visualizer") is a program package for post-processing and analyzing trajectories from molecular dynamics and Monte Carlo simulations, mostly focused on molecular condensed phase systems. It is an open source free software licensed under the GNU GPL, is platform independent, and does not require any external libraries. Nine years after the original publication of TRAVIS, we highlight some of the recent new functions and features in this article. At the same time, we shortly present some of the underlying algorithms in TRAVIS, which contribute to make trajectory analysis more efficient. Some modern visualization techniques such as Sankey diagrams are also demonstrated. Many analysis functions are implemented, covering structural analyses, dynamical analyses, and functions for predicting vibrational spectra from molecular dynamics simulations. While some of the analyses are known since several decades, others are very recent. For example, TRAVIS has been used to compute the first ab initio predictions in the literature of bulk phase vibrational circular dichroism spectra, bulk phase Raman optical activity spectra, and bulk phase resonance Raman spectra within the last few years.

4.
Br J Oral Maxillofac Surg ; 55(7): 703-708, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28629832

RESUMO

The aim of the present study was to evaluate retrospectively the clinical and radiographic behaviour of four commercially-available short implants with different macrodesigns and microdesigns in areas in which the height of the bone was reduced. We took into account the success and survival, peri-implant crestal bone loss, and the level of probing at which the gum bled. Patients were included if they had been given one or more short implants (≤8.5mm long) in the posterior jaws at least three years earlier. Three hundred and ninety-one short implants were placed in 170 subjects, and were divided in four groups based on the brand of implant. The implants were evaluated one, two, and three years after they had been inserted. Short implants had a three-year survival and success rate of 90% in all groups, and bone loss was acceptable after three years with no significant differences between them. These results support the use of short implants as an effective and safe treatment. However, within the limitations of this study, the design of the implant does seem to influence the behaviour of peri-implant bone at the crestal level.


Assuntos
Perda do Osso Alveolar , Implantação Dentária Endóssea , Implantes Dentários , Planejamento de Prótese Dentária , Adulto , Idoso , Perda do Osso Alveolar/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
5.
Med Oral Patol Oral Cir Bucal ; 22(4): e512-e519, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28624840

RESUMO

BACKGROUND: The aim of this systematic literature review was to evaluate the feasibility of topical bisphosphonate application for preserving/enhancing alveolar bone in oral implantology. MATERIAL AND METHODS: An electronic search was conducted in the PubMed/Medline, EMBASE, Scopus, Web of knowledge, and Google-Scholar databases for articles dated from January 2000 to December 2016. Two reviewers assessed the quality of the studies independently. RESULTS: A total of 154 abstracts were identified, of which 18 potentially relevant articles were selected; a final total of nine papers were included for analysis. Comparison of the findings of the selected studies was made difficult by the heterogeneity of the articles, all of them animal research papers that showed heterogeneity in the methodologies used and a high or moderate risk of bias. CONCLUSIONS: The topical application of bisphosphonate solution would appear to favor new bone formation in alveolar defects, and boosts the regenerative capacities of biomaterials resulting in increased bone density.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Implantação Dentária , Difosfonatos/administração & dosagem , Administração Tópica , Animais , Estudos de Viabilidade , Humanos
6.
Minerva Stomatol ; 64(1): 1-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25660589

RESUMO

AIM: The objective was to evaluate the mechanical behavior and the effects of interface abutment/implant on implants with Morse taper connections after the application of cyclic loads. METHODS: A total of 30 implants with Morse taper diameters of 4 mm and lengths of 11 mm with 30 straight solid pillars were divided into two groups. The control group (Gcon) (N.=15) was evaluated after receiving only 25 N of torque. The experimental group (Gexp) (N.=15) was subjected to torque and 360,000 cycles of mechanical fatigue at a load of 100 N and a frequency of 4 Hz. After testing, ten abutments from each group were removed from the implants to record removal torque values. The remaining five abutments/implants from each group were embedded in metallographic resin after testing and were cut along their perpendicular center axes of contact for analysis of the internal walls between the abutments and the implants. RESULTS: The removal torque increased by 19.7% (N.=29.9) for the Gexp group and decreased by 11.8% (N.=22.3) for the Gcon group, indicating a statistically significant difference (P=6.82-10) between the groups. The interface of the abutment/implant assembly was morphologically different between the Gcon group and the Gexp group. After mechanical cycling, spaces were no longer visible at the interface. CONCLUSION: After cyclic loading, the implant removal torque increased. The metallographic sections revealed that there was more contact between the inner walls of the abutment/implant sets after cyclic loading. This information is especially important in cases of single implants, because the system (abutment/implant) will have less chance of loosening.


Assuntos
Dente Suporte , Projeto do Implante Dentário-Pivô , Implantes Dentários , Torque
7.
J Biomech Eng ; 136(1): 011001, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24141522

RESUMO

Previous dynamic analyses of the temporomandibular joint (TMJ) disc have not included a true preload, i.e., a step stress or strain beyond the initial tare load. However, due to the highly nonlinear stress-strain response of the TMJ disc, we hypothesized that the dynamic mechanical properties would greatly depend on the preload, which could then, in part, account for the large variation in the tensile stiffnesses reported for the TMJ disc in the literature. This study is the first to report the dynamic mechanical properties as a function of prestress. As hypothesized, the storage modulus (E') of the disc varied by a factor of 25 in the mediolateral direction and a factor of 200 in the anteroposterior direction, depending on the prestress. Multiple constant strain rate sweeps were extracted and superimposed via strain-rate frequency superposition (SRFS), which demonstrated that the strain rate amplitude and strain rate were both important factors in determining the TMJ disc material properties, which is an effect not typically seen with synthetic materials. The presented analysis demonstrated, for the first time, the applicability of viscoelastic models, previously applied to synthetic polymer materials, to a complex hierarchical biomaterial such as the TMJ disc, providing a uniquely comprehensive way to capture the viscoelastic response of biological materials. Finally, we emphasize that the use of a preload, preferably which falls within the linear region of the stress-strain curve, is critical to provide reproducible results for tensile analysis of musculoskeletal tissues. Therefore, we recommend that future dynamic mechanical analyses of the TMJ disc be performed at a controlled prestress corresponding to a strain range of 5­10%.


Assuntos
Estresse Fisiológico/fisiologia , Disco da Articulação Temporomandibular/fisiologia , Suporte de Carga/fisiologia , Animais , Módulo de Elasticidade , Feminino , Tamanho do Órgão , Valores de Referência , Estresse Mecânico , Suínos , Disco da Articulação Temporomandibular/anatomia & histologia , Resistência à Tração , Viscosidade
8.
Int J Dent ; 2012: 489762, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22829825

RESUMO

The maxillary sinus grafting procedure has proven to be an acceptable modality for bone augmentation to provide a base for endosseous implants, routinely used for the rehabilitation of posterior maxilla. Perforation of the membrane is the most common complication in this type of procedure. This paper presents a technique for repairing a perforated Schneiderian membrane with a conjunctive connective tissue graft harvested from the palate and shows the histological and radiographic evaluation of the results. Ten consecutives cases with the occurrence of membrane perforation were included in this study. All were repaired with a flap of tissue removed from the palatine portion near to the surgical site. The technique is demonstrated through a clinical case. The results showed successful integration of 88.8% of the implants after 12 months from prosthesis installation. Histological evaluation of the samples showed that the use of nanocrystalized hydroxyapatite showed an adequate stimulation of boné neoformation within 6 months. Radiographic evaluation revealed a small apical implant bone loss, not compromising their anchorages and proservation. Thus, it can be concluded that the use of conjunctive technique with collected palate flap for sealing the perforation of the membrane of the sinus may have predictable result.

9.
Minerva Stomatol ; 61(6): 263-72, 2012 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-22669056

RESUMO

AIM: Occlusal loading has to be considered a key factor influencing bone resorption due to the stress transmitted to surrounding tissues by the implant-abutment structure. The aim of this study was to evaluate, through a photo-elastic investigation, the patterns of tensions distribution of two different implant shapes, which were cylindrical and conical. METHODS: A 100N load was applied to two implant-abutment structures (with and without a metal-ceramic crown) incorporated in photo-elastic resin. Modification in light refraction were recorded and analyzed through a computerized software. Measurements of stripe extension and position were evaluated. RESULTS: Stress distribution around tapered implant was evaluated to be more uniform than in cylindrical one which demonstrated a high stress concentration at the more cervical region and in the apical region. The presence of a metal-ceramic crown caused an increase in tensions at the implant-resin interface. CONCLUSION: Conical implants distributed stresses to a larger and well-defined volume of resin and this can cause a decrease of forces acting at the interface. This could be due to the "wedge effect" of this fixture shape which could be considered superior in terms of stress distribution than cylindrical one.


Assuntos
Implantes Dentários , Planejamento de Prótese Dentária , Análise do Estresse Dentário , Teste de Materiais
10.
J Dent Res ; 87(11): 1053-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18946014

RESUMO

Although the TMJ disc has been well-characterized under tension and compression, dynamic viscoelastic regional and directional variations have heretofore not been investigated. We hypothesized that the intermediate zone under mediolateral tension would exhibit lower dynamic moduli compared with the other regions of the disc under either mediolateral or anteroposterior tension. Specimens were prepared from porcine discs (3 regions/direction), and dynamic tensile sweeps were performed at 1% strain over a frequency range of 0.1 to 100 rad/sec. Generally, the intermediate zone possessed the lowest storage and loss moduli, and the highest loss tangent. This study further accentuates the known distinct character of the intermediate zone by showing for the first time that these differences also extend to dynamic behavior, perhaps implicating the TMJ disc as a structure primarily exposed to predominantly anteroposterior tension via anterior and posterior attachments, with a need for great distension mediolaterally across the intermediate zone.


Assuntos
Disco da Articulação Temporomandibular/fisiologia , Análise de Variância , Animais , Fenômenos Biomecânicos , Distribuição de Qui-Quadrado , Análise do Estresse Dentário , Elasticidade , Feminino , Sus scrofa , Disco da Articulação Temporomandibular/anatomia & histologia , Resistência à Tração , Viscosidade
11.
Eur J Clin Invest ; 37(5): 396-406, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17461986

RESUMO

BACKGROUND: Unquestionably viral diversity and genetic heterogeneity in hepatitis C virus (HCV) infection and other viral diseases play an essential role in viral immune escape and the development of chronicity. Despite this knowledge most vaccine approaches against HCV have excluded this important issue. Moreover the feasibility of developing an effective HCV vaccine has been questioned, mainly because prophylactic immunity against HCV cannot be achieved in chimpanzees by either vaccination or previous HCV infection, and reinfection in men has been reported, most likely due to genetic shift and immune escape. To analyse and characterize a new technique of a 'multigenotype'- and/or 'library'-vaccine, we established an envelope 1 (E1) plasmid vaccine against HCV and characterized humoral and cellular immune responses after vaccination in a mouse model. MATERIAL AND METHODS: Normally genetic information of one or two target proteins is cloned into a DNA-vaccine. In our approach we cloned a defined number of different genotypes and subtypes (defined vaccine, DV) or the genetic information from 20 patients (undefined) into a plasmid (library vaccine, LV). RESULTS: As expected, immunized animals showed both stronger humoral (ELISA) and cellular (T-cell proliferation, ELISPOT) immune responses against genotype 1, since the stimulating antigen was genotype 1 derived. However, not all genotype 1 immunized animals recognized this viral antigen leading to the assumption that some epitopes lost their immunogenicity through a change in the amino acid sequence. Interestingly, some of the genotype 4 and 5 immunized mice sera were able to react against E1 protein. CONCLUSION: Most of the assays showed immune reactivity against the DV or LV vaccine demonstrating the cross-reactive potential of such a vaccination approach. This cloning and immunization strategy based on the viral heterogeneity of the virus has in our view major implications for HCV, a virus with a broad viral genetic diversity, and may become in the future in the context of DNA- or viral-based vaccination strategies a possibility to overcome viral immune escape both in the prophylactic or therapeutic setting.


Assuntos
Hepatite C/prevenção & controle , Vacinas contra Hepatite Viral/genética , Animais , Modelos Animais de Doenças , Genótipo , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/biossíntese , Anticorpos Anti-Hepatite C/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Vacinação , Vacinas de DNA/genética , Vacinas contra Hepatite Viral/imunologia , Vacinas contra Hepatite Viral/uso terapêutico
12.
Eur J Clin Invest ; 35(10): 635-43, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16178883

RESUMO

BACKGROUND: Sex differences in drug pharmacokinetics have been well recognized and gender has been considered a risk factor for adverse events to medications. The aim of this study was to investigate the effect of gender on the expression of hepatocellular transport proteins involved in uptake and secretion of organic anions in rat. MATERIALS AND METHODS: Expression of the rat liver organic anion transporting polypeptides (Oatps) and multidrug resistance proteins (Mrps) was analysed by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis and immunofluorescence microscopy in male and female rats. Regulation of these transport proteins in response to the steroid dehydroepiandrosterone (DHEA) was investigated. RESULTS: In untreated rats, protein expression significantly differed between genders being higher (Mrp2, Mrp3), comparable [Oatp1a1 (Oatp1); Oatp1b2 (Oatp4)] or lower [Oatp1a4 (Oatp2)] in female than in male rat. DHEA treatment over 3 days (100 mg d(-1)) led to a further increase in Mrp3 expression only in female rats. Mrp2 expression was not influenced by DHEA treatment. Oatp1a1 and Oatp1b2 were significantly down-regulated after DHEA treatment in both male and female rats. In contrast, Oatp1a4 was down-regulated in male rats only. CONCLUSIONS: In rat, liver transport proteins of the Oatp and Mrp family are expressed and regulated in a gender-specific manner according to sexual differences in the hepatic metabolism of steroids and drugs. These findings may partly explain the well-known sex differences in hepatic handling of organic anions.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Fígado/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Caracteres Sexuais , Animais , Desidroepiandrosterona/farmacologia , Feminino , Imunofluorescência , Immunoblotting/métodos , Masculino , Proteínas Mitocondriais/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transportadores de Ânions Orgânicos/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteínas Ribossômicas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
Dtsch Med Wochenschr ; 130(24): 1494-6, 2005 Jun 17.
Artigo em Alemão | MEDLINE | ID: mdl-15942838

RESUMO

HISTORY: A 28 year young female presented to our hospital for further evaluation with recently diagnosed diabetes mellitus, hyperpigmentation of the skin, hepato- and splenomegaly, thrombocytopenia and an elevated transferrin saturation (96 %), but a negative test for HFE gene mutations such as C282Y and H63D. FINDINGS: Using the mini-laparascopic technique we diagnosed a smallnodular liver cirrhosis with an iron overload. DIAGNOSIS AND TREATMENT: This is the clinical presentation of one subtype of the so called Non-HFE-hemochromatosis, the juvenile hemochromatosis (HFE2). Other causes of primary and secondary iron overload have been ruled out. Different from the HFE-positive hemochromatosis (HFE 1) in which the gene defect is located on chromosome 6, the defect in HFE 2 is located on chromosome 1. The underlying genetic defect has been localized within recently identified HJV gene. Phlebotomy is the treatment of choice, to be performed until the ferritin level is lower than 50 microg/l. CONCLUSIONS: If liver cirrhosis is present in hemochromatosis, the overall risk of developing heptatocellular carcinoma is 20 times higher than in the normal population. Therefore it is suggested to perform an ultrasound examination of the liver and an AFP-test every 6 months, whereas an MRI-scan should be performed once a year, as a basis for further treatment options.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Hemocromatose/diagnóstico , Antígenos de Histocompatibilidade Classe I/genética , Hiperpigmentação/diagnóstico , Cirrose Hepática/diagnóstico , Proteínas de Membrana/genética , Transferrina/metabolismo , Adulto , Biópsia , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 6 , Análise Mutacional de DNA , Proteínas de Ligação a DNA , Diabetes Mellitus Tipo 1/genética , Feminino , Fatores de Transcrição Forkhead , Proteínas Ligadas por GPI , Hemocromatose/classificação , Hemocromatose/genética , Proteína da Hemocromatose , Humanos , Hiperpigmentação/genética , Ferro/metabolismo , Laparoscopia , Fígado/patologia , Cirrose Hepática/genética , Imageamento por Ressonância Magnética , Transativadores , Ultrassonografia
14.
Clin Genet ; 67(5): 425-8, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15811010

RESUMO

A large variety of mutations within the genes encoding hepcidin (HAMP) and hemojuvelin (HJV) have been identified in patients with the severe iron overload disorder juvenile hemochromatosis (JH). The aim of the present study was to evaluate the molecular background of JH in patients from central parts of Europe. Sequence analyses of HAMP and HJV were performed in seven JH patients from six families from Germany, Slovakia, and Croatia. For detection of the G320V mutation in HJV, a rapid polymerase chain reaction-based assay was developed. No mutations were found within the HAMP gene. Six of seven (86%) JH patients carried at least one copy of the G320V mutation within the HJV gene. Four of these patients were homozygous for the G320V mutation. In addition, two novel HJV mutations were identified (C119F and S328fsX337). Taken together, the present study demonstrates that molecular analysis of the HJV gene is a powerful tool for an early and reliable diagnosis of JH. As in affected patients from Greece, the G320V mutation seems to be widely distributed among JH patients from central parts of Europe. Therefore, detection of the G320V mutation could identify the majority of JH cases from these regions non-invasively.


Assuntos
Análise Mutacional de DNA , Hemocromatose/diagnóstico , Hemocromatose/genética , Proteínas de Membrana/genética , Adolescente , Adulto , Peptídeos Catiônicos Antimicrobianos/genética , Europa (Continente) , Feminino , Proteínas Ligadas por GPI , Genética Populacional , Proteína da Hemocromatose , Hepcidinas , Humanos , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
15.
J Endocrinol ; 184(2): 361-70, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15684344

RESUMO

It is generally accepted that iron homeostasis is mainly controlled in the gastrointestinal tract by absorption of dietary iron. However, recent studies have shown that the kidneys are also involved in iron metabolism. Since the iron-regulatory and antimicrobial peptide hormone hepcidin was originally isolated from human urine we have investigated the expression as well as the zonal and cellular localization of hepcidin in the mammalian kidney and developed an ELISA assay to analyze hepcidin concentrations in serum and urine. The expression of hepcidin was shown by RT-PCR and immunoblot experiments; its cellular localization was studied by immunocytochemistry in human, mouse and rat kidney, which revealed similar patterns of immunoreactivity. Hepcidin expression was absent from the proximal tubule and descending and ascending thin limbs. There was strong expression in the thick ascending limb of the cortex and in connecting tubules. Moderate expression was noted in the thick ascending limb and collecting ducts of the medulla and in collecting ducts of the papilla. Importantly, the cells of the macula densa were unstained. At the cellular level, hepcidin was localized to the apical cell pole of the renal epithelial cells. Based on its presence in urine, hepcidin may be released apically into the urine. Enhanced levels of hepcidin were determined in patients with chronic renal insuffciency (156.8 ng/ml, controls 104.2 ng/ml) indicating that the kidneys may metabolize and/or eliminate the circulating peptide. From the expression of hepcidin in the mammalian kidney, we have concluded that the iron-regulatory hormone is an intrinsic renal peptide which is not only eliminated by the kidney but is also synthesized in the kidney tubular system. Localization of hepcidin in the kidney implicates an iron-regulatory role of this peptide hormone in the renal tubular system, possibly in connection with the iron transporter divalent metal transporter-1.


Assuntos
Peptídeos Catiônicos Antimicrobianos/análise , Rim/química , Adulto , Animais , Peptídeos Catiônicos Antimicrobianos/biossíntese , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática/métodos , Células Epiteliais/química , Feminino , Hepcidinas , Homeostase , Humanos , Immunoblotting , Imuno-Histoquímica/métodos , Ferro/metabolismo , Rim/metabolismo , Falência Renal Crônica/metabolismo , Túbulos Renais/química , Túbulos Renais/metabolismo , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Tissue Antigens ; 64(4): 500-5, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15361129

RESUMO

Polymerase chain reaction-sequence-specific primer (PCR-SSP) typing for human leukocyte antigen (HLA)-B in a male 25-year-old Caucasian individual of Iranian origin and in a 42-year-old German Caucasian bone marrow donor revealed reaction patterns that did not agree with any known HLA specificity, thus suggesting in both cases the existence of a novel allele. Sequence-based typing (SBT) after allelic separation revealed the sequences of the new alleles HLA-B*5611 and B*3546. The sequence patterns of both new alleles might have been generated as the results of double crossing over, possibly over several generations. During the analysis of the HLA-B*3546 intron 2 sequence for possible crossing over points, a base insert, an additional G after position 700, was found. This insert was analyzed using SBT and PCR-SSP and was found to be present not only in all samples carrying B*35, but also in all HLA-B specificities tested. It appears that all known HLA-B alleles may contain a G insert at position 700 of intron 2, and that the published intron 2 sequence alignments of the HLA-B locus may contain errors at this position.


Assuntos
Alelos , Éxons/genética , Antígenos HLA-B/genética , Polimorfismo Conformacional de Fita Simples , Adulto , Sequência de Bases , Primers do DNA/genética , Alemanha , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
17.
Gut ; 53(5): 735-43, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15082594

RESUMO

BACKGROUND AND AIMS: The hepatic peptide hormone hepcidin, which has recently been isolated from human plasma and urine, is thought to be a central regulator of iron homeostasis. We investigated the presence and cellular localisation of hepcidin in the liver and developed a non-invasive assay to analyse its regulation in patients with hereditary haemochromatosis (HH), chronic renal insufficiency (CRI), and renal anaemia (RA). METHODS: Expression and localisation of hepcidin was shown by reverse transcription-polymerase chain reaction, western blot, immunocytochemistry, and immunofluorescence in human and guinea pig liver. Serum concentrations were determined in various groups of patients using a sensitive enzyme linked immunosorbent assay (ELISA). RESULTS: Western blot analysis with region specific antibodies identified a approximately 10 kDa peptide corresponding to the apparent molecular mass of pro-hepcidin. Localisation studies revealed that pro-hepcidin is expressed at the basolateral membrane domain of hepatocytes and is also present in blood. We developed a stable sensitive ELISA for detection and determination of pro-hepcidin in human serum. Mean pro-hepcidin level in human serum of healthy volunteers was 106.2 ng/ml. Enhanced levels of pro-hepcidin (148.1 ng/ml) were found in patients with CRI but normal haemoglobin values, indicating that the kidneys may metabolise and/or eliminate the circulating hormone. In contrast, concentrations of pro-hepcidin were significantly decreased in patients with HH (70.2 ng/ml) and also in patients with RA (115.0 ng/ml) compared with the CRI group. CONCLUSIONS: From the detection of pro-hepcidin in human serum, we conclude that the prohormone may be involved in the regulation of iron metabolism in HH. Decreased pro-hepcidin levels could play an important role in the pathogenesis of HH.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Hemocromatose/sangue , Fígado/metabolismo , Adulto , Sequência de Aminoácidos , Anemia/sangue , Animais , Peptídeos Catiônicos Antimicrobianos/sangue , Peptídeos Catiônicos Antimicrobianos/genética , Ensaio de Imunoadsorção Enzimática/métodos , Expressão Gênica , Cobaias , Hemocromatose/genética , Hepcidinas , Humanos , Técnicas Imunoenzimáticas , Falência Renal Crônica/sangue , Microscopia de Fluorescência , Dados de Sequência Molecular , Células Tumorais Cultivadas
18.
Diabetes Res Clin Pract ; 52(3): 175-83, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11323087

RESUMO

Oxidative stress plays a central role in the pathogenesis and progression of late microangiopathic complications (diabetic nephropathy) in diabetes mellitus. Previous studies suggested that treatment of diabetic patients with the antioxidant alpha-lipoic acid reduce oxidative stress and urinary albumin excretion. In this prospective, open and non-randomized study, the effect of alpha-lipoic acid on the progression of endothelial cell damage and the course of diabetic nephropathy, as assessed by measurement of plasma thrombomodulin and urinary albumin concentration (UAC), was evaluated in 84 patients with diabetes mellitus over 18 months. Forty-nine patients (34 with Type 1 diabetes, 15 with Type 2 diabetes) had no antioxidant treatment and served as a control group. Thirty-five patients (20 with Type 1 diabetes, 15 with Type 2 diabetes) were treated with 600 mg alpha-lipoic acid per day. Only patients with an urinary albumin concentration <200 mg/l were included into the study. After 18 months of follow up, the plasma thrombomodulin level increased from 35.9+/-9.5 to 39.7+/-9.9 ng/ml (P<0.05) in the control group. In the alpha-lipoic acid treated group the plasma thrombomodulin level decreased from 37.5+/-16.2 to 30.9+/-14.5 ng/ml (P<0.01). The UAC increased in patients without alpha-lipoic acid treatment from 21.2+/-29.5 to 36.9+/-60.6 ng/l (P<0.05), but was unchanged with alpha-lipoic acid. It is postulated that the significant decrease in plasma thrombomodulin and failure of UAC to increase observed in the alpha-lipoic acid treated group is due to antioxidative effects of alpha-lipoic acid, and if so that oxidative stress plays a central role in the pathogenesis of diabetic nephropathy. Furthermore, progression of the disease might be inhibited by antioxidant drugs. A placebo-controlled study is needed.


Assuntos
Albuminúria , Antioxidantes/uso terapêutico , Nefropatias Diabéticas/fisiopatologia , Endotélio Vascular/fisiopatologia , Ácido Tióctico/uso terapêutico , Trombomodulina/sangue , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo
19.
Gut ; 47(6): 858-60, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11076887

RESUMO

We report the case of a 52 year old male with diabetes mellitus and long standing evidence of hepatic iron excess. Initially considered to have haemochromatosis, this patient was reevaluated when hepatic iron stores were found to be unaffected by a prolonged course of weekly phlebotomy. The development of neurological disease prompted diagnostic consideration of aceruloplasminaemia, which we confirmed by demonstration of a novel frameshift mutation in the ceruloplasmin gene. Our inability to resolve the patient's iron overload by regular phlebotomy is consistent with recent animal studies indicating an essential role for ceruloplasmin in cellular iron efflux. Evaluation of this case underscores the clinical relevance of aceruloplasminaemia in the differential diagnosis of hepatic iron overload and provides insight into the pathogenetic mechanisms of hepatocellular iron storage and efflux.


Assuntos
Ceruloplasmina/deficiência , Sobrecarga de Ferro/etiologia , Ceruloplasmina/genética , Complicações do Diabetes , Diagnóstico Diferencial , Mutação da Fase de Leitura/genética , Hemocromatose/diagnóstico , Humanos , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/terapia , Masculino , Pessoa de Meia-Idade
20.
Biotechnol Appl Biochem ; 31(3): 185-96, 2000 06.
Artigo em Inglês | MEDLINE | ID: mdl-10814588

RESUMO

Triblock copolymers of the form PEO(alpha)PPO(beta)PEO(alpha) [where PEO is poly(ethylene oxide) and PPO is poly(propylene oxide)] have many biomedical applications, many of which depend on the surface properties of the copolymers and the influence that those properties have on the adsorption of proteins. As a tool to help us better understand, predict and exploit the influence of these triblock copolymers on protein adsorption, we developed a model system in which well-defined monolayers of the copolymers are supported by solid, hydrophobic, microscopic beads. At the bead/water interface, the copolymers all form stable films in which the nominal molecular areas correspond to those of the molecules when they are packed rather tightly at the air/water interface. Beads coated with condensed films of copolymers that contain short PEO segments and elicit appreciable inflammation absorb appreciable quantities of plasma proteins, including fibrinogen, from aqueous solution. Beads coated with fibrinogen aggregate when they are stirred in the presence of thrombin, a consequence of interbead fibrin formation. Beads coated with condensed films of copolymers that contain long PEO segments and elicit little inflammation absorb little plasma protein, and they do not aggregate in the presence of thrombin. Our data and observations are consistent with the prevailing notion that the utility of triblock copolymers as agents for modifying the surface properties of blood-contacting surfaces derives from the influence of the copolymers on the adsorption of plasma proteins. In this regard, the ability of the copolymers to influence fibrinogen-mediated adhesive events may be particularly important. As to the mechanism of protein resistance, our data support the proposal that sibling PEO segments of copolymers in condensed films fold back across their parental PPO cores, limiting access of proteins to the hydrophobic cores themselves.


Assuntos
Proteínas Sanguíneas/metabolismo , Teste de Materiais , Polietilenoglicóis/metabolismo , Propilenoglicóis/metabolismo , Adsorção , Fibrinogênio/metabolismo , Humanos , Microesferas , Polietilenoglicóis/química , Poliestirenos/química , Propilenoglicóis/química
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