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1.
J Appl Microbiol ; 123(1): 54-65, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28502107

RESUMO

AIMS: We evaluated the potential of a nanoparticle (NP) delivery system to improve methods of delivery of candidate peptide-based vaccines for Paratuberculosis in cattle. METHODS AND RESULTS: Peptides derived from Mycobacterium avium subsp. paratuberculosis (Map), and the pro-inflammatory monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly (d,l-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with macrophages to examine their effects on survival and function. PLGA/MPLA NPs, with and without Map antigens, are efficiently phagocytized by macrophages with no evidence of toxicity. PLGA/MPLA NP formulations did not alter the level of expression of MHC I or II molecules. Expression of TNFα and IL12p40 was increased in Map-loaded NPs. T-cell proliferation studies using a model peptide from Anaplasma marginale demonstrated that a CD4 T-cell recall response could be elicited with macrophages pulsed with the peptide encapsulated in the PLGA/MPLA NP. CONCLUSIONS: These findings indicate PLGA/MPLA NPs can be used as a vehicle for delivery and testing of candidate peptide-based vaccines. SIGNIFICANCE AND IMPACT OF THE STUDY: These results will assist on more in depth studies on PLGA NP delivery systems that may lead to the development of a peptide-based vaccine for cattle.

2.
J Vet Pharmacol Ther ; 40(6): 618-628, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28387027

RESUMO

Acetylsalicylic acid (ASA, aspirin) is an antiplatelet medication used for prevention of thromboembolism. Effects of ASA appear to vary widely between dogs, but the underlying mechanisms are not understood. The Multiplate analyzer is a newer form of whole-blood impedance aggregometry recently validated for use in healthy dogs. A method utilizing this instrument to measure ASA effects on platelet function has not been established. The goals of this study were to establish reference ranges for the Multiplate in healthy dogs and secondly, to develop a technique to determine the in vitro concentration of ASA needed to cause 50% inhibition of platelet aggregation (IC50). Reference ranges established from 40 dogs at multiple test times for three agonists were consistent with previously published values. In vitro IC50 values were calculated using the sigmoid Emax model in 20 healthy dogs on two occasions to determine individual repeatability. Calculated in vitro IC50 demonstrated four ASA response groups: responder (n = 16), poor responder (n = 1), variable responder (n = 2), and nonresponder (n = 1). Multiplate within-assay variability was  <10% for area under the curve (AUC), and between-assay baseline AUC variability was  <15%. The described technique allowed for determination of an in vitro IC50 for ASA in dogs using a multiple electrode impedance aggregometer.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Cães , Relação Dose-Resposta a Droga , Impedância Elétrica , Feminino , Masculino , Valores de Referência
3.
Skin Res Technol ; 21(1): 1-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24528115

RESUMO

BACKGROUND/PURPOSE: Age, gender, regional, and ethnic differences influence skin conditions. The purpose of this study was to observe the effects of environments, especially the air temperature, relative humidity, air pressure, duration of sunshine, and precipitation on skin, and the seasonal variation in skin hydration, sebum, scales, brightness, and elasticity in Korean females. METHODS: The study included 89 Korean subjects, aged 29.7 ± 6.2 years. The five skin biophysical parameters (skin hydration, sebum, scales, brightness, and elasticity) were measured at six sites: forehead, under the eye, frontal cheek, crow's foot, lateral cheek, and inner forearm. Skin hydration was measured using the Corneometer® CM 825. Skin sebum was measured with Sebumeter® SM 815. Skin scaliness was measured with Visioscan® VC 98. Skin brightness (L* value) was measured by using Spectrophotometer. A suction chamber device, Cutometer® MPA 580, was used to measure the skin elasticity. The measurements were performed every month for 13 months, from April 2007 to April 2008. RESULTS: There were significantly seasonal variations in environmental factors. The air temperature was the lowest in January (-1.7°C), and the highest in August (26.5°C). The relative humidity was the lowest in February (46%), and the highest in July and August (75%). There was a negative correlation between skin scaliness and three environmental factors such as air temperature, relative humidity, and highest precipitation. There was a positive correlation between skin scaliness and two environmental factors such as air pressure and duration of sunshine. Elasticity was correlated with air temperature positively and with air pressure negatively. CONCLUSION: The correlations shown between the skin biophysical parameters and environmental factors demonstrate that the skin biophysical parameters are affected by environmental factors.


Assuntos
Aclimatação/fisiologia , Estações do Ano , Sebo/metabolismo , Absorção Cutânea/fisiologia , Pigmentação da Pele/fisiologia , Perda Insensível de Água/fisiologia , Adulto , Módulo de Elasticidade/fisiologia , Feminino , Humanos , Umidade , Coreia (Geográfico) , Pressão , Chuva , Temperatura , Adulto Jovem
4.
Lett Appl Microbiol ; 60(5): 431-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25631558

RESUMO

UNLABELLED: Preservative agents determining the shelf life of cosmetic products must have effective antimicrobial activity while meeting safety requirements for topical use. In this study, we determined the antimicrobial activity of 1,2-hexanediol against several Gram-positive and Gram-negative bacteria. Antimicrobial susceptibility tests have shown that 1,2-hexanediol exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria with MICs of 0·5-2% (v/v). The bactericidal concentration of 1,2-hexanediol was ranging from 1 to 2 × MIC as demonstrated by time-kill curve assay. A membrane depolarization assay showed that 1,2-hexanediol disrupted the cytoplasmic membrane potential. A checkerboard assay indicated that the effective concentration of 1,2-hexanediol was reduced up to 0·25-0·5 × MIC when combined with macelignan and octyl gallate against Gram-positive bacteria. However, this combination was not effective against Gram-negative bacteria. A turbidity reduction assay demonstrated that the combination of a high concentration of 1,2-hexanediol with food-grade antimicrobial compounds could trigger lytic activity towards Bacillus cereus cells. The remaining cell turbidity was 24·6 and 22·2% when 2% of 1,2-hexanediol was combined with 8 mg l(-1) octyl gallate or with 32 mg l(-1) macelignan respectively. This study showed that food-grade antimicrobial compounds may be used in combination with 1,2-hexanediol to increase its efficacy as a preservative agent in cosmetics. SIGNIFICANCE AND IMPACT OF THE STUDY: The antimicrobial activity of 1,2-hexanediol against Gram-positive and Gram-negative bacteria was potentiated with food-grade antimicrobials including xanthorrhizol, macelignan, panduratin A and octyl gallate, which have already been reported to display anti-inflammatory and other beneficial activities related to cosmetics. Therefore, the combination of 1,2-hexanediol and these food-grade antimicrobial agents would have benefits not only for increasing the antimicrobial activity but also in cosmetics use.


Assuntos
Antibacterianos/farmacologia , Conservantes de Alimentos/farmacologia , Glicóis/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hexanos/farmacologia , Chalconas/farmacologia , Sinergismo Farmacológico , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacologia , Lignanas/farmacologia , Testes de Sensibilidade Microbiana , Fenóis/farmacologia
5.
J Eur Acad Dermatol Venereol ; 27(12): 1521-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23216687

RESUMO

BACKGROUND: Regional and ethnic (racial) differences in skin properties are well known. However, regional and racial studies are limited and have studied skin properties using an insufficient number of subjects and limited ethnic groups, except in the case of some recent studies. OBJECTIVE: The aim of this study was (1) to compare the skin biophysical parameter among the large scale of Southeast Asia females group and (2) to compare skin properties of the forehead and cheek. METHODS: We measured and compared seven skin biophysical parameters, such as skin hydration, sebum, skin pH, melanin index, erythema index, skin elasticity and transepidermal water loss (TEWL), of the forehead and cheek of a large population of Indonesian (n = 200), Vietnamese (n = 100) and Singaporean females (n = 97). RESULTS: At the point of site difference, there were significant differences in five biophysical parameters (skin hydration, skin pH, melanin index, erythema index and skin elasticity) in Indonesian females. In Vietnamese and Singaporean women, they were significant differences in five biophysical parameters (skin hydration, skin pH, melanin index, erythema index and TEWL). At the point of ethnic difference, the Indonesian women had the highest skin pH and melanin index between the different ethnic groups. Vietnamese women had the highest skin hydration and TEWL in the forehead, whereas Singaporean women had the highest skin elasticity. CONCLUSION: The skin biophysical parameters are different between the forehead and cheek among Southeast Asian females. It also reveals that the biophysical parameters are different in same racial group.


Assuntos
Etnicidade , Face , Fenômenos Fisiológicos da Pele , Adulto , Sudeste Asiático , Biofísica , Feminino , Humanos , Adulto Jovem
6.
Phys Rev Lett ; 109(11): 112501, 2012 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-23005622

RESUMO

The ß decays of neutron-rich nuclei near the doubly magic (78)Ni were studied at the Holifield Radioactive Ion Beam Facility using an electromagnetic isobar separator. The half-lives of (82)Zn (228±10 ms), (83)Zn (117±20 ms), and (85)Ga (93±7 ms) were determined for the first time. These half-lives were found to be very different from the predictions of the global model used in astrophysical simulations. A new calculation was developed using the density functional model, which properly reproduced the new experimental values. The robustness of the new model in the (78)Ni region allowed us to extrapolate data for more neutron-rich isotopes. The revised analysis of the rapid neutron capture process in low entropy environments with our new set of measured and calculated half-lives shows a significant redistribution of predicted isobaric abundances strengthening the yield of A>140 nuclei.

7.
Diabetes Obes Metab ; 13(7): 584-93, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21320266

RESUMO

AIM: AMP-activated protein kinase (AMPK) activators have shown potential as therapeutic agents for metabolic disorders. This study was conducted to evaluate therapeutic potential of panduratin (PAN) A, a natural AMPK stimulator, with activation of PPARα/δ for the treatment of obesity. METHODS: We used the novel AMPK activator PAN A, a natural compound isolated from Boesenbergia pandurata rhizomes, to investigate the regulation of LKB1-dependent AMPK-PPARα/δ signalling by western blot, reporter gene assay and small interfering RNA knockdown analysis. In addition, the antiobesity effects of PAN A were evaluated in C57BL/6J mice with high-fat diet (HFD)-induced obesity. RESULTS: PAN A stimulated AMPK signalling, induced nuclear translocation of the AMPKα2 subunit and activated PPARα/δ; LKB1, a kinase that lies upstream of AMPK, mediated these effects. PAN A stimulated the direct binding of the AMPKα2 subunit to PPARα/δ, but PPARδ activation required direct interaction with PPARγ coactivator 1α (PGC-1α). Further, PAN A (50 mg/kg/day) reduced weight gain, fat mass, fatty liver and improved serum lipid profiles in obese mice. Additionally, PAN A reduced ectopic fat accumulation and increased the proportion of slow-twitch myofibres and mitochondria content in skeletal muscle, thereby increasing running endurance. CONCLUSIONS: PAN A, an LKB1-dependent AMPK stimulator, activated PPARα/δ and attenuated HFD-induced obesity and dysregulation of lipid metabolism. Our findings suggest that PAN A is a potent AMPK activator and show a novel molecular mechanism for the treatment of metabolic disorders.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fármacos Antiobesidade/uso terapêutico , Chalconas/uso terapêutico , Obesidade/tratamento farmacológico , PPAR alfa/metabolismo , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Animais , Western Blotting , Avaliação Pré-Clínica de Medicamentos , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , PPAR alfa/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais
8.
Endoscopy ; 42(2): 114-20, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20140828

RESUMO

BACKGROUND AND AIMS: We compared the prevalence of adenomatous and cancerous colon polyps in patients who underwent endoscopic removal of gastric neoplasms and in healthy controls. MATERIALS AND METHODS: This retrospective study reviewed the medical records of 186 patients with gastric neoplasms and 186 healthy subjects from January 2002 to October 2008. The gastric neoplasm group was comprised of patients undergoing endoscopic removal of gastric adenomas or early gastric cancers and serial fiberoptic colonoscopy (FCS) for checkups. The control group was comprised of subjects undergoing fiberoptic esophagogastroduodenoscopy (FEGD) and FCS for general checkup and was matched for age and sex with the gastric neoplasm group. Advanced colonic neoplasm was defined by any of the following: (1) the presence of three or more polyps; (2) polyp size at least 1.0 cm; (3) high-grade dysplasia or adenocarcinoma confirmed by histopathologic examination. RESULTS: Of the 372 persons, colorectal polyps were detected in 124 (33.3 %), advanced colonic neoplasms in 44 (11.8 %), and adenocarcinomas in 10 (2.7 %). The overall prevalence of adenomatous or cancerous polyps ("all polyps") and the prevalence of advanced colonic neoplasms were significantly higher in the gastric neoplasm group than in the control group (all polyps: 40.9 % in the gastric neoplasm group vs. 25.8 % in the control group, P = 0.002; advanced colonic neoplasms: 15.6 % vs. 8.1 %, P = 0.025). The risk factors for all polyps were age, male sex, diabetes mellitus, and being assigned to the gastric neoplasm group, and those for advanced colonic neoplasms were age and being assigned to the gastric neoplasm group. Confining the analysis to the gastric neoplasm group, the risk factors for all polyps were identical with those for the total group; however, those for advanced colonic neoplasm were different (age vs. diabetes and hypertriglyceridemia). CONCLUSION: Endoscopists should consider performing routine FCS in patients undergoing endoscopic removal of gastric neoplasms.


Assuntos
Adenoma/cirurgia , Pólipos do Colo/epidemiologia , Gastrectomia/métodos , Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Adenoma/complicações , Pólipos do Colo/complicações , Feminino , Seguimentos , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico
9.
Transplant Proc ; 50(10): 3222-3227, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577189

RESUMO

PURPOSE: The use of expanded-criteria deceased-donor (ECD) kidneys must be evaluated within the objective perspective of critical organ shortage and graft function and survival. In this study, we aimed to compare the clinical outcomes of ECD reliance with concurrent use of ideal-criteria deceased donors (IDDs) and non-ECDs in adult renal transplantation. METHODS: Between February 2000 and December 2015, we analyzed 405 deceased-donor renal transplants, specifically 129 grafts (31.9%) from ECDs, 233 grafts (57.5%) from non-ECDs, and 43 grafts (10.6%) from IDDs. ECDs were classified according to the United Network for Organ Sharing guidelines, while an IDD was defined as a younger person (10-39 years of age) with no medical risk factors who died from a traumatic head injury. Donor and recipient risk factors were separately analyzed and correlated with recipient graft function, and survival was evaluated. RESULTS: ECDs were older (56.8 ± 6.3 years); showed increased incidence of hypertension, diabetes, and cerebrovascular brain death; and had a higher pre-retrieval serum creatinine level than the other groups. ECD kidney recipients were also older (50.6 ± 9.8 years), had a shorter waiting time (P = .031), and demonstrated a low frequency of re-transplantation (P = .028). Long-term renal function followed longitudinally was lower in ECD kidney recipients until five years after transplantation, while the glomerular filtration rate (GFR) level at 7 and 10 years did not differ significantly among the groups (P = .074 and .262, respectively). There were no significant differences in terms of graft survival (P = .394) or patient survival (P = .737) among the groups. CONCLUSIONS: Although the long-term renal function followed longitudinally was lower in ECD kidney recipients, the use of renal grafts from ECDs is an acceptable method to resolve the disparity of critical organ shortage. However, the classification of the high-risk group should be updated with consideration given to differences in regional characteristics.


Assuntos
Transplante de Rim/métodos , Doadores de Tecidos/classificação , Doadores de Tecidos/provisão & distribuição , Adolescente , Adulto , Criança , Feminino , Sobrevivência de Enxerto , Humanos , Rim/fisiopatologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
10.
J Vet Intern Med ; 31(6): 1827-1832, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28892209

RESUMO

BACKGROUND: Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is becoming increasingly popular as an alternative immunosuppressant in feline medicine. Pharmacokinetic information is not available for cats. OBJECTIVE: The purpose of this study was to determine whether MMF is biotransformed into the active metabolite MPA and to evaluate the disposition of MPA after a 2-hour constant rate intravenous (IV) infusion of MMF in healthy cats. ANIMALS: Healthy cats (n = 6). METHODS: This was a prospective pilot study. All cats were administered MMF at 20 mg/kg every 12 hours over a 2-hour constant rate infusion for 1 day. The concentrations of MPA and its derivatives in blood were determined using a validated UHPLC-UV method. RESULTS: All cats biotransformed MMF into MPA. The mean AUC0-14 h ranged from 6 to 50 h*mg/L after IV dosing of MMF. Transient large bowel diarrhea was recorded in 2 of 6 cats after medication administration. CONCLUSION AND CLINICAL IMPORTANCE: The disposition of MPA in plasma was highly variable, which could result in high interindividual variability in the safety and efficacy of treatment with MMF in cats.


Assuntos
Imunossupressores/farmacocinética , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacocinética , Animais , Área Sob a Curva , Gatos , Diarreia/veterinária , Feminino , Imunossupressores/administração & dosagem , Infusões Intravenosas/veterinária , Masculino , Ácido Micofenólico/administração & dosagem , Projetos Piloto , Estudos Prospectivos
11.
Transplant Proc ; 49(5): 982-986, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28583572

RESUMO

PURPOSE: Our objective was to investigate the effects of age on patient and graft survival in expanded criteria donor (ECD) renal transplantation. METHODS: Between February 2000 and December 2015, we analyzed 405 deceased donor renal transplants, including 128 grafts (31.9%) from ECDs. Based on recipient age and ECD criteria classification, the recipients were divided into four groups: Group I, non-ECD to recipient age <50 years; Group II, non-ECD to recipient age ≥50 years; Group III, ECD to recipient age <50 years; and Group IV, ECD to recipient age ≥50 years. RESULTS: Among the four groups, there were significant differences in baseline characteristics (age, body mass index [BMI], cause of end-stage renal disease [ESRD], number of kidney transplantations, and use of induction agent). The mean modification of diet in renal disease (MDRD) glomerular filtration rate (GFR) level at 1 month, 6 months, 1 year, 3 years, and 5 years after transplantation was significantly lower in patients with ECDs but MDRD GFR level at 7, 9, and 10 years did not differ significantly (P = .183, .041, and .388, respectively). There were no significant differences in graft survival (P = .400) and patient survival (P = .147). CONCLUSION: Our result shows that, regardless of recipient age, kidney transplants donated by deceased ECDs have similar graft and patient survival.


Assuntos
Fatores Etários , Sobrevivência de Enxerto , Transplante de Rim/métodos , Doadores de Tecidos , Adulto , Feminino , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
12.
Transplant Proc ; 48(3): 933-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27234771

RESUMO

BACKGROUND: Femoral motor neuropathy (FMN) induced after kidney transplantation (KT) can injure the patient and graft, and it sometimes can leave sequelae on gait. Nevertheless, the cause of FMN has not been determined. We assessed 5 cases of FMN in an attempt to determine the traits induced after KT. METHODS: Patient data about general characteristics, immunologic characteristics, operative findings, post-operative status, and FMN characteristics were assessed. A Bookwalter self-retaining retractor was used and quadruple immunosuppression was implemented in all cases. RESULTS: Five patients had FMN. Four of the 5 patients were women. The mean body mass index (BMI) was 20.38 ± 1.99 kg/m(2) prior to KT and 19.08 ± 1.98 kg/m(2) after KT. The mean graft-recipient weight ratio was 3.46 ± 0.99 g/kg. There was no case of psoas muscle abscess or hematoma. Motor function recovery was obtained 3 to 313 days after rehabilitation. Immediate graft function was favorable in all patients with no rejection or significant complications. CONCLUSIONS: FMN after KT may occur in patients with a lower BMI and higher graft-recipient weight ratio. This study was based on only 5 patients, and therefore further studies with a larger population size are necessary.


Assuntos
Neuropatia Femoral/diagnóstico , Neuropatia Femoral/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Neuropatia Femoral/cirurgia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
13.
Transplant Proc ; 48(3): 770-2, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27234732

RESUMO

BACKGROUND: Patients with high panel-reactive antibody (PRA) levels before transplantation tend to remain on the waiting list longer when considering cadaveric donor transplantation and have worse outcomes than those with lower PRA levels. This study investigated the impact of the pretransplantation PRA level on rejection and graft survival after kidney transplantation in patients with a negative crossmatch (CXM(-)) and no donor-specific antibody (DSA(-)). METHODS: We retrospectively analyzed 513 recipients of kidney allograft treated from January 2009 to April 2013. Those who tested positive on crossmatching, had donor-specific antibodies, were ABO incompatible, or had no PRA level data were excluded (n = 130). The remaining patients were stratified into 3 groups according to their PRA levels: group I, PRA = 0 (314 [80.1%]); group II, PRA ≤50% (27 [7.2%]); and group III, PRA >50% (27 [7.2%]). Graft failure was defined as a return to dialysis, transplant nephrectomy, or death with a functioning kidney. RESULTS: The mean patient follow-up was 30.4 ± 4.6 months. The rejection rate was 20.1% (group I, 18.5% [n = 58] vs group II, 23.8% [n = 10] vs group III, 33.3% [n = 9] [P = .053]). The graft failure rate was 21.7% (group I, 6.4% [n = 20] vs group II. 7.1% [n = 3] vs group III, 7.4% [n = 7] [P = .792]), and the 3-year graft survival rates were 96.3, 92.4, and 92.5%, respectively (P = .851). CONCLUSIONS: The pretransplant PRA level was not significantly associated with graft survival in patients with CXM(-) and DSA(-). However, the rejection rate tended toward significance as the PRA level increased (P = .053).


Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade , Transplante de Rim , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos
14.
J Mol Biol ; 201(1): 139-59, 1988 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-3047396

RESUMO

A combination of the empirical valence bond method and a free energy perturbation approach is used to simulate the activity of genetically modified enzymes. The simulations reproduce in a semiquantitative way the observed effects of mutations on the activity and binding free energies of trypsin and subtilisin. This suggests that we are approaching a stage of quantitative structure-function correlation of enzymes. The analysis of the calculations points towards the electrostatic energy of the reacting system as the key factor in enzyme catalysis. The changes in the charges of the reacting system and the corresponding changes in "solvation" free energy (generalized here as the interaction between the charges and the given microenvironment) are emphasized. It is argued that a reliable evaluation of these changes might be sufficient for correlating structure and catalysis. The use of free energy perturbation methods and thermodynamic cycles for evaluation of solvation energies and reactivity is discussed, pointing out our early contributions. The apparent elaborated nature of our treatment is clarified, explaining that such a treatment is essential for consistent calculations of chemical reactions in polar environments. The problems associated with seemingly more rigorous quantum mechanical methods are discussed, emphasizing the inconsistency associated with using gas phase charge distributions. The importance of dynamic aspects is examined by evaluating the autocorrelation of the protein "reaction field" on the reacting substrate. It is found that, at least in the present case, dynamic effects are not important. The nature of the catalytic free energy is considered, arguing that the protein provides preoriented dipoles (polarized to stabilize the transition state charge distribution) and small reorganization energy, thus reducing the activation free energy. The corresponding catalytic free energy is related to the folding free energy, which is being invested in aligning the active site dipoles.


Assuntos
Subtilisinas , Tripsina , Sequência de Aminoácidos , Catálise , Eletricidade , Ativação Enzimática , Matemática , Modelos Químicos , Mutação , Relação Estrutura-Atividade , Termodinâmica
15.
J Histochem Cytochem ; 45(7): 991-1003, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9212825

RESUMO

Recently, we have established nine nasopharyngeal carcinoma (NPC) cell lines in which only one cell line showed the p53 mutation. For investigation of the p53 mutation in this line, immunostaining using anti-p53 antibody was applied and showed the presence of p53 protein in the cytoplasm but not in the nucleus. Single strand conformation polymorphism analysis of the p53 gene showed one normal and one additional DNA band. Cloning and sequencing of PCR-amplified DNA showed an AGA (arginine) to ACA (threonine) heterozygous point mutation at codon 280. Transfection of the p53 DNA binding sequence and chloramphenicol acetyltransferase assay revealed loss of transcriptional activation function of endogenous p53 protein. Co-localization of the endogenous and the transfected exogenous p53 protein by polyclonal antibodies to anti-p53 protein revealed strong exogenous p53 staining in the transfected nuclei and weak staining of endogenous p53 protein in the cytoplasm. We concluded that (a) a heterozygous point mutation at codon 280 was identified in the NPC-TW 06 cell line; (b) the point mutation may cause the stagnation of mutant p53 protein in the cytoplasm, and loss of its transcriptional activation function; (c) endogenous and exogenous p53 protein can be co-localized at the same time in the transfected cells; and (d) 280 mutant p53 protein in NPC cells does not cause a decrease or increase in sensitivity to chemotherapy.


Assuntos
Neoplasias Nasofaríngeas/química , Proteína Supressora de Tumor p53/análise , Biópsia , Northern Blotting , Southern Blotting , Compartimento Celular , Núcleo Celular/química , Cloranfenicol O-Acetiltransferase , Clonagem Molecular , Citoplasma/química , Genes Reporter , Humanos , Imuno-Histoquímica/métodos , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia
16.
Obstet Gynecol ; 94(5 Pt 2): 827-30, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10546745

RESUMO

BACKGROUND: Preexisting aneurysms in several arterial locations have been associated with an increased risk of rupture in pregnancy. We report a rare case of uterine artery pseudoaneurysm that presented during the puerperium. CASE: A 31-year-old woman had moderate suprapubic pain on postpartum day 8. The diagnosis of uterine artery aneurysm was made by duplex Doppler sonography and confirmed by arteriography. It was successfully treated by embolization of the left uterine artery. CONCLUSION: In a rare case of pseudoaneurysm of the uterine artery, the complications of pregnancy-related aneurysmal rupture were prevented by prompt sonographic diagnosis and embolization therapy.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Transtornos Puerperais/diagnóstico por imagem , Útero/irrigação sanguínea , Adulto , Feminino , Humanos , Radiografia , Ultrassonografia
17.
J Bone Joint Surg Br ; 82(5): 711-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10963171

RESUMO

We evaluated scapular dysplasia and malposition in 15 patients with the Sprengel deformity using three-dimensional CT (3D-CT). The shape, height-to-width ratio, the areas of both scapulae, the anterior curvature of the supraspinous portion and glenoid version were assessed on scapular posterior, medial and inferior views. The degree of rotation and superior displacement were measured on the trunk posterior view. The omovertebral connection was also assessed and correlated with the operative findings. Most of the affected scapulae had a characteristic shape with a decrease in the height-to-width ratio and were larger than the contralateral scapulae. There was an inverse relationship between scapular rotation and superior displacement. The typical curve of the supraspinous portion of the scapula was seen in only three cases. There was no significant difference in glenoid version. The point of tethering of the omovertebral connection may determine the shape, rotation and superior displacement of the scapula. 3D-CT was helpful in delineating the deformity in detail, and in planning scapuloplasty.


Assuntos
Escápula/anormalidades , Ombro/anormalidades , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Escápula/diagnóstico por imagem , Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X
18.
J Biosci Bioeng ; 88(2): 183-8, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-16232595

RESUMO

Acetobacter xylinum BRC5 was cultivated in a jar fermentor using glucose as the sole carbon source. Strain BRC5 oxidized almost all of the glucose to gluconic acid; thereafter, it biosynthesized cellulose by utilizing gluconic acid accumulated in the broth. The optimal pH for metabolizing glucose to gluconic acid was 4.0, while a pH of 5.5 was preferred for cell growth and cellulose production from the accumulated gluconic acid in the medium. Shifting the pH from 4.0 to 5.5 during the cellulose production phase in batch cultures improved cellulose production and reduced the total fermentation time, compared to batch cultures at constant pH. In constant fed-batch culture, 10 g/l of cellulose was obtained from 40 g/l of glucose, a yield which was approximately 2-fold higher than in batch culture with the same initial glucose concentration, even without control of the level of dissolved oxygen. The highest cellulose yield was obtained in fed-batch cultures in which the dissolved oxygen concentration was controlled at 10% saturation. Control of pH and dissolved oxygen to optimal levels was effective for improving the production rate and yield of cellulose, to achieve a high cellulose productivity of 0.3 g cellulose/l x h. Approximately 15 g/l of cellulose was considered to be the highest yield obtainable using conventional fermentors because the culture broth then became too viscous to allow satisfactory aeration.

19.
J Ethnopharmacol ; 84(2-3): 181-5, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12648813

RESUMO

Kuwanon G was isolated from the ethyl acetate fraction of methanol extract of Morus alba and its structure was elucidated by 13C-NMR, 1H-NMR and FAB-MS. Antibacterial activity of kuwanon G was investigated by the minimum inhibitory concentration (MIC) test and the viable cell count method. MIC of kuwanon G against Streptococcus mutans causing dental caries was determined to be 8.0 microg/ml. The bactericidal test showed that kuwanon G completely inactivated S. mutans at the concentration 20 microg/ml in 1 min. Kuwanon G also significantly inhibited the growth of other cariogenic bacteria such as Streptococcus sobrinus and Streptococcus sanguis, and Porpyromonas gingivalis causing periodontitis. Transmission electron microscopy (TEM) of kuwanon G treated cells demonstrated remarkable morphological damage of the cell wall and condensation of the cytoplasm.


Assuntos
Antibacterianos/farmacologia , Flavonoides/farmacologia , Morus/química , Antibacterianos/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/ultraestrutura , Contagem de Colônia Microbiana , Flavonoides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Microscopia Eletrônica , Casca de Planta/química , Raízes de Plantas/química , Solventes
20.
J Dermatol ; 17(12): 750-4, 1990 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2086620

RESUMO

We report a case of Wells' syndrome (eosinophilic cellulitis) with acute cutaneous swelling followed by indolent infiltration. The histopathology is characterized by a dense infiltrate of eosinophils and "flame figures" in the dermis. The electron microscopic findings are peculiar. This case responded well to oral antihistamines. The skin signs and symptoms disappeared completely two weeks later.


Assuntos
Celulite (Flegmão)/patologia , Eosinofilia/patologia , Adulto , Celulite (Flegmão)/tratamento farmacológico , Ciproeptadina/uso terapêutico , Difenidramina/uso terapêutico , Cotovelo/patologia , Eosinofilia/tratamento farmacológico , Antebraço/patologia , Humanos , Masculino , Microscopia Eletrônica
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