Dual effect of serotonin on the dendritic growth of cultured hippocampal neurons: Involvement of 5-HT1A and 5-HT7 receptors.

Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT7R expressed early during hippocampus development, shows a progressive reduction in its expression postnatally. Considering these changes during development, we evaluated in cultured hippocampal neurons whether the 5-HT1AR and 5-HT7R change their expression, modulate dendritic growth, and activate signaling pathways such as ERK1/2, AKT/GSK3ß and LIMK/cofilin, which may sustain dendrite outgrowth by controlling cytoskeleton dynamics. We show that mRNA levels of both receptors increase between 2 and 7 DIV; however only protein levels of 5-HT7R increase significantly at 7 DIV. The 5-HT1AR is preferentially distributed in the soma, while 5-HT7R displays a somato-dendritic localization at 7 DIV. Through stimulation with 5-HT at 7 DIV during 24h and using specific antagonists, we determined that 5-HT1AR decreases the number of primary and secondary dendrites and restricts the growth of primary dendrites. The activation of 5-HT1AR and 5-HT7R promotes the growth of short secondary dendrites and triggers ERK1/2 and AKT phosphorylation through MEK and PI3K activation respectively; without changes in the phosphorylation of LIMK and cofilin. We conclude that 5-HT1AR restricts dendritogenesis and outgrowth of primary dendrites, but that both 5-HT1AR and 5-HT7R promote secondary dendrite outgrowth. These data support the role of 5-HT in neuronal outgrowth during development and provide insight into cellular basis of neurodevelopmental disorders.

Percentage of hypochromic erythrocytes and reticulocyte hemoglobin equivalent predictors of response to intravenous iron in hemodialysis patients.

INTRODUCTION: Reticulocyte hemoglobin content and percentage of hypochromic red cells are incorporated into the European best practice guidelines on anemia management in chronic kidney disease. Sysmex XN analyzer (Sysmex Corporation, Kobe, Japan) reports reticulocyte hemoglobin equivalent (Ret-He) and the hypochromic fraction of erythrocytes (%Hypo-He). Our aim was to assess the value of these parameters, in terms of the sensitivity and specificity for detecting functional iron deficiency, in hemodialysis (HD) patients. METHODS: Forty HD patients in the maintenance phase of erythropoietin therapy were included. Intravenous iron supplementation was interrupted at least 3 weeks before recruitment. Two samples were analyzed for each patient: the baseline after the iron-free period and the second sample after 4 weeks of IV iron administration. Hemogram and biochemical parameters of the iron status were measured. Patients were classified as responders or nonresponders to an iron load; responders had an increase in Hb of at least 10 g/L after iron administration, compared to the baseline. To identify the efficiency of the test for predicting the response to iron administration, receiver operating characteristic analysis (ROC) was performed. RESULTS: According to the established criteria, 21 patients were responders and 19 nonresponders. ROC analysis results: Ret-He area under curve (AUC) was 0.84 (95% CI 0.64-0.93), at cutoff 30.8 pg, sensitivity 78.7%, and specificity 87.2%. % Hypo-He AUC was 0.78 (95% CI 0.64-0.91), at cutoff 2.4%, sensitivity 72.2%, and specificity 88.1%. CONCLUSIONS: % Hypo-He and Ret-He are reliable parameters for the study of erythropoiesis status in HD patients.

Stability of noisy Metropolis-Hastings.

Pseudo-marginal Markov chain Monte Carlo methods for sampling from intractable distributions have gained recent interest and have been theoretically studied in considerable depth. Their main appeal is that they are exact, in the sense that they target marginally the correct invariant distribution. However, the pseudo-marginal Markov chain can exhibit poor mixing and slow convergence towards its target. As an alternative, a subtly different Markov chain can be simulated, where better mixing is possible but the exactness property is sacrificed. This is the noisy algorithm, initially conceptualised as Monte Carlo within Metropolis, which has also been studied but to a lesser extent. The present article provides a further characterisation of the noisy algorithm, with a focus on fundamental stability properties like positive recurrence and geometric ergodicity. Sufficient conditions for inheriting geometric ergodicity from a standard Metropolis-Hastings chain are given, as well as convergence of the invariant distribution towards the true target distribution.

Transmastoid approach for resurfacing of Superior Semicircular Canal dehiscence.

This paper explains and illustrates the surgical procedure, step by step, to close a dehiscence of Superior Semicircular Canal using a transmastoid approach. This approach has several advantages over the middle cranial fossa craniotomy. Firstly, the morbidity is substantially lower. Secondly, mastoid cortical bone graft is less likely to get reabsorbed than outer table temporal bone. Therefore, surgical result is bound to be better. Finally, most otologists are more familiar and feel more comfortable with the transmastoid route than with the middle fossa one.

Human papillomavirus-16 is integrated in lung carcinomas: a study in Chile.

The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356-609 392 per nanogram DNA). The expression of the HPV-16/18 E6 protein was found in only two HPV-16-positive SQCs (13%) but not in the case with the highest viral load. Although the viral load was in general very low and HPV E6 expression is none or weak, further studies seem warranted to examine aetiological involvement of high-risk HPV in lung carcinogenesis.

Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China.

To examine the potential roles of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (ESCC) development, we examined the presence of HPV DNA in paraffin-embedded ESCC tissues collected from two areas with different ESCC incidence rates in China, that is, Gansu (n=26) and Shandong (n=33), using PCR with SPF10 primers, or PCR with GP5+/GP6+ primers combined with Southern blot hybridisation. HPV genotype was determined by the INNO-LiPA HPV genotyping kit. HPV DNA was detected in 17 cases (65%) in Gansu, where ESCC incidence is much higher than in Shandong, where HPV was positive in two samples (6%). HPV genotypes 16 and 18 were detected in 79 and 16% of HPV-positive samples, respectively. Real-time PCR analysis suggested the presence of integrated form of HPV DNA in all the HPV-16-positive samples, but its viral load was estimated to be only <1-2 copies cell(-1). We could not detect HPV 16/18 E6 protein expression by immunostaining in any of the HPV-16-positive samples. Neither p16(INK4a) nor p53 expression was related to HPV presence in ESCCs. Further studies seem warranted to examine the possible aetiological roles of HPV in ESCC.

Environmental impact of unleaded gasolines in the bay of Cádiz (Spain).

Given the strategic situation of the José León de Carranza bridge, which spans the Bay of Cádiz (in the SW of Spain) and carries very heavy motor traffic, together with knowledge of the currents and tidal flows in the zone, we have used a technique of radioactive dating of sediments to study the temporal evolution presented by contamination from lead in the sediment column. This has allowed us to observe the environmental impact, in terms of the concentration of Pb in the sea bed sediments, that has been produced in the zone by the introduction of unleaded gasolines as substitutes for traditional automobile fuels that employ organic forms of tetra methyl lead as an antidetonant agent in the fuel.

Assessment of urban and industrial contamination levels in the bay of Cádiz, SW Spain.

Measuring the amount of pollution is of particular importance in assessing the quality and general condition of an ecosystem. In this paper, some of the results obtained as a consequence of the specific agreement between the Environmental Agency (Consejería de Medio Ambiente, Junta de Andalucía) and the University of Cadiz to assess the environmental condition of the marine bottom and waters are showed. Physical and chemical analyses in water and sediments were undertaken at various sampling sites close to urban and industrial locations. Later on, these results were studied under statistical analysis to reveal any possible relationships between the parameters employed, and to identify any analogous behaviour between the sampling sites. Physical-chemical data revealed that sediments and waters analysed were moderately contaminated and, in addition, no great differences were found between in rising and ebbing tide conditions. Finally, considering only the pollution level, from the cluster analysis of sediments two major groups appear, one of which corresponded to those sites located in the outer bay, and the other to those situated in the inner bay. However, number 6 and 14 sampling sites cannot be associated to those groups due to be related to points with important local discharges.

Dating of marine sediments and time evolution of heavy metal concentrations in the Bay of Cádiz, Spain.

In this paper the time evolution of heavy metal concentration of Pb, Zn, Cd and Hg, in the sediments of the Bay of Cádiz (southwest of Spain) is studied during the past century, as a result of the industrial influence in the zone. The study has been performed using sedimentary profiles that have been extracted from the seabed. The measurement of 210Pb and 137Cs radionuclides has provided the dating of the sediment layers, up to a depth corresponding to the age of 115 years. The relative sedimentation rates obtained are around 0.2 cm/year. The 137Cs activity profile reflects the concentration of this radionuclide in the atmosphere and into aquatic systems during the second half of the twentieth century. This profile has been used to ratify the results provided by the 210Pb dating method.

Diverticulitis aguda de sigma: valor de la ecografía como test diagnóstico inicial / Acute diverticulitis of the sigmoid colon: value of ultrasound as an initial diagnostic test

Objetivo: Comprobar el valor de la ecografía como método diagnóstico inicial en la diverticulitis aguda.Material y métodos: Se realizó ecografía en 76 pacientes con el diagnóstico clínico de diverticulitis aguda de sigma. El diagnóstico final se basó en el curso clínico en todos los casos, la TC (n = 46), el examen histopatológico de la pieza quirúrgica (n = 10), la colonoscopia (n = 4) y el enema opaco (n = 2). El criterio diagnóstico ecográfico fue el engrosamiento mural del sigma > de 4 mm y la presencia de al menos uno de los siguientes hallazgos: divertículos, flemón o absceso.El diagnóstico por TC se basó en dos hallazgos necesarios: engrosamiento de sigma > de 4 mm y la inflamación de la grasa pericólica.Resultados: El diagnóstico final fue diverticulitis aguda (n = 52), otro diagnóstico (n = 18) o desconocido (n = 6). La sensibilidad de la ecografía y la TC fue 81 por ciento y 94 por ciento respectivamente, y la especificidad 79 por ciento y 83 por ciento respectivamente. De los 10 falsos negativos de la ecografía siete correspondieron a diverticulitis simples y tres a diverticulitis complicadas (dos con absceso y una con neumoperitoneo). La TC diagnosticó correctamente ocho de estos casos, presentando dos falsos negativos ante diverticulitis leves.Conclusión: La ecografía resulta un buen test en el diagnóstico inicial de la diverticulitis aguda de sigma. Se debe realizar TC ante una ecografía no diagnóstica o negativa con una alta sospecha clínica de diverticulitis, y tambien ante la posibilidad de una diverticulitis complicada (AU)

Sonography in acute appendicitis: diagnostic utility and influence upon management and outcome.

A study is made of the diagnostic utility of echography in clinically suspected appendicitis, and its influence upon patient management and outcome. A total of 374 consecutive patients with possible appendicitis were prospectively evaluated by ultrasound. Two groups were established: group A (high clinical probability, > or =0.70) and group B (moderate clinical probability, 0.20-0.60). In group-A patients (n = 105, 28%), prevalence of appendicitis = 0.90) underwent surgery regardless of the echographic findings. In group B (n = 269, 72%), prevalence of appendicitis = 0.28) surgery was performed in the event of positive echography, whereas negative echographic findings did not definitively discard appendicitis. The diagnostic utility of echography was evaluated by applying the Pauker-Kasirer threshold approach to clinical decision making. The influence of ultrasound upon outcome was in turn evaluated by contrasting the total appendectomized patients (190 of 374) with a series of 181 individuals subjected to appendectomy prior to the introduction of echography. The probability of appendicitis in the presence of positive echography was 0.95 in group A (sensitivity = 0.92) and 0.89 in group B (sensitivity = 0.91). The probability of appendicitis in the event of negative ultrasound was 0.58 in group A (specificity = 0.55) and 0.03 in group B (specificity = 0.95) . In 46% of cases the echographic findings led to a change in therapeutic regimen. In addition, the incidence of negative appendectomies was significantly reduced (19.3 vs 11.6% with echography; p = 0.03), as was the delay in establishing a diagnosis (under 6 h in 68.5 vs 84.2% with echography; p = 0.002) and the number of medical acts required (three in 71.3 vs 84.1% with echography; p = 0.001). There was no significant reduction in the incidence of perforated appendicitis (17.1 vs 17.9% with echography), in the number of postoperative complications (13.8 vs 7.6% with echography), or in the days of hospital stay (4.44 vs 4.80 with echography). Echography proved useful in group B, and was generally of little utility in group A. The technique had a positive influence on treatment, with management reorientation in a considerable number of patients, and on outcome, since ultrasound contributed to establishing an earlier diagnosis, with a reduction of unnecessary appendectomies.

Pseudochylothorax. Report of 2 cases and review of the literature.

We report 2 cases of pseudochylothorax and review 172 published cases. Tuberculosis is by far the most frequent cause of pseudochylothorax, accounting for 54% of all caes, with a remarkable association with previous collapse therapy and long-term effusions. The remaining etiologies, including rheumatoid arthritis, are infrequent. Tuberculous pseudochylothorax is usually sterile. Successful treatment of an acute tuberculous pleurisy does not preclude the development of long-term complications such as pseudochylothorax. We do not recommend pleural biopsy initially because of its low yield for etiologic diagnosis. Currently, adenosine deaminase (ADA) values in pleural fluid are not useful to sustain diagnosis or therapeutic decisions. We advise draining only symptomatic cases and treating patients with positive Ziehl-Neelsen stain or Lowenstein culture, and those with growing effusions of suspected tuberculous origin, with antituberculous chemotherapy. Pulmonary decortication should be the last therapeutic step for recurrent and symptomatic cases.

[Immunoglobulin rearrangement in the differential diagnosis of primary gastric lymphoma]. / Reordenamiento de inmunoglobulinas en el diagnóstico diferencial del linfoma gástrico primario.

BACKGROUND: The traditional methods to distinguish Chronic Follicular Gastritis and Primary Gastric Lymphoma do not allow an adequate definitive diagnosis in a significant number of cases. The molecular Biology diagnostic methods are based on the rearrangement of immunoglobulin genes. The polymerase chain reaction (PCR) specifically amplifies this rearrangement and allows molecular analysis of minimal tissue samples obtained with endoscopical biopsies. AIM: To test the usefulness of this PCR method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma. MATERIAL AND METHODS: We analyzed the endoscopical biopsies of six Chronic Follicular Gastritis cases and eight surgically treated Primary Gastric Lymphoma cases, six with the correct diagnosis in the endoscopical biopsies and two with a diagnosis of Chronic Follicular Gastritis. RESULTS: A policlonal immunoglobulin rearrangement was found in the six cases with Chronic Follicular Gastritis. A monoclonal arrangement was found in 5 of 6 biopsies with the diagnosis of Primary Gastric Lymphoma. The same monoclonal rearrangement was observed in the two biopsies incorrectly diagnosed as Chronic Follicular Gastritis. CONCLUSIONS: PCR analysis of immunoglobulin rearrangement is a useful method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma.

[The incidence and opportunity for the diagnosis of diabetic retinopathy]. / Frecuencia y oportunidad del diagnóstico de retinopatía diabética.

This study aims to establish the frequency of diabetic retinopathy (DR) in patients with diabetes mellitus (DM) type II in Leon, Guanajuato, Mexico, as well as the opportunity for their diagnosis. A prospective study was carried out in a sample of 100 patients. DR was stratified using the classification of the Early Treatment Diabetic Retinopathy Study Research Group and diagnosed in 42 per cent of the sample. The evolution time of diabetes in this group was different from that of the group without RD (p < 0.0001). A direct proportional and significant relationship between the duration of DM and an increasing severity of DR was found. Opportune diagnosis was made in 70 per cent of the cases with DR. In 81 per cent of the 42 patients with DR, no previous diagnosis was made. This study shows a high proportion of RD without diagnosis. The intensification of educational strategies for the opportune detection and early treatment of DR is recommended.