Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function

Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion.     

Echocardiographic Parameters and Brain Natriuretic Peptide in Patients after Surgical Repair of Tetralogy of Fallot

Background: Although the residual lesions after surgical correction of tetralogy of Fallot (TOF) can be evaluated by Doppler echocardiography (DE), the relation of DE parameters with the proBNP level, a potential biomarker of right ventricle overload, is not well known. The objective of this study was to evaluate the DE parameters and their relation to proBNP levels. Methods: proBNP plasma level and Doppler echocardiography parameters were obtained on the same day in 49 patients later after repair of TOF (mean age of 14.7 years, 51% female, mean PO time of 9.5 years). The DE parameters studied were the dimensions of the right atrium (RA) and ventricle (RV), RV diastolic and systolic function, and residual pulmonary lesions. The relation between them and proBNP levels were analyzed and the cutoff values of DE parameters for elevated proBNP determined. Results: proBNP was elevated in 53% and correlated with RV diastolic diameter (r = 0.41; P = 0.003), RA longitudinal (r = 0.52; P = 0.0001) and transversal (r = 0.47; P = 0.001) diameters, pressure half time of pulmonary regurgitation (PR) velocity (PHT) (r =?0.42; P = 0.005), and the PR index (r =?0.60; P < 0.001). By multivariate analysis, the PR index (r =?597; P = 0,001; CI: ?913.2 to ?280.8) and RA longitudinal (r = 7.74; P < 0,001; CI 4.18 to 11.31) were independent predictors of elevated proBNP. PHT lower than 64 msec (0.76) and PRi lower than 0.65 (0.81) had the best accuracy for elevated proBNP. Conclusion: proBNP may be increased in patients after surgical repair of TOF, correlated with the size of right cardiac chambers and the severity of PR. (Echocardiography 2010;27:442‐447)     

Estándares de calidad asistencial para las consultas de enfermería en reumatología

BackgroundNursing clinics in rheumatology (NCR) are organizational models in the field of nursing care. There are various NCR models, but there is no consensus on its operational definition. Our objective is to develop quality standards to define and characterize a NCR.MethodTwo-round Delphi method. The panel consisted of 67 experts: Rheumatologists and nurses of the nursing working group of the Spanish Society of Rheumatology (SSR). The Delphi questionnaire was developed after a literature and experience review from previous SSR projects. The questionnaire consists of 7 sections: general considerations, standards of structure, process, treatment and monitoring, health education, training and research and quality of care. Each item was scored from 1 (least important) to 9 (most important) or by assigning a number (e.g., waiting days). The degree of agreement among the experts was categorized according to the coefficient of variation (CoV) between very high (CoV≤25%) and very low (CoV>100%).ResultsThe second round questionnaire (182 items) was answered by 46 panelists (34 rheumatologists and 12 nurses). A very important agreement was reached on the general standards of structure, process, treatment and monitoring, health education and quality of care. Less agreement was observed on standards related to training time, number of recommended nurses’ research projects and publications.ConclusionThe standards developed in this study would be useful for establishing desirable quality standards of structure and process, and criteria for clinical work, research and teaching that can be used to develop and evaluate the NCRs.     

Design and In-line Raman Spectroscopic Monitoring of a Protein Batch Crystallization Process

Raman spectroscopy was used to design and monitor a lysozyme protein batch crystallization process in a lab scale study to facilitate the design of a pharmaceutical protein manufacturing process. A D-optimal design that consisted of 18 experiments was performed to elucidate the effect of temperature, concentration of the precipitating agent, time of crystallization, and possible interactions between these three factors on the Raman scattering changes. A polynomial mathematical model was calculated relating the scattering of the lysozyme solutions measured at individual Raman shifts to the significant factors obtained in the previous crystallization experiment. The 2,940-cm⁻¹ band provided the highest correlation values indicative of small prediction errors and good predictive ability for the crystallization model. Raman scattering signals obtained during the experiments were used as input to obtain a response surface for the factors studied and elucidate the relationship between the crystallization process conditions and the crystals obtained. The main factors affecting the crystallization process were the sodium chloride concentration and temperature.     

The Sugiura procedure for patients with hemorrhagic portal hypertension secondary to extrahepatic portal vein thrombosis

The Sugiura procedure (SP) was performed upon 27 patients with hemorrhagic portal hypertension secondary to extrahepatic portal vein thrombosis (EPVT) without associated hepatic disease. There were 14 female and 13 male patients. The mean age was 28 +/- 14 years. The causes of EPVT were protein C deficiency in two; antithrombin III deficiency in one patient, a history of omphalitis in two patients, a history of pancreatitis in one patient and idiopathy in 21 patients. The SP was completed in two surgical stages in 14 patients and in one stage in nine. There was one operative death. One patient had mild postoperative encephalopathy, and two patients rebled at long term follow-up study. Actuarial survival rate was 82 per cent at five and ten years. It is concluded that the SP is a good alternative for the management of hemorrhagic portal hypertension secondary to EPVT.     

Intracranial aneurysms associated with unsuspected aortic coarctation

Intracranial aneurysms (IAs) are found more often in patients with aortic coarctation (AC) than in the general population and aneurysm rupture occurs much earlier in the lives of these patients when there is coexistent AC. The diagnosis of AC is frequently made only after a serious cerebrovascular complication has developed. The aim of this paper is to call attention to AC in patients presenting with aneurysmal subarachnoid hemorrhage. The literature is reviewed, the key clinical features are highlighted, and the proposed pathogenesis of this association is discussed. The authors present clinical information and imaging data obtained in three young patients with ruptured IAs that were associated with initially unnoticed AC. Abnormal results of cardiovascular examinations led the authors to consider an underlying AC, which was later confirmed by aortography. These aneurysms were successfully treated prior to correction of the ACs. The diagnosis of AC should be considered in adolescent and young adult patients presenting with IAs.     

Current role of surgery for the treatment of portal hypertension

Portal hypertension surgery has evolved widely in the last decades. Since the first surgical shunt was done in 1945 for the treatment of recurrent hemorrhage, many surgical options have been developed including selective shunts, low diameter shunts and extensive devascularization procedures. Many of them have been studied and compared showing their advantages and disadvantages, evolving also their role in the therapeutic armamentarium. Surgery is nowadays a second line treatment option (after b blockers and endoscopic therapy), and it's main indication is for patients whose main and only problem is history of bleeding, with good liver function (Child-Pugh A). For emergency situations it has a very limited role and for primary prophylaxis virtually has also no role. Patients with good liver function, electively operated with portal blood flow preserving procedures are the patients that benefit from surgical treatment. Patients with a bad liver function are better candidates for a liver transplant.