Bárbara Oliveiros

Hypoxia-induced redox alterations and their correlation with 99mTc-MIBI and 99mTc-HL-91 uptake in colon cancer cells

Colorectal cancer is one of the most common malignancies in the Western world and is an example of a solid tumour in which hypoxia is a common feature and develops because of the inability of the vascular system to supply adequate amounts of oxygen to growing tumours. Hypoxia effects on tumour cell biology can be detected and characterized using different methods. The use of imaging with gamma-emitting radionuclides to detect hypoxic tissue was first suggested by Chapman in 1979 [N Engl J Med 301 (1979) 1429-1432]. (99m)Tc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime, also known as (99m)Tc-HL-91, has been among the most studied hypoxia markers. The objective of this study was to correlate the uptake of (99m)Tc-HL-91 and (99m)Tc-MIBI in colon cancer cells under normoxic and hypoxic conditions and to compare this information with some parameters such as oxidative stress and mitochondrial dysfunction of the cells analyzed by flow cytometry. Our results show that the in vitro (99m)Tc-HL-91 uptake is higher in hypoxic conditions, which is confirmed by the decreased uptake of (99m)Tc-MIBI. Flow cytometry results demonstrate that hypoxic conditions used are not enough to induce cellular death, but are responsible for the alterations in the intracellular redox environment, namely, increase of ROS production, proteic pimonidazol-derived adduct formation and alteration in the mitochondrial membrane permeability. Therefore, these results confirm that (99m)Tc-HL-91 is a radiopharmaceutical with favourable characteristics for detecting hypoxia.

Aging of Low and High Level Vision: From Chromatic and Achromatic Contrast Sensitivity to Local and 3D Object Motion Perception

The influence of normal aging in early, intermediate and high-level visual processing is still poorly understood. We have addressed this important issue in a large cohort of 653 subjects divided into five distinct age groups, [20;30[, [30;40[, [40;50[, [50;60[and [60;[. We applied a broad range of psychophysical tests, testing distinct levels of the visual hierarchy, from local processing to global integration, using simple gratings (spatial contrast sensitivity -CS- using high temporal/low spatial frequency or intermediate spatial frequency static gratings), color CS using Landolt patches, moving dot stimuli (Local Speed Discrimination) and dot patterns defining 3D objects (3D Structure from Motion, 3D SFM). Aging data were fitted with linear or quadratic regression models, using the adjusted coefficient of determination (R2 a) to quantify the effect of aging. A significant effect of age was found on all visual channels tested, except for the red-green chromatic channel. The high temporal low spatial frequency contrast sensitivity channel showed a mean sensitivity loss of 0.75 dB per decade (R2 a = 0.17, p<0.001), while the lower intermediate spatial frequency channel showed a more pronounced decrease, around 2.35 dB (R2 a = 0.55, p<0.001). Concerning low-level motion perception, speed discrimination decreased 2.71°/s (R2 a = 0.18, p<0.001) and 3.15°/s (R2 a = 0.13, p<0.001) only for short presentations for horizontal and oblique meridians, respectively. The 3D SFM task, requiring high-level integration across dorsal and ventral streams, showed the strongest (quadratic) decrease of motion coherence perception with age, especially when the task was temporally constrained (R2 a = 0.54, p<0.001). These findings show that visual channels are influenced by aging into different extent, with time presenting a critical role, and high-level dorso-ventral dominance of deterioration, which accelerates with aging, in contrast to the other channels that show a linear pattern of deterioration.

The Role of the Amygdala in Facial Trustworthiness Processing: A Systematic Review and Meta-Analyses of fMRI Studies

Background Faces play a key role in signaling social cues such as signals of trustworthiness. Although several studies identify the amygdala as a core brain region in social cognition, quantitative approaches evaluating its role are scarce. Objectives This review aimed to assess the role of the amygdala in the processing of facial trustworthiness, by analyzing its amplitude BOLD response polarity to untrustworthy versus trustworthy facial signals under fMRI tasks through a Meta-analysis of effect sizes (MA). Activation Likelihood Estimation (ALE) analyses were also conducted. Data sources Articles were retrieved from MEDLINE, ScienceDirect and Web-of-Science in January 2016. Following the PRISMA statement guidelines, a systematic review of original research articles in English language using the search string “(face OR facial) AND (trustworthiness OR trustworthy OR untrustworthy OR trustee) AND fMRI” was conducted. Study selection and data extraction The MA concerned amygdala responses to facial trustworthiness for the contrast Untrustworthy vs. trustworthy faces, and included whole-brain and ROI studies. To prevent potential bias, results were considered even when at the single study level they did not survive correction for multiple comparisons or provided non-significant results. ALE considered whole-brain studies, using the same methodology to prevent bias. A summary of the methodological options (design and analysis) described in the articles was finally used to get further insight into the characteristics of the studies and to perform a subgroup analysis. Data were extracted by two authors and checked independently. Data synthesis Twenty fMRI studies were considered for systematic review. An MA of effect sizes with 11 articles (12 studies) showed high heterogeneity between studies [Q(11) = 265.68, p < .0001; I2 = 95.86%, 94.20% to 97.05%, with 95% confidence interval, CI]. Random effects analysis [RE(183) = 0.851, .422 to .969, 95% CI] supported the evidence that the (right) amygdala responds preferentially to untrustworthy faces. Moreover, two ALE analyses performed with 6 articles (7 studies) identified the amygdala, insula and medial dorsal nuclei of thalamus as structures with negative correlation with trustworthiness. Six articles/studies showed that posterior cingulate and medial frontal gyrus present positive correlations with increasing facial trustworthiness levels. Significant effects considering subgroup analysis based on methodological criteria were found for experiments using spatial smoothing, categorization of trustworthiness in 2 or 3 categories and paradigms which involve both explicit and implicit tasks. Limitations Significant heterogeneity between studies was found in MA, which might have arisen from inclusion of studies with smaller sample sizes and differences in methodological options. Studies using ROI analysis / small volume correction methods were more often devoted specifically to the amygdala region, with some results reporting uncorrected p-values based on mainly clinical a priori evidence of amygdala involvement in these processes. Nevertheless, we did not find significant evidence for publication bias. Conclusions and implications of key findings Our results support the role of amygdala in facial trustworthiness judgment, emphasizing its predominant role during processing of negative social signals in (untrustworthy) faces. This systematic review suggests that little consistency exists among studies’ methodology, and that larger sample sizes should be preferred.

Hepatectomy and liver regeneration: from experimental research to clinical application.

The mechanisms and kinetics of hepatic growth have continuously been investigated. This study concerns liver regeneration in animal and patients who underwent partial hepatectomy evaluated by the hepatic extraction fraction (HEF) calculated through radioisotopic methods.

Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic syndrome development, diagnosis, and prognosis: A pilot study

Abstract The imbalance between reactive oxygen species (ROS) production and their elimination by antioxidants leads to oxidative stress. Depending on their concentration, ROS can trigger apoptosis or stimulate cell proliferation. We hypothesized that oxidative stress and mitochondrial dysfunction may participate not only in apoptosis detected in some myelodysplastic syndrome (MDS) patients, but also in increasing proliferation in other patients. We investigated the involvement of oxidative stress and mitochondrial dysfunction in MDS pathogenesis, as well as assessed their diagnostic and prognostic values. Intracellular peroxides, superoxide, superoxide/peroxides ratio, reduced glutathione (GSH), and mitochondrial membrane potential (Δψmit) levels were analyzed in bone marrow cells from 27 MDS patients and 12 controls, by flow cytometry. We observed that all bone marrow cell types from MDS patients had increased intracellular peroxide levels and decreased GSH content, compared with control cells. Moreover, oxidative stress levels were MDS subtype— and risk group—dependent. Low-risk patients had the highest ROS levels, which can be related with their high apoptosis; and intermediate-2-risk patients had high Δψmit that may be associated with their proliferative potential. GSH levels were negatively correlated with transfusion dependency, and peroxide levels were positively correlated with serum ferritin level. GSH content proved to be an accurate parameter to discriminate patients from controls. Finally, patients with high ROS or low GSH levels, as well as high superoxide/peroxides ratio had lower overall survival. Our results suggest that oxidative stress and mitochondrial dysfunction are involved in MDS development, and that oxidative stress parameters may constitute novel diagnosis and/or prognosis biomarkers for MDS.

Study of perioperative liver function by dynamic monitoring of ICG-clearance.

BACKGROUND/AIMS To investigate the impact of liver resection on the perioperative hepatic function by evaluation of ICG-clearance. METHODOLOGY Twenty-five patients underwent major hepatic resection (Group A) and 36 underwent minor hepatic resection (Group B). Thirteen patients who received no liver surgery, acted as control group (Group C). ICG-clearance measured by a non-invasive technique was expressed in terms of plasma disappearance rate (PDR-ICG-%/min) and retention rate of ICG 15 min (ICG-R15-%) after administration ICG (0.5mg/kg) before anesthesia induction (T0), immediately after the surgery (T1) and 24h after (T2). RESULTS There was statistically significant differences between the three groups: ICG-PDR (p<0.004) and ICG-R15 (p<0.040). These differences were observed between groups A and C at T1, between A and B, or A and C, at T2 for ICG-PDR and between groups A and B at T2 for ICG-R15. There were no differences between groups for hemoglobin, platelets, PT, creatinine, albumin, total protein, bilirubin and ALP. CONCLUSIONS ICG clearance is a safe non-invasive dynamic tool to quantify the liver function in patients following hepatic surgery. It also can be used to evaluate the liver surgery impact on hepatic function which can help to diagnose early hepatic dysfunction and guide the therapeutic decision making process.

Quantitative scintigraphic analysis of pulp revascularization in autotransplanted teeth in dogs

OBJECTIVE The purpose of this study was to evaluate the pulpal changes associated with autogenous single-rooted immature tooth transplantation in dogs, using either one, or two-stage surgical techniques. METHODS Teeth from 3 beagle dogs, 5 months old, were extracted and transplanted to mechanically prepared recipient sockets. Group (A), where the teeth were transplanted using a one-stage method to recipient beds prepared immediately before transplantation. Group (B), where the teeth were transplanted using a two-stage method in which the recipient beds were prepared and left to heal for 7 days before transplantation. Clinical examinations were done every week during 9 weeks. After 9 weeks, the animals were injected with ⁹⁹(m)Technetium hydroxylmethylene diphosphonate (⁹⁹(m)Tc-HMDP) and 3h after injection, a whole body scintigraphic acquisition was performed. After scintigraphic acquisition the animals were euthanized and the teeth extracted and its radioactivity counted in a well counter calibrated to ⁹⁹(m)Tc. With the data obtained, the percentage of activity injected was calculated for each tooth. The data for each group of teeth were evaluated and analyzed using the Mann-Whitney test (p=0.05). RESULTS All the transplanted teeth in both groups survived. No statistically significant difference was found in the absorption of the ⁹⁹(m)Tc-HMDP, between the treatment groups (p=0.464) and between them and the control group (Group A vs. control p=0.713 and Group B vs. control p=0.157). CONCLUSIONS This study demonstrated that there was no difference between the two surgical techniques in terms of the pulp revascularization in transplanted teeth.

Functional hepatocellular regeneration in elderly patients undergoing hepatectomy

More than 50% of liver tumours occur in patients aged 65 years or more. Assessment of functional liver regeneration capacity is crucial to minimize postoperative liver failure. We aimed to study functional hepatocellular regeneration, through scintigraphic quantification of Mebrofenin hepatic extraction fraction (HEF), after partial hepatectomy, comparing elderly patients with younger ones.

Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn

OBJECTIVE Anesthetic and operative interventions in neonates remain hazardous procedures, given the vulnerability of the patients in this pediatric population. The aim was to determine the preoperative and intraoperative factors associated with 30-day post-operative mortality and describe mortality outcomes following neonatal surgery under general anesthesia in our center. METHODS Infants less than 28 days of age who underwent general anesthesia for surgery during an 11-year period (2000 - 2010) in our tertiary care pediatric center were retrospectively identified using the pediatric intensive care unit database. Multiple logistic regression was used to identify independent preoperative and intraoperative factors associated with 30-day post-operative mortality. RESULTS Of the 437 infants in the study (median gestational age at birth 37 weeks, median birth weight 2,760 grams), 28 (6.4%) patients died before hospital discharge. Of these, 22 patients died within the first post-operative month. Logistic regression analysis showed increased odds of 30-day post-operative mortality among patients who presented American Society of Anesthesiologists physical status (ASA) score 3 or above (odds ratio 19.268; 95%CI 2.523 - 147.132) and surgery for necrotizing enterocolitis/gastrointestinal perforation (OR 5.291; 95%CI 1.962 - 14.266), compared to those who did not. CONCLUSION The overall in-hospital mortality of 6.4% is within the prevalence reported for developed countries. Establishing ASA score 3 or above and necrotizing enterocolitis/gastrointestinal perforation as independent risk factors for early mortality in neonatal surgery may help clinicians to more adequately manage this high risk population.

Development and aging of visual hemifield asymmetries in contrast sensitivity.

The relation of development and aging with models of visual anisotropies and their influence on low-level visual processing remain to be established. Our main goal was to explore visual performance asymmetries in development and normal aging using low-level contrast sensitivity behavioral tasks [probing two distinct spatiotemporal frequency channels, (a) intermediate spatial and null temporal frequency (3.5 cycles per degree (cpd) and 0 Hz); and (b) low spatial and high temporal frequency (0.25 cpd undergoing 25 Hz counterphase flicker)]. Different patterns of functional asymmetries were investigated within four (two neurodevelopmental and two adult) age groups (N = 258 participants; 8-65 years). We found a left visual hemifield/right hemisphere advantage for only the intermediate spatial frequency channel that was present early in life and remained stable throughout adulthood. In contrast, inferior/superior visual hemifield asymmetries, with a direct ecological meaning, were found for both spatiotemporal frequency channels. This inferior visual hemifield advantage emerged early in life and persisted throughout aging. These findings show that both right hemispheric and dorsal retinotopic patterns of dominance in low-level vision emerge early in childhood, maintaining during aging.