RESUMO
Historically, patients who received bilateral sagittal split osteotomies (BSSO) required an inpatient admission for at least one night. Since March 2015, the Oral and Maxillofacial Department at the Royal Gwent Hospital has performed bilateral sagittal split osteotomies (BSSO) as a day case procedure for their medically and socially fit patients. Our team's service evaluation by Davies et al (2018) for this procedure, demonstrated that this could be done both routinely and successfully, whilst conforming to national day case procedural standards. The aim of this satisfaction survey was to evaluate this procedure from a patient's perspective, to further consolidate our results from 2018. The forty-five patients who underwent day case BSSO (DCBSSO) between February 2015 and February 2020 were retrospectively identified and deemed eligible for inclusion. Participation involved completion of a 10-part questionnaire via telephone consultation. Patients were asked questions focussing on their experience of discharge timing, management of postoperative symptoms, and overall recovery at home. Twenty-four patients consented to partake in the survey (response rate of 73%). Twenty-three (96%) were extremely happy to be discharged the day of their surgery and felt that the timing of discharge was appropriate. Only 17% of patients experienced discomfort overnight and 96% of these stated they could manage their symptoms at home. From this survey, we can confirm that the majority of patients receiving DCBSSO at the Royal Gwent Hospital were happy to be discharged the day of their surgery and recover at home.
Assuntos
Osteotomia Sagital do Ramo Mandibular , Encaminhamento e Consulta , Humanos , Mandíbula , Avaliação de Resultados da Assistência ao Paciente , Estudos Retrospectivos , TelefoneRESUMO
The Gulf Coast tick, Amblyomma maculatum Koch (Acari: Ixodidae), is a unique univoltine ectoparasite of seven vertebrate host classes in the Western Hemisphere that is increasingly recognized as a pest of livestock and wildlife, a vector of pathogens to humans and canines, and a putative vector of Ehrlichia ruminantium, the causal agent of heartwater, a fatal foreign animal disease of ruminants resident in the Caribbean. This review assembles current and historical literature encompassing the biology, ecology, and zoogeography of this tick and provides new assessments of changes in cyclical population distribution, habitat associations, host utilization, seasonal phenology, and life history. These assessments are pertinent to the emergence of A. maculatum as a vector of veterinary and medical importance, and its pest management on livestock and other animals.
Assuntos
Ecossistema , Ixodidae/fisiologia , Animais , Demografia , Humanos , Doenças Transmitidas por Carrapatos/transmissãoRESUMO
In Texas, great egret Casmerodius albus chicks attack younger nestmates, often fatally (siblicide). By contrast, the young of neighboring great blue herons Ardea herodias seldom strike or kill siblings. These interspecific differences seem related to prey size: only fish provided by egret parents are small enough for chicks to monopolize (a process facilitated by aggression). Experimentally cross-fostered heron chicks raised on small prey by egret parents became siblicidal, but the reverse procedure of cross-fostering egret chicks did not reduce aggression or siblicide.
RESUMO
Monocyte and lymphocyte surface-expressed viral antigens have been demonstrated after exposure of unseparated human mononuclear leukocytes to influenza virus in vitro. The current studies, using [35S]methionine pulse-labeled purified preparations of virus-exposed macrophages, depleted of lymphocytes, demonstrate that the presence of these viral proteins does represent new synthesis. However, purified lymphocytes, depleted of monocytes-macrophages and exposed to influenza virus, showed no detectable viral protein synthesis. In further experiments, unseparated mononuclear leukocytes were exposed to virus and subsequently separated by countercurrent centrifugal elutriation. Both macrophages and lymphocytes were then shown to synthesize influenza proteins. Cell-free control or influenza virus-infected macrophage-derived supernatant fluids did not facilitate influenza virus infection of the lymphocytes. The data suggest that macrophages are required for influenza virus infection of human lymphocytes, and raise the possibility that macrophage facilitation of an abortive infection of lymphocytes plays a role in the generation of effective immunity to viral antigens.
Assuntos
Transformação Celular Viral , Vírus da Influenza A/genética , Influenza Humana/sangue , Linfócitos/fisiologia , Macrófagos/fisiologia , Antígenos Virais/análise , Humanos , Metionina/metabolismo , Peso Molecular , Radioisótopos de Enxofre , Proteínas Virais/biossínteseRESUMO
We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or BALB/c mouse liver DNA. Elevated levels of p53 mRNA were detected in several tissues of two transgenic lines tested. Increased levels of p53 protein were also detected in most of the tissues analyzed by Western blotting (immunoblotting). Because both transgenes encoded p53 proteins that were antigenically distinct from wild-type p53, it was possible to demonstrate that overexpression of the p53 protein was mostly, if not entirely, due to the expression of the transgenes. Neoplasms developed in 20% of the transgenic mice, with a high incidence of lung adenocarcinomas, osteosarcomas, and lymphomas. Tissues such as ovaries that expressed the transgene at high levels were not at higher risk of malignant transformation than tissues expressing p53 protein at much lower levels. The long latent period and low penetrance suggest that overexpression of p53 alone is not sufficient to induce malignancies and that additional events are required. These observations provide direct evidence that mutant alleles of the p53 oncogene have oncogenic potential in vivo and that different cell types show intrinsic differences in susceptibility to malignant transformation by p53. Since recent data suggest that p53 may be a recessive oncogene, it is possible that the elevated tumor incidence results from functional inactivation of endogenous p53 by overexpression of the mutant transgene. The high incidence of lung and bone tumors suggests that p53 transgenic mice may provide a useful model to investigate the molecular events that underlie these malignancies in humans.
Assuntos
Neoplasias Experimentais/genética , Oncogenes , Alelos , Animais , Neoplasias Ósseas/genética , Epitopos , Genes Dominantes , Genes Recessivos , Neoplasias Pulmonares/genética , Linfoma/genética , Camundongos , Camundongos Transgênicos , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Fosfoproteínas/metabolismo , Transcrição Gênica , Proteína Supressora de Tumor p53RESUMO
src, abl, and fps/fes are prototypes for a family of genes encoding nonreceptor protein-tyrosine kinases. The oncogenic potential of the v-fps protein-tyrosine kinase was investigated by introduction of the gag-fps coding sequence of Fujinami sarcoma virus into the mouse germ line. Transgenic mice with v-fps under the transcriptional control of a 5' human beta-globin promoter (GF) or with both 5' and 3' beta-globin regulatory sequences (GEF) were viable. Unexpectedly, both GF and GEF transgenes were expressed in a wide variety of tissues and induced a spectrum of benign and malignant tumors. These tumors, which included lymphomas, thymomas, fibrosarcomas, angiosarcomas, hemangiomas, and neurofibrosarcomas, developed with various frequencies after latent periods of 2 to 12 months. The majority of lymphoid neoplasms appeared to be of T-cell origin and were monoclonal, as judged by rearrangements of the T-cell receptor beta or immunoglobulin genes. Some tissues that expressed the v-fps oncogene, such as heart, brain, lung, and testes, developed no malignant tumors. The v-fps protein-tyrosine kinase therefore has a broad but not unrestricted range of oncogenic activity in cells of lymphoid and mesenchymal origin. The incomplete penetrance of the neoplastic phenotype and the monoclonality of lymphoid tumors suggest that tumor formation in v-fps mice requires genetic or epigenetic events in addition to expression of the P130gag-fps protein-tyrosine kinase.
Assuntos
Hemangioma/genética , Linfoma/genética , Oncogenes , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Sarcoma Experimental/genética , Timoma/genética , Neoplasias do Timo/genética , Animais , Clonagem Molecular , Expressão Gênica , Globinas/genética , Hemangioma/enzimologia , Hemangioma/patologia , Humanos , Vírus da Leucemia Felina/genética , Linfoma/enzimologia , Linfoma/patologia , Masculino , Camundongos , Camundongos Transgênicos , Especificidade de Órgãos , Plasmídeos , Sarcoma Experimental/enzimologia , Sarcoma Experimental/patologia , Timoma/enzimologia , Timoma/patologia , Neoplasias do Timo/enzimologia , Neoplasias do Timo/patologiaRESUMO
Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated with hypocitrullinemia on NBS and subsequent confirmatory tests. An oral biotin trial is also warranted.
RESUMO
Although relationship distress is common, couples often forego professional help due to concerns such as time constraints, financial costs, and stigma. The two-session relationship checkup is an alternative format of couple intervention developed to address these concerns. In this qualitative study, we interviewed 20 coupled participants and six clinicians to examine the checkup's processes and outcomes. The phenomenological themes that emerged revealed sequential processes by which this format works. Couple themes included client motivation, the therapeutic relationship, and therapeutic change in terms of perceptions and behaviors-particularly with regard to communication. Clinician data largely mirrored these themes. The results suggest the intervention addressed barriers to help-seeking and may be a viable selective option for at-risk couples.
Assuntos
Terapia de Casal/métodos , Terapia Conjugal/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Relações Profissional-Paciente , Processos Psicoterapêuticos , Psicoterapia Breve/métodos , Adulto , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Adulto JovemRESUMO
The environment of the biotin binding site on avidin was investigated by determining the fluorescence enhancement of a series of fluorescent probes that are anilinonaphthalene sulfonic acid derivatives. Of the compounds tested, 2-anilinonaphthalene-6-sulfonic acid (2,6-ANS) exhibited the greatest enhancement under the conditions used (which would reflect both molar fluorescence enhancement and binding affinity) and exhibited more than 95% reversal upon addition of biotin. Thus, 2,6-ANS was chosen for more detailed characterization of the interaction with avidin. Only a single class of binding sites for 2,6-ANS was identified; the mean value for the Kd was 203 +/- 16 microM (X +/- 1 S.D.), and the molar ratio of 2,6-ANS binding sites to biotin binding sites was approx. 1. These results provide evidence that the biotin binding site and the 2,6-ANS binding site are at least partially overlapping, but the possibility that the probe binding site is altered by a conformational change induced by biotin binding cannot be excluded. At excitation = 328 nm and emission = 408 nm, the molar fluorescence of the bound probe was 6.8 +/- 1.0 microM-1 and that of the free probe was 0.061 +/- 0.008 microM-1 giving an enhancement ratio (molar fluorescence of bound probe/molar fluorescence of free probe) of 111 +/- 22. Upon binding, the wavelength of maximum fluorescence decreases. These findings also provide evidence that the fluorescence enhancement associated with the interaction of 2,6-ANS and avidin reflects the environment of the biotin binding site. The Kosower's Z factor, an empirical index of apolarity, was 82.1 for the 2,6-ANS binding site on avidin. This value reflects a degree of apolarity that is similar to apolar environments observed for substrate binding sites on several enzymes; although not the dominant factor, this environment may contribute to the strong binding of biotin.
Assuntos
Naftalenossulfonato de Anilina/metabolismo , Avidina/metabolismo , Biotina/metabolismo , Sítios de Ligação , Ligação Proteica , Solubilidade , Espectrometria de FluorescênciaRESUMO
The 2 most common forms of X-linked adreno-leukodystrophy (ALD) are the juvenile or childhood cerebral form with inflammatory demyelination and the adult adrenomyeloneuropathy (AMN) involving spinal cord tracts without significant inflammation. Modifier genes or environmental factors may contribute to the phenotypic variability. We performed immunohistochemical, an in situ polymerase chain reaction, and TUNEL analyses to identify several viruses, lymphocyte subpopulations, apoptotic cells, and effector molecules, focusing on morphologically normal white matter, dysmyelinative and acute demyelinative lesions. No distinguishing viral antigens were detected. Most lymphocytes were CD8 cytotoxic T cells (CTLs) with the alpha/beta TCR, and they infiltrated morphologically unaffected white matter. Only a few oligodendrocytes were immunoreactive for caspase-3. MHC class II- and TGF-beta-positive microglia were present. CD44, which can mediate MHC-unrestricted target cell death, was seen on many lymphocytes and white matter elements. CD1 molecules, which play major roles in MHC-unrestricted lipid antigen presentation, were noted. Our data indicate that unconventional CD8 CTLs are operative in the early stages of dysmyelination/demyelination and that cytolysis of oligodendrocytes, rather than apoptosis, appears to be the major mode of oligodendrocytic death. The presentation of lipid antigens may be a key pathogenetic element in ALD and AMN-ALD.
Assuntos
Adrenoleucodistrofia/patologia , Apresentação de Antígeno , Antígenos CD1/fisiologia , Encéfalo/patologia , Citotoxicidade Imunológica , Lipídeos/imunologia , Oligodendroglia/patologia , Linfócitos T Citotóxicos/imunologia , Adrenoleucodistrofia/imunologia , Adrenoleucodistrofia/metabolismo , Encéfalo/imunologia , Morte Celular/imunologia , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe II/análise , Humanos , Imuno-Histoquímica , Metabolismo dos Lipídeos , Oligodendroglia/imunologiaRESUMO
One method for the collection of urine samples from infants involves absorption of the urine on cotton balls placed in the diaper. Such samples are not timed and excretions are often expressed per mg of urinary creatinine. An assumption in this method is that the creatinine concentration is not changed by the absorption process. The concentration of creatinine in urine samples was measured before and after absorption of the urine by cotton balls, rayon balls, or diaper material over a range of wetness. For urine from both adults and infants, absorption on rayon balls and diaper material caused an important artifactual decrease in the concentration of creatinine. The effect was particularly striking in lightly wetted samples; the mean percent decrease was only 3 +/- 2% for cotton but was 9 +/- 5% for rayon (n = 10) and 13 +/- 4% for diaper material (n = 7). These data provide evidence that rayon balls and diaper material (and to a lesser extent cotton balls) selectively adsorb creatinine from human urine.
Assuntos
Celulose , Creatinina/urina , Cuidado do Lactente , Manejo de Espécimes/métodos , Adsorção , Adulto , Humanos , Lactente , Concentração Osmolar , Manejo de Espécimes/instrumentaçãoRESUMO
Estimates of the plasma concentration of biotin differ considerably. Variation in detectability of biotin bound covalently to protein is one potential source of disagreement. In this study we determined the amount of biotin covalently bound to plasma protein. First, greater than 99% of free and reversibly bound biotin was removed by dialysis; then greater than 90% of covalently bound biotin was released by acid hydrolysis. For plasma samples from 11 normal adults, the ratio of covalently bound biotin to free biotin was 0.15 +/- 0.09 (mean +/- SD). Taking into account the additional biotin that is reversibly bound to protein, this study provides evidence that approximately 12% of total biotin in plasma is covalently bound, 7% is reversibly bound, and 81% is free. We conclude that covalently bound biotin cannot account for the reported sixfold increase in biotin detected after acid hydrolysis. We speculate that the reported increase was an artifact caused by substances produced during acid hydrolysis of plasma.
Assuntos
Biotina/sangue , Proteínas Sanguíneas/metabolismo , Adulto , Idoso , Biotina/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hidrólise , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Diálise RenalRESUMO
Urinary excretion of biotin (total avidin-binding substances) was measured in adults and children who were adhering to one of the following self-selected diets: strict vegetarian (vegan), lactoovovegetarian, or mixed (containing meat and dairy products as well as plant-derived foods). In a subset of subjects, plasma biotin concentrations were also measured. In adults the biotin excretion rate was significantly greater in the vegan group than in either the lactoovovegetarian or the mixed-diet groups; the latter were not significantly different from one another. In children the biotin excretion rates in both the vegan group and the lactoovovegetarin group were significantly greater than in the mixed-diet group. A similar trend (vegan greater than lactoovovegetarian greater than mixed) was detected in the plasma concentrations of biotin of adults and children but differences were not generally statistically significant. These observations provide evidence that the biotin nutritional status of vegans is not impaired.
Assuntos
Biotina/deficiência , Dieta Vegetariana , Dieta , Estado Nutricional , Adulto , Biotina/sangue , Biotina/urina , Criança , HumanosRESUMO
BACKGROUND: Patients with carboxylase deficiency are treated with pharmacologic doses of biotin. OBJECTIVE: We sought to determine the bioavailability of biotin at pharmacologic doses. DESIGN: Biotin was administered orally (2.1, 8.2, or 81.9 micromol) or intravenously (18.4 micromol) to 6 healthy adults in a crossover design with > or =2 wk between each biotin administration. Before and after each administration, timed 24-h urine samples were collected. Urinary biotin and biotin metabolites were analyzed by an HPLC avidin-binding assay. RESULTS: Urinary recoveries of biotin plus metabolites were similar (approximately 50%) after the 2 largest oral doses and the 1 intravenous dose, suggesting 100% bioavailability of the 2 largest oral doses. For unexplained reasons, the apparent recovery of the smallest oral dose was about twice that of the other doses. For all 4 doses, biotin accounted for >50% of the total of biotin and biotin metabolites in urine. Bisnorbiotin (13-23%), biotin-d,l-sulfoxide (5-13%), bisnorbiotin methyl ketone (3-9%), and biotin sulfone (1-3%) accounted for the remainder. The percentage excretion of biotin was greater when biotin was administered intravenously and for the largest oral dose than for the 2 smallest oral doses. CONCLUSION: Our data provide evidence that oral biotin is completely absorbed even when pharmacologic doses are administered. Biotin metabolites account for a substantial portion of total urinary excretion and must be considered in bioavailability studies. We speculate that renal losses of biotin (as a percentage of the dose administered) are moderately elevated when pharmacologic doses of biotin are administered.
Assuntos
Biotina/administração & dosagem , Biotina/farmacocinética , Administração Oral , Adulto , Análise de Variância , Disponibilidade Biológica , Biotina/urina , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Masculino , Micronutrientes , Deficiência Múltipla de Carboxilase/tratamento farmacológicoRESUMO
In previous studies using the HPLC and avidin-binding assay, five unidentified avidin-binding substances were observed in human urine. The present study investigated the identity of these substances. Urine was collected before and after intravenous administration of 18.5 mumol biotin to healthy adults. Unknown substances 1 and 3 were initially identified as biotin sulfone and bisnorbiotin methyl ketone, respectively, by coelution with authentic standards on HPLC. Identities were confirmed by thin-layer chromatography and by derivatization with p-dimethyl-aminocinnamaldehyde. As expected for biotin metabolites, the urinary excretion of biotin sulfone and bisnorbiotin methyl ketone increased with biotin administration. The urinary excretion of biotin sulfone increased 21-fold from 0.2 nmol/h before to 4.2 nmol/h after administration; the excretion of bisnorbiotin methyl ketone increased 130-fold from 0.4 to 51.8 nmol/h. At presumed steady state in free-living subjects (n = 6), biotin sulfone and bisnorbiotin methyl ketone accounted for 3.6% and 7.9% of total biotin excretion, respectively. Traces of tetranorbiotin-l-sulfoxide were also identified by using thin-layer chromatography and derivatization with p-dimethylaminocinnamaldehyde. However, tetranorbiotin-l-sulfoxide was not detectable in urine by the HPLC and avidin-binding assay because this metabolite has weak avidin-binding affinity. We conclude that biotin sulfone and bisnorbiotin methyl ketone are present in measurable quantities in human urine; their quantitation should allow more accurate studies on human biotin metabolism and turnover.
Assuntos
Biotina/análogos & derivados , Biotina/metabolismo , Sulfonas/urina , Sulfóxidos/urina , Adulto , Biotina/administração & dosagem , Biotina/urina , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Fina/métodos , Feminino , Humanos , Injeções Intravenosas , MasculinoRESUMO
This study examined the effects of chronic ethanol feeding and acute ethanol exposure in vitro on biotin transport in rat intestine. Transport studies were performed with intestinal everted sacs. Ethanol was fed to rats for 6-7 wk. Compared with pair-fed controls, ethanol feeding significantly decreased plasma biotin concentrations and transport at physiological concentrations (0.01, 0.1, and 0.3 mumol/L) but not at pharmacological concentration (100 mumol/L). When added to the incubation medium of everted jejunal sacs from dry-food-fed rats, ethanol (2% vol:vol) significantly inhibited the transport of biotin at a physiological concentration (0.1 mumol/L) but not at a pharmacological concentration (100 mumol/L). The inhibitory effect of ethanol on the transport of 0.1 mumol biotin/L increased with increasing concentration of ethanol in the incubation medium [0.5% to 5% (vol:vol)]. Acetaldehyde, the major ethanol metabolite, also significantly inhibited biotin transport at 0.2% (vol:vol). These data demonstrate that chronic ethanol feeding and acute ethanol exposure in vitro inhibit the intestinal transport of biotin by the carrier-mediated process. Chronic ethanol feeding is also associated with a significant decrease in plasma biotin concentrations. The ethanol-induced inhibition in intestinal transport of biotin may be a contributing factor in reducing plasma biotin concentrations.
Assuntos
Alcoolismo/metabolismo , Biotina/farmacocinética , Etanol/efeitos adversos , Jejuno/metabolismo , Animais , Transporte Biológico , Técnicas de Cultura , Modelos Animais de Doenças , Jejuno/efeitos dos fármacos , Masculino , Ratos , Ratos EndogâmicosRESUMO
To assess the utility of various indicators of biotin status, marginal biotin deficiency was induced experimentally in normal adults. Ten subjects consumed a diet that contained enough avidin to bind seven times more biotin than that in the diet. Blood and 24-h urine samples were collected before the diet began and twice weekly thereafter for 20 d. The urinary excretion and serum concentration of biotin and its two principal inactive metabolites bisnorbiotin and biotin sulfoxide were determined after HPLC separation with an avidin-binding assay. The urinary concentration of 3-hydroxyisovaleric acid, an indicator of reduced activity of a biotin-dependent enzyme, was quantitated by gas chromatography-mass spectrometry. The urinary excretion of 3-hydroxyisovaleric acid increased significantly (P < 0.0001). For all subjects, the urinary excretion of both biotin and bisnorbiotin decreased significantly (P < 0.0001 for each). In contrast, the mean serum concentration of biotin did not decrease significantly (P = 0.06). These data provide evidence that the urinary excretion of 3-hydroxyisovaleric acid and the urinary excretion of biotin are early and sensitive indicators of biotin deficiency and that the serum concentration of biotin is not.
Assuntos
Biotina/deficiência , Biotina/urina , Valeratos/urina , Adulto , Análise de Variância , Avidina/metabolismo , Avidina/farmacologia , Biotina/análogos & derivados , Biotina/sangue , Biotina/metabolismo , Cromatografia Líquida de Alta Pressão , Clara de Ovo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The decreased immune response associated with aging may, in part, reflect intrinsic age-related biochemical alterations in lymphocytes from older animals. We measured levels of lymphocyte adenosine triphosphate (ATP) and continuous [3H]thymidine incorporation in phytohemagglutinin-stimulated lymphocytes from young and old humans, and the effects thereon of inhibitors of mitochondrial oxidative phosphorylation and protein synthesis. No difference was found in adenine nucleotide content between young and old subjects. After 24 hours of culture there was a decrease in ATP, with recovery and 2--3-fold increase at 48 hours in young cells after phytohemagglutinin stimulation. We observed a clearcut delay in older lymphocytes of the increase in ATP and [3H]thymidine incorporation following phytohemagglutinin stimulation. We found no evidence for decreased viability or diminished number of responding units in aged cultures. The evidence suggests that mitochondrial dysfunction may play a role in the immunodeficiency of aging.
Assuntos
Trifosfato de Adenosina/biossíntese , Envelhecimento , Ativação Linfocitária , Linfócitos/metabolismo , Nucleotídeos de Adenina/metabolismo , Adulto , Idoso , Células Cultivadas , Cianetos/farmacologia , Cicloeximida/farmacologia , DNA/biossíntese , Feminino , Humanos , Cinética , Masculino , Mitocôndrias/fisiologia , Fito-Hemaglutininas/farmacologia , Puromicina/farmacologiaRESUMO
Using serum biotin concentration as the indicator, a previous study reported biotin deficiency resulting from long-term anticonvulsant therapy. However, serum biotin may not be a good indicator of tissue biotin status. Using better indicators of biotin status in anticonvulsant-treated subjects, we found increased urinary excretion of biotin catabolites and 3-hydroxyisovaleric acid, an organic acid produced in greater quantities secondary to reduced activity of a biotin-dependent carboxylase. We conclude that anticonvulsant treatment led to increased biotin catabolism and probably to reduced biotin status.
Assuntos
Anticonvulsivantes/metabolismo , Anticonvulsivantes/uso terapêutico , Biotina/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Adolescente , Adulto , Biotina/análogos & derivados , Biotina/sangue , Biotina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Valeratos/sangue , Valeratos/urinaRESUMO
The study of bone cancer has been difficult in part due to a lack of appropriate in vitro osteosarcoma model systems. The development of such systems is essential if a clearer understanding of the biology of and mechanisms behind the formation and progression of bone cancers is to be obtained. We report here the development of an in vitro model system which demonstrates important characteristics generally associated with osteosarcoma. The chick periosteal osteogenesis model was infected with the Fujinami Sarcoma Virus (FSV) containing the v-fps oncogene which encodes for a P140gag-fps protein-tyrosine kinase. Under the appropriate conditions FSV infected cultures developed bone and cartilaginous tissues which showed histopathological findings consistent with osteosarcoma. Biochemical data indicating massive increases in alkaline phosphatase activity, protein content, 3H-Thymidine incorporation as well as expression of active P140gag-fps confirm that transformation has occurred in FSV infected cultures. This novel in vitro model system should prove most useful in the study of bone cancer.