Long-term dynamics of somatosensory activity in a stroke model of distal middle cerebral artery oclussion

A constant challenge in experimental stroke is the use of appropriate tests to identify signs of recovery and adverse effects linked to a particular therapy. In this study, we used a long-term longitudinal approach to examine the functional brain changes associated with cortical infarction in a mouse model induced by permanent ligation of the middle cerebral artery (MCA). Sensorimotor function and somatosensory cortical activity were evaluated with fault-foot and forelimb asymmetry tests in combination with somatosensory evoked potentials. The stroke mice exhibited both long-term deficits in the functional tests and impaired responses in the infarcted and intact hemispheres after contralateral and ipsilateral forepaw stimulation. In the infarcted hemisphere, reductions in the amplitudes of evoked responses were detected after contralateral and ipsilateral stimulation. In the intact hemisphere, and similar to cortical stroke patients, a gradual hyperexcitability was observed after contralateral stimulation but no parallel evidence of a response was detected after ipsilateral stimulation. Our results suggest the existence of profound and persistent changes in the somatosensory cortex in this specific mouse cortical stroke model. The study of evoked potentials constitutes a feasible and excellent tool for evaluating the fitness of the somatosensory cortex in relation to functional recovery after preclinical therapeutic intervention

Increasing blood glucose variability is a precursor of sepsis and mortality in burned patients.

High glycemic variability, rather than a mean glucose level, is an important factor associated with sepsis and hospital mortality in critically ill patients. In this retrospective study we analyze the blood glucose data of 172 nondiabetic patients 18-60 yrs old with second and third-degree burns of total body surface area greater than 30% and 5%, respectively, admitted to ICU in 2004-2008. The analysis identified significant association of increasing daily glucose excursion (DELTA) accompanied by evident episodes of hyperglycemia (>11 mmol/l) and hypoglycemia (<2.8 mmol/l), with sepsis and forthcoming death, even when the mean daily glucose was within a range of acceptable glycemia. No association was found in sepsis complication and hospital mortality with doses of intravenous insulin and glucose infusion. A strong increase in DELTA before sepsis and death is treated as fluctuation amplification near the onset of dynamical instability

Comparison of clinical characteristics and glucose, cortisol, and insulin indices of three ICU groups: survivors without sepsis (Group 1), survivors with sepsis (Group 2) and non-survivors (Group 3).

<p>Data are numbers (%) or medians [interquartile range]. APACHE = Acute Physiology and Chronic Health Evaluation; ICU = Intensive Care Unit, IU = International Units.</p>1<p>P₁₂ value was determined with the use of Mann-Whitney U-test between survivors without sepsis and survivors with sepsis.</p>2<p>P₂₃ value was determined with the use of Mann-Whitney U-test between survivors with sepsis and non-survivors.</p>3<p>To convert the values for glucose from mmol/l to mg/dl, multiply by 18.018.</p>4<p>During the whole ICU stay.</p>5<p>One day before a date when sepsis was identified.</p>6<p>One day before death.</p

Distribution of DELTA before sepsis and death.

<p>(a) Three and (b) one day before sepsis. (c) Three and (d) one day before death. The solid lines are Gaussian approximations.</p

Time series of glucose measurements for patients from Group 1 (survivors without sepsis).

<p>Instant BG concentration (left axis), mean daily glucose (left axis), and daily glucose variation DELTA (right axis) are shown, respectively, by black squares, blue dots, and red triangles.</p

Time series of glucose measurements for patients from Group 2 (survivors with sepsis).

<p>The arrows indicate the measurements in which the blood culture was identified. DELTA reaches a maximum value in a sepsis state. Patient G had two sepsis episodes during his ICU stay.</p

Increasing DELTA near critical point.

<p>Red crosses and black squares indicate, respectively, DELTA of survived and non-survived patients before sepsis and before death. Red and black curves are the exponential approximations with 2.6 and 5.6 growth rates, respectively.</p

Optical Hyperthermia Using Anti-Epidermal Growth Factor Receptor-Conjugated Gold Nanorods to Induce Cell Death in Glioblastoma Cell Lines

Gold nanorods (GNRs) are able to efficiently convert absorbed light into localized heat within a short period of time due to the surface plasmon resonance effect. This property, along with their easy bioconjugation, allows the use of GNRs in photothermal therapy as selective photothermal agents to target cancer cells. In this study, GNRs were combined with an antibody against anti-epidermal growth factor receptor (EGFR), a receptor that is frequently overexpressed in brain tumors, and the potential of the nanoconjugate (EGFR-GNRs) to eliminate tumor cells was assessed in vitro. Two human glioblastoma cell lines (U373-MG and 1321N1) expressing EGFR at different levels were incubated with unfunctionalized GNRs and EGFR-GNRs, and then exposed to irradiation with a continuous-wave laser at 808 nm. The pretreatment with the EGFR-GNR nanoconjugate significantly increased the cell death rate after laser irradiation compared to unconjugated GNRs. No photothermal cell destruction was observed in the absence of GNRs. Our data suggest that the EGFR modification improves GNR-mediated cell death after laser irradiation, even when EGFR is present at low doses in cancer cells, and may have the potential to be used clinically as a tool to help complete resection of brain tumors during surgery.Fil: Fernández Cabada, Tamara. Universidad Politécnica de Madrid; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pablo, Cristina Sánchez López de. Universidad Politécnica de Madrid; España. Centro de Investigación Biomédica en Red; EspañaFil: Pisarchyk, Liudmila. Universidad Politécnica de Madrid; EspañaFil: Serrano Olmedo, José Javier. Universidad Politécnica de Madrid; España. Centro de Investigación Biomédica en Red; EspañaFil: Ramos Gómez, Milagros. Universidad Politécnica de Madrid; España. Centro de Investigación Biomédica en Red; Españ

Whole-Body and Hepatic Insulin Resistance in Obese Children

<div><p>Background</p><p>Insulin resistance may be assessed as whole body or hepatic.</p><p>Objective</p><p>To study factors associated with both types of insulin resistance.</p><p>Methods</p><p>Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound.</p><p>Results</p><p>The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver.</p><p>Conclusion</p><p>In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance.</p></div