Enhanced Hippocampal Neurogenesis in APP/Ps1 Mouse Model of Alzheimer's Disease After Implantation of VEGF-loaded PLGA Nanospheres.

During adult life, hippocampus is an important brain region involved in neurogenesis. The generation and cell death of newly generated neuronal cells in this region have critical roles in brain maintenance and alterations in these processes are seen in Alzheimer's disease (AD). For the purpose of carrying out a neuroregenerative strategy, we propose a novel approach based on the encapsulation of vascular endothelial growth factor (VEGF) in poly (lactic co-glycolic acid) (PLGA) biodegradable nanospheres (NS) administered by craniotomy to stimulate the proliferation of neuronal precursors in a transgenic mouse model of AD. VEGF loaded nanospheres were prepared by double emulsion solvent evaporation technique, obtaining 200 nm nanospheres with a biphasic release profile. After demonstrating their efficacy in the proliferation and differentiation of neuronal cell cultures, in vivo studies were carried out. 3 months after VEGF-NS were implanted directly into the cerebral cortex of APP/Ps1 mice, the determination of BrdU(+) cells in the whole hippocampal region and specifically in the dentate gyrus, demonstrated a significantly enhanced cellular proliferation in VEGF-NS treated group. These results were also confirmed showing an increased number of DCX(+) and NeuN(+) cells. Hence, PLGA-VEGF nanospheres may be a potential strategy to modulate proliferative neuronal progenitors in the hippocampal region, and therefore, provide new insight for future therapeutic approaches in AD.

Prevalencia de contraindicaciones a succinilcolina en unidades de cuidados intensivos / Contraindications to succinylcholine in the intensive care unit. A prevalence study

Objetivo Conocer la prevalencia de contraindicaciones a succinilcolina en pacientes ingresados en unidades de cuidados intensivos (UCI). Diseño Estudio observacional, describiendo la frecuencia de contraindicaciones a succinilcolina por estancias. Análisis univariante de asociación de contraindicaciones con variables poblacionales. Ámbito UCI polivalente de hospital de tercer nivel. Pacientes Pacientes adultos críticos polivalentes. Se analizan en 30 días consecutivos todas las estancias. Intervenciones Ninguna. Variables descriptivas de la población: edad, sexo, APACHE, SOFA, patología, días de ingreso, ventilación mecánica, depuración extrarrenal. Contraindicaciones: hiperpotasemia, encamamiento, rabdomiólisis, traumatismo muscular, quemadura, perfusión de bloqueante neuromuscular, fracaso renal agudo, insuficiencia renal crónica, hipertensión intraocular, hipertensión endocraneal, estatinas crónicas, antecedente de hipertermia maligna, enfermedad neuromuscular, sección medular, bradicardia < 50 lpm, alergia al fármaco, déficit de pseudocolinesterasa. Resultados Ingresan 102 pacientes de 60±16 años, 56,9% varones, que generan 657 estancias. Patologías principales: cirugía cardiaca programada (33%), fallo respiratorio (22%) y sepsis (14%). Documentamos 466 estancias (70,9%) con alguna contraindicación, destacando encamamiento (140), bloqueante neuromuscular (101), fracaso renal agudo (126), estatinas (167), enfermedad neuromuscular (159) y bradicardia (76). Encontramos 74 estancias (11,3%) con alto riesgo de complicación (EARC) al asociarse factor de hiperkalemia con factor de disregulación de receptor. Se asocian a EARC: edad avanzada, hospitalización prolongada, estancia en UCI prolongada, APACHE-II superior, SOFA superior y estar en ventilación mecánica o depuración extrarrenal. Conclusiones Dada la elevada prevalencia de contraindicaciones a succinilcolina observada desaconsejamos su uso en pacientes ingresados en UCI (AU)

Objective To determine the prevalence of contraindications to succinylcholine in patients admitted to the ICU. Design An observational study was carried out, describing the frequency of succinylcholine contraindication by stays, and associating the contraindications to population variables. Setting The adult general ICU of a reference hospital. Patients Clinical-surgical critically ill patients. Thirty consecutive days were analyzed. Interventions None. Variables Population variables: age, sex, APACHE II and SOFA scores, illness, days of hospitalization, mechanical ventilation and renal replacement therapy. Contraindications: hyperkalemia, bedridden patients, rhabdomyolysis, muscle trauma, burns, infusion of neuromuscular blocking agents, acute renal failure, chronic renal failure, intraocular hypertension, intracranial hypertension, statin use, malignant hyperthermia, neuromuscular disease, spinal cord sectioning, bradycardia < 50 bpm, succinylcholine allergy, and pseudo-cholinesterase deficiency. Results A total of 102 patients were admitted, aged 60±16 years (56.9% males), with the generation of 657 stays. Main diseases: elective heart surgery (33%), respiratory failure (22%) and sepsis (14%). We documented 466 stays (70.9%) with contraindications, particularly bedridden patients (n=140), neuromuscular blocking agents (n=101), acute renal failure (n=126), statin use (n=167), neuromuscular disease (n=159) and bradycardia (n=76). We recorded 74 stays (11.3%) at high risk of complications, secondary to hyperkalemic risk associated to receptor dysregulation. A high risk of complications was associated to advanced age, prolonged hospitalization, prolonged length of stay in the ICU, higher APACHE II and SOFA scores, mechanical ventilation and renal replacement therapy. Conclusion Given the high prevalence of contraindications to succinylcholine observed, we discourage its use in patients admitted to the ICU (AU)

[Contraindications to succinylcholine in the intensive care unit. A prevalence study]. / Prevalencia de contraindicaciones a succinilcolina en unidades de cuidados intensivos.

OBJECTIVE: To determine the prevalence of contraindications to succinylcholine in patients admitted to the ICU. DESIGN: An observational study was carried out, describing the frequency of succinylcholine contraindication by stays, and associating the contraindications to population variables. SETTING: The adult general ICU of a reference hospital. PATIENTS: Clinical-surgical critically ill patients. Thirty consecutive days were analyzed. INTERVENTIONS: None. VARIABLES: Population variables: age, sex, APACHE II and SOFA scores, illness, days of hospitalization, mechanical ventilation and renal replacement therapy. CONTRAINDICATIONS: hyperkalemia, bedridden patients, rhabdomyolysis, muscle trauma, burns, infusion of neuromuscular blocking agents, acute renal failure, chronic renal failure, intraocular hypertension, intracranial hypertension, statin use, malignant hyperthermia, neuromuscular disease, spinal cord sectioning, bradycardia < 50 bpm, succinylcholine allergy, and pseudo-cholinesterase deficiency. RESULTS: A total of 102 patients were admitted, aged 60 ± 16 years (56.9% males), with the generation of 657 stays. Main diseases: elective heart surgery (33%), respiratory failure (22%) and sepsis (14%). We documented 466 stays (70.9%) with contraindications, particularly bedridden patients (n=140), neuromuscular blocking agents (n=101), acute renal failure (n=126), statin use (n=167), neuromuscular disease (n=159) and bradycardia (n=76). We recorded 74 stays (11.3%) at high risk of complications, secondary to hyperkalemic risk associated to receptor dysregulation. A high risk of complications was associated to advanced age, prolonged hospitalization, prolonged length of stay in the ICU, higher APACHE II and SOFA scores, mechanical ventilation and renal replacement therapy. CONCLUSION: Given the high prevalence of contraindications to succinylcholine observed, we discourage its use in patients admitted to the ICU.

Leptin gene therapy attenuates neuronal damages evoked by amyloid-ß and rescues memory deficits in APP/PS1 mice.

There is growing evidence that leptin is able to ameliorate Alzheimer's disease (AD)-like pathologies, including brain amyloid-ß (Aß) burden. In order to improve the therapeutic potential for AD, we generated a lentivirus vector expressing leptin protein in a self-inactivating HIV-1 vector (HIV-leptin), and delivered this by intra-cerebroventricular administration to APP/PS1 transgenic model of AD. Three months after intra-cerebroventricular administration of HIV-leptin, brain Aß accumulation was reduced. By electron microscopy, we found that APP/PS1 mice exhibited deficits in synaptic density, which were partially rescued by HIV-leptin treatment. Synaptic deficits in APP/PS1 mice correlated with an enhancement of caspase-3 expression, and a reduction in synaptophysin levels in synaptosome preparations. Notably, HIV-leptin therapy reverted these dysfunctions. Moreover, leptin modulated neurite outgrowth in primary neuronal cultures, and rescued them from Aß42-induced toxicity. All the above changes suggest that leptin may affect multiple aspects of the synaptic status, and correlate with behavioral improvements. Our data suggest that leptin gene delivery has a therapeutic potential for Aß-targeted treatment of mouse model of AD.

Prevalence of diabetes in a cancer population in a Malaga hospital.

BACKGROUND: There are multiple risk factors for cancer, including obesity, sedentary lifestyle, diabetes (DM). Hormon Insulin is a growth factor that promotes cellular differentiation. AIMS: The aim of our study is to observe impaired glycaemia in cancer population compared with control. METHODS: We studied the prevalence of diabetes (DM) and impaired fasting glycaemia (IFG) in 374 patients with different types of cancer before treatment, by medical records in a Malaga hospital (Spain). We compared the prevalence of basal hyperglycaemia in these patients with general population, within an age range and by gender. RESULTS AND DISCUSSION: The prevalence of diabetes was 32.35% in our cancer patients. The comparison depends of age range, and by gender prevalence was: 45-54 years, DM: 40.91% in men cases, versus (vs.) 14.5% in men control (p = 0.005). 55-64 years, IFG: 23.08% in women cases, vs. 5.9% in women control (p = 0.001). 65-74 years, DM: 47.13% in men cases, vs. 25.4% in men control (p = 0.000), and IFG: 23.81% in women cases, vs. 9.5% in women control (p = 0.019). We found a higher prevalence of diabetes in specific types of cancer such as prostate (p < 0.005). Moreover, men had a higher prevalence of diabetes or less diabetes control than women in our cancer sample. CONCLUSIONS: We recommend an OGTT (oral glucose tolerance test) for better diagnosis of possible DM in patients with cancer, and an appropriate treatment. It may be an independent risk factor for cancer to have decreased insulin activity, or DM.

Prevalence of diabetes in a cancer population in a Malaga hospital / Prevalencia de diabetes en una población con cáncer de un hospital de Málaga

Background: There are multiple risk factors for cancer, including obesity, sedentary lifestyle, diabetes (DM). Hormon Insulin is a growth factor that promotes cellular differentiation. Aims: The aim of our study is to observe impaired glycaemia in cancer population compared with control. Methods: We studied the prevalence of diabetes (DM) and impaired fasting glycaemia (IFG) in 374 patients with different types of cancer before treatment, by medical records in a Malaga hospital (Spain). We compared the prevalence of basal hyperglycaemia in these patients with general population, within an age range and by gender.Results and discussion: The prevalence of diabetes was 32.35% in our cancer patients. The comparison depends of age range, and by gender prevalence was: 45-54 years, DM: 40.91% in men cases, versus (vs.) 14.5% in men control (p = 0.005). 55-64 years, IFG: 23.08% in women cases, vs. 5.9% in women control (p = 0.001). 65-74 years, DM: 47.13% in men cases, vs. 25.4% in men control (p = 0.000), and IFG: 23.81% in women cases, vs. 9.5% in women control (p = 0.019). We found a higher prevalence of diabetes in specific types of cancer such as prostate (p < 0.005). Moreover, men had a higher prevalence of diabetes or less diabetes control than women in our cancer sample. Conclusions: We recommend an OGTT (oral glucose tolerance test) for better diagnosis of possible DM in patients with cancer, and an appropriate treatment. It may be an independent risk factor for cancer to have decreased insulin activity, or DM (AU)

Introducción: Existen múltiples factores de riesgo para que una célula degenere en crecimiento indiferenciado o cáncer. Entre otros factores se ha observado que la obesidad, el sedentarismo y la diabetes aumentan este riesgo. La insulina es un factor de crecimiento que promueve la diferenciación celular. Objetivos: El objetivo de nuestro estudio es observar la glucemia basal en una población con cáncer y comparar con una población control. Métodos: Estudiamos la presencia de diabetes mellitus (DM) y de glucosa alterada en ayunas (GAA) en 374 pacientes de distintos tipos de cáncer mediante sus historiales observando la glucemia basal del ingreso antes de su tratamiento. Comparamos con la glucemia basal en población normal por rangos de edad y sexo. Resultados y discusión: La prevalencia de diabetes en los pacientes con cáncer fue de 32,35%. Comparación por sexo y rangos de edad: observamos que entre 45-54 años, DM: 40,91% en hombres cancerosos versus (vs) 14.5% en hombres control (p = 0,005). Entre 55-64 años, GAA: 23,08% en mujeres cancerosas vs 5,9% en mujeres control (p = 0001). Entre 65-74 años, DM: 47,13% en hombres cancerosos vs 25,4% en hombres control (p = 0,000), y GAA: 23,81% en mujeres cancerosas vs 9,5% en mujeres control (p = 0,019). Encontramos una mayor prevalencia de diabetes en unos tipos específicos de cáncer más que en otros, como por ejemplo en el cáncer de próstata (p < 0,005). Así mismo observamos que los hombres tienen una mayor prevalencia de diabetes o un menor control de la enfermedad que las mujeres en nuestra muestra de casos de cáncer. Conclusiones: Recomendamos un diagnóstico sistemático de diabetes en los pacientes con cáncer mediante test de tolerancia oral de glucosa (OGTT) y su conveniente tratamiento. Es posible que la diabetes, o el tener disminuida la actividad insulínica, sea un factor más de riesgo para el cáncer (AU)

Compliance with cardiovascular drug prevention measures in a general population: the Multidisciplinary Intervention in Primary Care (IMAP) study.

AIMS: To evaluate adherence to guideline-recommended drug therapies for primary and secondary cardiovascular prevention in a general Mediterranean population. SUBJECTS AND METHODS: A cross-sectional study was conducted in a random sample of 2270 individuals (18-80 years) assigned to a health centre in Malaga (Spain). The appropriate use was analysed of statins, antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB), based on the criteria of the European Guidelines on Cardiovascular Prevention and the European Society of Hypertension-European Society of Cardiology. RESULTS: The prescription rate of statins, antithrombotics, beta-blockers, and ACEI/ARB was 7.8%, 5.1%, 3.3%, and 11%, respectively. The prescription of these drugs was inappropriate in 36.2%, 22.4%, 64.5%, and 0%, respectively. Overtreatment was more frequent in subjects with greater comorbidity or ≥ 2 vascular risk factors (p < 0.001). The percentage of individuals with prescription criteria but who did not receive the treatment was 19.5%, 4.7%, 2%, and 9.3%, respectively, increasing significantly with age, Charlson index, and the presence of ≥ 2 risk factors (p < 0.001). Only 11% of patients in secondary prevention received combination therapy with statins, antithrombotics, and ACEI/ARB. Patients with ischaemic heart disease, as compared to non-coronary vascular patients, more frequently received statins (56.1% vs. 25.6%; p = 0.0001) and antithrombotic drugs (66.7% vs. 56.4%; p = 0.02). CONCLUSIONS: We detected a low adherence to existing pharmacological guidelines for the prevention of cardiovascular disease. A priority is to establish appropriate training and dissemination of cardiovascular prevention guidelines in the field of primary care.

Prevalence of cardiovascular risk factors in an urban adult population from southern Spain. IMAP Study.

AIMS: To study the prevalence of cardiovascular risk factors in an urban population of Malaga, Spain and its relationship with educational level. METHODS: A cross-sectional study was performed with a random representative sample of 2270 individuals from the adult population (18­80 years) from a specific Health-Care Centre in Malaga City. All participants underwent a clinical interview, including social-demographical information and a physical examination. A blood sample was also drawn. RESULTS: The mean age of the participants was 43.6 ± 15.6 years and 57.6% had a low educational level. The prevalence of cardiovascular risk factors was: smoking 27.7%, hypertension 33.1%, diabetes 7.1% and dyslipidaemia 65.4%. Over 60% were either overweight or obese, and 76.7% had a sedentary lifestyle. Except for smoking and a low-HDL cholesterol, the prevalence of the other cardiovascular risk factors increased with age. A low educational level was associated with a high prevalence of cardiovascular risk factors, and this association was significant with regard to smoking, obesity, abdominal obesity and hypertriglyceridaemia. CONCLUSIONS: The population studied presents a high prevalence of cardiovascular risk factors, especially dyslipidaemia and obesity. The low academic level was associated with an increased prevalence of smoking, obesity and dyslipidaemia. People with a low socio-cultural level are a priority target for introducing policies to prevent and control cardiovascular disease.

Tratamiento perioperatorio de una gestante con infarto cerebral reciente secundario a miocardiopatía no compactada / Perioperative treatment of a pregnant woman with recent cerebral infarction secondary to noncompaction cardiomyopathy

La miocardiopatía no compactada (MNC) es una entidadde reciente acuñamiento, de presentación infrecuentepero con manifestaciones clínicas importantes y pronósticosombrío. El infarto cerebral es una de sus formasde presentación; y el embarazo, estado de hipercoagulabilidad,lo favorece. Se presenta el caso de una mujerembarazada que fue llevada a urgencias con un infartocerebral isquémico, en cuyo estudio se demostró etiologíacardioembólica, con diagnóstico de MNC. Días después,tras su estabilización, fue sometida a cesárea electivabajo anestesia general. La intervención transcurriósin incidencias, al igual que el postoperatorio, tras elcual fue trasladada al Servicio de Rehabilitación. Esobligatorio en estos casos evitar el daño miocárdico y laprogresión del accidente cerebrovascular; para ello previoa la cirugía se debe estabilizar al paciente e iniciartratamiento antiagregante y/o anticoagulante. Es necesariomantener la estabilidad hemodinámica durante todoel perioperatorio, evitando en lo posible la depresión delneonato tras su extracción. Para ello existen diferentesestrategias, que deben adecuarse al estado y al momentoen el que se encuentre la paciente

Recent-onset noncompaction of the myocardium is arare but serious entity with uncertain prognosis. Cerebralinfarction is among the forms of presentation, andpregnancy and hypercoagulability increase risk. Wereport the case of a pregnant woman brought to theemergency department with ischemic cerebral infarction.Investigation demonstrated the cause to be cardiac embolism,and noncompaction of the myocardium was diagnosed.She was stabilized and a few days later underwentelective cesarean section under general anesthesia. Surgeryand postoperative recovery were uneventful, and shewas transferred for rehabilitation. Myocardial injury andprogression to cerebrovascular accident must beprevented in such cases; the patient must be stabilizedand antiplatelet and/or anticoagulant therapy initiatedbefore surgery. Hemodynamic stability must be maintainedthroughout the perioperative period and neonataldepression avoided after delivery. Various approaches areavailable to be adapted to the patient's situation

[Perioperative treatment of a pregnant woman with recent cerebral infarction secondary to noncompaction cardiomyopathy]. / Tratamiento perioperatorio de una gestante con infarto cerebral reciente secundario a miocardiopatía no compactada.

Recent-onset noncompaction of the myocardium is a rare but serious entity with uncertain prognosis. Cerebral infarction is among the forms of presentation, and pregnancy and hypercoagulability increase risk. We report the case of a pregnant woman brought to the emergency department with ischemic cerebral infarction. Investigation demonstrated the cause to be cardiac embolism, and noncompaction of the myocardium was diagnosed. She was stabilized and a few days later underwent elective cesarean section under general anesthesia. Surgery and postoperative recovery were uneventful, and she was transferred for rehabilitation. Myocardial injury and progression to cerebrovascular accident must be prevented in such cases; the patient must be stabilized and antiplatelet and/or anticoagulant therapy initiated before surgery. Hemodynamic stability must be maintained throughout the perioperative period and neonatal depression avoided after delivery. Various approaches are available to be adapted to the patient's situation.

Siringomielia y malformación de Chiari tipo I, con parálisis bilateral de cuerdas vocales y síndrome de apnea obstructiva del sueño asociadas / Syringomyelia and Chiari type 1 malformation with associated bilateral vocal cord paralysis and obstructive sleep apnea syndrome

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Saccade Velocity as a Surrogate DiseaseMarker in Spinocerebellar Ataxia Type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal-dominant disorder mani-festing with gait, limb, and speech incoordination, and with distinctive symptomssuch as early slowing of horizontal eye movements and early neuropathy.1–3 Neuro-pathological analysis has demonstrated severe olivopontocerebellar atrophy (OPCA)early in the course of disease, progressing to involve the anterior horn, substantia ni-gra, thalamus, and somatosensory pathways.4,5 Clinical onset is usually in midlife,but has been observed to range from 1 to 65 years of age, depending on the size ofthe underlying mutation, a CAG (cytosine-adenine-guanine)-trinucleotide repeat ex-pansion in exon 1 of the SCA2 gene...(AU)

[The adenoid cystic carcinoma]. / Carcinoma adenoide quístico de CAE.

The adenoid cystic carcinoma arising in the external auditory canal is a rare tumor, as other malignant neoplasias of the EAC and middle ear. The early diagnosis of these malignant tumors of the ear is very important to improve the prognosis. In this sense, the clinic experience is frequently the most useful diagnosis instrument to suspect this pathology when we have a confrontation with chronic otorrea and otalgia, common presentation form of this disease. In this report we show a new case of adenoid cystic carcinoma of external auditory canal and review the most significant medical literature existing in relationship with this pathology.

Carcinoma adenoide quístico de CAE / The adenoid cystic carcinoma

El carcinoma adenoide quístico con origen en el conducto auditivo externo es un tumor infrecuente, como ocurre en general con otras neoplasias malignas que asientan en el CAE y oído medio. El diagnóstico precoz de estos tumores malignos del oído es fundamental para mejorar su pronóstico. En este sentido, la experiencia clínica es muchas veces el instrumento diagnóstico más útil para sospechar esta patología cuando nos enfrentamos ante una otorrea y una otalgia crónicas, modo de presentación frecuente de esta enfermedad. En este artículo recogemos un nuevo caso de carcinoma adenoide quístico del conducto auditivo externo y revisamos la literatura médica más relevante que existe en relación con esta patología

The adenoid cystic carcinoma arising in the external auditory canal is a rare tumor, as other malignant neoplasias of the EAC and middle ear. The early diagnosis of these malignant tumors of the ear is very important to improve the prognosis. In this sense, the clinic experience is frequently the most useful diagnosis instrument to suspect this pathology when we have a confrontation with chronic otorrea and otalgia, common presentation form of this disease. In this report we show a new case of adenoid cystic carcinoma of external auditory canal and review the most significant medical literature existing in relationship with this pathology

Saccade velocity as a surrogate disease marker in spinocerebellar ataxia type 2.

We measured in 82 spinocerebellar ataxia type 2 (SCA2) patients and in 80 controls maximal saccade velocity (MSV) and correlated it to polyglutamine expansion size and disease duration. MSV is strongly decreased in SCA2 patients and is influenced mostly by polyglutamine size.

Sífilis y analgesia obstétrica: implicaciones anestésicas / Obstetric analgesia in syphilis: anesthetics implications

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[Economic management of institutional pharmacies of the city of Rosario. Quality indicators proposal]. / Gestión económica en establecimientos asistenciales de la ciudad de Rosario. Propuesta de indicadores de calidad.

OBJECTIVE: To compare structures, procedures and results of the pharmaceutical management of institutional pharmacies in the city of Rosario (Argentina), to define the current situation and thus recommend changes. METHOD: Descriptive study, using a questionnaire and quality indicators of an Accreditation Program of Hospital Pharmacies. Evaluated dimensions: selection, acquisition, reception, storage and stock control of drugs and medical devices. Data was collected for a one-year-period in order to obtain indicators. After tabulation, data was discussed in meetings with all the pharmacists that participate in this study, in order to evaluate the situation and propose changes for the Pharmacies, as well as to evaluate the Program based on usefulness of these indicators. RESULTS: The general results illustrate how each institution has different health policies. 43.2% of indicators were answered, 67.6% reached standard values. CONCLUSIONS: This work allowed for an exhaustive analysis of the current situation. The pharmacists made proposals and unified criteria in order to obtain an improved use of the economic resources of each institution.

[Sarcoma of the larynx. Report of two cases]. / Sarcomas de laringe. A propósito de 2 nuevos casos.

In relation with other laryngeal neoplasms, sarcomas are uncommon tumours. With the object to put in knowledge one chondrosarcoma and one liposarcoma located in the larynx seen in our hospital in a small period of time, we decided to do this publication, discussing the differential clinical aspects of these laryngeal cancers.