The mitochondrial division inhibitor Mdivi-1 rescues mammalian neurons from anesthetic-induced cytotoxicity.

BACKGROUND: Concerns have risen regarding the potential side effects of clinical exposure of the pediatric population to inhalational anesthetics, and how they might impact cognitive, learning, and memory functions. However, neither the mechanisms of anesthetic cytotoxicity, nor potential protective strategies, have yet been fully explored. In this study, we examined whether two of the most commonly used inhalational anesthetics, sevoflurane and desflurane, affect neuronal viability and synaptic network assembly between cultured rat cortical neurons. RESULTS: Primary rat cortical neuron cultures were exposed to equipotent sevoflurane or desflurane for 1 hour. Neuron viability, synaptic protein expression, mitochondrial morphology, and neurite growth were assayed with immunostaining and confocal microscopy techniques. The effects of anesthetics on the functional development of neural networks were evaluated with whole-cell patch clamp recordings of spontaneous synaptic currents. Our results demonstrate that an acute exposure to sevoflurane and desflurane inhibits the development of neurite processes, impacts the mitochondria, and compromises synaptic proteins - concomitant with a reduction in synaptic function in mature networks. Interestingly, pretreatment of neurons with a mitochondrial division inhibitor (Mdivi-1) not only protected mitochondria integrity but also played a protective role against anesthetic-induced structural and functional neurotoxicity. CONCLUSIONS: We show that Mdivi-1 likely plays a protective role against certain harmful effects of general anesthetics on primary rat neuronal cultures. In addition, Mdivi-1 alone plays a direct role in enhancing growth and modulating synaptic activity. This study highlights the importance of further study into possible protective agents against anesthetic neurotoxicity.

Red blood cell distribution width as a prognostic marker of mortality in patients on chronic dialysis: a single center, prospective longitudinal study.

AIM: To determine if red cell distribution width (RDW) is associated with all-cause mortality in patients on chronic dialysis and to evaluate its prognostic value among validated prognostic biomarkers. METHODS: This is a single center, prospective longitudinal study. At the time of inclusion in January 2011, all patients were physically examined and a routine blood analysis was performed. A sera sample was preserved for determination of NT-pro-brain natriuretic peptide (NT-pro-BNP) and eosinophil cationic protein. Carotid intima media thickness (IMT) was also measured. Following one year, all-cause mortality was evaluated. RESULTS: Of 100 patients, 25 patients died during the follow-up period of one-year. Patients who died had significantly higher median [range] RDW levels (16.7% [14.3-19.5] vs 15.5% [13.2-19.7], P<0.001. They had significantly higher Eastern Cooperative Oncology Group (ECOG) performance status (4 [2-4] vs 2 [1-4], Plt;0.001), increased intima-media thickness (IMT) (0.71 [0.47-1.25] vs 0.63 [0.31-1.55], P=0.011), increased NT-pro-BNP levels (8300 [1108-35000] vs 4837 [413-35000], P=0.043), and increased C-reactive protein (CRP) levels (11.6 [1.3-154.2] vs 4.9 [0.4-92.9], Plt;0.001). For each 1% point increase in RDW level as a continuous variable, one-year all cause mortality risk was increased by 54% in univariate Cox proportional hazard analysis. In the final model, when RDW was entered as a categorical variable, mortality risk was significantly increased (hazard ratio, 5.15, 95% confidence interval, 2.33 to 11.36) and patients with RDW levels above 15.75% had significantly shorter survival time (Log rank Plt;0.001) than others. CONCLUSIONS: RDW could be an additive predictor for all-cause mortality in patients on chronic dialysis. Furthermore, RDW combined with sound clinical judgment improves identification of patients who are at increased risk compared to RDW alone.

Anti-citrullinated protein antibody and rheumatoid factor in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) as diagnostic tools for RA. METHODS: We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1-12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. RESULTS: Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. CONCLUSIONS: Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition.

[Biochemical markers in the diagnosis of acute coronary syndrome]. / Biokemijski biljezi u dijagnostici akutnog koronarnog sindroma.

Acute coronary syndrome is a set of symptoms interpreted as being the result of cardiac ischemia. The subtypes of acute coronary syndrome, depending on the degree of cardiac ischemia, include unstable angina and two forms of myocardial infarction. Determination of serum cardiac markers plays a key role in the diagnosis of acute myocardial infarction. Serum markers such as aspartate transaminase, lactate dehydrogenase, and creatine kinase are no longer used because they lack cardiac specificity and sensitivity. According to the NACB (National Academy of Clinical Biochemistry) recommendations, two serum cardiac markers need to be determined for routine diagnosis of acute myocardial infarction, i.e. one showing early elevation in serum (up to six hours after chest pain), and the other, late marker that is elevated six to nine hours after chest pain, has high sensitivity and specificity for detection of myocardial injury, and remains elevated for several days of the symptom onset. In current clinical practice, myoglobin, CKMB mass (improved diagnostic sensitivity in relation to CKMB activity) and cardiac troponins are commonly determined. CKMB mass is a cardiospecific marker, but can also be elevated in skeletal muscle damage. Myoglobin is not cardiospecific, but has high early sensitivity (fast and reliable exclusion of acute myocardial infarction) and the possibility of rapid assessment of the success of thrombolytic therapy. Cardiac troponins are late markers for the diagnosis of myocardial injury. They are markers with highest specificity and sensitivity for acute myocardial infarction. New markers such as ischemia modified albumin, heart fatty acid binding protein, glycogen phosphorylase isoenzyme BB, carboanhydrase 3, and new tehnologies are under investigation to advance our knowledge about heart disease.

Carotid endarterectomy unexpectedly resulted in optimal blood pressure control.

Resistant hypertension is defined as hypertension that remains above 140/90 mmHg despite the provision of three or more antihypertensive drugs in a rational combination at full doses and including a diuretic. It is associated with adverse clinical outcome and therefore requires aggressive medical treatment. We present a case of 70-year-old woman who was treated for resistant hypertension with a diuretic, ACE-inhibitor, calcium channel blocker, and with centrally acting antihypertensive, moxonodine. Despite of aggressive medical treatment her blood pressure remained above 160/90 mmHg continuously. Large diagnostic workup excluded common causes of secondary hypertension, but revealed significant carotid stenosis present on left internal carotid artery. Carotid endarterectomy was performed in order to improve cerebrovascular prognosis, but unexpectedly resulted in optimal control of her blood pressure. Two months after operation patient was on only one antihypertensive drug, having blood pressure below 130/85 mmHg. We suggest that in selected patients resistant hypertension could be associated with carotid stenosis and carotid sinus baroreceptor dysfunction. For definite conclusions further studies are warranted.

The right atrial thrombus: the sword of Damocles with real risk of massive pulmonary embolism.

Cases of 6 patients admitted at the intensive care unit for massive pulmonary embolism are reported. All patients presented with dyspnea, tachypnea, and tachycardia, and 4 were hypotensive and had syncope. Lung ventilation/ perfusion scans revealed perfusion defects in 4 patients. Transthoracic echocardiography (TTE) demonstrated acute cor pulmonale. It also revealed mobile right atrial thrombi in 5 patients, adherent thrombus in the right atrium in 1 patient and patent foramen ovale in 4 patients. Thrombolytic therapy was initiated in 4 patients, and 2 patients received heparin infusion only. Effects of thrombolysis were monitored using bedside TTE during the first 24 hours and in follow-up. The outcome of 4 patients who received thrombolytic therapy was good whereas other 2 patients, who received only heparin, died. Thrombotic mass disappeared 8 to 12 hours after initiation of therapy, and 10 weeks after discharge TTE showed normalized right ventricle dimensions and function in all 4 patients.