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Biomedical subjects

Fernando Díaz

Publications and source records attributed to Fernando Díaz.

15 recordsLinked to original sources
PubMed2006

Insulin sensitivity in streptozotocin-induced diabetic rats treated with different doses of 17beta-oestradiol or progesterone.

It has been reported that in streptozotocin (STZ)-induced diabetes, hyperglycaemia leads to progressive insulin resistance of the peripheral tissues. In this study, we tried to elucidate the effects of hyperglycaemia on insulin sensitivity and insulin signalling in ovariectomized (STZ)-induced diabetic rats. In addition, we attempted to demonstrate the role of 17beta-oestradiol and progesterone on insulin sensitivity, focusing on their effects on key proteins of skeletal muscle, insulin receptor (IR) and glucose transporter-4 (Glut-4). Our results show that hyperglycaemia could modulate insulin signalling, at the IR and Glut-4 level, in different ways depending on exposure time. 17beta-Oestradiol and progesterone have different effects on insulin signalling. 17beta-Oestradiol treatment improves insulin sensitivity, but its action is dependent on the exposure time and its plasma level. During the early period of treatment (days 6-11), this hormone counteracts the effects of hyperglycaemia downstream of the IR, whereas during the later period of treatment (days 11-16), it may counteract the effects of hyperglycaemia by modulating IR relative tyrosine phosphorylation. By contrast, progesterone only improves insulin sensitivity during the early period of treatment (days 6-11), and this effect is not associated with changes in IR and Glut-4 content. Both hormones have a protective role in skeletal muscle against the effects of glucose toxicity, but their effects begin at different stages of treatment. These new findings improve our understanding of insulin resistance in type 1 diabetes mellitus and of the risk/benefit ratio when 17beta-oestradiol and progesterone are used in oral contraceptives or hormone replacement therapy taken by menopausal women with controlled type 1 diabetes mellitus.

Animals↗
PubMed2006

Farnesyltransferase inhibitors reverse taxane resistance.

The combination of farnesyltransferase inhibitors (FTIs) and taxanes has been shown to result in potent antiproliferative and antimitotic synergy. Recent phase I and II clinical trials have shown that this combination shows clinical activity in taxane-refractory or taxane-resistant cancer patients. To understand the mechanism behind these clinical observations, we used a cancer cell model of paclitaxel resistance and showed that the FTI/taxane combination retains potent antiproliferative, antimitotic, and proapoptotic activity against the paclitaxel-resistant cells, at doses where each drug alone has little or no activity. To probe the mechanistic basis of these observations, paclitaxel activity was monitored in living cells using the fluorescently conjugated paclitaxel, Flutax-2. We observed that all FTIs tested increase the amount of microtubule-bound Flutax-2 and the number of microtubules labeled with Flutax-2 in both paclitaxel-resistant and paclitaxel-sensitive cells. Importantly, we observed a consequential increase in microtubule stability and tubulin acetylation with the combination of the two drugs, even in paclitaxel-resistant cells, confirming that the enhanced taxane binding in the presence of FTI affects microtubule function. Furthermore, this mechanism is dependent on the function of the tubulin deacetylase, HDAC6, because in cells overexpressing a catalytically inactive HDAC6, FTIs are incapable of enhancing Flutax-2-microtubule binding. Similar results were obtained by using an FTI devoid of farnesyltransferase inhibitory activity, indicating that functional inhibition of farnesyltransferase is also required. Overall, these studies provide a new insight into the functional relationship between HDAC6, farnesyltransferase, and microtubules, and support clinical data showing that the FTI/taxane combination is effective in taxane-refractory patients.

Antineoplastic Agents↗
PubMed2006

Positive effects of 17beta-estradiol on insulin sensitivity in aged ovariectomized female rats.

Aging is associated with insulin resistance, which represents a common factor in age-related diseases. We aimed to determine the role of 17beta-estradiol on insulin sensitivity and memory during aging using ovariectomized rats (2-26 months of age) treated with physiological doses of 17beta-estradiol. Our results indicate a lack of effect of 17beta-estradiol replacement on spatial memory assessed in a water maze. Conversely, estradiol treatment improved insulin sensitivity in aging rats. These data imply that relatively low doses of 17beta-estradiol may have beneficial effects on glucose homeostasis due to the protective effects of estrogen. However, estradiol treatment used in the present study did not prevent memory impairment associated with aging.

Aging↗
PubMed2006

Cognitive reserve, age, and neuropsychological performance in healthy participants.

The first aim of this study was to explore the relation between cognitive reserve, age, and neuropsychological functioning in a healthy sample; and second, to determine the risk of showing cognitive deficits as a function of cognitive reserve. One hundred forty-six healthy participants between the ages of 20 and 79 were submitted to neuropsychological assessment, focusing on attention, memory, visuo-construction, conceptualization and reasoning. Premorbid IQ as measured with the Wechsler Adult Intelligence Scale Vocabulary subtest was used as a proxy of cognitive reserve. Multivariate regression analysis with age and premorbid IQ as explanatory factors revealed a significant effect in all neuropsychological tests. Logistic regression revealed that participants with low cognitive reserve were more likely to obtain deficient scores (< or =1.5 SD below the mean) in the cognitive domains of attention (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.059.29), memory (OR, 6.17; 95% CI, 1.69-22.61) and global functioning (OR, 6.44; 95% CI, 2.56-16.22) than participants with high cognitive reserve. Results suggest that cognitive reserve acts as a protective factor against the expression of cognitive decline related to age in healthy individuals.

Adult↗
PubMed2005

What happens to the readiness potential when the movement is not executed?

The purpose of this study was to investigate and compare the movement-related brain potentials recorded from two groups of right-handed male study participants. One of the groups prepared for and conducted repetitive toe movements while the other prepared to carry out the same type of movement but finally did not execute it. The readiness potential, premotion positivity, motor potential and reafferent potential were recorded from 20 electroencephalogram electrodes. The most salient result was the greater readiness potential amplitude discovered in participants who ended up carrying out the movement, which indicates that the level of preparation in a repetitive task is greater when a final response is required. No group differences were found for the other potentials.

Acoustic Stimulation↗
PubMed2005

The contribution of AERPs (MMN and LDN) to studying temporal vs. linguistic processing deficits in children with reading difficulties.

One of the factors responsible for the appearance of reading problems seems to be a difficulty in discriminating auditory stimuli presented in rapid succession, known as the 'temporal processing hypothesis'. In this study automatic discrimination processes were evaluated in 31 children with reading difficulties and 24 control children between 4 and 8 years of age, using a passive oddball paradigm, in which syllables (/ba/ and /da/) and complex tones were presented. Analysis of the MMN component revealed significant differences between the groups only in the task involving linguistic stimuli, detecting longer latency of the component in the experimental group. The LDN component showed lower amplitudes and delayed latencies in the experimental group during the processing of both types of stimuli. These differences, however, were more marked in the task involving syllables, where a higher mean amplitude was observed in the experimental group than in the control group in the right hemisphere. The task involving complex tones also revealed differences between the groups at the frontal electrodes, indicating different maturative courses of the potential. The findings demonstrate the existence of a strongly pronounced preattentional auditory deficit during phonological processing, and also reveal important differences between the various stages of automatic information processing in children with and without reading disabilities.

Analysis of Variance↗
PubMed2005

Stimulus intensity effects on P300 amplitude across repetitions of a standard auditory oddball task.

An evaluation was made of whether stimulus intensity affects changes of P300 amplitude in response to repeated presentation of the target stimulus in a standard auditory oddball task. P300 latency values were also evaluated. Three samples were selected, one for each intensity used: 65, 85 and 105 dB SPL (sound pressure level). Five hundred tones (5 subblocks, 100 tones each) were presented. P300 amplitude (1) increased from Fz to Pz, (2) was larger at 105 than 65 or 85 dB SPL, (3) increased from the first to second subblock and decreased from the second subblock onwards at the three intensities, replicating our previous findings at 85 dB SPL and demonstrating a consistent phenomenon, and (4) at 105 dB SPL, the decrease was less pronounced, which we attribute to the more intense stimuli capturing the attention in a sustained manner during the task and interfering with the possible automation of the context-updating process.

Acoustic Stimulation↗
PubMed2005

Effect of food restriction on the insulin signalling pathway in rat skeletal muscle and adipose tissue.

We tried to elucidate the effects of a brief and severe model of food restriction on insulin sensitivity in female rats, focusing on key proteins involved in the insulin signalling pathway in skeletal muscle and adipose tissue after 5, 10 and 15 days of food restriction. Using euglycemic clamp, we detected that food-restricted rats are significantly less sensitive to insulin action than control rats. However, the time of restriction promotes a progressive increase on insulin sensitivity. The analysis of the insulin signalling pathway showed a tissue-specific regulation of several proteins involved in insulin signalling. In skeletal muscle, insulin receptor substrate 1 and Glut4 are up-regulated at the end of the food restriction period, just the opposite of what we found in adipose tissue. In conclusion, a 50% reduction of food intake modulates insulin sensitivity through a tissue-specific regulation of the insulin signalling pathway in the main target tissues for this hormone.

Adipose Tissue↗
PubMed2004

Changes in P300 amplitude during an active standard auditory oddball task.

This study evaluated whether P300 amplitude declines in response to repeated presentation of the target in a standard auditory oddball task; to what extent the decrease is affected by the number of targets presented, interrupted by an interblock interval (IBI, 3 min) and consistent. We also aimed to identify factors inducing P300 amplitude decrease and its psychological significance. Two blocks of 500 tones (each divided into five subblocks of 100 tones) were presented. First block: P300 amplitude was smaller in the first subblock than in the second, which we attribute to processing resources during the first subblock being divided between the task of identifying the target and the process of estimating subjective probability. Amplitude decreased from the second subblock onwards. The interblock interval was sufficient for amplitude to return to pre-decrease levels. The intrablock decline was replicated in the second block. The decline in P300 amplitude might to reflect a progressive automation of the context-updating operations.

Adolescent↗
PubMed2004

Implication of inflammation-related cytokines in the natural history of liver cirrhosis.

BACKGROUND/AIMS: Increased serum concentrations of pro-inflammatory cytokines have been detected in patients with liver cirrhosis. However, their role in the natural history of cirrhosis and portal hypertension, in the absence of infection, and the prognostic significance of inflammation-related cytokines have not been reported. Our objective was the analysis of the prognostic value of inflammation-related cytokines in cirrhotic patients. PATIENTS AND METHODS: Serum concentrations of tumor necrosis factor (TNF-alpha) and its soluble receptors I and II and interleukin 6 (IL-6), as well as mean blood pressure, plasma renin activity, aldosterone, vasopressin and norepinephrine concentrations were determined in 72 cirrhotic patients (Child-Pugh score: A 50%, B 33.3%, C 16.7%), without any evidence of infection, and in 25 healthy controls. Patients were followed up for a median of 35.9 (range 6-60) months. RESULTS: Increased concentrations of soluble TNF receptors were detected in cirrhotic patients when compared with healthy controls. TNF receptors and IL-6 concentrations were both significantly more elevated in advanced phases of cirrhosis (Child-Pugh score C vs B and vs A). Sixteen patients died as a related consequence of liver cirrhosis. Multivariant analysis demonstrated that Child-Pugh score, mean blood pressure and serum levels of TNF receptor I were associated with mortality. CONCLUSIONS: In addition to the classic factors implicated in mortality (Child-Pugh score and hemodynamic parameters), alterations in inflammation-related components are of prognostic significance in cirrhotic patients.

Aged↗
PubMed2003

Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus.

To evaluate the factors associated with the evolution of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients, a cross-sectional analysis of 41 HIV-infected patients with chronic hepatitis C (known as "HIV-HCV [hepatitis C virus]-coinfected patients") and a control group of patients with chronic hepatitis C who did not have HIV infection (known as "non-HIV-infected patients") was performed. The association of histological variables with demographic parameters, HCV load and genotype, HIV load, CD4(+) T cell count, and response to highly active antiretroviral therapy (HAART) was evaluated. HIV-HCV-coinfected patients showed a significantly higher HCV load, more-advanced fibrosis, and a higher liver fibrosis progression rate (FPR) than did non-HIV-infected patients. A high HCV load and a low CD4(+) T cell count were associated with a higher FPR. The immune response induced by HAART did not influence this progression. In conclusion, HIV-HCV-infected patients, mainly such patients with a high HCV load and an immunodepressed state, have a higher FPR. An independent effect of the immune response to HAART was not evident.

Adult↗
PubMed2002

Dilutional hyponatremia in patients with cirrhosis and ascites.

OBJECTIVES: To analyze the predisposing factors, modifications of vasoactive systems, and prognosis of patients with cirrhosis and hyponatremia. PATIENTS AND METHODS: Fifty-four patients with hyponatremia (serum sodium level of <130 mEq/L after 5 days of hyponatremic diet and no diuretic therapy). Twenty cirrhotic patients served as controls. We measured plasma renin activity and levels of plasma aldosterone, norepinephrine, and antidiuretic hormone. Follow-up identified the development of hepatorenal syndrome and death. RESULTS: A higher percentage of patients with hyponatremia had decreased liver size, higher levels of plasma renin activity, and higher serum concentrations of aldosterone and norepinephrine. Renal insufficiency was detected in 31 of them (57%). Precipitating factors (hemorrhage or infections) were detected in 27 patients (50%). Incidence of hepatorenal syndrome and death were higher in patients with spontaneous development of hyponatremia (n = 23 [85%] and n = 25 [93%], respectively) than in patients with precipitating factors (n = 15 [56%] and n = 12 [44%], respectively) and cirrhotic controls (n = 1 [5%] and n = 5 [25%], respectively) (P<.001). Results of multivariate analysis showed that Child-Pugh index, presence of hepatocarcinoma, and serum concentration of urea were associated with mortality. After excluding those patients with kidney failure at the time of admission, only Child-Pugh index and norepinephrine concentrations were independent predictors of mortality. CONCLUSIONS: Hyponatremia is an alteration in patients with advanced liver disease. Although survival is significantly reduced in patients with spontaneous development of hyponatremia, a reduced sodium concentration cannot be considered as a independent predictor of the risk for death.

Age Distribution↗
PubMed2002

Role of 17beta-estradiol administration on insulin sensitivity in the rat: implications for the insulin receptor.

The role of 17beta-estradiol in the early steps of insulin action is only partially known, although its effect on glucose homeostasis has been reported. In this paper, we attempt to prove the influence of 17beta-estradiol on the insulin receptor of ovariectomized rats treated with different hormonal doses. Our results show that high doses of estradiol impair insulin sensitivity while low doses improve it. We think that these results are the consequence of changes at a molecular level, because high doses of estradiol produced lower expression of the insulin receptor gene, lower content of this receptor in target tissues, and lower phosphorylation of insulin receptor in these tissues. However, low doses of estradiol seem to produce just the opposite. The possible existence of consensus response elements in the insulin receptor gene promoter to estradiol could be controlling the expression of this gene, this control being dose and timing dependent. Moreover, we cannot discard a possible effect of estradiol on the activity of protein tyrosine phosphatases, and therefore, on the activity of the insulin receptor. These new findings improve knowledge about the possible risk for insulin resistance in women taking oral contraceptives or receiving hormonal replacement therapy around the menopause, but could also open the door towards the possible utilization of 17beta-estradiol in some diabetes cases.

Adipose Tissue↗