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- Des-Acyl-Ghrelin (DAG) Normalizes Hyperlactacidemia and Improves Survival in a Lethal Rat Model of Burn Trauma. [JOURNAL ARTICLE]
- Peptides 2014 Jul 22.
Critical illness, including burn injury, results in elevated plasma lactate levels. Dysregulation of PI3K/Akt signaling has been shown to play a predominant role in the inactivation of skeletal muscle PDC and, hence, in hyperlactacidemia in rat models of sepsis and endotoximia. This observation, and our previous finding that DAG can reverse burn-induced skeletal muscle proteolysis through the activation of PI3K/Akt pathway, led us to hypothesize that DAG may also attenuate hyperlactacidemia in burn injury. Our investigations revealed that burn injury significantly elevated both skeletal muscle lactate production and plasma lactate levels. Moreover, this was accompanied in skeletal muscle by a 5-7 fold increase in mRNA expression of pyruvate dehydrogenase kinases (PDK) 2 and 4, and a ∼30% reduction in PDC activity. DAG treatment of burn rats completely normalized not only the mRNA expression of the PDKs and PDC activity, but also hyperlactacidemia within 24h of burn injury. DAG also normalized epinephrine-induced lactate production by isolated skeletal muscles from normal rats. Moreover, DAG also improved survival in a lethal rat model of burn trauma. These findings with DAG may have clinical implications because chances of survival for critically ill patients are greatly improved if plasma lactate levels are normalized within 24h of injury.
- Cardiac arrest teams and time of day: effects on surviving in-hospital resuscitation. [Journal Article]
- Int J Gen Med 2014.:319-23.
Little is known about the factors that influence survival following in-hospital resuscitation, but previous investigations have suggested that in-hospital resuscitations outside of regular working hours are associated with worse survival rates.In-hospital cardiac arrest teams at our hospital were instructed to complete a questionnaire following every emergency call between July 2011 and June 2013. Data on all resuscitation attempts were collected and analyzed.A total of 65 in-hospital resuscitations were recorded in 42 males (64.6%) and 23 females (35.4%) (mean age 72.0±14.3 years). A total of 54 (83.1%) cardiac arrests were witnessed; seven (10.8%) showed a shockable rhythm at the time of the first ECG. Resuscitation attempts lasted 29.3±41.3 minutes, and 4.1±3.1 mg epinephrine was given. Return of spontaneous circulation could be achieved in 38 patients (58.5%); 29 (44.6%) survived the first day, 23 (35.4%) the seventh day, and 15 patients (23.1%) were discharged alive. Significantly more in-hospital resuscitations were obtained for those performed during non-regular working hours (P<0.001), with higher neuron-specific enolase levels at 72 hours after resuscitation during nonregular working hours (P=0.04). Patients who were discharged alive were significantly younger (P=0.01), presented more often with an initial shockable rhythm (P=0.04), and had a shorter duration of resuscitation (P<0.001) with the need of a lower dose of epinephrine (P<0.001).Survival rates following in-hospital resuscitation were poor at any time, but appear to depend less on time-dependent effects of the quality of resuscitation and more on time-dependent effects of recognition of cardiac arrests.
- Short- and Long-Term Outcome in Elderly Patients After Out-of-Hospital Cardiac Arrest: A Cohort Study. [JOURNAL ARTICLE]
- Crit Care Med 2014 Jul 22.
Determinants of outcome and long-term survival are unknown in elderly patients successfully resuscitated after out-of-hospital cardiac arrest. Our aim was to identify factors associated with short- and long-term neurologic outcome in such patients.Retrospective cohort study.Tertiary hospital in Paris, France.Patients aged over 75 admitted in our ICU after an out-of-hospital cardiac arrest between 2000 and 2009.None.Two hundred twenty-five patients were included in the study. Fifty-seven patients (25.3%) had a good neurologic outcome at ICU discharge (Cerebral Performance Category 1-2). By multivariate logistic regression analysis, factors associated with good short-term outcome were time from collapse to cardiopulmonary resuscitation less than or equal to 3 minutes (odds ratio = 4.06; 95% CI, 1.49-11.09, p = 0.006) and blood lactate level less than or equal to 5.1 mmol/L (odds ratio = 3.30; 95% CI, 1.05-10.39, p = 0.04), but age less than or equal to 79.5 years and use of induced hypothermia were not. Long-term survivors were assessed for cognitive and functional status (using Cerebral Performance Category and Overall Performance Category scales), and their survival was compared with a large community-based cohort of participants over 75 years. The 1-year survival of ICU survivors (mean follow-up, 28.4 mo) was 69.3% (95% CI, 55.8-79.5) as compared with 95.3% (95% CI, 93.3-97.3) in the control community-based cohort (p< 0.001), resulting in a standardized mortality ratio of 3.49 (95% CI, 2.42-4.85). By multivariate Cox proportional hazard model, factors associated with long-term survival were initial shockable rhythm (hazard ratio = 1.41; 95% CI, 1.01-1.96; p = 0.04), epinephrine cumulate dose less than or equal to 3 mg (hazard ratio = 1.48; 95% CI, 1.06-2.08; p = 0.02), and blood lactate level less than or equal to 5.1 mmol/L (hazard ratio = 2.11; 95% CI, 1.5-2.96; p < 0.001). When available at end of follow-up, 91% and 74% of the patients were classified Cerebral Performance Category 1 and Overall Performance Category 1, respectively.Neurologic outcome in successfully resuscitated elderly patients depends on cardiac arrest characteristics rather than age. Short-term survival is 25% with acceptable long-term outcome among survivors.
- Effects of lycium barbarum polysaccharides on neuropeptide Y and heat-shock protein 70 expression in rats exposed to heat. [JOURNAL ARTICLE]
- Biomed Rep 2014 Sep; 2(5):687-692.
The purpose of the present study was to investigate the effects of high ambient temperature on the neuropeptide Y (NPY) mRNA level in the hypothalamus, the plasma concentration of corticotropin-releasing hormone (CRH), cortisol (Cor), heat-shock protein 70 (HSP70) and epinephrine (EPI), and the intervention of lycium barbarum polysaccharides (LBPs) in rats. Compared to the control (CN) group, the plasma levels of CRH, Cor, HSP70 and EPI were markedly increased, and the level of NPY mRNA was downregulated in the high ambient temperature (HT) group. By contrast, rats in the HT + LBP (HTL) group had: i) a significantly enhanced expression of HSP70 compared to the HT and CN groups; ii) clearly increased plasma levels of CRH, Cor and EPI compared to the CN group; and iii) a markedly upregulated expression of NPY mRNA compared to the HT group. Thus, the results showed that high-temperature environments may damage the body, and LBPs have a potentially protective function by increasing the expression of HSP70 and NPY.
- Platelet function in Takotsubo cardiomyopathy. [JOURNAL ARTICLE]
- J Thromb Thrombolysis 2014 Jul 23.
Takotsubo cardiomyopathy (TK) includes a transient left ventricular dysfunction without obstructive coronary disease, sometimes after stressful situations with elevated cathecolamines. Since catecholamines activate platelets we aimed to study the platelet influence in a TK setting. We included 32 patients with a TK diagnosis, 13 with an acute coronary syndrome (ACS) and 18 healthy volunteers. Once consent informed was obtained, blood samples were extracted and processed (at admission and after 3 months follow-up). Clinical, ecg, echocardiographic and angiographic features were thoroughly recorded.Previous treatment before admission was similar between groups. No differences were observed in clinical features or any of the acute markers studied regarding platelet reactivity between TK compared to ACS. After follow-up, aggregation levels and platelet reactivity showed differences, mainly due to the antithrombotic therapy prescribed at discharge, but similar to volunteers. Circulating epinephrine during the acute phase was significantly higher in TK (p < 0.001). Patients with higher levels of epinephrine had elevated platelet activation and aggregation after 3 months. No differences were observed in Takotsubo acute platelet aggregation compared to patients with ACS, in spite of higher blood levels of adrenaline. Takotsubo patients had elevated platelet aggregation and activation compared with ACS patients at 3 months follow-up because they were less frequently on chronic clopidogrel and ASA. However, they had similar platelet aggregation and activation levels to healthy volunteers despite treatment with low-dose ASA. Takotsubo patients who had higher levels of adrenaline in the acute phase displayed increased platelet reactivity during follow-up.
- Nicotinic cholinergic receptors in glucose homeostasis: the acute hyperglycemic and chronic insulin-sensitive effects of nicotine suggest dual opposing roles of the receptors in male mice. [JOURNAL ARTICLE]
- Endocrinology 2014 Jul 22.:en20141320.
Cigarette smoking causes insulin resistance. However, nicotine induces anti-inflammation and improves glucose tolerance in insulin resistant animal models. Here, we determined the effects of nicotine on glucose metabolism in insulin sensitive C57BL/J6 mice. Acute nicotine administration (30 min) caused fasting hyperglycemia and lowered insulin sensitivity acutely, which depended on the activation of nicotinic-cholinergic receptors (nAChRs) and correlated with increased catecholamine secretion, nitric oxide (NO) production, and glycogenolysis. Chlorisondamine (CSM), an inhibitor of nAChRs, reduced acute nicotine-induced hyperglycemia. Quantitative RT-PCR analysis revealed that the liver and muscle express predominantly β4>α10>α3>α7 and β4>α10>β1>α1 mRNA for nAChR subunits respectively, whereas the adrenal gland expresses β4>α3>α7>α10 mRNA. Chronic nicotine treatment significantly suppressed expression of α3-nAChR (predominant peripheral α-subunit) in liver. While acute nicotine treatment raised plasma norepinephrine (NE) and epinephrine (Epi) levels, chronic nicotine exposure raised only Epi. Acute nicotine treatment raised both basal and glucose-stimulated insulin secretion (GSIS). After chronic nicotine treatment, basal insulin level was elevated, but GSIS after acute saline or nicotine treatment was blunted. Chronic nicotine exposure caused an increased buildup of NO in plasma and liver, leading to decreased glycogen storage, along with a concomitant suppression of Pepck and G6Pase mRNA, thus preventing hyperglycemia. The insulin sensitizing effect of chronic nicotine was independent of weight loss. Chronic nicotine treatment enhanced PI-3K activities and increased Akt and GSK-3β phosphorylation in a nAChR-dependent manner coupled with decreased CREB phosphorylation. The latter effects caused suppression of Pepck and G6Pase gene expression. Thus, nicotine causes both insulin resistance and insulin sensitivity depending on the duration of the treatment.
- Spinal anesthesia revisited: toxicity of new and old drugs and compounds. [JOURNAL ARTICLE]
- Curr Opin Anaesthesiol 2014 Jul 19.
Neural toxicity of substances injected into the intrathecal space has been a matter of debate since the introduction of spinal anesthesia in clinical practice. In recent years, new local anesthetics and adjuvants have been proposed for intrathecal use, and new techniques such as the use of ultrasound have been propagated. The present review summarizes recent clinical and experimental data on the neurotoxic effects of drugs and substances used for or in conjunction with spinal anesthesia.Chloroprocaine has been demonstrated to be associated with a lower risk of transient neurologic symptoms compared with lidocaine. However, despite extensive research, the issue of chloroprocaine or bisulfite neurotoxicity has not yet been resolved.Recent experimental data have identified a smaller neurotoxic potential for ropivacaine compared to levobupivacaine, procaine and bupivacaine. The addition of epinephrine has not been shown to increase lidocaine neurotoxicity. In-vivo experimental data suggest that lidocaine and bupivacaine neurotoxicity is not enhanced in diabetic patients.Furthermore, intrathecal introduction of aqueous ultrasound gel has been demonstrated to cause a distinct neuroinflammatory reaction. Finally, a large cohort study did not find the use of chlorhexidine gluconate for skin disinfection before neuraxial block to be associated with the risk of adhesive arachnoiditis.Clinical data suggest a high safety profile for intrathecal drugs and substances used for or in conjunction with spinal anesthesia. Recent experimental models for toxicity have provided further insight into the mechanisms and demonstrated possible, albeit clinically small differences in the relative neurotoxic potential of intrathecal drugs. This may contribute to a further increase in the safe use of spinal anesthesia in the clinical setting.
- Simultaneous determination of epinephrine and dopamine by electrochemical reduction on the hybrid material SiO2/graphene oxide decorated with Ag nanoparticles. [JOURNAL ARTICLE]
- Analyst 2014 Jul 22.
This paper describes the synthesis, characterization and applications of a new hybrid material composed of mesoporous silica (SiO2) modified with graphene oxide (GO), SiO2/GO, obtained by the sol-gel process using HF as the catalyst. The hybrid material, SiO2/GO, was decorated with silver nanoparticles (AgNPs) with a size of less than 20 nanometres, prepared directly on the surface of the material using N,N-dimethylformamide (DMF) as the reducing agent. The resulting material was designated as AgNP/SiO2/GO. The Ag/SiO2/GO material was characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) and high-resolution transmission electron microscopy (HR-TEM). A glassy carbon electrode modified with AgNP/SiO2/GO was used in the development of a sensitive electrochemical sensor for the simultaneous determination of epinephrine and dopamine employing electrocatalytic reduction using squarewave voltammetry. Well-defined and separate reduction peaks were observed in PBS buffer at pH 7. No significant interference was seen for primarily biological interferents such as uric acid and ascorbic acid in the detection of dopamine and epinephrine. Our study demonstrated that the resultant AgNP/SiO2/GO-modified electrode is highly sensitive for the simultaneous determination of dopamine and epinephrine, with the limits of detection being 0.26 and 0.27 μmol L(-1), respectively. The AgNP/SiO2/GO-modified electrode is highly selective and can be used to detect dopamine and epinephrine in a human urine sample.
- Clinicopathologic Characteristics of Incidentally Identified Pheochromocytoma. [JOURNAL ARTICLE]
- Ann Surg Oncol 2014 Jul 22.
Pheochromocytomas are rare neuroendocrine tumors. With the widespread use of cross-sectional imaging, increasing numbers are identified incidentally, but their clinicopathologic traits have been incompletely characterized.We performed a retrospective cohort study of patients who underwent initial adrenalectomy for pheochromocytoma (1997-2014). Patients were classified as identified by guided investigation (GIP) if imaging was performed for symptoms or surveillance and as incidentally identified pheochromocytomas (IIP) if imaging was performed for other indications. Student's t test, Chi square test, or rank-sum tests were used as appropriate.Of 126 patients, 47 % were IIP (n = 59). IIP patients had more nonspecific symptoms, including abdominal or back pain (39.0 vs. 6.0 %, p < 0.001), but lower rates of classic symptoms, such as hypertension (54.2 vs. 77.6 %, p = 0.005), palpitations or arrhythmias (18.9 vs. 50.0 %, p = 0.001), flushing or diaphoresis (25.4 vs. 46.3 %, p = 0.015), and headache (20.3 vs. 44.8 %, p = 0.004). IIP was associated with lower median 24-hour urine metanephrine (2102 vs. 7299 μg, p = 0.020), normetanephrine (2253 vs. 4383 μg, p = 0.005), and epinephrine (23 vs. 116 μg, p = 0.004) levels. Histopathology demonstrated no difference between IIP and GIP in malignant traits, including extraadrenal extension (8.6 vs. 12.3 %, p = 0.568), capsular invasion (26.9 vs. 20.3 %, p = 0.133), lymphovascular invasion (25.0 vs. 24.6 %, p = 0.264), and necrosis (32.4 vs. 20.0 %, p = 0.224). Rates of malignancy were equivalent (5.1 vs. 6.0 %, p = 0.862) between IIP and GIP cohorts.Half of patients presenting for surgical resection of pheochromocytoma were identified incidentally. These patients had equivalent rates of malignancy and pathologic traits associated with malignant potential and require definitive evaluation and early surgical referral.
- Differential circadian catecholamine and cortisol responses between healthy women with and without a parental history of hypertension. [JOURNAL ARTICLE]
- Am J Hum Biol 2014 Jul 15.
Previous studies suggest that otherwise healthy individuals who have a parental history of hypertension (PH+) have an accentuated reactive rise in catecholamines and cortisol to laboratory stressors as well as elevated plasma levels when compared with those with no parental history (PH-); however, few, if any, studies have evaluated whether parental history affects the responses of these hormones to changing environmental circumstances in everyday life. The purpose of this study was to compare urinary catecholamine (epinephrine and norepinephrine) and cortisol excretion and ambulatory blood pressures (BPs) across three daily microenvironments between women with and without a parental history of hypertension.The women in the study (PH+, N = 62, age = 35.2 ± 9.1; PH-, N = 72, age = 33.8 ± 10.0) worked in clerical, technical, or professional positions at a major medical center in New York City. Urinary hormone excretion rates and ambulatory BP were measured across three daily microenvironments: work (11 am to 3 p.m.), home (approximately 6 p.m. to 10 p.m.), and during sleep (approximately 10 p.m. to 6 a.m.). History group comparisons by microenvironment were made using repeated-measures ANCOVA and ANOVA analyses.The results show that epinephrine excretion among PH+ women was 36% higher than PH- women (P < 0.008) over the entire day and that nocturnal cortisol excretion was also greater among PH+ women (P < 0.045). PH+ women also had statistically significantly higher systolic (4 mm Hg higher; P < 0.01) and diastolic (2 mm Hg higher, P < 0.03) BP when compared with PH- women across all daily microenvironments.These findings suggest that there may be genetically linked mechanisms which elevate tonic epinephrine levels and nocturnal cortisol levels that contribute to elevating circadian BP. Am. J. Hum. Biol., 2014. © 2014 Wiley Periodicals, Inc.