Cardiac segments dosimetric benefit from deep inspiration breath hold technique for left-sided breast cancer radiotherapy.

Background: The objective was to compare dosimetry in left-sided breast cancer (LSBC) patients receiving deep inspiration breath hold (DIBH) radiotherapy (RT) with free-breathing (FB) treatment plans. Materials and methods: Voluntary DIBH with a spirometer-based video-assisted system and CT-simulation were performed under FB and DIBH conditions on 40 LSBC patients, segmented according Duane's atlas. IMRT plans kept the same dosimetric goals on FB and DIBH conditions. Target, lungs and heart volumes were measured. Planning target volume (PTV) dose distribution, organs at risk (OARs) dose/volume parameters, including cardiac substructures, were calculated. Results: Lungs and left-lung volumes increased in DIBH conditions (ΔV = 1637.8 ml ± 555.3 and 783.5 ml ± 286.4, respectively). Heart volume slightly decreased in apnea (p = 0.04), but target volumes, CTV and PTV were similar in FB or DIBH plans. PTV dose coverage was similar irrespective of respiratory conditions (median D50% = 41.1 Gy vs 41.0 Gy, p = 0.665; V95% = 96.9% vs. 97%). Mean dose for the whole heart (MHD), left ventricle (LV), and LV segments were significantly reduced in DIBH plans. V20 values for heart subvolumes were significantly different only for those that received considerable doses (apical and anterior). DIBH plans provided significantly smaller doses (Dmax, D2%, and V20) to the LAD artery. Conclusion: Important dosimetric improvements can be achieved with DIBH technique for LSBC patients, reducing the dose to the LAD artery and heart, particularly to the segments closer to the chest wall. Apical/anterior LV segments, should be considered as separate organ at risk in breast RT.

Confirmation of the presence of serotonergic cells in the fetal cerebral cortex in cultures and in situ.

BACKGROUND: Early appearance of serotonin in the fetal brain and its effects on brain morphogenesis support its neurotrophic role. OBJECTIVE: To determine the presence of serotonergic cells and the expression of tryptophan-5-hydroxylase (TPH), 5-hydroxytryptamine (5-HT), serotonin transporter (SERT), 5-HT1A receptor and Pet-1 during the development of the cerebral cortex, both in situ and in tissue cultures. MATERIAL AND METHODS: A descriptive, observational study was carried out in pregnant Wistar rats. The presence of the plug was regarded as the beginning of gestation. On days 13, 16 and 17, cesarean sections were performed to obtain the fetuses, and the brains were then immediately dissected to identify the presence of serotonergic cells, TPH, 5-HT, SERT, 5-HT1A and Pet-1 in tissue cultures and in situ by immunostaining detected on a confocal microscope. RESULTS: Serotonergic cells and terminals were observed in the midbrain on day 17 of gestation, and in neopallium cocultures on days 13 and 16. TPH, 5-HT, SERT and Pet-1 immunopositive cells were also observed in the neopallium on day 12 of culture. CONCLUSIONS: The presence of serotonergic cells and other elements of the serotonergic system in the early cerebral cortex was confirmed, which may be transient and participate in cortical maturation processes during brain development.

ANTECEDENTES: La aparición temprana de serotonina en el cerebro fetal y sus efectos en la morfogénesis cerebral apoyan su papel neurotrófico. OBJETIVO: Determinar la presencia de células serotoninérgicas y la expresión de triptófano-5-hidroxilasa (TPH), 5-hidroxitriptamina (5-HT), transportador de serotonina (SERT), receptor 5-HT1A y Pet-1 durante el desarrollo de la corteza cerebral, tanto in situ como en cultivo de tejidos. MATERIAL Y MÉTODOS: Se realizó estudio observacional descriptivo en ratas Wistar preñadas. La presencia del tapón se consideró el inicio de la gestación; en los días 13, 16 y 17 se practicaron cesáreas para obtener los fetos e inmediatamente se disecaron los cerebros para identificar células serotoninérgicas, TPH, 5-HT, SERT, 5-HT1A y Pet-1 en cultivo de tejido e in situ mediante inmunomarcaje detectado en un microscopio confocal. RESULTADOS: Células y terminales serotoninérgicas fueron observadas en el mesencéfalo el día 17 de gestación y en cocultivos de neopalio los días 13 y 16. También se observaron células inmunopositivas a TPH, 5-HT, SERT y Pet-1 en el neopalio en el día 12 del cultivo. CONCLUSIONES: Se confirmó la presencia de células serotoninérgicas y otros elementos del sistema serotoninérgico en la corteza cerebral temprana, la cual puede ser transitoria y participar en los procesos de maduración cortical durante el desarrollo cerebral.

Removal capability, implant-abutment connection damage and thermal effect using ultrasonic and drilling techniques for the extraction of fractured abutment screws: an in vitro study.

The aim of this work was to analyze and compare the removal capability, conical internal hex implant-abutment connection damage and thermal effect using ultrasonic and drilling techniques for the extraction of fractured abutment screws. Twenty abutment screws were randomly fractured into twenty dental implants and randomly extracted using the following removal techniques: Group A: drilling technique without irrigation (n = 10) (DT) and Group B: ultrasonic technique without irrigation (n = 10) (UT). The dental implants were submitted to a preoperative and postoperative micro-computed tomography (micro-CT) scan to obtain a Standard Tessellation Language (STL) digital file that determined the wear comparison by morphometry. Moreover, the thermographic effects generated by the DT and UT removal techniques were registered using a thermographic digital camera. Comparative analysis was performed by comparing the volumetric differences (mm3) between preoperative and postoperative micro-CT scans and thermographic results (°C) using the Student t test. The DT extracted 8/10 and the US 9/10 abutment screws. The pairwise comparison revealed statistically significant differences between the volumetric differences of postoperative and preoperative micro-CT scans of the DT (- 0.09 ± - 0.02mm3) and UT (- 0.93 ± - 0.32mm3) study groups (p = 0.0042); in addition, the pairwise comparison revealed statistically significant differences between the thermographic values of the DT (38.12 ± - 10.82 °C) and UT (78.52 ± 5.43 °C) study groups (p < 0.001). The drilling technique without irrigation provides a less removal capability, less conical internal hex implant-abutment connection damage and less thermal effect than ultrasonic technique for the extraction of fractured abutment screws; however, the ultrasonic technique resulted more effective for the extraction of fractured abutment screws.

Diabetes mellitus causes changes in the activity and expression of brain tryptophan-5-hydroxylases and in the number of serotonergic neurons, which do not return to normal with insulin treatment.

INTRODUCTION: Diabetes mellitus (DM) inhibits brain serotonin biosynthesis through changes in tryptophan-5-hydroxylase (TPH) activity and expression. OBJECTIVES: To determine whether DM-induced changes in brain TPH1 or TPH2 expression and in the number of serotonergic neurons return to normal in diabetic rats treated with insulin. METHODS: Rats with streptozotocin-induced diabetes were divided in two groups: one treated with insulin and the other without treatment. On day 14, brain stems were obtained in order to quantify L-tryptophan and 5-hydroxytryptamine levels, as well as to determine TPH activity. The expression of TPH1 and TPH2 by West-ern blot, and the number of serotonergic neurons by immunohistochemistry. RESULTS: In diabetic rats, a decrease in the levels of L-tryptophan, 5-hydroxytryptamine, and TPH activity was confirmed, as well as lower TPH1 and TPH2 expression and lower numbers of serotonergic neurons. When diabetic rats were treated with insulin, L-tryptophan returned to normal, but not 5-hy-droxytryptamine, TPH expression, or the number of serotonergic neurons. CONCLUSIONS: DM chronically inhibits the synthesis of brain 5-hydroxytryptamine through changes in TPH1 and TPH2 expression and a decrease in the number of serotonergic neurons, which persist despite insulin treatment.

INTRODUCCIÓN: La diabetes mellitus (DM) inhibe la biosíntesis de serotonina cerebral mediante cambios en la actividad y expresión de la triptófano-5-hidroxilasa (TPH). OBJETIVOS: Determinar si los cambios en la expresión de TPH1 o TPH2 cerebral y en el número de neuronas serotoninérgicas causados por la DM retornan a la normalidad en las ratas con diabetes tratadas con insulina. MÉTODOS: Ratas con diabetes inducida con estreptozotocina se dividieron en dos grupos: uno tratado con insulina y otro sin tratamiento. En el día 14, se obtuvieron tallos cerebrales para cuantificar niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH. La expresión de TPH1 y TPH2 fue mediante Western blot y el número de neuronas serotoninérgicas por inmu­nohistoquímica. RESULTADOS: En las ratas con diabetes se confirmó disminución de los niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH, así como una menor expresión de TPH1 y 2 y un menor número de neuronas serotoninérgicas. Cuando las ratas diabéticas fueron tratadas con insulina, el L-triptófano regreso a la normalidad, no así la 5-hidroxitriptamina, la expresión de TPH y el número de neuronas serotoninérgicas. CONCLUSIONES: La DM inhibe crónicamente la síntesis de 5-hidroxitriptamina cerebral mediante modificaciones en la expresión de TPH1 y TPH2 y disminución de las neuronas seroto­ninérgicas, que persisten a pesar del tratamiento con insulina.

Serotonin and dopamine in the hypothalamus of control and malnourished mother rats during pregnancy and lactation and body composition of their offspring.

OBJECTIVE: To determine concentrations of serotonin and dopamine in the hypothalamus of undernourished rats and controls during pregnancy and lactation and body composition of their offspring. METHODS: Malnourished rats along with control rats were used during pregnancy and lactation. At birth of their offspring, control mothers nursed their young and malnourished rats and the undernourished mothers nursed their offspring and control pups. On days 5, 10, 15, and 21 of lactation (at the beginning and end of a feeding), L-tryptophan (L-Trp)-free, bound and total, plasma prolactin (PRL) and milk composition were determined. Serotonin and dopamine were measured in the hypothalamus. Body composition of offspring was determined. RESULTS: Increase of free L-Trp was confirmed in undernourished mothers. Furthermore, hypothalamic serotonin was elevated at the start of suckling and decreased at termination. There was also a decrease in dopamine in the hypothalamus at the beginning and end of suckling followed by an increase of plasma PRL that was greater in control mothers who breastfed malnourished offspring. Interestingly, undernourished offspring consumed more milk and showed a clear recovery of body composition with accumulation of body fat. DISCUSSION: Changes observed in hypothalamic neurotransmitters appear to be closely related to nutritional status and to the response and control of PRL production, possibly to adapt the offspring to the metabolic changes. It was also confirmed that on-demand feeding of undernourished offspring is the main factor involved in nutritional recovery and a predisposition to overweight in the recovered undernourished animals.

Disturbance of serotonergic neurotransmission in patients with postmyocardial infarction and depression.

The objective of this study was to assess the hypothesis that patients who develop depression after myocardial infarction (MI) have a lower level of brain serotonergic neurotransmission through measurement of plasma free fraction of L-tryptophan and intensity-dependence auditory-evoked potentials (IDAEPs). A cross-sectional study was carried out in 74 adults after MI. Thirty-four patients suffered from depression and 40 patients did not demonstrate depressive symptoms. We measured the free fraction, bound and total plasma L-tryptophan, and neutral amino acids as well as recording IDAEPs. Patients who developed depression after MI showed a significantly lower level in the free fraction of L-tryptophan and in the ratios of free fraction of L-tryptophan/total L-tryptophan and free fraction of L-tryptophan/neutral amino acids. It is noteworthy that the slope of the amplitude/stimulus intensity functions (ASF slope) of the N1/P2 component was significantly higher post-MI in depressed patients. Higher ASF slope of the N1/P2 component associated with a low free fraction of L-tryptophan in plasma reflect a low brain serotonergic neurotransmission. These findings suggest an important deterioration of brain serotonergic activity as a pathophysiological mechanism in post-MI patients for the development of clinical depression. Therefore, we propose these biochemical and electrophysiological procedures as noninvasive clinical indicators of brain serotonergic activity in these patients.

Development and validation of an educational software based in artificial neural networks for training in radiology (JORCAD) through an interactive learning activity.

The use of Computer Aided Detection (CAD) software has been previously documented as a valuable tool to improve specialist training in Radiology. This research assesses the utility of an educational software tool aimed to train residents in Radiology and other related medical specialties and students from Medicine degree. This in-house developed software, called JORCAD, integrates a CAD system based in Convolutional Neural Networks (CNNs) with annotated cases from radiological image databases. The methodology followed for software validation was expert judgement after completing an interactive learning activity. Participants received a theoretical session and a software usage tutorial and afterwards utilized the application in a dedicated workstation to analyze a series of proposed cases of thorax computed tomography (CT) and mammography. A total of 26 expert participants from the Radiology Department at Salamanca University Hospital (15 specialists and 11 residents) fulfilled the activity and evaluated different aspects through a series of surveys: software usability, case navigation tools, CAD module utility for learning and JORCAD educational capabilities. Participants also graded imaging cases to establish JORCAD usefulness for training radiology residents. According to the statistical analysis of survey results and expert cases scoring, along with their opinions, it can be concluded that JORCAD software is a useful tool for training future specialists. The combination of CAD with annotated cases from validated databases enhances learning, offering a second opinion and changing the usual training paradigm. Including software as JORCAD in residency training programs of Radiology and other medical specialties would have a positive effect on trainees' background knowledge.

New Prognostic Factors in Operated Extracapsular Hip Fractures: Infection and GammaTScore.

There is no universal postoperative classification of extracapsular hip fractures (ECFs). We wondered if infection (according to infection after fracture fixation criteria (IAFF)), immediate partial weight bearing (PWB) and/or the new GammaTScore tool could predict early cut-out. We also examined the correlation between GammaTScore and time to consolidation and studied long-term survival. This was a retrospective cohort study of low-energy complete ECFs operated with Gamma3T nailing in 2014 and fully monitoring, in patients aged over 65. Ten not distally locked cases, one late cut-out, one cut-through, one osteonecrosis and one pseudarthrosis were discarded. Patients were classified into early cut-out (7/204; 3.55%) and no early cut-out (197/204; 96.45%). There was a lower percentage of A2 fractures according to the AO Foundation/Orthopaedic Trauma Association classification (AO/OTA, 1997) in early cut-out. IAFF and only the GammaTScore reduction parameter were different for early cut-out, in opposition to immediate PWB, tip-to-apex distance (TAD) or the Baumgaertner-Fogagnolo classification. GammaTScore inversely correlated with consolidation (p < 0.01). Long-term survival time was not statistically significantly lower in the early cut-out group. Small sample of cases may limit our results. Apart from an important role of IAFF, GammaTScore would be useful for predicting consolidation, avoiding complications and reducing costs. Further studies are needed for reliability.

Association of metabolic syndrome with reduced central serotonergic activity.

The aim of this study was to determine the differences between two groups of adolescents with metabolic syndrome (MetS) and normal controls in relation to brain serotonergic activity through intensity-dependent auditory-evoked potentials (IDAEPs) and plasma free fraction of L-tryptophan. Eighteen adolescents with MetS and thirteen controls were studied. Free fraction, bound and total plasma L-tryptophan, glucose, cholesterol, triglycerides, HDL-cholesterol, albumin and IDAEPs were determined. Glycemia, triglycerides were significantly elevated, and HDL-cholesterol in plasma was significantly reduced. Free fraction and free fraction/total L-tryptophan ratio were decreased. The slope of the amplitude/stimulus intensity function of the N1/P2 component significantly increased in adolescents with MetS. Decrease of free fraction of L-tryptophan in plasma and increase of the slope of the N1/P2 component suggest a low brain serotonin tone. Cortex responses are regulated by serotonergic innervations and may show a different behavior in young patients with MetS. Therefore, the slope of the N1/P2 component along with the free fraction of L-tryptophan in plasma, indicate that in adolescents with MetS the state of serotonergic brain activity is depressed and possibly related to psychiatric disorders.

How intrauterine growth restriction due to nutritional stress changes the function of key proteins in brain serotonin metabolism during development.

This review aimed to describe and comment on how experimental intrauterine nutritional stress in animals produced some changes in tryptophan-5-hydroxylases (TPH) 1 and 2 in the brain and other key proteins such as plasma albumin, and how the intrauterine nutritional stress could produce long-lasting alterations in serotonin function in the brain of human infants.

El objetivo de esta revisión es describir y comentar cómo el estrés nutricional intrauterino experimental en animales produjo algunos cambios en las triptófano-5-hidroxilasas 1 y 2 en el cerebro y en otras proteínas clave, como la albúmina plasmática, y de qué manera el estrés nutricional intrauterino podría producir alteraciones duraderas en la función de la serotonina en el cerebro de lactantes.

Asian Tiger Mosquito in Yucatan Peninsula: First Record of Aedes (Stegomyia) albopictus (Diptera: Culicidae) in Campeche, Mexico.

This report describes the presence of Aedes albopictus Skuse (Diptera: Culicidae) in Yucatan Peninsula and represents the first record of the Asian tiger invasive mosquito in Campeche State, southeastern Mexico. We collected specimens using 11,326 ovitraps put into houses of urban and rural areas, as part of the entomological surveillance by the local Ministry of Health from January 2019 to February 2020. We found Ae. albopictus in five of the 12 municipalities of Campeche (San Francisco de Campeche, Tenabo, Hecelchakán, Calkíni and Escárcega). We record 68 positive ovitraps and 226 Ae. albopictus larvae. This finding increases the number of mosquito species recorded in Campeche, Mexico, and possibly the potential for 22 arbovirus transmission.

Development of 5-HT(1B), SERT and thalamo-cortical afferents in early nutrionally restricted rats: an emerging explanation for delayed barrel formation.

Barrel formation is delayed in nutritionally restricted rats. The underlying cause of such delay is yet unclear. Because barrels appear upon the arrival of somatosensory thalamo-cortical afferents and the reorientation of the dendritic arborizations of cortical spiny stellate neurons, it is likely that at least one of these processes is altered by nutritional restriction. Also, the serotoninergic afferent system has been implicated in regulating barrel segregation and growth during early postnatal life. We then evaluated the pattern of immunostaining of the serotonin transporter (SERT) and of the serotonin receptor 1B (5-HT(1B)), as well as the growth and arrival time of somatosensory thalamo-cortical afferents, to infer the contribution of these elements in the delayed formation of barrels observed in nutritionally restricted rats. It was found that the rates of development and the segregation of thalamo-cortical fibers were normal in nutritionally restricted rats. SERT, but not 5-HT(1B) immunoreactivity, was decreased in the primary somatosensory cortex during barrel specification. The availability of both proteins in nutritionally restricted rats was lower than that observed in their well fed counterparts at later developmental times. It is concluded that the delayed formation of barrels observed in nutritionally restricted rats is due to a retarded reorientation of dendritic arbors of cortical neurons. This might happen as a secondary effect of decreasing the availability of SERT and/or increasing the availability of 5-HT(1B) receptor early in postnatal life.

Reproductive health surveillance in the US-Mexico border region, 2003-2006: the Brownsville-Matamoros Sister City Project for Women's Health.

INTRODUCTION: High birth and immigration rates in the US-Mexico border region have led to large population increases in recent decades. Two national, 10 state, and more than 100 local government entities deliver reproductive health services to the region's 14 million residents. Limited standardized information about health risks in this population hampers capacity to address local needs and assess effectiveness of public health programs. METHODS: We worked with binational partners to develop a system for reproductive health surveillance in the sister communities of Matamoros, Tamaulipas, Mexico, and Cameron County, Texas, as a model for a broader regional approach. We used a stratified, systematic cluster-sampling design to sample women giving birth in hospitals in each community during an 81-day period (August 21-November 9) in 2005. We conducted in-hospital computer-assisted personal interviews that addressed prenatal, behavioral, and lifestyle factors. We evaluated survey response rates, data quality, and other attributes of effective surveillance systems. We estimated population coverage using vital records data. RESULTS: Among the 999 women sampled, 947 (95%) completed interviews, and the item nonresponse rate was low. The study sample included 92.7% of live births in Matamoros and 98.3% in Cameron County. Differences between percentage distributions of birth certificate characteristics in the study and target populations did not exceed 2.0. Study population coverage among hospitals ranged from 92.9% to 100.0%, averaging 97.3% in Matamoros and 97.4% in Cameron County. CONCLUSION: Results indicate that hospital-based sampling and postpartum interviewing constitute an effective approach to reproductive health surveillance. Such a system can yield valuable information for public health programs serving the growing US-Mexico border population.

Confirmación de la presencia de células serotoninérgicas en la corteza cerebral fetal en cultivos e in situ / Confirmation of the presence of serotonergic cells in the fetal cerebral cortex in cultures and in situ

Resumen Antecedentes: La aparición temprana de serotonina en el cerebro fetal y sus efectos en la morfogénesis cerebral apoyan su papel neurotrófico. Objetivo: Determinar la presencia de células serotoninérgicas y la expresión de triptófano-5-hidroxilasa (TPH), 5-hidroxitriptamina (5-HT), transportador de serotonina (SERT), receptor 5-HT1A y Pet-1 durante el desarrollo de la corteza cerebral, tanto in situ como en cultivo de tejidos. Material y métodos: Se realizó estudio observacional descriptivo en ratas Wistar preñadas. La presencia del tapón se consideró el inicio de la gestación; en los días 13, 16 y 17 se practicaron cesáreas para obtener los fetos e inmediatamente se disecaron los cerebros para identificar células serotoninérgicas, TPH, 5-HT, SERT, 5-HT1A y Pet-1 en cultivo de tejido e in situ mediante inmunomarcaje detectado en un microscopio confocal. Resultados: Células y terminales serotoninérgicas fueron observadas en el mesencéfalo el día 17 de gestación y en cocultivos de neopalio los días 13 y 16. También se observaron células inmunopositivas a TPH, 5-HT, SERT y Pet-1 en el neopalio en el día 12 del cultivo. Conclusiones: Se confirmó la presencia de células serotoninérgicas y otros elementos del sistema serotoninérgico en la corteza cerebral temprana, la cual puede ser transitoria y participar en los procesos de maduración cortical durante el desarrollo cerebral.

Abstract Background: Early appearance of serotonin in the fetal brain and its effects on brain morphogenesis support its neurotrophic role. Objective: To determine the presence of serotonergic cells and the expression of tryptophan-5-hydroxylase (TPH), 5-hydroxytryptamine (5-HT), serotonin transporter (SERT), 5-HT1A receptor and Pet-1 during the development of the cerebral cortex, both in situ and in tissue cultures. Material and methods: A descriptive, observational study was carried out in pregnant Wistar rats. The presence of the plug was regarded as the beginning of gestation. On days 13, 16 and 17, cesarean sections were performed to obtain the fetuses, and the brains were then immediately dissected to identify the presence of serotonergic cells, TPH, 5-HT, SERT, 5-HT1A and Pet-1 in tissue cultures and in situ by immunostaining detected on a confocal microscope. Results: Serotonergic cells and terminals were observed in the midbrain on day 17 of gestation, and in neopallium cocultures on days 13 and 16. TPH, 5-HT, SERT and Pet-1 immunopositive cells were also observed in the neopallium on day 12 of culture. Conclusions: The presence of serotonergic cells and other elements of the serotonergic system in the early cerebral cortex was confirmed, which may be transient and participate in cortical maturation processes during brain development.

Cambios en la actividad y expresión de las triptófano-5-hidroxilasas cerebrales y en el número de neuronas serotoninérgicas por la diabetes mellitus, que no retornan a la normalidad con la insulina / Diabetes mellitus causes changes in brain tryptophan-5-hydroxylases activity and expression and in the number of serotonergic neurons, which do not return to normal with insulin treatment

Resumen Introducción: La diabetes mellitus (DM) inhibe la biosíntesis de serotonina cerebral mediante cambios en la actividad y expresión de triptófano-5-hidroxilasa (TPH). Objetivos: Determinar si los cambios en la expresión de TPH1 y TPH2 cerebral y en el número de neuronas serotoninérgicas causados por la DM retornan a la normalidad en ratas con diabetes tratadas con insulina. Métodos: Ratas con diabetes inducida con estreptozotocina se dividieron en dos grupos uno tratado con insulina y otro sin tratamiento. En el día 14, se obtuvieron tallos cerebrales para cuantificar niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH. La expresión de TPH1 y TPH2 fue mediante Western blot y el número de neuronas serotoninérgicas por inmunohistoquímica. Resultados: En las ratas con diabetes se confirmó disminución de los niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH, así como menor expresión de TPH1 y TPH2 y menor número de neuronas serotoninérgicas. Cuando las ratas diabéticas fueron tratadas con insulina, el L-triptófano regresó a la normalidad, no así la 5-hidroxitriptamina, la expresión de TPH ni el número de neuronas serotoninérgicas. Conclusiones: La DM inhibe crónicamente la síntesis de 5-hidroxitriptamina cerebral mediante modificaciones en la expresión de TPH1 y TPH2 y disminución de las neuronas serotoninérgicas, que persisten a pesar del tratamiento con insulina.

Abstract Introduction: Diabetes mellitus (DM) inhibits brain serotonin biosynthesis through changes in tryptophan-5-hydroxylase (TPH) activity and expression. Objectives: To determine whether DM-induced changes in brain TPH1 and TPH2 expression and in the number of serotonergic neurons return to normal in diabetic rats treated with insulin. Methods: Rats with streptozotocin-induced diabetes were divided in two groups: one treated with insulin and the other without treatment. On day 14, brain stems were obtained in order to quantify L-tryptophan and 5-hydroxytryptamine levels, as well as to determine TPH activity. The expressión of TPH1 and THP2 by Western blot, and the number of serotonergic neurons by immunohistochemistry. Results: In diabetic rats, a decrease in the levels of L-tryptophan, 5-hydroxytryptamine and TPH activity was confirmed, as well as lower TPH1 and TPH2 expression and lower numbers of serotonergic neurons. When diabetic rats were treated with insulin, L-tryptophan returned to normal, but not 5-hydroxytryptamine, TPH expression, or the number of serotonergic neurons. Conclusions: DM chronically inhibits the synthesis of brain 5-hydroxytryptamine through changes in TPH1 and TPH2 expression and a decrease in the number of serotonergic neurons, which persist despite insulin treatment.

[Anatomopathological findings during development of diabetic cardiomyopathy in rats]. / Hallazgos anatomopatológicos durante el desarrollo de la miocardiopatía diabética en la rata.

BACKGROUND: The diabetic cardiomyopathy occurs in both type 1 and type 2 diabetes mellitus. Hyperglycemia and associated metabolic changes participate in the pathogenesis of this disease. OBJECTIVE: To characterizes various pathological changes occurring during the development of diabetic cardiomyopathy in rats. METHODS: Diabetic rats were used for streptozotocin administration. At 7, 14, 21 and 30 days after toxic administration, the heart was obtained and placed in a Hartman solution and 4% p-formaldehyde. Five-micrometer thick sections were stained with hematoxylin-eosin, Masson trichrome and immunocytochemistry using anti-ß-tubulin antibody. RESULTS: At 14 days after application of streptozotocin, dilated sinusoids with endothelial lining in the myocardium and collagen deposits in the cardiac interstitium and between the Purkinje fibers were observed. At 21 days there was a slight decrease of the arteriolar lumen due to hyperplasia of the medial layer. It is important to note that cardiac sinusoids as well as collagen deposits became more evident at 30 day of the study, as well as a major derangement of the microtubular system of the cardiomyocytes. CONCLUSIONS: Cardiac sinusoids representing fetal vascular pattern and interstitial fibrosis in the myocardium and the microtubular derangement of cardiomyocytes support the fact that the pathophysiological mechanism of diabetic cardiomyopathy begins in the coronary microcirculation due to changes in cardiac metabolism, contributing to the development of myocardial dysfunction in diabetes.

Antecedentes: la miocardiopatía diabética ocurre en ambos tipos de diabetes mellitus y en su patogenia intervienen la hiperglucemia y los cambios metabólicos asociados. Objetivo: caracterizar los diferentes cambios patológicos que aparecen durante la evolución de la miocardiopatía diabética en la rata. Material y métodos: estudio transversal comparativo en dos grupos de ratas diabéticas por la administración de estreptozotocina. A los 14, 21 y 30 días de la administración del tóxico se obtuvieron los corazones, que se colocaron en p-formaldehído al 4%. Se efectuaron cortes de 5 µm y se tiñeron con hematoxilina-eosina, tricrómica de Masson e inmunocitoquímica con anticuerpos anti ß-tubulina. Resultados: a los 14 días de la aplicación de la estreptozotocina se observaron en el miocardio sinusoides dilatadas y depósito de colágena entre las fibras de Purkinje e intersticio cardiaco. A los 21 días disminuyó la luz arteriolar por hiperplasia de la capa media. A los 30 días del estudio se hicieron más evidentes los sinusoides cardiacos y los depósitos de colágena y un importante desarreglo del sistema microtubular de los cardiomiocitos. Conclusiones: los sinusoides cardiacos, que representan un patrón vascular fetal y la fibrosis intersticial en el miocardio y el desarreglo microtubular de los cardiomiocitos, apoyan el hecho de que el mecanismo fisiopatológico de la miocardiopatía diabética se inicia en la microcirculación coronaria debido a cambios en el metabolismo cardiaco que contribuyen a la disfunción miocárdica durante el estado diabético.

Increased expression of tryptophan-5-hydroxylase 1, but not 2, in brainstem as a result of intrauterine malnutrition.

The aim of this study was to determine whether intrauterine malnutrition (IUM) produces a change in the expression of tryptophan-5-hydroxylase (TPH) 1 and/or 2 as the primary mechanism to explain the observed chronic cerebral acceleration of the synthesis of 5-hydroxytryptamine (5-HT). We used an IUM model and controls with ages of 1, 15 and 21 days. The brainstem was obtained to determine L-tryptophan, 5-HT and TPH activity. Expression of TPH1 and TPH2 via specific antibodies for each was also evaluated by immunocytochemistry and Western blot. Malnourished offspring had a significant elevation of L-Trp, TPH activity and 5-HT in the brainstem. Both isoforms (1 and 2) of TPH were expressed from birth in both groups; however, TPH1 expression was significantly higher in offspring with IUM in relation to the controls. Importantly, these malnourished offspring showed reduced expression of TPH2 compared to controls. It was confirmed that IUM produces an increase in 5-HT in the brainstem and also showed increased expression of TPH1 at birth, with decreased expression of TPH2. These findings together allow us to propose that chronic elevation of synthesis of 5-HT observed in the brain of the offspring with IUM is probably due to a change in the expression and activity of TPH1 induced from fetal life.

Dihydropteridine reductase activity in the brainstem of intrauterine growth-restricted rats.

The aim of this study was to determine whether intrauterine growth restriction produces an increase of dihydropteridine reductase activity as a compensatory mechanism that maintains the necessary concentration of cofactor, tetrahydrobiopterin, during accelerated brain serotonin biosynthesis. Intrauterine growth-restricted offspring and controls were used. On days 1, 10, 15 and 21 of life, the brainstem was dissected and l-tryptophan, serotonin, tryptophan-5-hydroxylase and dihydropteridine reductase activities were determined. Intrauterine growth-restricted pups showed a significant increase of l-tryptophan, 5-hydroxytryptamine, tryptophan-5-hydroxylase and also dihydropteridine activity in the brainstem in comparison to normal pups. These results confirm that intrauterine growth restriction produces an increase of serotonin biosynthesis in the brainstem. This is accompanied by an increase in dihydropteridine activity that appears to be a compensatory mechanism to maintain sufficient tetrahydrobiopterin for the donation of electrons during the accelerated synthesis of brain serotonin in intrauterine growth-restricted rats.

Another abnormal trait in the serotonin metabolism path in intrauterine growth-restricted infants.

BACKGROUND: The present study was aimed to obtain information on the interaction kinetics of L-tryptophan (L-Trp) with plasma albumin from normal, intrauterine growth-restricted (IUGR) and nutritionally recovered (NR) newborn infants. METHODS: A case study cohort was planned in 37 newborns during the first 3 months of life. At birth two groups were formed. The first group included 20 newborns with IUGR. The control group (C) included 17 appropriate for gestational age newborns. At 30 days of age, 9 infants of the IUGR group showed a return to normal of the anthropometric parameters, these infants formed the NR group. Free, bound and total L-Trp were measured. To assess binding kinetics albumin was freed of fatty acids and tested in mole to mole samples from IUGR, NR and control babies. RESULTS: Plasma free L-Trp was increased, K(d) (dissociation constant) elevated and B(max )(maximal binding)decreased in IUGR patients up to postnatal day 90. These changes remained even after nutritional recovery. CONCLUSIONS: Abnormal kinetics of L-Trp binding to albumin explains the increased availability of this precursor amino acid in the plasma of IUGR infants. This finding corroborates previous results in IUGR rats and newborn babies, indicating enhanced potential for brain serotonergic synthesis.

Disfunción diastólica subclínica del ventrículo izquierdo en adolescentes con diabetes tipo 1 / Subclinical left ventricular diastolic dysfunction in adolescents with type 1 diabetes

Introducción: El objetivo de este trabajo fue determinar la prevalencia de disfunción diastólica subclínica del ventrículo izquierdo (DDVI) y su asociación con el descontrol metabólico en adolescentes con diabetes tipo 1. Métodos: Se trató de un estudio en 53 adolescentes con diabetes tipo 1 en dos fases: primero, un estudio transversal descriptivo y, después de realizar un ecocardiograma, un transversal comparativo. Se consideró DDVI cuando tuvieron tres o más datos ecocardiográficos alterados: velocidad de contracción auricular (relación E/A), tiempo de desaceleración (TD), tiempo de relajación volumétrico (TRIVI) y función sistólica mayor de 50%. Además, se les determinaron los niveles de glucosa, de hemoglobina glucosilada y microalbuminuria. Resultados: El 16.98% de los adolescentes diabéticos mostraron datos ecocardiográficos de DDVI, y el 15.10% correspondió al sexo masculino. El patrón pseudonormalizado se observó en 7.54%, en relación con el 5.66% del patrón de alteración de la relajación y del 3.77% del restrictivo. Estos pacientes, además, mostraron mayor tiempo de la enfermedad, obesidad y un aumento en la glucemia, en la hemoglobina glucosilada y de la microalbuminuria. Conclusiones: La DDVI es una complicación frecuente en los adolescentes con diabetes tipo 1. Aquellos con DDVI presentaron con mayor frecuencia obesidad, mayor tiempo de evolución de la enfermedad y un peor control metabólico. Se propone que en estos pacientes se realice un diagnóstico oportuno y sistemático a través de un ecocardiograma.

Background: To determine the prevalence of subclinical left ventricular diastolic dysfunction (LVDD) and its association with metabolic control in adolescents with type 1diabetes. Methods: We carried out a study in 53 adolescents with type 1 diabetes in two phases: cross-sectional and after performing two-dimensional M-mode echocardiogram and color Doppler, a cross-sectional comparison. Subjects were divided into two groups: the first without LVDD and the second with LVDD. LVDD was considered when there were three or more alterations according to echocardiographic data (rate of atrial contraction, time of deceleration, time of volumetric relaxation) accompanied by systolic function >50%. We also determined glucose, hemoglobin, glycosylate, and microalbuminuria. Results: Of the adolescents with diabetes, 16.98% showed echocardiographic data of LVDD; 15.10% were male. Pseudonormalized pattern was observed in 7.54% compared to 5.66% with impaired relaxation pattern and 3.77% with restrictive pattern. Furthermore, there was a longer time of disease evolution, obesity and a significant increase of glycemia, glycosylated hemoglobin and microalbuminuria. Conclusions: LVDD is a frequent complication in adolescents with type 1 diabetes. Those with LVDD had a higher prevalence of obesity, longer time of disease, and poorer metabolic control. Therefore, we propose that a timely and systematic search with echocardiogram is important in patients with type 1 diabetes.