The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease.

INTRODUCTION: Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear. METHODS: The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC-FID. The MCI subjects were followed up for 58 ± 12.5 months. RESULTS: In controls, CSF has a more neuroprotective LFA than plasma. In CSF, a higher content of docosahexaenoic acid was associated with a reduced risk of MCI-to-AD progression. In plasma, higher oleic acid content was associated with lower risk of AD, MCI, and MCI-to-AD progression, whereas higher levels of vaccenic acid and docosahexaenoic acid were associated with greater risk of AD and MCI, and higher rate of MCI-to-AD progression, respectively. DISCUSSION: The circulating LFA is involved in the pathogenesis and progression of AD. HIGHLIGHTS: The lipidome fatty acid profile in CSF and plasma was markedly different. Higher levels of vaccenic acid and lower levels of oleic acid in plasma were associated with greater risk of Alzheimer's disease. In plasma, higher levels of oleic acid were associated with a reduced risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in CSF were associated with a lower risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in plasma were associated with a greater rate of MCI-to-AD progression.

Plasma and cerebrospinal fluid nonenzymatic protein damage is sustained in Alzheimer's disease.

BACKGROUND: Oxidative stress is considered to play an important role in the pathogenesis of Alzheimer's disease (AD). It has been observed that oxidative damage to specific protein targets affecting particular functional networks is one of the mechanisms by which oxidative stress contributes to neuronal failure and consequently loss of cognition and AD progression. Studies are lacking in which oxidative damage is measured at both systemic and central fluid levels and in the same cohort of patients. We aimed to determine the levels of both plasma and cerebrospinal fluid (CSF) nonenzymatic protein damage in patients in the continuum of AD and to evaluate the relation of this damage with clinical progression from mild cognitive impairment (MCI) to AD. METHODS: Different markers of nonenzymatic post-translational protein modification, mostly from oxidative processes, were detected and quantified in plasma and CSF by isotope dilution gas chromatography‒mass spectrometry using selected ion monitoring (SIM-GC/MS) for 289 subjects: 103 AD, 92 MCI, and 94 control subjects. Characteristics of the study population such as age, sex, Mini-mental state examination, CSF AD biomarkers, and APOE ϵ4, were also considered. RESULTS: Forty-seven (52.8%) MCI patients progressed to AD during follow-up (58 ± 12.5 months). After controlling for age, sex, and APOE ϵ4 allele, plasma and CSF concentrations of protein damage markers were not associated with either diagnosis of AD or MCI. The CSF levels of nonenzymatic protein damage markers were associated with none of the CSF AD biomarkers. In addition, neither in CSF nor in plasma were the levels of protein damage associated with the MCI to AD progression. CONCLUSION: The lack of association between both CSF and plasma concentrations of nonenzymatic protein damage markers and AD diagnosis and progression suggests that oxidative damage in AD is a pathogenic mechanism specifically expressed at the cell-tissue level, not in extracellular fluids.

Lesión carotídea arteriosclerótica en pacientes con cirugía coronaria / Carotid atherosclerotic lesion in patients with coronary surgery

Introducción: Las enfermedades cardiovasculares isquémicas constituyen la primera causa de muerte en el mundo desarrollado o en vías de serlo, por encima de las oncológicas, de los accidentes del tránsito y de las enfermedades vásculo-cerebrales. El diagnóstico temprano de una lesión coronaria permite lograr la prevención del ataque isquémico agudo, y realizar el tratamiento revascularizador oportuno con evaluación de riesgo quirúrgico, que permita obtener cifras de morbimortalidad aceptables. Objetivo: Describir las características ultrasonográficas de las arterias carotídeas como riesgo de accidente cerebro-vascular en pacientes con revascularización miocárdica. Métodos: Se realizó un estudio observacional, descriptivo y longitudinal en 208 pacientes revascularizados del sector coronario, con estudio ultrasonográfico prequirúrgico de las arterias carotídeas como método predictivo de enfermedad vásculo-cerebral isquémica. Resultados: En 20 pacientes se presentaron síntomas cerebrales que se clasificaron en menores y mayores. Existió preponderancia de los menores y, entre ellos, de la agitación. Se evaluaron los factores de riesgo primarios y en las características de las placas ateroescleróticas se destacó el grado de irregularidad. Conclusiones: El estudio ultrasonográfico del árbol arterial carotídeo debe formar parte esencial del estudio predictivo del paciente que va a ser sometido a una revascularización coronaria(AU)

Introduction: Ischemic cardiovascular diseases are the leading cause of death in the developed world or in the process of becoming so, above oncological ones, traffic accidents and vascular-cerebral diseases. The early diagnosis of a coronary lesion allows to achieve the prevention of acute ischemic attack, and to perform the appropriate revascularization treatment with surgical risk assessment, which allows to obtain acceptable morbidity and mortality figures. Objective: To describe the ultrasonographic characteristics of carotid arteries as a risk of stroke in patients with myocardial revascularization. Methods: An observational, descriptive and longitudinal study was conducted in 208 coronary sector´s revascularized patients, with pre-surgical ultrasonographic study of the carotid arteries as a predictive method of ischemic cerebral vascular disease. Results: In 20 patients there were brain symptoms that were classified into minor and major. There was a predominance of minors and, among them, of agitation. The primary risk factors were evaluated and the degree of irregularity was highlighted in the characteristics of the atherosclerotic plaques. Conclusions: The ultrasonographic study of the carotid arterial tree should be an essential part of the predictive study of the patient who is undergoing coronary revascularization(AU)

Lactoferrin as Immune-Enhancement Strategy for SARS-CoV-2 Infection in Alzheimer's Disease Patients.

Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Severe illness of COVID-19 largely occurs in older people and recent evidence indicates that demented patients have higher risk for COVID-19. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage. A balance between the immune and inflammatory response is necessary to control the infection. Thus, antimicrobial and anti-inflammatory drugs are hopeful therapeutic agents for the treatment of COVID-19. Accumulating evidence suggests that lactoferrin (Lf) is active against SARS-CoV-2, likely due to its potent antiviral and anti-inflammatory actions that ultimately improves immune system responses. Remarkably, salivary Lf levels are significantly reduced in different Alzheimer's disease (AD) stages, which may reflect AD-related immunological disturbances, leading to reduced defense mechanisms against viral pathogens and an increase of the COVID-19 susceptibility. Overall, there is an urgent necessity to protect AD patients against COVID-19, decreasing the risk of viral infections. In this context, we propose bovine Lf (bLf) as a promising preventive therapeutic tool to minimize COVID-19 risk in patients with dementia or AD.

JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function.

BACKGROUND AND AIM: The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements. METHODS: Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP­ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss. RESULTS: Our studies demonstrated that HFD in Jnk3-/- lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed. CONCLUSIONS: Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.

Aneurisma de la aorta abdominal asociado a íctero / Aneurysm of the abdominal aorta associated with icterus

El aneurisma de la aorta abdominal como causa de íctero obstructivo es una situación de excepción en la clínica. El objetivo de esta presentación fue exponer la coexistencia del aneurisma de la aorta abdominal y el íctero. Una asociación muy poco frecuente y de difícil diagnóstico, que coloca al cirujano vascular en la toma de una especial conducta terapéutica. La cuidadosa revisión de los antecedentes patológicos y el análisis del comportamiento clínico del paciente permitieron la solución terapéutica adecuada. Se logró demostrar que el íctero obedecía a una lesión maligna de vías biliares conocida como colangiocarcinoma, que concomitó con la existencia de un aneurisma del V segmento aórtico y no fue el resultado de una compresión extrínseca de la dilatación de la aorta, sobre las vías biliares. La conducta quirúrgica, encaminada a erradicar el íctero y evitar la ruptura aneurismática con resección del aneurisma y colocación de prótesis, no resultó posible por lo avanzado de la lesión tumoral y el grado de metástasis ya establecidos. Solo se realizó resección de la vesícula biliar y seguimiento posterior por oncología(AU)

Abdominal aortic aneurysm as a cause of obstructive icterus is an exceptional situation in the clinic. The aim of this presentation was to expose the coexistence of abdominal aortic aneurysm and icterus. A very rare and difficult to diagnose association, which places the vascular surgeon in a special therapeutic approach. The careful review of the pathological history and the analysis of the patient's clinical behavior allowed the appropriate therapeutic solution. It was possible to demonstrate that the icterus was due to a malignant lesion of the biliary tract known as cholangiocarcinoma, which concomitated with the existence of an aneurysm of the V aortic segment and was not the result of extrinsic compression of the dilatation of the aorta on the biliary tract. The surgical procedure, aimed at eradicating the icterus and avoiding aneurysmal rupture with aneurysm resection and prosthesis placement, was not possible due to the advanced tumor lesion and the degree of metastasis already established. Only gallbladder resection was performed and subsequent follow-up by oncology(AU)

Effects of Nutrition on Cognitive Function in Adults with or without Cognitive Impairment: A Systematic Review of Randomized Controlled Clinical Trials.

New dietary approaches for the prevention of cognitive impairment are being investigated. However, evidence from dietary interventions is mainly from food and nutrient supplement interventions, with inconsistent results and high heterogeneity between trials. We conducted a comprehensive systematic search of randomized controlled trials (RCTs) published in MEDLINE-PubMed, from January 2018 to July 2021, investigating the impact of dietary counseling, as well as food-based and dietary supplement interventions on cognitive function in adults with or without cognitive impairment. Based on the search strategy, 197 eligible publications were used for data abstraction. Finally, 61 articles were included in the analysis. There was reasonable evidence that dietary patterns, as well as food and dietary supplements improved cognitive domains or measures of brain integrity. The Mediterranean diet showed promising results, whereas the role of the DASH diet was not clear. Healthy food consumption improved cognitive function, although the quality of these studies was relatively low. The role of dietary supplements was mixed, with strong evidence of the benefits of polyphenols and combinations of nutrients, but with low evidence for PUFAs, vitamin D, specific protein, amino acids, and other types of supplements. Further well-designed RCTs are needed to guide the development of dietary approaches for the prevention of cognitive impairment.

Aneurismas por Estreptococo Pneumoniae / Aneurysms by Streptococcal Pneumoniae

El Estreptococo Pneumoniae es un microorganismo patógeno capaz de causar en humanos diversas infecciones y procesos invasivos severos, siempre graves y potencialmente letales. El objetivo de este trabajo fue mostrar la infrecuente presencia del Estreptococo Pneumoniae en la aparición de los aneurismas micóticos aórticos y de arterias periféricas, una asociación muy particular que coloca al cirujano vascular ante una especial conducta terapéutica encaminada a erradicar la infección, evitar la ruptura y sustituir la arteria, para mantener la continuidad de la luz del vaso y prevenir situaciones graves de isquemia(AU)

Streptococcal Pneumoniae is a pathogenic microorganism capable of causing in humans various infections and severe, always serious and potentially lethal invasive processes. The objective of this work was to show the rare presence of Streptococcal Pneumoniae in the onset of aortic mycotic aneurysms and peripheral arteries, a very particular association that places the vascular surgeon in an special therapeutic behavior aimed at eradicating the infection, preventing ruptures and replacing the artery, to maintain the continuity of vessel's light and prevent serious ischemia's situations(AU)

Decreased salivary lactoferrin levels are specific to Alzheimer's disease.

BACKGROUND: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. METHODS: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-ß (Aß) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. FINDINGS: The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0•95 (0•911-0•992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0•97 (0•924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0•93 (0•876-0•989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. INTERPRETATION: Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker. FUNDING: Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01) to E.C.; Spanish Ministry of Economy and Competitiveness (SAF2017-85310-R) to J.L.C., and (PSI2017-85311-P) to M.A.; International Centre on ageing CENIE-POCTEP (0348_CIE_6_E) to M.A.; Instituto de Salud Carlos III (PIE16/00021, PI17/01799), to H.B.

Early diagnosis of mild cognitive impairment and Alzheimer's disease based on salivary lactoferrin.

INTRODUCTION: The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid ß (Aß) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity. METHODS: Here, we show a novel, straight-forward, and noninvasive approach for assessment of early stages of cognitive decline. Salivary samples from cases of amnestic mild cognitive impairment (aMCI) and AD, and neurology controls were analyzed. RESULTS: We have discovered and validated a new single saliva biomarker, lactoferrin, which in our cross-sectional investigation perfectly discriminates clinically diagnosed aMCI and AD patients from a cognitively healthy control group. The accuracy for AD diagnosis shown by salivary lactoferrin was greater than that obtained from core cerebrospinal fluid (CSF) biomarkers, including total tau and CSF Aß42. Furthermore, salivary lactoferrin can be used for population screening and for identifying those underdiagnosed subjects with very early stages of mild cognitive impairment and AD. CONCLUSION: This biomarker may offer new insights in the early diagnostics for AD.

Endarterectomía satisfactoria en paciente con oclusión y rama anómala de la carótida interna / Satisfactory endarterectomy in patient with occlusion and anomalous branch of the internal carotid

La oclusión de la arteria carotidea interna no es infrecuente, típicamente su evolución impide la endarterectomía debido a que el trombo se extiende hasta el origen de la arteria oftálmica y hace inadecuada su reconstrucción. La carótida interna solo emite ramas intracraneales, pero extraordinariamente, existe una rama extracraneal de la carótida interna que mantiene el flujo distal a la oclusión y hace viable la revascularización como en el caso que se describe a continuación. Se trata de un paciente masculino, blanco, de 67 años de edad, fumador inveterado con antecedentes de dislipidemia. Acude por presentar disminución de la visión del ojo izquierdo acompañado de cuadros vertiginosos. Con el ultrasonido vascular y la angiotomografía computarizada se comprobó la oclusión de la emergencia de la carótida interna izquierda, con recanalización distal y presencia de vaso colateral anómalo. Se realizó endarterectomía carotidea y restitución del flujo a la carótida interna con preservación del vaso anómalo. El paciente evolucionó de forma satisfactoria. El conocimiento de las variantes anatómicas y una técnica cuidadosa permiten alcanzar buenos resultados en la cirugía de la oclusión carotidea(AU)

Occlusion of internal carotid artery is not uncommon; its progression frequently hinders endarterectomy because the thrombus extends into the origin of the ophthalmic artery, making the carotid artery inadequate for reconstruction. The internal carotid only emits intracranial branches, but exceptionally, there is an extracranial branch of the internal carotid that keeps the distal flow to the occlusion and makes the revascularization viable as it occurs in the case described here. This is a 67 years old Caucasian male patient, heavy smoker with a history of dyslipidemia. He went to the doctors because of decreased vision in his left eye and dizzy changes. Vascular US and angiotomography showed occlusion of left internal carotid artery, with distal recanalization and presence of collateral anomalous vessel. The treatment consisted of carotid endarterectomy and reestablishment of the flow to the left internal carotid with preservation of the anomalous collateral vessel with satisfactory recovery. The knowledge of the anatomical variations and a careful surgical technique allow reaching good results in carotid occlusion surgery(AU)

Bypass carótido-subclavio con vena safena como alternativa de tratamiento en la oclusión de la arteria subclavia izquierda / Carotid-subclavian bypass with saphenous vein as a choice in treating occlusion of the left subclavian artery

La oclusión de la arteria subclavia izquierda es un cuadro poco frecuente y que cursa de forma asintomática generalmente. La presencia de síntomas y posibles complicaciones indican el tratamiento quirúrgico. El bypass carótido-subclavio es la técnica quirúrgica más utilizada gracias a su baja morbilidad, mortalidad y elevados índices de permeabilidad a largo plazo. El propósito de este trabajo es presentar un procedimiento alternativo para el tratamiento quirúrgico de esta oclusión, en este caso, el bypass carótido-subclavio con injerto de vena safena interna. Se describe el caso de una paciente de 56 años, fumadora inveterada que acudió al Servicio de Cirugía Cardíaca y Vascular del Cardiocentro "Ernesto Guevara", Villa Clara en diciembre de 2014 por presentar dolor frecuente en el miembro superior izquierdo que limitaba la actividad física. Se diagnosticó oclusión de la primera porción de la arteria subclavia izquierda. Se realizó bypass carótido-subclavio con injerto de vena safena interna que solucionó su cuadro clínico. La paciente evolucionó satisfactoriamente con bypass permeable con ultrasonido y angio-tomografía computarizada a los dos años de operada. El bypass carótido-subclavio con injerto de vena safena interna representa una alternativa efectiva y segura en el tratamiento de la oclusión sintomática de la arteria subclavia izquierda(AU)

The occlusion of the left subclavian artery is an uncommon situation and mostly asymptomatic. The presence of symptoms and possible complications indicate the surgical treatment. The carotid-subclavian bypass is the classical surgical technique, due to its low morbidity and mortality rates, and long term permeability indexes. The objective of this paper was to present an alternative procedure for surgical treatment of this type of occlusion, that is, the carotid-subclavian bypass with internal saphenous vein graft. Here is a 56 year-old female , heavy smoker patient who went to the heart and vascular surgery of "Ernesto Guevara" cardiological center in Villa Clara province on December 2014. She presented with frequent pain in the left upper limb that restricted her daily physical activity; the diagnosis was occlusion of the first portion of the left subclavian artery. The patient underwent left carotid-subclavian bypass surgery using a greater saphenous vein graft that eliminated the clinical picture. The patient recovered satisfactorily with a permeable bypass and she was performed ultrasound and angiographic computer tomography after two years of operation. Carotid-subclavian bypass with greater saphenous vein graft represents an effective and safe alternative in the treatment of the symptomatic occlusion of the left subclavian artery(AU)

Experimental Analysis of the Influence of Drill Point Angle and Wear on the Drilling of Woven CFRPs.

This paper focuses on the effect of the drill geometry on the drilling of woven Carbon Fiber Reinforced Polymer composite (CFRPs). Although different geometrical effects can be considered in drilling CFRPs, the present work focuses on the influence of point angle and wear because they are the important factors influencing hole quality and machining forces. Surface quality was evaluated in terms of delamination and superficial defects. Three different point angles were tested representative of the geometries commonly used in the industry. Two wear modes were considered, being representative of the wear patterns commonly observed when drilling CFRPs: flank wear and honed cutting edge. It was found that the crossed influence of the point angle and wear were significant to the thrust force. Delamination at the hole entry and exit showed opposite trends with the change of geometry. Also, cutting parameters were checked showing the feed's dominant influence on surface damage.

Effect of a smoking ban and school-based prevention and control policies on adolescent smoking in Spain: a multilevel analysis.

We evaluated the impact of a smoking ban in schools and of school-based smoking prevention and control policies on adolescent smoking. Annual surveys carried out between 2001 and 2005 that were representative of students in the 4th year of secondary education in the Madrid region, with 203 schools and 9127 students participating. The student questionnaire gathered information about personal and family variables. The contextual factors were: the periods before (years 2001-2002) and after the law; and through a survey of school management boards: compliance with the law, policy reflected in the school regulations, existence of complaints against smoking, and undertaking of educational activities regarding smoking. Multilevel logistic regression models were constructed with two dependent variables: current smoking and the proportion giving up smoking. Smoking declined in 2003, the first year after the law came into force (Odds ratio: 0.80; CI 95%: 0.66-0.96), and this decline was maintained in 2005. By contrast, smoking increased in those schools that did not undertake educational programmes regarding smoking (Odds ratio: 1.34; CI 95%: 1.13-1.59), and in those that received complaints about smoking (Odds ratio: 1.12; CI 95%: 0.96-1.29). This association is partly due to the effect of the increase in giving up smoking. The inclusion of contextual variables into the model with the individual factors reduces the variability of smoking between schools by 32.6%. In summary, the coming into force of a law banning smoking in schools, and the implementing of educational policies for the prevention and control of smoking are related to a lower risk of adolescent smoking.

Individual and contextual factors associated to smoking on school premises.

INTRODUCTION: Despite regulations, tobacco consumption in schools is still very common. The objective was to evaluate the relationship of personal, family, and school-level contextual factors with smoking on school premises. METHODS: A representative survey was undertaken of students in the 4th year of secondary education in the Madrid region (Spain), including 79 schools and 3,622 individuals. The student questionnaire gathered information about personal and family variables. The contextual factors were type of school, perception of compliance with the law, smoking policy, existence of complaints against smoking, and undertaking of educational activities regarding smoking. Analysis was carried out in the smoking population (n = 1,179) using multilevel logistic regression models. RESULTS: During the last 30 days, 50.6% of smokers had smoked on school premises. Having a father with a university education (in comparison with fathers who have not attained any educational level) reduces this probability (odds ratio [OR]: 0.43; 95% CI: 0.19-0.96), whereas smoking a larger number of cigarettes (p < .001), illicit drug consumption (p < .001), and low academic achievement (p = .052) increases it. The probability is reduced when there is no parental permission to smoke (OR: 0.66; 95% CI: 0.43-1.01) and is lower both in nonsubsidized private schools (OR: 0.29; 95% CI: 0.12-0.67) and in state subsidized private schools (OR: 0.17; 95% CI: 0.09-0.34) than in public schools. CONCLUSIONS: A very low level of educational attainment by the father, smoking a higher number of cigarettes, as well as illicit drug consumption, low academic achievement, having parental permission to smoke, and attending public schools are all related to a higher probability of smoking on school premises.

[Cytoprotective effect of low-dose tacrolimus on islets of Langerhans in cultures subjected to stimulation by acute rejection cytokines]. / Efecto citoprotector del tacrolimus a dosis bajas sobre islotes de Langeerhans en cultivo sometidos a estímulos por citocinas del rechazo agudo.

INTRODUCTION: The improvement in pancreatic islet transplantation results is due to immunosuppression protocols that include, among others, low-dose tacrolimus. Both anti-inflammatory and anti-oxidant effects of tacrolimus could be useful in preventing primary rejection. AIM: To evaluate in vitro islet low-dose tacrolimus response after pro-inflammatory stimulation. MATERIAL AND METHODS: Isolated rat islets were cultured in RPMI medium in the presence of IL-1 (50 UI/mL) plus IF-gamma (1000 UI/mL) and tacrolimus (5 ng/mL). The 24 h production of lipoperoxide (LPO) and nitric oxide (NO) were measured as oxidative stress markers. Determination of apoptosis markers (nucleosome content and Bcl-2) was also performed. RESULTS: Oxidative stress (LPO 10.1+/-1.16 pmol/islet x 24; NO 19.1+/-3.28 pmol/isletx24 h) and apoptosis (nucleosome 0.24+/-0.04 UI/islet; Bcl-2 0.69+/-0.212 UI/islet) markers showed a very significant increase after cytokine stimulation (p<0.01). Both effects improved by adding tacrolimus to the medium. Protective effect was complete when lipoperoxide (1.58 pmol/isletx24 h), nitric oxide (9.81 pmol/isletx24 h) and Bcl-2 (1.37+/-0.23 UI/islet) were determined. CONCLUSION: In vitro cytoprotective effect of low-dose tacrolimus on isolated rat islets decreases both oxidative stress and apoptosis markers after stimulation of pro-inflammatory mediators.

Association between airborne pollen and epidemic asthma in Madrid, Spain: a case-control study.

BACKGROUND Despite the fact that airborne pollen is an important factor in precipitating asthma attacks, its implication in increases of epidemic asthma in usual meteorological conditions has not been reported. A study was undertaken to estimate the relationship between various types of aeroallergens and seasonal epidemic asthma in the region of Madrid, Spain. METHODS A case-control study was carried out in individuals aged 4-79 years who received emergency healthcare for asthma during 2001 in a base hospital covering a population of 750 000 inhabitants of Madrid. A skin prick test was performed with grass pollen, plantain pollen, olive pollen, cypress pollen, plane tree pollen, dust mites and Alternaria and the prevalence of skin reactivity was compared between subjects with asthma requiring emergency care for asthma within (cases) and outside (controls) the seasonal epidemic period. Data were analysed using logistic regression adjusting for age and sex. RESULTS The response rate was 61.7% for cases (n=95) and 51.6% for controls (n=146). The OR of sensitisation to grass pollen for cases compared with controls was 9.9 (95% CI 4.5 to 21.5); plantain pollen: 4.5 (95% CI 2.5 to 8.2); olive pollen: 7.3 (95% CI 3.5 to 15.2); plane tree pollen: 3.6 (95% CI 2.0 to 6.4); cypress pollen: 3.5 (95% CI 2.0 to 6.2); dust mites: 1.1 (95% CI 0.6 to 1.9); Alternaria: 0.9 (95% CI 0.5 to 1.9). The association with grasses was maintained after adjusting simultaneously for the remaining aeroallergens (OR 5.0 (95% CI 1.5 to 16.4)); this was the only one that retained statistical significance (p=0.007). CONCLUSIONS These results suggest that allergy to pollen, particularly grass pollen, is associated with the epidemic increase in asthma episodes during the months of May and June in the Madrid area of Spain.

A sampling design for a sentinel general practitioner network.

OBJECTIVE: To construct a design for probabilistic sampling of reporting physicians in sentinel networks. METHODS: We performed a multi-stage sample selection study. Data on primary care physicians and their patients were obtained from the Madrid Health Institute for 2005. The geographical unit of reference was the basic health area. A factorial analysis was performed on the basis of demographic, socio-cultural and socio-occupational variables. A cluster analysis was conducted to group the 247 basic health areas into homogeneous strata, which were then tested using a discriminant analysis. The general practitioners and pediatricians needed in each stratum were selected by simple random sampling. The representativeness of the population monitored by the selected physicians was studied with respect to the population of Madrid. RESULTS: Factorial analysis yielded five factors. Using these, 14 strata were obtained, which were shown to be homogeneous and mutually different by discriminant analysis. The minimum population that needed to be monitored consisted of 146,946 adults and 24,518 children, proportionally distributed among the respective strata. Eighty-eight general practitioners and 32 pediatricians were selected, who respectively covered populations of 154,610 and 31,336 persons representative of the general population. CONCLUSIONS: Obtaining samples through suitable designs improves the accuracy of the information gathered by health sentinel networks in epidemiologic surveillance. Ensuring the representativeness of the study population vis-à-vis the general population is essential; cluster analysis and simple random sampling are methods that meet this need. Selecting physicians by means of probabilistic methods enables the accuracy of estimates to be ascertained.