RESUMO
PURPOSE: To describe the main causes of explantation of phakic intraocular lenses (PIOLs) according to the anatomical site of implantation (angle supported, iris fixated, or posterior chamber). METHODS: This multicentric, retrospective, and consecutive study sponsored by the Spanish Ministry of Health comprised a total of 240 eyes (226 patients) explanted due to PIOL complications. Clinical data of 144 angle-supported lenses, 24 iris-fixated lenses, and 72 posterior chamber lenses explanted were recorded preoperatively and postoperatively. RESULTS: Mean age of the patients at explantation was 46.30 ± 11.84 years (range: 25 to 80 years). The mean time between implantation and explantation was 381.14 ± 293.55 weeks (range: 0.00 to 1,551.17 weeks). It was 422.33 ± 287.81 weeks for the angle-supported group, 488.03 ± 351.95 weeks for the iris-fixated group, and 234.11 ± 4,221.60 weeks for the posterior chamber group. It was 8.10 ± 5.52 years for the angle-supported group, 9.36 ± 6.75 years for the iris-fixated group, and 4.49 ± 4.25 years for the posterior chamber group. This period of time was significantly shorter in the posterior chamber group (P < .001). Overall, the main causes of explantation were cataract formation (132 eyes, 55%), endothelial cell loss (26 eyes, 10.83%), corneal decompensation (22 eyes, 9.17%), PIOL dislocation/decentration (16 eyes, 6.67%), inadequate PIOL size or power (12 eyes, 5%), and pupil ovalization (10 cases, 4.17%). Cataract development was the cause of explantation in 51.39% of angle-supported cases, 45.83% of iris-fixated cases, and 65.28% of posterior chamber cases. Endothelial cell loss was the cause of explantation in 15.97% of angle-supported PIOLs, 8.33% of iris-fixated PIOLs, and 1.39% of posterior chamber PIOLs. CONCLUSIONS: Cataract is the main cause of PIOL explantation, especially in posterior chamber PIOLs. In the angle-supported group, endothelial cell loss was the second cause of explantation.
Assuntos
Catarata/complicações , Implante de Lente Intraocular/efeitos adversos , Miopia/cirurgia , Lentes Intraoculares Fácicas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Erros de Refração , Adulto , Idoso , Idoso de 80 Anos ou mais , Catarata/patologia , Glaucoma/complicações , Humanos , Pessoa de Meia-Idade , Miopia/complicações , Descolamento Retiniano/complicações , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The need for effective 'anti-ageing' treatments, in particular for the management of photodamaged skin, prompted us to develop a novel method to identify new active ingredients. The model utilized a gene profiling study with corresponding connectivity mapping (Cmap) to identify novel anti-ageing compounds using all-trans retinoic acid (RA) as the lead compound due to its beneficial effect on photodamaged skin and skin firmness. METHOD: A vehicle-controlled clinical study including nine healthy Caucasian female volunteers aged 57 ± 7 (mean ± SEM) exhibiting photodamage on their lower outer forearms was conducted. The volunteers applied RA once daily on photodamaged skin for 7 days, and biopsies were subjected to Affymetrix gene arrays. Connectivity mapping (Cmap), examining hundreds of gene expression profiles, was run on the gene signature of RA-treated photodamaged skin to identify small bioactive compounds. RESULTS: Affymetrix gene array identified 19 genes significantly differentially expressed after application of RA. Corresponding Cmap analysis revealed six natural bioactive compounds including N-acetyl aspartic acid (A-A-A) showing similar activity to RA on the differentially expressed genes identified. CONCLUSION: Based on RA mimicking gene array activity, potential use within skincare on molecular size, safety assessment and sourcing, we identified the natural amino acid, A-A-A as a potential candidate to treat ageing skin.
Assuntos
Envelhecimento da Pele/efeitos dos fármacos , Idoso , Ácido Aspártico/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Veículos Farmacêuticos , Tretinoína/farmacologiaRESUMO
OBJECTIVE: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. METHOD: Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. RESULTS: Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient. CONCLUSION: In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base.
Assuntos
Ácido Aspártico/análogos & derivados , Colágeno Tipo IV/metabolismo , Proteínas dos Microfilamentos/metabolismo , Absorção Cutânea , Pele/efeitos dos fármacos , Administração Tópica , Idoso , Ácido Aspártico/farmacocinética , Cromatografia Líquida , Fibrilina-1 , Fibrilinas , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Pele/metabolismo , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
BACKGROUND: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap), aiming for identification of new compounds with anti-ageing properties. OBJECTIVE: The aim of this study was to use structural activity relationship (SAR) analysis to identify a predictive mechanism of action of A-A-A. The findings from SAR will be further characterized by in vitro activity testing. Furthermore, we aimed to investigate the role of polymerized filamentous F-actin in ageing fibroblasts and to evaluate the effect of A-A-A on this model. METHODS: To predict the mode of action of A-A-A, we used the PASS computer program as a SAR model. In vitro, scratch motility tests with immortalized keratinocytes were used as a model for wound healing potential. Matrix metalloproteinase 1-3 (MMP 1-3) was analysed using multiplex protein assays (Luminex), and polymerized actin was detected by phalloidin staining in dermal fibroblasts (HDF). RESULTS: SAR analysis predicted that A-A-A would possess both epidermal and dermal activities with identification of wound healing and MMP inhibition potential. Further in vitro studies confirmed the wound healing potential using keratinocyte scratch motility assays. We were also able to confirm the dermal activities predicted by inhibition of MMP (MMP 1-3) in HDF by A-A-A. In addition, we found a positive relationship between age and F-actin expression. We also discovered that stimulation of HDF with A-A-A for 72 h significantly reduced the polymerized cytoskeletal network as visualized by inhibition of F-actin expression. In fact, A-A-A leveraged the expression of F-actin in middle-aged female fibroblasts (50 years of age) to the level of young female fibroblasts (30 years of age), corresponding to a 40% reduction in F-actin expression. CONCLUSION: Using an in silico and in vitro approach, we were able to demonstrate that A-A-A has the capacity to target different compartments of the skin through keratinocyte regeneration, MMP inhibition and relief in fibroblasts stiffness by reduction of F-actin cytoskeletal network in HDF.
Assuntos
Ácido Aspártico/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Ácido Aspártico/química , Linhagem Celular Transformada , Humanos , Técnicas In Vitro , Metaloproteinases da Matriz/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Relação Estrutura-AtividadeRESUMO
Several studies investigating the role of statins and fibrates in chronic hepatitis C virus (HCV) infection offered so far conflicting evidence regarding the antiviral potency of these medications, whereas combination of these drugs with pegylated interferon and ribavirin improved in some trials therapeutic outcome. We conducted a literature search to identify trials that included monoinfected HCV patients, treated with statins or fibrates as monotherapy with the primary end point of our meta-analysis being the quantitative change of HCV-RNA induced by these medications. Logarithmic changes of the viral load (ΔlogVL) and confidence intervals (CIs) were calculated according to the DerSimonian-Laird estimate. Statistical heterogeneity was assessed with the I² statistic. We identified eight observational studies that evaluated the potency of bezafibrate and different statins as monotherapy to induce a significant reduction of HCV-RNA in HCV-monoinfected patients (n = 281). Overall, a significant reduction of viral load with mean 0.19 [log10 IU/mL] (95%-confidence interval, (CI) 0.11-0.28) could be observed when antihyperlipidemic medications were administered. Bezafibrate featured the highest antiviral efficacy (0.45 log10 reduction, 95%-CI, 0.17-0.72) among all medications and fluvastatin (0.20 log10 reduction, 95%-CI, 0.09-0.31) among all statins tested. Based on meta-analysis, fibrates and statins induce a reduction of HCV viral load. We suggest that the addition of statins and fibrates to antiviral regimes, especially in HCV patients with concomitant dyslipidemia, could beside the established reduction of cardiovascular risk increase the potency of antiviral therapy.
Assuntos
Hepatite C Crônica/virologia , Hipolipemiantes/administração & dosagem , Carga Viral , Bezafibrato/administração & dosagem , Humanos , Pessoa de Meia-Idade , RNA Viral/sangue , Resultado do TratamentoRESUMO
A micromechanical model is presented that predicts the stiffness of wood tissues in their three principal anatomical directions, across various hardwood species. The wood polymers cellulose, hemicellulose, and lignin, common to all wood tissues, serve as the starting point. In seven homogenisation steps, the stiffnesses of these polymers are linked to the macroscopic stiffness. The good agreement of model predictions and corresponding experimental data for ten different European and tropical species confirms the functionality and accuracy of the model. The model enables investigating the influence of individual microstructural features on the overall stiffness. This is exploited to elucidate the mechanical effects of vessels and ray cells. Vessels are shown to reduce the stiffness of wood at constant overall density. This supports that a trade-off exists between the hydraulic efficiency and the mechanical support in relation to the anatomical design of wood. Ray cells are shown to act as reinforcing elements in the radial direction.
Assuntos
Modelos Biológicos , Madeira/fisiologia , Fenômenos Biomecânicos , Celulose/metabolismo , Elasticidade , Porosidade , Especificidade da Espécie , Árvores/química , Árvores/citologia , Árvores/fisiologia , Água/metabolismo , Madeira/química , Madeira/citologiaRESUMO
In this study, we developed an organoculture of human skin to investigate the effect of topical applied all-trans retinoic acid using a gene array approach. We could by using this approach confirm previous studies on genes activated by RA in keratinocyte monocultures and also provide new insights on genes that are relevant to RA-activation in human skin. The results in the present study show this model represent a valuable pre-clinical model for studying the effects of retinoids in skin.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Tretinoína/farmacologia , Adulto , Feminino , Perfilação da Expressão Gênica , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA/química , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Gênica/efeitos dos fármacos , Tretinoína/administração & dosagem , Adulto JovemRESUMO
Fluvastatin or simvastatin has demonstrable antiviral activity against hepatitis C virus (HCV) as monotherapy. The safety and efficacy of adding fluvastatin or simvastatin to peginterferon/ribavirin for 48 weeks was tested in HCV genotype 1 naïve-to-treatment veterans. Thirty-seven naïve-to-treatment genotype 1 HCV patients were randomized to either a control group (n = 20) to receive peginterferon alfa plus ribavirin or an experimental group (n = 18) to similarly receive peginterferon alfa plus ribavirin as well as fluvastatin 20 mg/day. In addition, seven patients who presented for HCV treatment already were on simvastatin and could not be withdrawn. These simvastatin users were not randomized but were entered into a concurrent prospective pilot arm. There were no unique safety issues with fluvastatin or simvastatin when these drugs were given with peginterferon/ribavirin for 48 weeks. Thirteen of 25 statin patients achieved sustained viral response (SVR), while 5 of 20 control patients achieved SVR. Analysis of SVR by intention-to-treat showed P = 0.078. In this phase 2 study, there were no safety issues with the addition of fluvastatin or simvastatin to peginterferon and ribavirin for 48 weeks. There was a trend towards improvement in SVR when fluvastatin or simvastatin was administered with peginterferon/ribavirin. The size of the groups did not reach the prestudy size thought needed to show significant difference (type II error). These results support the significant results of two other larger randomized controlled trials reported using the same dose of fluvastatin in naïve-to-treatment genotype 1 HCV patients.
Assuntos
Antivirais/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Hepatite C/tratamento farmacológico , Indóis/administração & dosagem , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Antivirais/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Ácidos Graxos Monoinsaturados/efeitos adversos , Fluvastatina , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/virologia , Humanos , Indóis/efeitos adversos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Ribavirina/efeitos adversos , Resultado do TratamentoRESUMO
Carbon dioxide (CO(2)) is an important long-range chemosensory cue used by blood-feeding female mosquitoes to find their hosts. The CO(2) receptor in Drosophila melanogaster was previously determined to be a heterodimer comprised of two gustatory receptor (Gr) proteins, DmGr21a and DmGr63a. In the mosquito Aedes aegypti, two putative orthologous genes, AaGr1 and AaGr3, were identified in the genome database, along with an apparent paralogue of AaGr1, AaGr2. In this study, RNA interference (RNAi)-mediated gene knockdown of either AaGr1 or AaGr3 resulted in a loss of CO(2) sensitivity in both male and female mosquitoes, suggesting that these two proteins, like the Drosophila orthologues, function as a heterodimer. RNAi-mediated knockdown of AaGr2 expression had no impact on CO(2) reception. All three Gr genes were expressed in the maxillary palps of both Ae. aegypti and the West Nile virus vector mosquito, Culex pipiens quinquefasciatus. Interestingly, expression of the two CO(2) receptor genes was not equivalent in the two sexes and the implications of differential sex expression of the CO(2) receptor in different species are discussed. The functional identification of the CO(2) receptor in a mosquito could prove invaluable in the strategic design of compounds that disrupt the mosquito's ability to find hosts.
Assuntos
Aedes/genética , Proteínas de Insetos/genética , Receptores de Superfície Celular/genética , Animais , Dióxido de Carbono/fisiologia , Feminino , Masculino , Interferência de RNARESUMO
PURPOSE: To evaluate the safety and efficacy during 5-year follow-up of phakic intraocular lens (PIOL) implantation to correct high anisometropia in amblyopic children who were non-compliant with traditional medical treatment including spectacles or contact lenses. METHODS: Retrospective study of 10 eyes of 10 children with high anisometropia who underwent PIOL implantation (9 with an iris-supported IOL and 1 with a posterior chamber IOL). Patient age at the time of implantation ranged from 2 to 15 years. Mean preoperative spherical equivalent refraction was -10.14 ± 6.96 diopters (D) (range: +8.00 to -18.00 D). Mean logMAR corrected distance visual acuity (CDVA) was 0.84 ± 0.52. Postoperative data at 6, 24, and 60 months were evaluated. RESULTS: Corrected distance visual acuity improved in all children. At 24 months, logMAR CDVA was 0.39 ± 0.35 and at 5 years was 0.36 ± 0.38 (range for both: 0.1 to 1.0) (P=.01). Improvement of more than three logMAR lines of CDVA was achieved in all children except for one (one line improvement) who was implanted with a posterior chamber PIOL. No loss of CDVA was detected in any patient. Five years after surgery, endothelial cell count was >2000 cells/mm(2) in eight (80%) patients; for the remaining two patients, one reported frequent eye rubbing and the other suffered ocular trauma. CONCLUSIONS: Phakic IOL implantation in children with anisometropic amblyopia showed a positive long-term impact on visual acuity.
Assuntos
Ambliopia/cirurgia , Anisometropia/cirurgia , Implante de Lente Intraocular/métodos , Lentes Intraoculares Fácicas , Refração Ocular/fisiologia , Adolescente , Ambliopia/complicações , Ambliopia/fisiopatologia , Anisometropia/complicações , Anisometropia/fisiopatologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Acuidade VisualRESUMO
PURPOSE: To evaluate and compare the clinical and confocal microscopic outcomes achieved with two different procedures for cross-linking (CXL) in eyes with keratoconus: CXL with epithelial debridement and CXL with intrastromal pocket. METHODS: This retrospective study included 27 eyes of 21 patients (age range: 18 to 53 years) diagnosed with keratoconus who underwent implantation of intracorneal ring segments and CXL with two different techniques: CXL with previous epithelial debridement (classic group, 16 eyes) and CXL with intrastromal pocket for riboflavin infusion (pocket group, 11 eyes). Visual, refractive, topographic, aberrometric, and pachymetric data were evaluated during 12-month follow-up. RESULTS: No statistically significant differences between the classic and pocket groups were found in postoperative visual acuity (P ≥.71), refraction (P ≥.15), keratometry (P ≥.28), corneal aberrations (P ≥.13), or central pachymetry (P ≥.21). A statistically significant improvement in uncorrected visual acuity found at 3 months postoperatively in both groups (P<.03) was consistent with a change in manifest sphere. Mean keratometric reduction at 12 months was 0.03 diopters (D) in the classic group (P=.55) and 0.40 D in the pocket group (P=.05). No significant changes in corneal higher order aberrations or central corneal thickness were found in either group (P ≥.14). CONCLUSIONS: Cross-linking surgery with creation of an intrastromal pocket seems to provide similar clinical outcomes compared to the classic CXL technique.
Assuntos
Reagentes de Ligações Cruzadas/administração & dosagem , Desbridamento , Epitélio Corneano/cirurgia , Ceratocone/tratamento farmacológico , Implantação de Prótese , Adolescente , Adulto , Colágeno/metabolismo , Substância Própria/efeitos dos fármacos , Substância Própria/metabolismo , Topografia da Córnea , Remoção de Dispositivo , Progressão da Doença , Seguimentos , Humanos , Ceratocone/metabolismo , Ceratocone/fisiopatologia , Microscopia Confocal , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/administração & dosagem , Refração Ocular/fisiologia , Estudos Retrospectivos , Riboflavina/administração & dosagem , Acuidade Visual/fisiologia , Adulto JovemRESUMO
BACKGROUND: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. OBJECTIVES: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. METHODS: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. RESULTS: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. CONCLUSIONS: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma
Assuntos
Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Receptores do Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Administração Oral , Adolescente , Adulto , Idoso , Antiasmáticos/efeitos adversos , Benzamidas , Edema/etiologia , Exantema/etiologia , Feminino , França , Humanos , Hidroxicorticosteroides/administração & dosagem , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Piperidinas , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Piridinas , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Resultado do TratamentoRESUMO
The mesocorticolimbic system is the reward centre of the brain and the major target for drugs of abuse including alcohol. Neuroadaptive changes in this region are thought to underlie the process of tolerance and dependence. Recently, several research groups have searched for alcohol-responsive genes using high-throughput microarrays and well-characterized human post-mortem material. Comparison of data from these studies of cortical regions highlights the differences in experimental approach and selection of cases. However, alcohol-responsive gene sets associated with transcription, oxidative stress and energy production were common to these studies. In marked contrast, alcohol-responsive genes in the nucleus accumbens and the ventral tegmental area are primarily associated with changes in neurotransmission and signal transduction. These data support the concept that, within cortical regions, changes in gene expression are associated with alcoholism-related pathology. In the dopaminergic tract of the mesocorticolimbic system, alcohol-responsive gene sets suggest long-term neuroplastic changes in synaptic transmission.
Assuntos
Alcoolismo/genética , Alcoolismo/metabolismo , Córtex Cerebral/metabolismo , Perfilação da Expressão Gênica , Proteínas do Tecido Nervoso/metabolismo , Lateralidade Funcional/genética , Lateralidade Funcional/fisiologia , Expressão Gênica , Humanos , Sistema Límbico/metabolismo , Córtex Motor/metabolismo , Proteínas do Tecido Nervoso/genética , Análise de Sequência com Séries de Oligonucleotídeos , Córtex Pré-Frontal/metabolismo , Lobo Temporal/metabolismoAssuntos
Antivirais/efeitos adversos , Ácidos Graxos Monoinsaturados/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hepacivirus/crescimento & desenvolvimento , Hepatite C/tratamento farmacológico , Indóis/efeitos adversos , Carga Viral , Antivirais/uso terapêutico , Ácidos Graxos Monoinsaturados/uso terapêutico , Fluvastatina , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C/complicações , Hepatite C/virologia , Humanos , Indóis/uso terapêutico , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Replicação Viral/efeitos dos fármacosRESUMO
AIM: To evaluate the impact of hepatitis B virus (HBV) on US health care system, we reviewed the Organ Procurement and Transplantation (OPTN, formerly UNOS) HBV database. METHOD: We reviewed records of liver transplantations (LTx) performed in the United States listed for the diagnoses of HBV between 1993 and mid-October 2004. Both acute as well as chronic cases were included. Coinfection with hepatitis C virus was excluded from study. The specific states selected for review were chosen from those areas that are receiving large numbers of new immigrants from high HBV endemic areas (ie, Texas, Pennsylvania, California, New York, and Florida). One-, 3-, and 5-year patient survival rates for both cadaveric and living related donors were analyzed. Survival rates were obtained from OPTN database as Kaplan-Meyer survival test. RESULTS: Between 1993 and mid-October 2004, 53,312 LTx had been performed nationwide. Of these, 2314 (4.34%) were performed for the diagnosis of HBV; 1816 cases (78%) were due to chronic HBV infection (45 of them were living donor LTx) and 498 cases (22%) were due to HBV-induced acute liver failure (seven of them were living donor LTx). Three- and 5-year survival rates of chronic HBV-related LTx patients were better than acute HBV-related and overall LTx patients. CONCLUSION: HBV is generally considered to have a minor health significance by many community gastroenterologists. With growing immigration from overseas, it may eventually have a higher impact on LTx. Therefore, it is crucial to further educate gastroenterologists and primary care physicians caring for this specific group of patients.
Assuntos
Hepatite B/cirurgia , Transplante de Fígado/estatística & dados numéricos , Geografia , Hepatite B/epidemiologia , Humanos , Falência Hepática/cirurgia , Falência Hepática/virologia , Prontuários Médicos , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
The human immunodeficiency virus type 1 (HIV-1) Tat protein is a key regulatory protein in the HIV-1 replication cycle. Tat interacts with cellular transcriptional factors and cytokines, such as tumor necrosis factor (TNF-alpha), and alters the expression of a variety of genes in HIV-1-infected and noninfected cells. To further elucidate the mechanisms by which HIV-1 Tat amplifies the activity of TNF-alpha, we transfected the HIV-1 tat gene into an epithelial (HeLa) cell line. We observed that Tat-expressing cells had increased NF-kappa B-dependent trans-activational activity due to enhanced NF-kappa B--DNA binding in response to TNF-alpha treatment. Tumor necrosis factor receptor (TNFR) p55 was the prominent receptor, as neutralizing antibodies to TNFR p55, but not to TNFR p75, blocked TNF-alpha-mediated NF-kappa B activation. Furthermore, tat-transfected cells were more sensitive to TNF-alpha-induced cytotoxicity and only the neutralizing antibodies to TNFR p55 completely protected the cells. To determine whether TNFR p55 was involved in amplification of cellular response to TNF-alpha by HIV-1 Tat, we investigated the effect of TNF-alpha on TNFR p55 expression in the tat-transfected cells. TNF-alpha treatment resulted in a reduction in both TNFR p55 mRNA and protein levels in the control cells but not in the tat-transfected cells as determined with Northern blot and Western blot analyses, respectively. Our results indicate that HIV-1 Tat may inhibit TNF-alpha-induced repression of TNFR p55 and thereby amplify TNF-alpha activity in these stably transfected cells.
Assuntos
Antígenos CD/metabolismo , Produtos do Gene tat/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Western Blotting , Regulação Viral da Expressão Gênica , Produtos do Gene tat/genética , HIV-1/metabolismo , Células HeLa , Humanos , NF-kappa B/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral , Ativação Transcricional , Transfecção , Fator de Necrose Tumoral alfa/farmacologia , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
Prostaglandins of the A series exhibit the most pronounced antiviral activity in cells infected with RNA or DNA viruses as compared to other prostaglandins. Clavulone is a prostaglandin A analog found in the soft coral Clavularia viridis. Using vesicular stomatitis virus in mouse L929 fibroblasts as a model system, 50% inhibition of viral yield was seen at a concentration of 1-1.5 microM, whereas 50% cytotoxicity required 50-70 times higher inhibitor concentrations. For a further elucidation of the antiviral mechanism a temperature-sensitive mutant, tsG 41, was used, which is replication-negative at the restrictive temperature. Results obtained with this mutant suggest that inhibition of VSV replication occurs at the level of transcription.
Assuntos
Antivirais/farmacologia , Prostaglandinas A/farmacologia , Vírus da Estomatite Vesicular Indiana/efeitos dos fármacos , Animais , Northern Blotting , Western Blotting , Morte Celular/efeitos dos fármacos , Técnicas In Vitro , Células L/efeitos dos fármacos , Camundongos , Estrutura Molecular , Prostaglandinas A/química , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , RNA Viral/análise , RNA Viral/genética , Ensaio de Placa Viral , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
OBJECTIVES: To define normal values of the beginning and duration of the hepatic arterial phase (HAP) during contrast-enhanced computed tomography (CT). METHODS: Twenty-five volunteers (16 men, 9 women; mean age, 60.0 years) without history or suspicion of liver disease were examined with dynamic single-section CT. Scanning was performed at a single level that included the liver, aorta, and portal vein. A series of 25 scans was obtained over a period of 88 seconds (1 baseline scan followed by 16 scans every 2 seconds and 8 scans every 7 seconds) beginning with the injection of a bolus of contrast agent (40 mL, 10 mL/s) and a 40-mL NaCl bolus chaser. Contrast enhancement in the liver, aorta, and portal vein was measured with regions of interest, and time-density curves were obtained. These data were processed with a pharmacodynamic fitting program and the duration of the HAP was calculated. The onsets of the HAP and the portal venous phase were assessed as lag times, referring to the beginning of enhancement in the abdominal aorta. RESULTS: The mean lag time of the HAP was 5.4 seconds after the aorta and the mean duration was 8.6 seconds. The mean lag time of the portal venous phase was 13.9 seconds after the aorta. CONCLUSIONS: These data can be used to optimize protocols for routine CT. Because of the short duration of the HAP, imaging of the entire liver during this phase is possible only with multidetector CT scanners.
Assuntos
Artéria Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Fígado/irrigação sanguínea , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Intensificação de Imagem Radiográfica , Fatores Sexuais , Tomografia Computadorizada por Raios X/métodosRESUMO
RATIONALE AND OBJECTIVES: To assess normal values of hepatic perfusion by dynamic, single-section computed tomography, to compare two methods of data processing (a smoothing with a fitting procedure), and to evaluate the influence of motion artifacts. METHODS: Twenty-five volunteers with no history or suspicion of liver disease were examined (age range, 32.8-81.1 years). All examinations were subjectively ranked into groups 1 through 3 according to the degree of motion artifacts (negligible, moderate, severe). All data were processed with a smoothing procedure and a pharmacokinetic fitting procedure (TopFit). The arterial, portal venous, and total hepatic perfusion; the hepatic perfusion index (HPI); and the arterial/portal venous ratio (A/P ratio) were calculated with both procedures. RESULTS: Mean hepatic perfusion, as assessed with the fitting procedure and the smoothing procedure, respectively, was as follows: arterial, 0.20 and 0.22 mL x min(-1) x mL(-1); portal venous, 1.02 and 1.24 mL x min(-1) x mL(-1); total perfusion, 1.22 and 1.47 mL x min(-1) x mL(-1); HPI, 16.4% and 15.4%; and A/P ratio, 0.20 and 0.19. The differences were significant for the portal venous and total hepatic perfusion. The portal venous and total hepatic perfusion values showed significant differences between group 1 and groups 2 and 3 for both procedures. HPI and the A/P ratio showed no significant differences at all. CONCLUSIONS: Motion artifacts and the type of data processing influence the assessment of the arterial, portal venous, and total hepatic perfusion but do not influence measurement of the HPI and the A/P ratio.
Assuntos
Artefatos , Circulação Hepática , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Movimento (Física) , Veia Porta/diagnóstico por imagem , Fatores de TempoRESUMO
Assessment of cervical status is an important component of the management of patients at risk for preterm delivery. Although digital examination is the most common method of cervical assessment, there has been recent interest in sonographic cervical examination. To compare the accuracy of digital examination and ultrasound, 20 nongravid women undergoing total hysterectomy for gynecologic indications had measurements of cervical length performed digitally and with both transabdominal and transvaginal ultrasound before surgery. These measurements were then compared with measurements made with a ruler immediately after hysterectomy. Separate examiners performed the digital, ultrasound, and ruler measurements, and each was blinded to the results of the others. Digital examination underestimated cervical length by an average of 13.6 mm and was significantly shorter than ruler measurement (P = .0001). Neither ultrasound method differed significantly from ruler measurement (P greater than .9 for each), and measurements were similar between the sonographic techniques (P greater than .9). These results validate the accuracy of sonographic estimation of cervical length. In addition, they suggest that sonographic measurement is more accurate than digital examination in predicting true cervical length. Finally, in the nonpregnant women, neither ultrasound technique seems superior to the other.