Systemic acidemia impairs cardiac function in critically Ill patients.

BACKGROUND: Acidemia, is associated with reduced cardiac function in animals, but no studies showing an effect of acidemia on cardiac function in humans are reported. In the present study, we examined the effect of acidemia on cardiac function assessed with transpulmonary thermodilution technique with integrated pulse contour analysis (Pulse Contour Cardiac Output, PiCCO™) in a large cohort of critically ill patients. METHODS: This was a prospective multicenter observational cross-sectional study of 297 patients from 6 intensive care units in London, England selected from all patients admitted consecutively between May 2018 and March 2019. Measurements of lowest plasma pH and concurrent assessment of cardiac function were obtained. FINDINGS: There was a significant difference between two pH categories (pH ≤ 7.28 vs. pH > 7.28) for the following variables of cardiac function: SVI (difference in means 32.7; 95% CI: 21 to 45 mL/m2; p < 0.001); GEF (18; 95% CI: 11 to 26%; p < 0.001), dPmax (-331; 95% CI: -510 to -153 mmHg/s; p = 0.001), CFI (0.7; 95% CI: 0.2 to 1.3 1/min; p = 0.01) and CPI (0.09; 95% CI: 0.03 to 0.15 W/m2; p < 0.001). However, there was no significant difference in CI (0.13; 95% CI: -0.20 to 0.47 L/min/m2; p = 0.12) between the pH categories. Also, a significant relationship was found between the quantitative pH and the following variables: SVI (132; 95% CI: 77 to 188 mL/m2; p < 0.001), GEF (74.7; 95% CI: 37.1 to 112.4%; p < 0.001), dPmax (-1587; 95% CI: -2361 to -815 mmHg/s; p < 0.001), CFI (3.5; 95% CI: 0.9 to 6.1 /min; p = 0.009), CPI (0.62; 95% CI: 0.36 to 0.88 W/m2; p < 0.001) and CI (regression coefficient 1.96; 95% CI:0.45 to 3.47 L/min/m2; p = 0.01). INTERPRETATION: Acidemia is associated with impaired cardiac function in seriously ill patients hospitalized in the intensive care unit supporting the potential value of early diagnosis and improvement of arterial pH in these patients. FUNDING: The study was partially supported by unrestricted funds from the UCLA School of Medicine.

Presión positiva continua en la vía aérea mediante dispositivos no convencionales en insuficiencia respiratoria severa secundaria a SARS-CoV-2: estudio observacional de cohorts / Home-made continuous positive airway pressure dispositives at management of severe respiratory failure due to SARS-COV-2: a cohort study

OBJETIVO: Conocer el efecto de un sistema artesanal de CPAP sobre la oxigenación y la supervivencia en pacientes con insuficiencia respiratoria secundaria a COVID-19. MATERIAL Y MÉTODO: Estudio de cohortes desarrollado en un hospital universitario de 400 camas, incluyéndose pacientes con insuficiencia respiratoria por SARS-COV-2 en los que se requirió emplear un sistema artesanal de CPAP (n= 64) o una mascarilla con reservorio convencional (n= 64). La utilización del sistema artesanal de CPAP consistía en un reservorio que recibía oxígeno (flujo de 15 L*min-1) conectado a una mascarilla oronasal sin fugas y a una rama espiratoria sellada con una válvula de PEEP. Se analizó la mortalidad, el fracaso del soporte respiratorio (muerte o paso a VMI) y la evolución del cociente SpO2/FIO2 en función del tipo de soporte respiratorio empleado. Se realizó un análisis mediante métodos de regresión y posteriormente un ajuste estadístico teniendo en cuenta las principales diferencias entre ambos grupos. RESULTADOS: La mortalidad fue de 46,9% con reservorio convencional y del 56,3% con "CPAP artesanal" (OR ajustada 1,45, p= 0,573). El fracaso del soporte respiratorio fue del 67,2% y 54,7% respectivamente (OR ajustada 0,53, p= 0,329). La evolución del cociente SpO2/FIO2 no mostró diferencias significativas entre ambos grupos en el análisis ajustado (-4, p = 0,876). Conclusiones. El sistema artesanal estudiado no modifica negativamente la mortalidad, pudiendo ser segura su utilización. Aun así, no muestra un impacto positivo sobre la oxigenación ni la evolución clínica que permita recomendar su uso

OBJECTIVE: Improve knowledge about a "home-made" CPAP system used during first COVID-19 outbreak and its effect on oxygenation and mortality. MATERIALS AND METHODS: Cohort study developed in a university hospital of 400 beds. All included patients had respiratory failure due to SARS-CoV-2 infection. 64 of them used a home-made CPAP system and 64 patients used a conventional high-concentration oxygen mask. The home-made CPAP system consists of an antistatic reservoir bag that receives oxygen at a flow of 15 litters per minute connected to an oronasal mask and to a PEEP valve. Mortality, respiratory support failure (death or change to IVM), and SpO2/FiO2 evolution were analyzed according to the type of respiratory support used. An analysis was carried out using regression methods and later a statistical adjustment taking into account the main differences between both groups. RESULTS: Mortality was of 46.9% at the high-concentration oxygen mask group and 56.3% at the "home-made" CPAP system group (Adjusted OR 1.45, p= 0.573). Respiratory support failure was of 67.2% y 54.7% respectively (Adjusted OR 0.53, p= 0.329). SpO2/FiO2 evolution didn't show a significative difference between both groups at adjusted analysis (-4, p= 0.876). Conclusions. The "home-made" CPAP system didn't show a negative impact on mortality, so it could be safe to consider its use. Even so, the "home-made" CPAP system didn't show a positive impact on oxygenation or clinical evolution, so its use cannot be recommended

Maternal mortality in Spain and its association with country of origin: cross-sectional study during the period 1999-2015.

BACKGROUND: The available literature suggests that there are significant differences in maternal mortality according to maternal origin in high income countries. The objective of this study was to quantify the risk of maternal death by maternal origin and region of Spain where the birth occurred and to identify the most important causes of maternal death in our country. METHODS: An ecological cross-sectional study was conducted that included all deliveries that resulted in maternal survival and cases of maternal death during 1999-2015 in Spain. A descriptive analysis of the maternal mortality rate by maternal origin, region and year of birth was performed. The risk of maternal death was calculated using univariate and multivariate logistic regression analysis, with adjustment for the variables included in the descriptive analysis. RESULTS: There were 272 maternal deaths during this period, most of which were due to haemorrhage (63 cases, 23.16%).Women whose continent of origin was South America had the highest adjusted risk of maternal death, with an OR of 3.92 (95% CI 2.75-5.58). The region of Spain with the highest risk of maternal death was Ceuta, with an OR of 12.11 (95% CI 2.02-72.68). CONCLUSIONS: This study shows that there are inequalities in maternal mortality according to maternal origin and region where labour occurred. These findings highlight the need to establish strategies at the national and European levels to analyse the most relevant causes and risk factors associated with maternal mortality in order to reduce it and pay closer attention in identifying and carefully managing pregnant women from this at risk groups.

Sintomatología clínica residual y factores asociados en supervivientes de un fracaso multiorgánico: una hipoteca a largo plazo / Clinical residual symptomatology and associated factors in multiple organ failure survivors: a long-term mortgage

Objetivo. Evaluar la sintomatología clínica residual que puedan presentar los supervivientes de un fracaso multiorgánico (FMO) tras su alta de la Unidad de Cuidados Intensivos (UCI) e identificar aquellos factores que puedan estar asociados. Material y métodos. Fueron seleccionados de forma consecutiva en el estudio un total de 545 pacientes adultos con FMO a su ingreso. Se realizó una encuesta a los 6 y 12 meses tras el alta de una UCI médico-quirúrgica en España. Se realizó una encuesta telefónica sobre los síntomas clínicos presentes al alta de UCI. Resultados. Se realizó seguimiento a un total de 266 pacientes supervivientes al FMO; un 62,2% eran varones, la edad media fue de 60±18 años y un 67,8% eran pacientes médicos. Los síntomas más comunes presentados tras el alta hospitalaria fueron astenia (173; 76%), alteraciones en el sueño (112; 50%) y depresión (109; 48%). Conclusiones. El seguimiento reveló la presencia frecuente de síntomas clínicos «residuales» que persistieron al menos un año; de forma más notable, la artromialgia y la astenia. La presencia de síntomas depresivos tras los primeros 6 meses del alta poshospitalaria también fue común entre los pacientes supervivientes de FMO. La duración de la sintomatología se relacionó principalmente con una situación basal pobre a los 6 y 12 meses, un ingreso hospitalario largo y una puntuación de gravedad alta al ingreso en la UCI (AU)

Purpose. To evaluate which residual clinical symptoms multi-organ failure (MOF) patients may exhibit post discharge from Intensive Care Units (ICU) and to identify the associated factors that cause such symptoms. Material and methods. A total of 545 adult patients admitted to a medical & surgical ICU in Spain diagnosed with MOF on admission were included in the study. Follow up in the form of a telephone survey regarding the patients clinical symptoms were conducted at 6 and 12 months after discharge from ICU. Results. A total of 266 patients were followed up at both 6 and 12 months post ICU discharge; 62.2% were male; age 60±18 years; 67.8% medical patients. The most common symptoms to appear following hospital discharge included: asthenia (173; 76%), sleep disturbances (112; 50%) and depression (109; 48%). Conclusions. The study revealed frequent residual clinical symptoms persisting for almost a year post ICU discharge, most notably arthromyalgia and asthenia. Depression symptoms during the first 6 months post-hospital discharge were also common among multiple organ failure survivors. The presence of symptomatology over time was found to be related to a poor functional situation at 6 and12 months post ICU discharge, length of hospital stay and severity of illness score on ICU admission (AU)

Human Development Index (HDI) of the maternal country of origin as a predictor of perinatal outcomes - a longitudinal study conducted in Spain.

BACKGROUND: In an era of worldwide population displacement, recent studies have identified strong associations between social situations and perinatal outcomes among immigrants. Little is known about the effect of maternal social background on pregnancy outcomes. The Human Development Index (HDI) assesses the following dimensions of human development: life expectancy, education level and income. The objective of our study was to determine if maternal HDI may be used to identify women at increased odds of poor pregnancy outcomes. METHODS: We conducted a longitudinal population-based study in a tertiary centre in Madrid, Spain. The outcome variables were maternal and perinatal/antenatal mortality, preeclampsia (PE), low birth weight (LBW), gestational diabetes mellitus (GDM), preterm delivery (PTD) before 37 and 34 gestational weeks, abnormal cardiotocography (CTG) during delivery, C-section (CS) due to abnormal CTG, pH < 7.10 at birth, Apgar at 5 min ≤ 7, and resuscitation type ≥3. We performed multivariate logistic regression analyses adjusted for potential confounding variables to evaluate the associations between maternal HDI and perinatal outcomes. RESULTS: In total, 38,719 singleton infants who were born in our maternity ward between 2010 and 2016 and had perinatal outcome data available were included in this study. The neonates of women from medium/low HDI countries had significantly lower odds of low birth weight (LBW) than their very high HDI country counterparts (OR 0.63, 95% CI 0.55-0.72). However, the odds of PTD before 37 gestational weeks and PE were higher in the medium/low HDI group than the very high HDI group (OR 1.26, 95% CI 1.04-1.53; OR 1.35, 95% CI 1.02-1.79, respectively). Poorer neonatal outcomes were identified in the medium/low HDI group than the very high HDI group, including greater odds of abnormal CTG, CS due to abnormal CTG and Apgar 2 ≤ 7 (p < 0.05). CONCLUSIONS: Our findings suggest that the infants of mothers from medium/low HDI had lower odds of LBW but higher odds of PTD, PE and poor neonatal outcomes. These results support the hypothesis that maternal HDI can be used to understand the impact of maternal origin on pregnancy outcomes. Further studies are needed to confirm its validity.

Clinical residual symptomatology and associated factors in multiple organ failure survivors: A long-term mortgage. / Sintomatología clínica residual y factores asociados en supervivientes de un fracaso multiorgánico: una hipoteca a largo plazo.

PURPOSE: To evaluate which residual clinical symptoms multi-organ failure (MOF) patients may exhibit post discharge from Intensive Care Units (ICU) and to identify the associated factors that cause such symptoms. MATERIAL AND METHODS: A total of 545 adult patients admitted to a medical & surgical ICU in Spain diagnosed with MOF on admission were included in the study. Follow up in the form of a telephone survey regarding the patients clinical symptoms were conducted at 6 and 12 months after discharge from ICU. RESULTS: A total of 266 patients were followed up at both 6 and 12 months post ICU discharge; 62.2% were male; age 60±18 years; 67.8% medical patients. The most common symptoms to appear following hospital discharge included: asthenia (173; 76%), sleep disturbances (112; 50%) and depression (109; 48%). CONCLUSIONS: The study revealed frequent residual clinical symptoms persisting for almost a year post ICU discharge, most notably arthromyalgia and asthenia. Depression symptoms during the first 6 months post-hospital discharge were also common among multiple organ failure survivors. The presence of symptomatology over time was found to be related to a poor functional situation at 6 and12 months post ICU discharge, length of hospital stay and severity of illness score on ICU admission.

Oligomers of ß-amyloid protein (Aß1-42) induce the activation of cyclooxygenase-2 in astrocytes via an interaction with interleukin-1ß, tumour necrosis factor-α, and a nuclear factor κ-B mechanism in the rat brain.

Despite growing evidence indicating the effects of cytokines, including interleukin-1beta (IL-1ß) and tumour necrosis factor-α (TNFα), and the enzyme cyclooxygenase-2 (COX-2) in Alzheimer's diseases, little is known about the signalling mechanisms that mediate its activation in response to beta-amyloid protein (Aß). The aim of this study was first to investigate whether Aß1-42 peptide induced the up-regulation of COX-2. We then examined the expression of COX-2 and cytokines, such as IL-1ß and TNFα, in reactive astrocytes. Finally, we analyzed the role of nuclear factor kappa-B (NF-κB) as a signalling pathway in early stages of Aß-toxicity. In Wistar rats anaesthetised with equitesine, a single microinjection of Aß1-42 oligomers was made in the left retrosplenial cortex. Control animals were injected with Aß42-1 peptide into the corresponding region of the cerebral cortex. By COX-2 immunoblotting, we detected two immunopositive protein bands, at 70 and 50 kDa molecular mass. In the Aß1-42-injected animals the 50 kDa fragment showed a significant increase at 3 and 14 days, as compared with that seen in control animals. The 70 kDa fragment showed a maximal increase at 14 days. In the Aß1-42-injected animals immunoblot staining of NF-κB detected an active protein band at 50 kDa molecular mass, showing a maximal increase at the 72 h time point. Confocal analysis revealed that COX-2 protein co-localized with Aß-IR material at the injection site and in endothelial blood vessels, increasing at 72 h. In the Aß oligomer-treated animals, COX-2, IL-1ß, and TNFα proteins were expressed in reactive astrocytes surrounding the injection site and blood vessels at early stages of Aß toxicity. Double-labelling immunofluorescence studies also revealed that GFAP and COX-2 proteins co-localized with NF-κB-positive material at early time-points. In conclusion, our results suggest that in reactive astrocytes and in COX-2 positive cells NF-κB may mediate pro-, and/or inflammatory gene expression and that, develop strategies that target the GFAP/NF-κB and COX-2/NF-κB pathways might contribute to reducing Aß-induced toxicity.

[Short-tau inversion-recovery (STIR) sequence magnetic resonance imaging evaluation of orbital structures in Graves' orbitopathy]. / Evaluación de la órbita mediante secuencias short-tau inversion-recovery (STIR) en resonancia nuclear magnética en la orbitopatía de Graves.

OBJECTIVE: To evaluate the orbital structures and to establish correlations with disease activity and severity in patients with Graves' hyperthyroidism and orbitopathy (GO) using short-tau inversion-recovery (STIR) sequence magnetic resonance imaging (MRI). METHODS: Observational, cross-sectional, case-control study. Twenty-eight patients with euthyroid status after treatment and GO (GO group) and 15 control subjects (control group) were included. Patients underwent a complete ophthalmologic examination and were then assessed according to the EUGOGO (European Group on Graves' Orbitopathy) recommendations. Muscle cross-sectional areas, orbital tissue volumes and the signal intensity ratio (SIR) from the most inflamed extraocular muscle were calculated using a STIR-T2 weighted sequence MRI. Correlations between clinical and MRI measurements were analyzed. RESULTS: Enlargements in the cross-sectional areas and volumes were significant for most EOMs (P<.001), but not for the lateral rectus muscle cross-sectional area. A significant difference in SIR values between patients with GO and control subjects (P<.001) was found. No significant correlations were found between muscle cross-sectional areas, orbital tissue volumes, SIR values and the clinical activity parameters. CONCLUSIONS: Given the small sample size of our study, with the obvious need for larger clinical trials, we were unable to demonstrate that the STIR sequences in MRI are a sensitive tool in assessing patients with longstanding GO in order to detect inflammatory changes and activity follow-up, possibly because it is in inactive phase. Meanwhile, it is still necessary to continue performing a thorough clinical evaluation in the therapeutic management of GO.

Evaluación de la órbita mediante secuencias short-tau inversion-recovery (STIR) en resonancia nuclear magnética en la orbitopatía de Graves / Short-tau inversion-recovery (STIR) sequence magnetic resonance imaging evaluation of orbital structures in Graves’ orbitopathy

Objetivo: Evaluar las estructuras orbitarias mediante secuencias short-tau inversion-recovery (STIR) en resonancia nuclear magnética (RNM) y establecer correlaciones con los signos de actividad clínica (CAS) y severidad en pacientes con hipertiroidismo y orbitopatía Graves (OG). Métodos: Estudio clínico de casos y controles, observacional y transversal. Veintiocho pacientes en estatus eutiroideo postratamiento y OG (grupo OG) y 15 sujetos controles (grupo control) fueron evaluados. Se realizó una exploración oftalmológica completa a los participantes y se determinó la actividad y severidad de la OG, según recomendaciones EUGOGO (Grupo Europeo en Orbitopatía Graves). Áreas de sección transversal de los músculos extraoculares (MOE), volúmenes de los tejidos orbitarios y ratios (SIR) de intensidad de señal del MOE más inflamado fueron calculados usando secuencias STIR-T2 en RNM. Se establecieron correlaciones entre variables. Resultados: Los incrementos en las áreas de sección transversal y volúmenes fueron significativos en la mayoría de los MOE (p<0,001), pero no en el área de sección transversal del recto lateral. Se encontraron diferencias significativas en valores SIR entre ambos grupos (p<0,001). No se establecieron correlaciones significativas entre el área total de sección transversal de los MOE, volúmenes de los tejidos orbitarios, valores SIR y signos de actividad clínica. Conclusiones: Dado el tamaño muestral del estudio, con la necesidad obvia de estudios más amplios, no podemos demostrar que las secuencias STIR en RNM sean una herramienta sensible para evaluar cambios inflamatorios y actividad clínica en la OG de larga evolución, posiblemente debido a que se halle en fase inactiva(AU)

Objective: To evaluate the orbital structures and to establish correlations with disease activity and severity in patients with Graves’ hyperthyroidism and orbitopathy (GO) using short-tau inversion-recovery (STIR) sequence magnetic resonance imaging (MRI). Methods: Observational, cross-sectional, case-control study. Twenty-eight patients with euthyroid status after treatment and GO (GO group) and 15 control subjects (control group) were included. Patients underwent a complete ophthalmologic examination and were then assessed according to the EUGOGO (European Group on Graves’ Orbitopathy) recommendations. Muscle cross-sectional areas, orbital tissue volumes and the signal intensity ratio (SIR) from the most inflamed extraocular muscle were calculated using a STIR-T2 weighted sequence MRI. Correlations between clinical and MRI measurements were analyzed. Results: Enlargements in the cross-sectional areas and volumes were significant for most EOMs (P<.001), but not for the lateral rectus muscle cross-sectional area. A significant difference in SIR values between patients with GO and control subjects (P<.001) was found. No significant correlations were found between muscle cross-sectional areas, orbital tissue volumes, SIR values and the clinical activity parameters. Conclusions: Given the small sample size of our study, with the obvious need for larger clinical trials, we were unable to demonstrate that the STIR sequences in MRI are a sensitive tool in assessing patients with longstanding GO in order to detect inflammatory changes and activity follow-up, possibly because it is in inactive phase. Meanwhile, it is still necessary to continue performing a thorough clinical evaluation in the therapeutic management of GO(AU)

Soluble oligomeric forms of beta-amyloid (Abeta) peptide stimulate Abeta production via astrogliosis in the rat brain.

The aim of this study was to investigate the interaction between beta-amyloid (Abeta) peptide and astrogliosis in early stages of Abeta toxicity. In Wistar rats, anaesthetised with equitesine, a single microinjection of Abeta1-42 oligomers was placed into the retrosplenial cortex. Control animals were injected with Abeta42-1 peptide into the corresponding regions of cerebral cortex. Immunocytochemical analysis revealed an intense Abeta immunoreactivity (IR) at the level of Abeta1-42 injection site, increasing from the first 24 h to later (72 h) time point. Control injection showed a light staining surrounding the injection site. In Abeta oligomers-treated animals, Abeta-immunopositive product also accumulates in cortical cells, particularly in frontal and temporal cortices at an early (24 h) time point. Abeta-IR structures-like diffuse aggregates forms were also observed in hippocampus and in several cortical areas, increasing from the first 24 h to later (72 h) time point. In control animals no specific staining was seen neither in cortical cells nor in structures-like diffuse aggregates forms. Injections of Abeta oligomers also induce activation of astrocytes surrounding and infiltrating the injection site. Astrocyte activation is evidenced by morphological changes and upregulation of glial fibrillary acidic protein (GFAP). By GFAP immunoblotting we detected two immunopositive protein bands, at 50 and 48 kDa molecular mass. Confocal analysis also showed that GFAP co-localized with Abeta-IR material in a time-dependent manner. In conclusion, our results indicate that astrocyte activation might have a critical role in the mechanisms of Abeta-induced neurodegeneration, and that should be further studied as possible targets for therapeutic intervention in AD.

Beta-amyloid peptide-induced modifications in alpha7 nicotinic acetylcholine receptor immunoreactivity in the hippocampus of the rat: relationship with GABAergic and calcium-binding proteins perikarya.

The effects of the injected beta-amyloid (Abeta) protein on the alpha7 subtype of nicotinic acetylcholine receptor protein (alpha7nAChR) in the hippocampus were studied in rats. Injections of Abeta into the retrosplenial cortex resulted in a decrease in alpha7nAChR-immunoreactivity in the hippocampus. Quantitative analysis revealed a significant reduction in alpha7nAChR-immunoreactivity in the dorsal part of the CA1 ipsilateral to the Abeta-injected side as compared to the corresponding hemisphere of non-treated control animals and with that seen in the contralateral hemisphere, which corresponds to the control (PBS)-injected side. A significant decrease in alpha7nAChR-immunoreactivity was also found in the dorsal part of the ipsilateral CA1 as compared with that in the ventral part of the CA1, in CA2, and in CA3 ipsilateral to the Abeta-injected side. The analysis also revealed a significant decrease in alpha7nAChR-immunoreactivity in the dentate gyrus ipsilateral to the Abeta-injected side as compared to the corresponding hemisphere of non-treated control animals and with that in the PBS-injected side co-localization studies showed that the alpha7nAChR protein is highly localized in GABA- and Parv-immunoreactive cells, while only few Calb-positive cells expressed immunoreactivity for alpha7nAChR. In addition, injections of Abeta protein resulted in a significant reduction in the number of GABA- and Parv-immunoreactive cells in the dorsal part of the ipsilateral CA1 as compared to the corresponding region of non-treated control animals and with that in the corresponding region of the PBS-injected side. Our findings suggest that Abeta induces a reduction in alpha7nAChR-containing cells, which may contribute to impairment of GABAergic synaptic transmission in the hippocampus.

Effects of beta-amyloid peptide on the density of M2 muscarinic acetylcholine receptor protein in the hippocampus of the rat: relationship with GABA-, calcium-binding protein and somatostatin-containing cells.

AIMS: The deposition of amyloid peptides (A beta) in the cortex and hippocampus is the primary trigger of Alzheimer's disease (AD). Recent studies also indicated that the M2 subtype of muscarinic acetylcholine receptors (M2mAChR) may be a key molecule involved in cognitive dysfunction. Thus, the purpose of this study was to determine the effects of extracellular deposition of A beta on the density of M2mAChR in the hippocampus of the rat by M2mAChR-immunohistochemistry. METHODS: Special attention was paid to discerning any interaction between A beta and M2mAChR in GABA-, and calcium-binding protein containing cells by double-labelling immunohistochemistry. Densitometric analysis of M2mAChR-immunoreactivity was performed using Scion Image Beta Software. Quantitative analysis of GABA-, and calcium-binding protein interneurones containing M2mAChR protein was performed using a NeuroLucida morphometric system. RESULTS: Injections of A beta into the retrosplenial cortex resulted in a significant reduction in M2mAChR-immunoreactivity in the CA1 ipsilateral to the A beta-injected side as compared with the corresponding hemisphere of non-treated control animals and with that in the corresponding region of the CA1 in the phosphate-buffered saline-injected side. Co-localization studies showed that the M2mAChR is localized in a subset of GABA-positive cells of the hippocampus, in cells that contain calcium-binding proteins, and in a subpopulation of cells that contain the neuropeptide somatostatin. CONCLUSIONS: Our findings suggest that A beta induces a significant reduction in M2mAChR-immunoreactivity in the CA1 of the hippocampus and a reduction in GABAergic interneurones containing M2mAChR, which may contribute to impairment of GABAergic synaptic transmission in area CA1 of hippocampus.

Interaction between â-amyloid protein andthe á7 nicotinic acetylcholine receptorin cholinergic, gabaergic and calcium-bindingproteins-containing neurons in theseptum-diagonal band complex of the rat

The effects of intracerebral injection of thebeta-amyloid protein (Aâ1-40) on the á7subtype of nicotinic acetylcoline receptor protein(nAChR) in neurons of the septum-diagonalband (MS-nDBB) complex were studiedin rats. Focal deposition of Aâ in the retrosplenialcortex resulted in a selective reductionin the number of á7nAChR-immunoreactivecells in different parts of the MS-nDBB complex,especially in the horizontal nucleus ofthe diagonal band of Broca (HDB). The analysisrevealed a significant decrease of 37.27%in the number of á7nAChR-immunoreactivecells in the HDB ipsilateral to the Aâ-injectedside as compared to the correspondinghemisphere of non-treated control animals,and a reduction of 31.55% was observed inthe HDB ipsilateral to the Aâ-injected side ascompared to the contralateral HDB, whichcorresponds to the control (PBS)-injected side.A significant reduction (up to 20%) ofá7nAChR-containing neurons was also foundin the medial septal nucleus when comparedwith the corresponding hemisphere in nontreatedcontrol animals. The results alsorevealed that á7nAChR-positive immunoreactivityis highly localized within cytoplasmicgranules in cholinergic neurons and in a smallsubset of putative GABAergic cells of the MSnDBBcomplex. In conclusion, these findingssuggest an interaction of Aâ1-40 with theá7nAChR, which may contribute to impairmentsin cholinergic and GABAergic transmissionin the MS-nDBB complex (AU)

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[Esophageal tuberculosis. Presentation of a case and review of the literature]. / Tuberculosis esofágica. Presentación de un caso y revisión de la literatura.

We describe the case of a 63-year-old woman who had recently developed dysphagia. Oral endoscopy revealed an ulcerated fungating lesion in the middle third of the esophagus. The histologic examination showed granulomas with caseous central necrosis, and the culture in a Lowenstein medium produced M. tuberculosis. There were mediastinic adenopathies, but no other organic involvement with this mycobacterium was demonstrated. We review the other 21 cases reported in the English and Spanish literature over the past ten years.