RESUMO
Repeated cocaine exposure causes dendritic spine loss in the orbitofrontal cortex, which might contribute to poor orbitofrontal cortical function following drug exposure. One challenge, however, has been verifying links between neuronal structural plasticity and behavior, if any. Here we report that cocaine self-administration triggers the loss of dendritic spines on excitatory neurons in the orbitofrontal cortex of male and female mice (as has been reported in rats). To understand functional consequences, we locally ablated neuronal ß1-integrins, cell adhesion receptors that adhere cells to the extracellular matrix and thus support dendritic spine stability. Degradation of ß1-integrin tone: 1) caused dendritic spine loss; 2) exaggerated cocaine-seeking responses in a cue-induced reinstatement test; and 3) impaired the ability of mice to integrate new learning into familiar routines - a key function of the orbitofrontal cortex. Stimulating Abl-related gene (Arg) kinase, over-expressing Proline-rich tyrosine kinase (Pyk2), and inhibiting Rho-associated coiled-coil containing kinase (ROCK) corrected response strategies, uncovering a ß1-integrin-mediated signaling axis that controls orbitofrontal cortical function. Finally, use of a combinatorial gene silencing/chemogenetic strategy revealed that ß1-integrins support the ability of mice to integrate new information into established behaviors by sustaining orbitofrontal cortical connections with the basolateral amygdala.SIGNIFICANCE STATEMENTCocaine degenerates dendritic spines in the orbitofrontal cortex, a region of the brain involved in interlacing new information into established behaviors. One challenge has been verifying links between cellular structural stability and behavior, if any. In this second of two related investigations, we study integrin family receptors, which adhere cells to the extracellular matrix and thereby stabilize dendritic spines (see also DePoy et al., 2019, Journal of Neuroscience). We reveal that ß1-integrins in the orbitofrontal cortex control food- and cocaine-seeking behaviors. For instance, ß1-integrin loss amplifies cocaine-seeking behavior and impairs the ability of mice to integrate new learning into familiar routines. We identify likely intracellular signaling partners by which ß1-integrins support orbitofrontal cortical function and connectivity with the basolateral amygdala.
RESUMO
An essential aspect of goal-directed decision-making is selecting actions based on anticipated consequences, a process that involves the orbitofrontal cortex (OFC) and potentially, the plasticity of dendritic spines in this region. To investigate this possibility, we trained male and female mice to nose poke for food reinforcers, or we delivered the same number of food reinforcers non-contingently to separate mice. We then decreased the likelihood of reinforcement for trained mice, requiring them to modify action-outcome expectations. In a separate experiment, we blocked action-outcome updating via chemogenetic inactivation of the OFC. In both cases, successfully selecting actions based on their likely consequences was associated with fewer immature, thin-shaped dendritic spines and a greater proportion of mature, mushroom-shaped spines in the ventrolateral OFC. This pattern was distinct from spine loss associated with aging, and we identified no effects on hippocampal CA1 neurons. Given that the OFC is involved in prospective calculations of likely outcomes, even when they are not observable, constraining spinogenesis while preserving mature spines may be important for solidifying durable expectations. To investigate causal relationships, we inhibited the RNA-binding protein fragile X mental retardation protein (encoded by Fmr1), which constrains dendritic spine turnover. Ventrolateral OFC-selective Fmr1 knockdown recapitulated the behavioral effects of inducible OFC inactivation (and lesions; also shown here), impairing action-outcome conditioning, and caused dendritic spine excess. Our findings suggest that a proper balance of dendritic spine plasticity within the OFC is necessary for one's ability to select actions based on anticipated consequences.SIGNIFICANCE STATEMENT Navigating a changing environment requires associating actions with their likely outcomes and updating these associations when they change. Dendritic spine plasticity is likely involved, yet relationships are unconfirmed. Using behavioral, chemogenetic, and viral-mediated gene silencing strategies and high-resolution microscopy, we find that modifying action-outcome expectations is associated with fewer immature spines and a greater proportion of mature spines in the ventrolateral orbitofrontal cortex (OFC). Given that the OFC is involved in prospectively calculating the likely outcomes of one's behavior, even when they are not observable, constraining spinogenesis while preserving mature spines may be important for maintaining durable expectations.
Assuntos
Antecipação Psicológica/fisiologia , Espinhas Dendríticas/fisiologia , Plasticidade Neuronal/fisiologia , Córtex Pré-Frontal/fisiologia , Recompensa , Animais , Condicionamento Operante , Tomada de Decisões , Espinhas Dendríticas/ultraestrutura , Dependovirus/genética , Comportamento Alimentar , Feminino , Proteína do X Frágil da Deficiência Intelectual/antagonistas & inibidores , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/fisiologia , Técnicas de Silenciamento de Genes , Genes Reporter , Vetores Genéticos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Optogenética , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Reforço PsicológicoRESUMO
BACKGROUND: Early identification of psychosocial distress is important to address the needs of vulnerable populations and influence symptom management. Older veterans diagnosed with life-limiting cancers are particularly vulnerable because they often have unmet needs, experiencing psychological or emotional problems and gaps in healthcare communication, which extends suffering. Lack of emotional support, ongoing physical pain, and unresolved symptom control can further increase distress among older veterans, contributing to complexity of decision-making for end of life (EOL) care. OBJECTIVE: We explored older veterans' experiences and identification of psychosocial distress in cancer care to better understand how they describe distress while facing the end of life. METHODS: Guiding this study is a conceptual framework from psychosocial oncology with the multifactorial experience of distress indicated by NCCN guidelines for distress screening. We use a phenomenological approach to explore the experience of psychosocial distress among older veterans diagnosed with advanced cancers at risk for dying within a year. INCLUSION CRITERIA: Provider response of "no" to, "Would you be surprised if your patient died within a year?" and "yes", to the question, "Have you talked with your patient about the severity of their illness as being life-limiting, terminal?" RESULTS: Five themes emerged: (1) the meaning of distress: "It's hard to explain"; (2) severity of advanced cancer: "There's no stage five"; (3) distressing thoughts about the possibility of dying: "Either way, it's life limiting"; (4) coping: "Deal with it and hope for a better day"; and (5) personal factors: "I don't want to be anything but a man who can handle adversity." Findings suggest older veterans may have unique cancer experiences different from other populations. CONCLUSION: Older veterans in this study exhibited distressing symptoms which demonstrate they are at risk for declining health and in need of support for their distress. Healthcare providers are urged to understand the complexity of distress to provide the best possible treatment for older veterans.
Assuntos
Neoplasias/psicologia , Cuidados Paliativos , Psico-Oncologia/métodos , Angústia Psicológica , Veteranos/psicologia , Idoso , Pessoal de Saúde , Cuidados Paliativos na Terminalidade da Vida/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Estresse Psicológico/etiologia , Assistência Terminal/psicologiaRESUMO
Without a functioning prefrontal cortex, humans and other animals are impaired in measures of cognitive control and behavioral flexibility, including attentional set-shifting. However, the reason for this is unclear with evidence suggesting both impaired and enhanced attentional shifting. We inhibited the medial prefrontal cortex (mPFC) of rats while they performed a modified version of an attentional set-shifting task to explore the nature of this apparent contradiction. Twelve adult male Lister hooded rats received AAV5-CaMKIIa-hM4D(Gi)-mCherry viral vector bilaterally into mPFC to express inhibitory 'Designer Receptors Exclusively Activated by Designer Drugs' (iDREADDs). The receptors were activated by systemic clozapine N-oxide (CNO) to inhibit mPFC function. The rats were tested in the standard attentional set-shifting task four times: twice after i.p. administration and twice after oral administration of vehicle or CNO (10 mg/kg). They were then tested twice in a modified task, with or without oral CNO. The modified task had an extra stage before the extradimensional shift, in which the relevant exemplars remained relevant and new exemplars that were fully predictive but redundant replaced the previous irrelevant exemplars. These exemplars then became relevant at the subsequent ED stage. In the standard task, mPFC inactivation impaired attentional set-shifting, consistent with previous findings. However, in the modified task, mPFC inactivation abolished ED shift-costs. The results support the suggestion that the mPFC is needed for the downregulation of attention that prevents learning about redundant and irrelevant stimuli. With mPFC inactivated, the rat learns more rapidly when previously redundant exemplars become the only relevant information.
RESUMO
Fetuin-A (Fet-A), secreted by the liver and adipose tissue, inhibits insulin receptor tyrosine kinase activity and modulates insulin action. Numerous studies have shown association of elevated serum Fet-A concentrations with obesity, non-alcoholic fatty liver disease, and type 2 diabetes. Both moderate body weight loss (5%-10%) and significant body weight loss have been shown to decrease serum Fet-A and improve insulin sensitivity. Currently, there are no studies examining the effects of a single bout of exercise on serum Fet-A or Ser312-pFet-A (pFet-A) responses. We hypothesized that a single bout of moderate-intensity exercise will lower serum Fet-A and that these changes will be associated with an improvement in insulin sensitivity. Thirty-one individuals with obesity and 11 individuals with normal body weight were recruited. Participants underwent a single bout of treadmill walking, expending 500 kcal at 60%-70% VO2max . Oral glucose tolerance tests (OGTT) were administered before the single bout of exercise (Pre Ex) and 24 h after exercise (24h Post Ex). In individuals with obesity, we observed a transient elevation of serum Fet-A concentrations, but not pFet-A, immediately after exercise (Post Ex). Further, a single bout of exercise decreased glucoseAUC , insulinAUC , and insulin resistance index in individuals with obesity. Consistent with this improvement in insulin sensitivity, we observed that Fet-AAUC , pFet-AAUC , 2 h pFet-A, and 2 h pFet-A/Fet-A were significantly lower following a single bout of exercise. Further, reductions in serum Fet-AAUC 24h Post Ex were correlated with a reduction in insulin resistance index. Together, this suggests that alterations in serum Fet-A following a single bout of moderate-intensity endurance exercise may play a role in the improvement of insulin sensitivity. CLINICAL TRIAL REGISTRATION: NCT03478046; https://clinicaltrials.gov/ct2/show/NCT03478046.
Assuntos
Exercício Físico/fisiologia , Resistência à Insulina/fisiologia , Insulina/sangue , alfa-2-Glicoproteína-HS/metabolismo , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2 , Humanos , Obesidade/sangue , Redução de Peso/fisiologiaRESUMO
Fibrous apatite has been grown by the enzymatic hydrolysis of calcium beta-glycerophosphate on reconstituted calfskin collagen tapes which had been modified by the addition of a phosphoprotein, phosvitin, in the presence of a cross-linking agent, dimethylsuberimidate. The deposits were identified as a carbonate-bearing hydroxyapatite by x-ray diffraction, and scanning electron micrographs confirmed their fibrous character.
Assuntos
Fosfatase Alcalina/metabolismo , Calcificação Fisiológica , Cartilagem , Proteínas do Ovo , Glicerofosfatos/metabolismo , Hidroxiapatitas , Fosvitina , Cristalização , Dimetil Suberimidato , Hidroxiapatitas/metabolismo , Técnicas In Vitro , Microscopia Eletrônica de VarreduraRESUMO
Distinct isoforms of the PI3K catalytic subunit have specialized functions in the brain, but their role in cognition is unknown. Here, we show that the catalytic subunit p110ß plays an important role in prefrontal cortex (PFC)-dependent cognitive defects in mouse models of Fragile X syndrome (FXS), an inherited intellectual disability. FXS is caused by loss of function of the fragile X mental retardation protein (FMRP), which binds and translationally represses mRNAs. PFC-selective knockdown of p110ß, an FMRP target that is translationally upregulated in FXS, reverses deficits in higher cognition in Fmr1 knockout mice. Genetic full-body reduction of p110ß in Fmr1 knockout mice normalizes excessive PI3K activity, restores stimulus-induced protein synthesis, and corrects increased dendritic spine density and behavior. Notably, adult-onset PFC-selective Fmr1 knockdown mice show impaired cognition, which is rescued by simultaneous p110ß knockdown. Our results suggest that FMRP-mediated control of p110ß is crucial for neuronal protein synthesis and cognition.
Assuntos
Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Cognição/fisiologia , Síndrome do Cromossomo X Frágil/patologia , Animais , Comportamento Animal , Classe Ia de Fosfatidilinositol 3-Quinase/química , Espinhas Dendríticas/metabolismo , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Masculino , Camundongos , Camundongos Knockout , Córtex Pré-Frontal/metabolismo , Biossíntese de Proteínas , Estrutura Terciária de Proteína , Receptor de Glutamato Metabotrópico 5/metabolismoRESUMO
hUBC9, an E2 ubiquitin conjugating enzyme, was identified by yeast two-hybrid screening and coprecipitation studies to interact with MEKK1 and the type I TNF-alpha receptor, respectively. Because both of these proteins regulate NFkappaB activity, the role of hUBC9 in modulating NFkappaB activity was investigated. Overexpression of hUBC9 in HeLa cells stimulated the activity of NFkappaB as determined by NFkappaB reporter and IL-6 secretion assays. hUBC9 also synergized with MEKK1 to activate NFkappaB reporter activity. Thus, hUBC9 modulates NFkappaB activity which, at least in part, can be attributed to its interaction with MEKK1 and the type I TNF-alpha receptor.
Assuntos
Antígenos CD/metabolismo , Ligases/metabolismo , MAP Quinase Quinase Quinase 1 , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Enzimas de Conjugação de Ubiquitina , Regulação da Expressão Gênica/genética , Genes Reporter/genética , Células HeLa , Humanos , Interleucina-6/metabolismo , Ligases/genética , Mutagênese , Receptores Tipo I de Fatores de Necrose Tumoral , Proteínas Recombinantes de Fusão/metabolismo , Transfecção/genéticaRESUMO
In order to investigate whether the change in length of simple repetitive genomic sequences (microsatellite instability) is associated with prostate cancer, we analyzed 40 prostate cancer samples with 44 microsatellite loci markers on chromosomes 1, 3, 5, 6, 8, 9, 11, 13, 16, 17 and X. DNA was extracted from normal and tumor cells of 40 microdissected cancer samples, amplified by PCR and analyzed for microsatellite instability using 44 primers for dinucleotide, trinucleotide, tetranucleotide and pentanucleotide repeat sequences. The results of this study demonstrate that 45% of the prostate cancer specimens (18 out of 40) showed microsatellite instability (MSI) at a minimum of one locus using dinucleotide repeat sequences. Two out of 40 samples (5%) showed MSI at a minimum of one locus using three different trinucleotide repeat primers (AR, SR and TBP). Ten out of 40 (25%) samples showed MSI at a minimum of one locus using five different tetranucleotide repeat primers (HPRT1, HPRTII, MYCL1, RB, REN). There were no MSI observed in samples using pentanucleotide repeat sequences. There were no MSI in benign prostatic hyperplasia samples (25 samples). These experiments suggest that the microsatellite instability of dinucleotide tandem repeat sequences is much higher than trinucleotide, tetranucleotide and pentanucleotide repeat sequences in prostate cancer. The MSI with different lengths of nucleotide repeat sequences did not correlate with the stage and grades of prostate cancer.
Assuntos
Repetições de Microssatélites/genética , Neoplasias da Próstata/genética , Repetições de Dinucleotídeos/genética , Humanos , Masculino , Repetições de Trinucleotídeos/genéticaAssuntos
Educação de Pós-Graduação , Docentes , Ciência , Mulheres , Feminino , Humanos , Masculino , Universidades , Mulheres TrabalhadorasRESUMO
A vacuum-sealed specimen stage for investigation of air-sensitive materials has been designed. This stage is useful for instruments equipped with a vacuum antechamber and allows facile sample mounting in a dry box or glove bag. The sample cell is subsequently introduced into the antechamber of the instrument and the appropriate measurement or photograph is taken. Sample integrity can be maintained in the cell for subsequent investigations.
RESUMO
We recently reported that prolonged exposure to the glucocorticoid receptor (GR) ligand corticosterone impairs decision-making that is dependent on the predictive relationship between an action and its outcome (Gourley et al.; Proceedings of the National Academy of Sciences, 2012). Additionally, acute GR blockade, when paired with action-outcome conditioning, also blocks new learning. We then showed that dendritic spines in the prelimbic prefrontal cortex remodeled under both conditions. Nonetheless, the relationship between deep-layer dendritic spines and outcome-based decision-making remains opaque. We report here that a history of prolonged corticosterone exposure increases dendritic spine density in deep-layer prelimbic cortex. When spines are imaged simultaneously with corticosteroid exposure (i.e., without a washout period), dendritic spine densities are, however, reduced. Thus, the morphological response of deep-layer prelimbic cortical neurons to prolonged corticosteroid exposure may be quite dynamic, with spine elimination during a period of chronic exposure and spine proliferation during a subsequent washout period. We provide evidence, using a Rho-kinase inhibitor, that GR-mediated dendritic spine remodeling is causally related to complex decision-making. Finally, we conclude this report with evidence that a history of early-life (adolescent) GR blockade, unlike acute blockade in adulthood, enhances subsequent outcome-based decision-making. Together, our findings suggest that physiological levels of GR binding enable an organism to learn about the predictive relationship between an action and its outcome, but a history of GR blockade may, under some circumstances, also have beneficial consequences.
RESUMO
Supercontinuum extending to visible wavelengths is generated in a hybrid silica nonlinear fiber pumped at 1560 nm by a femtosecond, erbium-doped fiber laser. The hybrid nonlinear fiber consists of a short length of highly nonlinear, germano-silicate fiber (HNLF) spliced to a length of photonic crystal fiber (PCF). A 2 cm length of HNLF provides an initial stage of continuum generation due to higher-order soliton compression and dispersive wave generation before launching into the PCF. The visible radiation is generated in the fundamental mode of the PCF.
RESUMO
Femtosecond fiber lasers together with nonlinear fibers are compact, reliable, all-fiber supercontinuum sources. Maintaining an all-fiber configuration, however, necessitates pulse compression in an optical fiber, which can lead to nonlinearities for subhundred femtosecond, nanojoule pulses. In this work we show that using large-mode-area fibers for pulse compression mitigates the nonlinearity, resulting in compressed pulses with significantly reduced satellite pulses. Consequently, supercontinua generated with these pulses are shown to have as much as a 10 dB increase in coherence fringe contrast. By using a hybrid highly nonlinear fiber-photonic crystal fiber, the continuum can be extended to visible wavelengths while still maintaining high coherence.
RESUMO
The gonadoblastoma locus on the Y chromosome (GBY) predisposes the dysgenetic gonads of XY females to develop in situ tumors. It has been mapped to a critical interval on the short arm and adjacent centromeric region on the Y chromosome. Currently there are five functional genes identified on the GBY critical region, thereby providing likely candidates for this cancer predisposition locus. To evaluate the candidacy of one of these five genes, testis-specific protein Y-encoded (TSPY), as the gene for GBY, expression patterns of TSPY in four gonadoblastoma from three patients were analyzed by immunohistochemistry using a TSPY specific antibody. Results from this study showed that TSPY was preferentially expressed in tumor germ cells of all gonadoblastoma specimens. Additional study on two cases of testicular seminoma demonstrated that TSPY was also abundantly expressed in all stages of these germ cell tumors. The present observations suggest that TSPY may either be involved in the oncogenesis of or be a useful marker for both types of germ cell tumors.
Assuntos
Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Gonadoblastoma/genética , Proteínas Nucleares , Seminoma/genética , Neoplasias Testiculares/genética , Fatores de Transcrição , Cromossomo Y/genética , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA/análise , Feminino , Expressão Gênica , Genótipo , Células Germinativas/química , Células Germinativas/metabolismo , Células Germinativas/patologia , Gonadoblastoma/química , Gonadoblastoma/patologia , Humanos , Imuno-Histoquímica , Masculino , Mosaicismo/genética , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Fenótipo , Seminoma/química , Seminoma/patologia , Proteína da Região Y Determinante do Sexo , Neoplasias Testiculares/química , Neoplasias Testiculares/patologiaRESUMO
PURPOSE: We hypothesized that alterations in Y chromosome gene expression may be associated with prostate cancer. To test this hypothesis we analyzed the expression of 19 Y chromosome genes in benign and malignant prostate tissue. MATERIALS AND METHODS: To study the expression of Y chromosome genes RNA was extracted from prostate cancer and benign prostatic hyperplasia (BPH) tissue as well as from prostate cancer cell lines. RNA was reverse transcribed and polymerase chain reaction amplified using specific primers. These primers were designed for each gene sequence obtained from the gene data bank. We analyzed 19 Y chromosome genes using 6 cell lines, 7 BPH and 7 prostate cancer tissues. Normal testis RNA served as a positive control. RESULTS: Of the 19 genes analyzed in cell lines BPH-1 cells expressed the RPS4Y, USP9Y, TMSB4Y and DBY genes; DUPro expressed RPS4Y, USP9Y, TMSB4Y, DBY and UTY; DU145 expressed DAZ, RPS4Y, USP9Y, TMSB4Y, DBY, EIAFIY, PRKY and SMCY; LNCaP expressed TSPY, SRY, BPY1, PRY, DAZ, RBMIH, RPS4Y, DBY, EIAFIY, PRKY and SMCY; ND1 expressed DAZ, RPS4Y, USP9Y, TMSB4Y, DBY, EIAFIY, PRKY and SMCY; and PC3 expressed RPS4Y, USP9Y and DBY. BPH tissue expressed the SRY, PRY, DBY, PRKY, RPS4Y, TMSB4Y, USP9Y and ZFY genes. Prostate cancer tissue expressed the PRY, TSPY, USP9Y, UTY, DBY, SMCY, ZFY, EIAFIY, TMSB4Y and RPS4Y genes. CONCLUSIONS: The differential expression of Y chromosome genes in prostate cancer, BPH tissue and prostate cancer cell lines indicates that they may have a role in prostate cancer.
Assuntos
Adenocarcinoma/genética , Expressão Gênica , Neoplasias da Próstata/genética , Cromossomo Y/genética , Humanos , Masculino , Reação em Cadeia da Polimerase , Hiperplasia Prostática/genética , RNA Neoplásico/análise , Células Tumorais CultivadasRESUMO
To identify the amino acid residues of the Harvey (Ha) ras-encoded protein that are involved in protein-protein interactions, we have created a series of mutant Ha-ras proteins. In particular, amino acid substitutions have been introduced within two regions, residues 32-42 and 61-80, that are conserved among ras proteins from different species. We observed that amino acid substitutions at positions 35, 36, 38, 40, and, to a lesser extent, 39 and 78 reduce the biological potency of Ha-ras protein in both mammalian and Saccharomyces cerevisiae cells, without noticeably affecting the known intrinsic biochemistry of these proteins. The reduction of in vivo activity for these mutant ras proteins correlates with their reduced ability to stimulate yeast adenylate cyclase. The ras-protein-neutralizing antibody Y13-259 binds to six residues: Glu-63, Ser-65, Ala-66, Met-67, Gln-70, and Arg-73. Single substitutions for these residues reduce Y13-259 antibody binding by at least a factor of 1000 but do not significantly affect biological activity. These data are discussed in terms of the model for Ha-ras protein based on the structure of the elongation factor EF-Tu-GDP complex.
Assuntos
Proteínas de Ligação ao GTP/genética , Proteínas Oncogênicas Virais/genética , Adenilil Ciclases/metabolismo , Sequência de Aminoácidos , Anticorpos Monoclonais/imunologia , Ligação Competitiva , Membrana Celular/metabolismo , Clonagem Molecular , Epitopos , Proteínas de Ligação ao GTP/imunologia , Proteínas de Ligação ao GTP/metabolismo , Técnicas de Imunoadsorção , Modelos Moleculares , Mutação , Oligopeptídeos/imunologia , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/metabolismo , Fatores de Alongamento de Peptídeos/metabolismo , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-AtividadeRESUMO
Near infrared spectroscopy (NIRS) is becoming a widely used research instrument to measure tissue oxygen (O2) status non-invasively. Continuous-wave spectrometers are the most commonly used devices, which provide semi-quantitative changes in oxygenated and deoxygenated hemoglobin in small blood vessels (arterioles, capillaries and venules). Refinement of NIRS hardware and the algorithms used to deconvolute the light absorption signal have improved the resolution and validity of cytochrome oxidase measurements. NIRS has been applied to measure oxygenation in a variety of tissues including muscle, brain and connective tissue, and more recently it has been used in the clinical setting to assess circulatory and metabolic abnormalities. Quantitative measures of blood flow are also possible using NIRS and a light-absorbing tracer, which can be applied to evaluate circulatory responses to exercise along with the assessment of tissue O2 saturation. The venular O2 saturation can be estimated with NIRS by applying venous occlusion and measuring changes in oxygenated vs. total hemoglobin. These various measurements provide the opportunity to evaluate several important metabolic and circulatory patterns in very localized regions of tissue and may be fruitful in the study of occupational syndromes and a variety of diseases.