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1.
Cryobiology ; 113: 104588, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37813176

RESUMO

Chub (reophillic cyprinids) is one of the most sensitive bioindicator fish of environmental changes following anthropogenic activities. The improvement of different biotechnological procedures could help support its conservation and strengthen the natural populations. The aim of this study was to compare the effects of two different hormonal agents (carp pituitary extract and Ovopel™) on various motility parameters (pMOT-%, DAP-µm, VCL µm s-1, VSL-µm s-1, LIN-%, ALH-µm, BCF-Hz) of fresh and cryopreserved/thawed sperm (stored at 4 °C for 6 h). Additionally, we sought to develop a novel, large-scale cryopreservation method for chub sperm, assessing freezing methods (Styrofoam box and a controlled-rate freezer) and different containers (0.5, 5 mL straw and 4 mL cryotube) for sperm cryopreservation. The results of this study indicated no difference between the carp pituitary extract and Ovopel treated groups in either the fresh or frozen/thawed sperm (at 0, 3, 6, hour post thawing, P = 0.4351). In contrast, the quality of the thawed chub sperm was negatively affected after 3 h chilled storage in both hormonal treatments (P = 0.0036, P < 0.0001). When assessing the motility parameters of the sperm between the 5 mL straw and 4 mL cryotube groups cryopreserved in a Styrofoam Box, no difference was observed (P = 0.103). Additionally, sperm loaded in 4 mL cryotubes showed no difference in motility when cryopreserved with either the Styrofoam box or controlled-rate freezer methods (P = 0.109). A similar hatching rate was observed in sperm preserved using the Styrofoam box (35 ± 7 %) and controlled rate freezer (25 ± 9 %) methods (P = 0.300). In a second fertilization trial, hatching rate was similar between control (72 ± 19 %) and cryopreserved (4 mL cryotube and Styrofoam box, 61 ± 5 %) groups. (P = 0.257). Based on our findings and its standard features (less species specific, precise dose calculation), Ovopel can be a good candidate for the stimulation of spermiation in chub sperm prior to cryopreservation. Furthermore, our study presents a novel and applicable method for the large-scale cryopreservation of chub sperm.


Assuntos
Carpas , Cyprinidae , Preservação do Sêmen , Animais , Masculino , Criopreservação/métodos , Sêmen , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Motilidade dos Espermatozoides , Espermatozoides , Crioprotetores/farmacologia
2.
Cryobiology ; 94: 26-31, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32389624

RESUMO

In our study, a systematic development of a new large-scale sperm cryopreservation protocol was carried out in northern pike (Esox lucius). The effect of 2 sugar based (glucose and trehalose) extenders, 3 dilution ratios (1:3, 1:9 and 1:19) 2 vol straws (0.5 and 5 mL) and a 10 mL cryotube, 2 different cryopreservation methods (Polystyrene box-P. box and Controlled Rate Freezer-CRF), as well as 3 different thawing periods (3, 3.5 and 4 min) were investigated on the motility of thawed sperm. The glucose based extender showed significantly higher pMOT (1:3-18 ± 16%, 1:9-20 ± 13%, 1:19-16 ± 12%) at all dilution ratios than in the trehalose based extender (1:3-0.3 ± 1%, 1:9-1±1%, 1:19-4±2%). A similar tendency was recorded in VCL and STR at a ratio 1:3 and 1:9. No significant difference was measured in sperm movement between the P. box and CRF using the 0.5 mL straw. Similarly no significant difference was observed in all motility parameters with 10 mL cryotube frozen in CRF at a ratio 1:3-1:19. An effective and short thawing period (3 min) was experimentally specified for the 10 mL cryotube cryopreserved in the CRF. In all large-scale cryopreservation methods, high pMOT (straw CRF: 57 ± 10%, straw P. box: 50 ± 9%, cryotube CRF: 41 ± 10%), and STR were measured, and no significant difference was recorded in all motility parameters. Our results demonstrate the effectiveness of our newly developed extender and the applicability of 3 different large-scale cryopreservation methods in pike sperm. Our protocols could be new prospective candidates for future exploitation in hatchery practice.


Assuntos
Criopreservação/métodos , Esocidae , Preservação do Sêmen/métodos , Espermatozoides , Animais , Crioprotetores/farmacologia , Glucose/farmacologia , Masculino , Trealose/farmacologia
3.
Biochem Biophys Res Commun ; 519(4): 838-845, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31558321

RESUMO

Metastasis is the leading cause of mortality in patients with solid tumors. In this regard, we previously reported that Pseudopodium-Enriched Atypical Kinase One (PEAK1) is necessary for non-canonical Transforming Growth Factor ß (TGFß) signaling and TGFß/fibronectin-induced metastasis. Here, we demonstrate that inhibition of DHPS-dependent eIF5A1/2 hypusination blocks PEAK1 and E-Cadherin expression, breast cancer cell viability and TGFß/fibronectin-induced PEAK1-dependent breast cancer metastasis. Interestingly, TGFß stimulation of high-grade metastatic breast cancer cells increases and sustains eIF5A1/2 hypusination. We used a suite of bioinformatics platforms to search biochemical/functional interactions and clinical databases for additional control points in eIF5A1/2 and PEAK1-Epithelial to Mesenchymal Transition (EPE) pathways. This effort revealed that interacting EPE genes were enriched for TP53 transcriptional targets and were commonly co-amplified in breast cancer patients harboring inactivating TP53 mutations. Taken together, these results suggest that combinatorial therapies targeting DHPS and protein activities elevated in TP53-mutant breast cancers may reduce systemic tumor burden and improve patient outcomes.


Assuntos
Neoplasias da Mama/metabolismo , Fibronectinas/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/genética , Neoplasias da Mama/patologia , Caderinas/antagonistas & inibidores , Caderinas/genética , Caderinas/metabolismo , Feminino , Guanina/análogos & derivados , Guanina/farmacologia , Humanos , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/antagonistas & inibidores , Fatores de Iniciação de Peptídeos/antagonistas & inibidores , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Fator de Iniciação de Tradução Eucariótico 5A
4.
Phys Rev Lett ; 122(6): 062501, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30822069

RESUMO

New rotational bands built on the ν(h_{11/2}) configuration have been identified in ^{105}Pd. Two bands built on this configuration show the characteristics of transverse wobbling: the ΔI=1 transitions between them have a predominant E2 component and the wobbling energy decreases with increasing spin. The properties of the observed wobbling bands are in good agreement with theoretical results obtained using constrained triaxial covariant density functional theory and quantum particle rotor model calculations. This provides the first experimental evidence for transverse wobbling bands based on a one-neutron configuration, and also represents the first observation of wobbling motion in the A∼100 mass region.

5.
Cryobiology ; 81: 125-131, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29397922

RESUMO

The present study investigated the effects of chilled storage and cryopreservation on ide sperm motility and fertilizing capacity alongside the longevity of sperm movement. The parameters of motility (progressive motility-pMOT, curvilinear velocity-VCL and straightness-STR) have been recorded during 48 h of chilled storage (4 °C) at 24-h intervals. The longevity of sperm movement was measured following activation for up to 120 s (in a range at 10-120 s) in freshly stripped and thawed sperm. A formerly established cryopreservation method was tested on ide sperm where motility parameters, hatching rate and larval malformation (according to 7 category groups) were investigated. Significant decrement of pMOT has already been observed after 24 h (6 ±â€¯5%) compared to the freshly stripped sperm (49 ±â€¯22%). pMOT and STR showed no significant changes for up to 120 s following activation in fresh sperm, whereas VCL showed significant difference between 10 (51 ±â€¯11 µm/s), 90 (33 ±â€¯3 µm/s) and 120 (31 ±â€¯4 µm/s) seconds as well as between 20 (48 ±â€¯12 µm/s), and 120 s. No negative effect of cryopreservation was recorded on pMOT (fresh: 49 ±â€¯19%, cryopreserved: 22 ±â€¯22%), VCL (fresh: 45 ±â€¯9 µm/s and cryopreserved: 57 ±â€¯5 µm/s), STR (fresh: 81 ±â€¯3% and cryopreserved: 92 ±â€¯1%) hatching rate (fresh: 22 ±â€¯15%, cryopreserved: 33 ±â€¯18%) or larval malformation (fresh: 12 ±â€¯4%, cryopreserved: 12 ±â€¯4%). No significant correlation was found between the three motility parameters and hatching rate. Cryopreservation had no effect on hatching and the prevalence of larval deformity. Furthermore craniofacial and eye deformities were characteristic in the group originating from fertilization with cryopreserved sperm, while edemas (pericardial, yolk) occurred more frequently in the control. The formerly developed cryopreservation protocol (method for cyprinids) was applicable to ide sperm.


Assuntos
Criopreservação/veterinária , Cyprinidae , Preservação do Sêmen/veterinária , Animais , Fertilização , Masculino , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia
6.
BMC Bioinformatics ; 18(1): 73, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28143617

RESUMO

BACKGROUND: Detection of somatic mutations is one of the main goals of next generation DNA sequencing. A wide range of experimental systems are available for the study of spontaneous or environmentally induced mutagenic processes. However, most of the routinely used mutation calling algorithms are not optimised for the simultaneous analysis of multiple samples, or for non-human experimental model systems with no reliable databases of common genetic variations. Most standard tools either require numerous in-house post filtering steps with scarce documentation or take an unpractically long time to run. To overcome these problems, we designed the streamlined IsoMut tool which can be readily adapted to experimental scenarios where the goal is the identification of experimentally induced mutations in multiple isogenic samples. METHODS: Using 30 isogenic samples, reliable cohorts of validated mutations were created for testing purposes. Optimal values of the filtering parameters of IsoMut were determined in a thorough and strict optimization procedure based on these test sets. RESULTS: We show that IsoMut, when tuned correctly, decreases the false positive rate compared to conventional tools in a 30 sample experimental setup; and detects not only single nucleotide variations, but short insertions and deletions as well. IsoMut can also be run more than a hundred times faster than the most precise state of art tool, due its straightforward and easily understandable filtering algorithm. CONCLUSIONS: IsoMut has already been successfully applied in multiple recent studies to find unique, treatment induced mutations in sets of isogenic samples with very low false positive rates. These types of studies provide an important contribution to determining the mutagenic effect of environmental agents or genetic defects, and IsoMut turned out to be an invaluable tool in the analysis of such data.


Assuntos
Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Software , Algoritmos , Genômica/métodos , Humanos , Mutação , Deleção de Sequência
7.
Nature ; 469(7328): 68-71, 2011 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-21179086

RESUMO

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.

8.
J Anim Breed Genet ; 130(4): 312-20, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23855633

RESUMO

The genetic relationship between 195 Mangalica and 79 non-Mangalica pigs was studied using mitochondrial D-loop SNP genotyping. Altogether, 35 polymorphic sites and 27 haplotypes were identified. Of the haplotypes, eight and 16 are Mangalica and non-Mangalica specific, respectively, while three contain both Mangalica and non-Mangalica individuals. Genetic distance values and phylogenetic analysis indicate that Mangalica individuals are very closely related, and five haplotypes represent approximately 92% of the Mangalica pigs involved in the study, thus determining the major maternal lineages. In contrast to previous microsatellite studies, individuals of Mangalica could not be distinguished as three separate breeds using mtDNA genotyping. Comparing modern and archaeological mtDNA sequences revealed that present day Mangalica is related to pigs that lived in the Carpathian basin where postulated ancestors of Mangalica also lived. This is the first DNA-based genetic evidence to support the described breeding history of Mangalica.


Assuntos
DNA Mitocondrial/química , DNA Mitocondrial/genética , Filogenia , Polimorfismo de Nucleotídeo Único , Sus scrofa/genética , Animais , Evolução Molecular , Feminino , Técnicas de Genotipagem
9.
Eur J Clin Microbiol Infect Dis ; 31(6): 1243-50, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21997771

RESUMO

Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella. The present study was designed to ascertain whether this drug could efficiently augment the action of an antibiotic or a non-antibiotic when tested in combination. A total of 12 bacterial strains belonging to various genera were selected for this study and were sensitive to the antibiotics penicillin (Pc), ampicillin, chloramphenicol, tetracycline, streptomycin, gentamicin, erythromycin, ciprofloxacin, and to the non-antibiotics methdilazine, triflupromazine, promethazine, and Fp. Pronounced and statistically significant synergism (p < 0.01) was observed when Fp was combined with Pc following the disc diffusion assay system. With the help of the checkerboard method, the fractional inhibitory concentration (FIC) index of this pair was found to be 0.375, confirming synergism. This pair of Fp+ Pc was then subjected to in vivo experiments in mice challenged with Salmonella enterica serovar Typhimurium NCTC 74. Statistical analysis of the mouse protection test suggested that this combination was highly synergistic (p < 0.001, Chi-squared analysis). Fp also revealed augmentation of its antimicrobial property when combined with streptomycin, gentamicin, ciprofloxacin, and the non-antibiotic methdilazine. The results of this study may provide alternatives for the therapy of problematic infections such as those associated with Salmonella spp.


Assuntos
Antibacterianos/farmacologia , Antipsicóticos/farmacologia , Bactérias/efeitos dos fármacos , Sinergismo Farmacológico , Flupentixol/farmacologia , Animais , Antibacterianos/administração & dosagem , Antipsicóticos/administração & dosagem , Modelos Animais de Doenças , Flupentixol/administração & dosagem , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Salmonelose Animal/tratamento farmacológico , Resultado do Tratamento
10.
JEMS ; 37(11): 36, 41, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23718094

RESUMO

Driving an EMS rig in winter conditions requires patience and slowing down, but many times operators get in trouble because they simply exceed the operating capabilities of their rig in the given conditions. This can stem from over confidence, but it can also come from lack of training. We'd like to believe otherwise, but we're susceptible to the same perils as the ordinary driver, and having decals on the side of our truck doesn't change that. So take the time to know your rig before heading out into the wintry muck, and make sure you have enough supplies and equipment should you inadvertently find yourself part of the problem rather than the solution. Above all, know your own driving limitations and give yourself the buffer you need. Getting there slowly is better than not getting there at all.


Assuntos
Ambulâncias , Serviços Médicos de Emergência , Tempo (Meteorologia) , Desenho de Equipamento , Humanos
11.
Sci Adv ; 7(4)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523947

RESUMO

One of the most intriguing questions in vertebrate evolution is how tetrapods gained the ability to walk on land. Although many hypotheses have been proposed, few have been rigorously tested using the fossil record. Here, we build three-dimensional musculoskeletal models of the pectoral appendage in Eusthenopteron, Acanthostega, and Pederpes and quantitatively examine changes in forelimb function across the fin-to-limb transition. Through comparison with extant fishes and tetrapods, we show that early tetrapods share a suite of characters including restricted mobility in humerus long-axis rotation, increased muscular leverage for humeral retraction, but not depression/adduction, and increased mobility in elbow flexion-extension. We infer that the earliest steps in tetrapod forelimb evolution were related to limb-substrate interactions, whereas specializations for weight support appeared later. Together, these results suggest that competing selective pressures for aquatic and terrestrial environments produced a unique, ancestral "early tetrapod" forelimb locomotor mode unlike that of any extant animal.

12.
Br J Cancer ; 103(2): 178-85, 2010 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-20551959

RESUMO

BACKGROUND: The multidrug resistance (MDR) proteins are present in a majority of human tumours. Their activity is important to understand the chemotherapeutic failure. A search for MDR-reversing compounds was conducted among various Betti-base derivatives of tylosin. METHODS: Here, we evaluate the in vitro and in vivo P-glycoprotein (P-gp)-modulating activity of the most promising compound N-tylosil-1-alpha-amino-(3-bromophenyl)-methyl-2-naphthol (TBN) using human MDR1 gene-transfected and parental L5178 mouse lymphoma cell lines. RESULTS: In vitro experiments showed that TBN dramatically increased the P-gp-mediated cellular uptake of the fluorescent substrate rhodamine 123. Similarly, TBN was found to act as a very potent enhancer of the cytotoxicity of doxorubicin on the resistant cell line. We also provide in vivo evidence using DBA/2 mice in support for an increased tumoural accumulation of doxorubicin, without affecting its tissue distribution, resulting in an enhanced antitumoural effect. CONCLUSION: Our results suggest that TBN is a potent modulator of the P-gp membrane pump and that the compound could be of clinical relevance to improve the efficacy of chemotherapy in MDR cancers.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Doxorrubicina/uso terapêutico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lactonas/farmacologia , Naftóis/farmacologia , Tilosina/análogos & derivados , Tilosina/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Camundongos , Camundongos Endogâmicos DBA , Rodamina 123/metabolismo , Transfecção , Tilosina/química , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Cell Biol ; 87(2 Pt 1): 427-33, 1980 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7430249

RESUMO

The present study demonstrates the ability of plasma fibronectin or cold-insoluble globulin (Clg) to promote the uptake of 125I-labeled, gelatin-coated latex beads (g-Ltx*) by monolayers of peritoneal macrophages (PM). The uptake of g-Ltx* by PM was enhanced by Clg in a concentration-dependent fashion and required the presence of heparin (10 U/ml) as an obligatory cofactor for maximal particle uptake. Treatment of PM monolayers with trypsin (1 mg/ml) for 15 min at 37 degrees C after particle uptake removed less than 15% of the radioactivity incorporated by the monolayers. However, a similar trypsin treatment of the monolayers before the addition of latex particles depressed Clg-dependent uptake by greater than 75%. Pretreatment of PM monolayers with inhibitors of glycolysis effectively reduced the Clg-dependent uptake of latex. Similarly, pretreatment of monolayers with either inhibitors of protein synthesis or agents that disrupt cytoskeletal elements also significantly depressed Clg-dependent particle uptake. Phagocytosis of g-Ltx* by PM in the presence of Clg and heparin was confirmed by electron microscopy. Finally, g-Ltx* could also be effectively opsonized with Clg at 37 degrees C before their addition to the monolayers. These studies suggest that the recognition of g-Ltx* in the presence of Clg required cell surface protein(s) and that subsequent phagocytosis of these particles by PM was energy dependent and required intact intracellular cytoskeleton elements. Thus, PM monolayers provide a suitable system for further studies on the function of Clg in the recognition and phagocytosis of gelatin-coated particles by phagocytic cells.


Assuntos
Fibronectinas/fisiologia , Macrófagos/fisiologia , Fagocitose , Animais , Líquido Ascítico/citologia , Colchicina/farmacologia , Cicloeximida/farmacologia , Citocalasina B/farmacologia , Gelatina , Látex , Masculino , Microesferas , Fagocitose/efeitos dos fármacos , Puromicina/farmacologia , Ratos
14.
Exp Oncol ; 41(4): 291-299, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31868338

RESUMO

Chaos theory (nonlinear dynamics) defines cancer as a complex adaptive system in which each cyclic point corresponds to the bifurcation at which changes in signaling pathways emerge. Quantitative assessment of chaos in digital medical images such as electron microscopy, histology and cytology sections collected from patients with malignant cutaneous melanoma employed the following calculation parameters: the irregularity of external contours, internal heterogeneity based on brightness distribution of macromo-lecules, chromosomes, organelles, inclusion bodies, cells and tissues, kurtosis, entropy and the asymmetry coefficient. The present study undertook a nonlinear analysis of the chaotic hierarchy of malignant melanoma. However, considerably more studies will need to be carried out to determine the exact interrelationship between different levels of the hierarchy in the biological system. Multidisciplinary collaborations are therefore essential to find evidence to answer questions that remain open to researchers and oncologists.


Assuntos
Melanoma/patologia , Modelos Biológicos , Dinâmica não Linear , Neoplasias Cutâneas/patologia , Humanos , Melanoma/metabolismo , Transdução de Sinais , Neoplasias Cutâneas/metabolismo
15.
Burns ; 45(4): 772-782, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30578048

RESUMO

INTRODUCTION: Split-thickness skin grafts (STSG) are the standard of care (SOC) for burns undergoing autografting but are associated with donor skin site morbidity and limited by the availability of uninjured skin. The RECELL® Autologous Cell Harvesting Device (RECELL® System, or RECELL) was developed for point-of-care preparation and application of a suspension of non-cultured, disaggregated, autologous skin cells, using 1cm2 of the patient's skin to treat up to 80cm2 of excised burn. METHODS: A multi-center, prospective, within-subject controlled, randomized, clinical trial was conducted with 30 subjects to evaluate RECELL in combination with a more widely meshed STSG than a pre-defined SOC meshed STSG (RECELL treatment) for the treatment of mixed-depth burns, including full-thickness. Treatment areas were randomized to receive standard meshed STSG (Control treatment) or RECELL treatment, such that each subject had 1 Control and 1 RECELL treatment area. Effectiveness measures were assessed and included complete wound closure, donor skin use, subject satisfaction, and scarring outcomes out to one year following treatment. RESULTS: At 8 weeks, 85% of the Control-treated wounds were healed compared with 92% of the RECELL-treated wounds, establishing the non-inferiority of RECELL treatment for wound healing. Control-treated and RECELL-treated wounds were similar in mean size; however, mean donor skin use was significantly reduced by 32% with the use of RECELL (p<0.001), establishing the superiority of RECELL treatment for reducing donor skin requirements. Secondary effectiveness and safety outcomes were similar between the treatments. CONCLUSIONS: In combination with widely meshed STSG, RECELL is a safe and effective point-of-care treatment for mixed-depth burns without confluent dermis, achieving short- and long-term healing comparable to standard STSG, while significantly decreasing donor skin use.


Assuntos
Queimaduras/terapia , Transplante de Células/métodos , Transplante de Pele/métodos , Cicatrização , Adolescente , Adulto , Idoso , Criança , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Pele/citologia , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto Jovem
16.
Diabetes Obes Metab ; 10(1): 41-52, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18095949

RESUMO

AIM: The aim of this study was to determine the role of tissue angiotensin-converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure in randomized placebo-controlled clinical trials using pooled meta-analysis techniques. METHODS: Randomized placebo-controlled clinical trials of at least 12 months duration in patients with diabetes mellitus without left ventricular systolic dysfunction or heart failure who had experienced a prior cardiovascular event or were at high cardiovascular risk were selected. A total of 10 328 patients (43 517 patient-years) from four selected trials were used for meta-analysis. Relative risk estimations were made using data pooled from the selected trials and statistical significance was determined using the Chi-squared test (two-sided alpha error <0.05). The number of patients needed to treat was also calculated. RESULTS: Tissue ACE inhibitors significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022), myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary revascularization by 14% (p = 0.015) when compared to placebo. The risk of all-cause mortality also tended to be lower among patients randomized to tissue ACE inhibitors, whereas the risks of stroke and hospitalization for heart failure were not significantly affected. Treating about 65 patients with tissue ACE inhibitors for about 4.2 years would prevent one myocardial infarction, whereas treating about 85 patients would prevent one cardiovascular death. CONCLUSION: Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue ACE inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiopatias Diabéticas/prevenção & controle , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento
17.
Int J Radiat Biol ; 94(11): 985-995, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30332320

RESUMO

PURPOSE: The recent rapid increase of hadron therapy applications requires the development of high performance, reliable in vivo models for preclinical research on the biological effects of high linear energy transfer (LET) particle radiation. AIM: The aim of this paper was to test the relative biological effectiveness (RBE) of the zebrafish embryo system at two neutron facilities. MATERIAL AND METHODS: Series of viable zebrafish embryos at 24-hour post-fertilization (hpf) were exposed to single fraction, whole-body, photon and neutron (reactor fission neutrons () and (p (18 MeV)+Be, = 3.5 MeV) fast neutron) irradiation. The survival and morphologic abnormalities of each embryo were assessed at 24-hour intervals from the point of fertilization up to 192 hpf and then compared to conventional 6 MV photon beam irradiation results. RESULTS: The higher energy of the fast neutron beams represents lower RBE (ref. source LINAC 6 MV photon). The lethality rate in the zebrafish embryo model was 10 times higher for 1 MeV fission neutrons and 2.5 times greater for p (18 MeV)+Be cyclotron generated fast neutron beam when compared to photon irradiation results. Dose-dependent organ perturbations (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, pericardial edema and inhibition of yolk sac resorption) and microscopic (marked cellular changes in eyes, brain, liver, muscle and the gastrointestinal system) changes scale together with the dose response. CONCLUSION: The zebrafish embryo system is a powerful and versatile model for assessing the effect of ionizing radiation with different LET values on viability, organ and tissue development.


Assuntos
Embrião não Mamífero/efeitos da radiação , Transferência Linear de Energia , Peixe-Zebra/embriologia , Animais , Nêutrons/efeitos adversos , Fótons/efeitos adversos , Eficiência Biológica Relativa , Análise de Sobrevida
18.
Med Chem ; 2(6): 565-8, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17105437

RESUMO

Physicochemical characteristics of two structurally different cage dimeric 1,4-dihydropyridines HX (1) and CC (2) have been determined and compared to their P-glycoprotein inhibiting properties. While the weakly basic compound (1) showed pH-dependent apparent partition coefficients (log D), the neutral compound (2) proved to have almost identical log D values at varying pH-values. The subsequent determination of partition coefficients (log P) resulted in comparably low log P values revealing a less lipophilic compound character. Determined significantly differing P-glycoprotein (P-gp) inhibitory properties indicated that the lipophilicity of the compounds does not play a decisive role for the P-gp activity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Di-Hidropiridinas/química , Di-Hidropiridinas/farmacologia , Dimerização , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Relação Estrutura-Atividade
19.
Eat Weight Disord ; 11(4): 195-200, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17272949

RESUMO

The purpose of this study was to replicate and expand upon previous research that has examined the potential association between vegetarianism and disordered eating. Limitations of previous research studies are addressed, including possible low reliability of measures of eating pathology within vegetarian samples, use of only a few dietary restraint measures, and a paucity of research examining potential differences in body image and food choice motives of vegetarians versus nonvegetarians. Two hundred and fifty-six college students completed a number of measures of eating pathology and body image, and a food choice motives questionnaire. Interestingly, no significant differences were found between vegetarians and nonvegetarians in measures of eating pathology or body image. However, significant differences in food choice motives were found. Implications for both researchers and clinicians are discussed.


Assuntos
Dieta Vegetariana , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Adolescente , Adulto , Imagem Corporal , Comportamento de Escolha , Comportamento Alimentar , Feminino , Humanos , Inquéritos e Questionários
20.
Biochim Biophys Acta ; 886(1): 33-9, 1986 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-3955079

RESUMO

Tryptophan, phenylalanine and leucine have two parallel effects in cultured lymphocytes, they inhibit cellular proteolysis and increase the translocation of non-histone proteins to the nucleus. The latter is associated with an increased cellular binding of [3H]actinomycin D, indicating an altered structure of chromatin. The amino acids also inhibit the cellular uptake of [3H]chloroquine, suggesting that inhibited protein degradation is lysosomal. Several amine catabolites of tryptophan and phenylalanine, some of which are known to play a role as biogenic amines, have similar actions, and can explain, at least in part, the effects of their parent amino acids. Fractionation of the nuclear 3H-labeled non-histone proteins according to pH 2.5-6.5 shows that such proteins with a high rate of degradation in untreated cells correspond to the 3H-labeled non-histone proteins with a high rate of translocation in tryptophan treated cells. These data suggest that the degradation and the translocation of the non-histone proteins are linked and that the increased translocation of the non-histone proteins to the nucleus may be the consequence of inhibited lysosomal degradation of these proteins by the amino acids.


Assuntos
Núcleo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Leucina/farmacologia , Linfócitos/metabolismo , Fenilalanina/farmacologia , Proteínas/metabolismo , Triptofano/farmacologia , Aminoácidos/metabolismo , Transporte Biológico , Células Cultivadas , Cloroquina/metabolismo , Dactinomicina/metabolismo , Humanos , Cinética , Biossíntese de Proteínas , Trítio
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