Increased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy.

Chronic stimulation of cardiac α1A-adrenergic receptors (α1A-ARs) improves symptoms in multiple preclinical models of heart failure. However, the translational significance remains unclear. Human engineered heart tissues (EHTs) provide a means of quantifying the effects of chronic α1A-AR stimulation on human cardiomyocyte physiology. EHTs were created from thin slices of decellularized pig myocardium seeded with human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and fibroblasts. With a paired experimental design, EHTs were cultured for 3 wk, mechanically tested, cultured again for 2 wk with α1A-AR agonist A61603 (10 nM) or vehicle control, and retested after drug washout for 24 h. Separate control experiments determined the effects of EHT age (3-5 wk) or repeat mechanical testing. We found that chronic A61603 treatment caused a 25% increase of length-dependent activation (LDA) of contraction compared with vehicle treatment (n = 7/group, P = 0.035). EHT force was not increased after chronic A61603 treatment. However, after vehicle treatment, EHT force was increased by 35% relative to baseline testing (n = 7/group, P = 0.022), suggesting EHT maturation. Control experiments suggested that increased EHT force resulted from repeat mechanical testing, not from EHT aging. RNA-seq analysis confirmed that the α1A-AR is expressed in human EHTs and found chronic A61603 treatment affected gene expression in biological pathways known to be activated by α1A-ARs, including the MAP kinase signaling pathway. In conclusion, increased LDA in human EHT after chronic A61603 treatment raises the possibility that chronic stimulation of the α1A-AR might be beneficial for increasing LDA in human myocardium and might be beneficial for treating human heart failure by restoring LDA.NEW & NOTEWORTHY Chronic stimulation of α1A-adrenergic receptors (α1A-ARs) is known to mediate therapeutic effects in animal heart failure models. To investigate the effects of chronic α1A-AR stimulation in human cardiomyocytes, we tested engineered heart tissue (EHT) created with iPSC-derived cardiomyocytes. RNA-seq analysis confirmed human EHT expressed α1A-ARs. Chronic (2 wk) α1A-AR stimulation with A61603 (10 nM) increased length-dependent activation (LDA) of contraction. Chronic α1A-AR stimulation might be beneficial for treating human heart failure by restoring LDA.

Kinesiotape on quadriceps and gluteus in counter movement jump and sprint in soccer players.

BACKGROUND: Kinesiotape (KT) is a technique commonly used in sports practice. It may be beneficial in enhancing muscle function by additional cutaneous afferent stimulation. The objective of this study was to analyse the effect of KT on countermovement jump (CMJ) and 20-m sprints (sp) immediately and 24 h after its application on the quadriceps and gluteus maximus. METHODS: 37 male soccer players (19.7 ± 0.9 years old) were randomly assigned to one of 3 groups: experimental group: KT activation (KTact), placebo group: sham tape (KTst), and control group (CG). Participants performed a 30-min preliminary warm-up, after which they conducted CMJ and 20-m sp tests. These tests were repeated later (with KT application or not) and after 24 h. RESULTS: Intergroup results found no significant differences either post-test (CMJ, p = 0.115; sp, p = 0.307) or after 24 h (p = 0.053). Intragroup results showed no significant results for CMJ, although 20-m sp seemed to display significant differences in the (KTst) (p = 0.002, post-hoc: 0.015 in pre_sp vs post_sp) and the (KTact) (0.021, in post-hoc: 0.007 in pre_sp vs post_sp), with a moderate effect in pre_sp vs post_sp (0.66) in the (KTact) after KT was applied. CONCLUSION: KT application on the gluteus maximus and quadriceps in young soccer players increases the sprint execution time immediately and 24 h after application, even that the sprint execution time had not been grater that one tenth of the second (0.08 s). It also has no effect on CMJ.

Sevoflurane-Induced Dysregulation of Cation-Chloride Cotransporters NKCC1 and KCC2 in Neonatal Mouse Brain.

The cation-chloride cotransporters Na+-K+-2Cl--1 (NKCC1) and K+-2Cl--2 (KCC2) critically regulate neuronal responses to gamma-aminobutyric acid (GABA). NKCC1 renders GABA excitatory in immature neurons while expression of KCC2 signals GABA maturation to its inhibitory role. Imbalances in NKCC1/KCC2 alter GABA neurotransmission, which may contribute to hyperexcitability and blunted inhibition in neurocircuitry after neonatal exposure to anesthesia. Thus, we hypothesized that anesthetics may dysregulate NKCC1 and/or KCC2 in developing brain. We exposed postnatal day (PND) 7 mice to sevoflurane or carrier gases and assessed NKCC1 and KCC2 expression across three brain regions 6 h and 24 h after initial exposure. To test differences in behavior, we challenged pups receiving sevoflurane or carrier gases on PND7 with propofol on PND8 and recorded parameters of anesthesia induction and maintenance. Sevoflurane exposure increased cortical NKCC1 at 6 h (p = 0.03) and decreased cortical and hippocampal KCC2 at 24 h (p = 0.009 and p = 0.007, respectively). NKCC1/KCC2 ratio was significantly increased at both 6 h (p = 0.02) and 24 h (p = 0.03) in cortex and at 24 h (p = 0.02) in hippocampus. After propofol challenge on PND8, pups previously exposed to sevoflurane on PND7 regained righting reflex significantly faster than their non-exposed cohort (p < 0.001). Disturbing NKCC1/KCC2 balance may underlie circuit hyperexcitability and contribute to neurodevelopmental impairments we have observed in previous studies of neonatal anesthesia exposure. Human infants previously exposed to anesthesia may require higher concentrations of anesthetic drugs, potentially compounding their susceptibility for neurodevelopmental sequalae.

Leg loss in Lutzomyia longipalpis (Diptera: Psychodidae) due to pyrethroid exposure: Toxic effect or defense by autotomy?

BACKGROUND & OBJECTIVES: Phlebotomine sandflies lose their legs after exposure to pyrethroids. In some insects leg loss helps to defend them from intoxication and predation, a phenomenon known as autotomy. A field observation has shown that sandflies that have lost some legs are still able to blood-feed. The aims of the study were to determine whether leg loss in sandflies, after exposure to deltamethrin, is due to autotomy and to establish the effect of the leg loss on blood-feeding. METHODS: Two experiments were carried out with Lutzomyia longipalpis: (i) Females were individually exposed to a sublethal time of deltamethrin and mortality and the number of leg loss were recorded; and (ii) Groups of females with complete legs or with 1-3 legs lost due to pyrethroid exposure were offered a blood meal and percentages of blood-fed and fully-fed females were recorded. RESULTS: Most females lost a median of 1 leg within 1-48 h post-exposure to deltamethrin. Mortality (after 24 h) was significantly higher for exposed females with lost legs (31.1%), compared to exposed females with complete legs (7.3%), and there were no differences in mortality between females with complete legs and the control (unexposed females). There were no differences between the three treatments in the percentages of blood-fed and fully-fed females. INTERPRETATION & CONCLUSION: Leg loss in sandflies is a toxic effect of pyrethroids and there was no evidence of autotomy. The loss of up to three legs after exposure to pyrethroids does not affect blood-feeding behaviour in laboratory and probably also in wild conditions.

Ruidos artículares y su relación con la presencia de interferencias oclusales en el lado de no trabajo, mediante evaluación clínica en adultos entre 20 y 40 años de edad / Temporomandibular joint (TMJ) sounds and their relation to occlusal interferences in the non-working side: a clinical evaluation in patients between 20 and 40 years of age

Considerada como una articulación glinglimoartrorial, la Articulación Témporo-mandibular (ATM) realiza todos los movimientos en el espacio, sin presentar ningún signo o síntoma en condiciones normales, sin embargo en presencia de anomalías manifiesta ruidos, partiendo de este enfoque nos centramos a analizar si estos ruidos articulares se encuentran relacionados con la oclusión dental, específicamente con la presencia de interferencias oclusales en el lado de no trabajo, en adultos de ambos sexos de entre 20 - 40 años de edad totalmente dentados. De esta forma 31 participantes que presentaron ruidos articulares en los diferentes movimientos mandibulares, fueron evaluados en cuanto a la clase de Angle, guías laterales, presencia de guía canina normal y presencia o ausencia de función de grupo. Analizando clínicamente la presencia de interferencias en el lado de no trabajo y comprobando estas interferencias en articulador semiajustable (ASA) tipo Bioart. Los datos obtenidos fueron analizados en el programa SPSS versión XX, revelando una relación entre los ruidos articulares y la presencia de interferencias oclusales en el lado de no trabajo, sin embargo, evidenciando cierta relación entre la presencia de interferencias oclusales con género, presente con mayor prevalencia en el género masculino que en femenino.

Considered as a glinglymoarthrodial articulation, the temporomandibular joint) (TMJ) is both a hinging and a sliding joint. In a healthy condition the joint doesn't show any particular sign or symptom, however if there is a dysfunction it will present noises during jaw movement. Starting from this principle, we analyzed if the TMJ dysfunction sounds are connected to dental malocclusion, focusing on occlusal interferences in the non-working side, in patients between 20 and 40 years of age. Thirty-one patients presented articular noises during jaw movement, so we proceeded to evaluate Angle class (molar relationship), lateral guidance, normal canine guidance and the presence or absence of group function. Clinically, we analyzed the presence of interferences in the non-working side and we studied them using a Semi-adjustable Articulator (ASA) (Bioart). The data, evaluated using the program SPSS Version XX, revealed a clear relation between articular noises and interferences in the non-working side, however the population of men showed a higher rate of occlusal interferences than that of women.

Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized.

Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations.

Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized.

Public health measures to control tuberculosis in low-income countries: ethics and human rights considerations.

In low-income countries, tuberculosis (TB) control measures should be guided by ethical concerns and human rights obligations. Control programs should consider the principles of necessity, reasonableness and effectiveness of means, proportionality, distributive justice, and transparency. Certain measures-detention, infection control, and treatment to prevent transmission-raise particular concerns. While isolation is appropriate under certain circumstances, quarantine is never an acceptable control measure for TB, and any detention must be limited by necessity and conducted humanely. States have a duty to implement hospital infection control to the extent of their available resources and to provide treatment to health care workers (HCWs) infected on the job. HCWs, in turn, have an obligation to provide care unless conditions are unreasonably and unforeseeably unsafe. Finally, states have an obligation to provide adequate access to treatment, as a means of preventing transmission, as broadly as possible and in a non-discriminatory fashion. Along with treatment, states should provide support to increase treatment adherence and retention with respect for patient privacy and autonomy. Compulsory treatment is almost never acceptable. Governments should take care to respect human rights and ethical obligations as they execute TB control programs.

Respuesta inmune sistémica y mucosal contra Neisseria meningitidis B inducida por estrategia de vacunación simultànea mucosal y parental

Immunization is one of the most successful and cost-effective health interventions ever. Immunization have been helping to reduce child mortality, improving maternal health and combating infectious diseases. In spite of its, undisputed past success and promising future, however, immunization remains an unfinished agenda because of them inadequate coverage. Several factors have been largely responsible of a difficulty to attain immunization coverage and have been recognized as a problems of current vaccines, such as: the number of dose, excessive use of parenteral route, a small number of adjuvants approve for use in human, higher reactogenicity and unavailability against intracellular pathogens, infected or altered cells and scanty feasibility to combined more than one antigen in the same formulation. For bacterial meningitis WHO estimates that 1,2 million cases occur annually and Neisseria meningitidis is the etiological agent in more than 40 percent of these cases although some meningococcal vaccines are available. To bear in mind these principals problems, a novel protocol for vaccination against N meningitidis called Single Time Vaccination Strategy (SinTimVaS) is proposed. Using female BALB/c mice, we induce systemic and mucosal immune responses against N meningitidis with only one parenteral and one mucosal dose at the same time, employing the Finlay Adjuvants derivate from N meningitidis, AFPL1 and AFCo1, respectively. In conclusion, SinTimVaS could increase the vaccination coverage and reduce the time-cost of vaccine campaigns, adding the possibility to increase the herd immunity by mucosal specific response induction(AU)

Enfoques mucosales en vacunologia de Neisseria

Meningococcal B strains accounts for some 72 percent and 28 percent of meningococcal diseases in infants and toddlers in Europe and the USA, respectively. Nevertheless, meningococcal diseases are rare in Cuba owing to the wide spread program on antimeningococcal vaccination in the country. Finlay Institute is one of the pioneering organizations in Neisseria Vaccinology mainly by its contribution to N. meningitidis serogroup B outer membrane-based bivalent vaccine, VA-MENGOC-BC™. This vaccine was given intramuscularly in more than 60 million doses corresponding 10,7 millions of them to Cuban young adults, children, and infants. However, most dangerous or commensally Neisseria strains enter and establish in the mucosa, where the secretory (S) IgA is the main specific guardian and is mainly induced by mucosal routes. However, few mucosal vaccines exist principally due to the absent of mucosal adjuvants. We develop a Finlay Adjuvant (AF) platform based in outer membrane vesicles (Proteoliposome, PL) and its derivate Cochleate (Co). AFPL1 derived from serogroup B N meningitidis is a potent Th1/CTL driving parenteral adjuvant. AFCo1 is a potent mucosal adjuvant. Therefore, we sought to go deeper in the possible mucosal cross recognition between N. meningitidis serogroups and Neisseria species and explore a concurrent mucosal and parenteral immunization strategy (SinTimVaS) in order to develop suitable mucosal vaccines. Experiments were conducted in Balb/c or C57Bl6 mice with mucosal and systemic immunization using AFCo1 and AFPL1. Human sera and saliva were also analyzed for cross cognition. Mucosal cross recognition at SIgA level in human saliva between N. meningitidis serogroups B, A, C, Y, and W135 were observed. This SIgA cross recognition response was also observed between pathogenic (N meningitidis serogroup B, N gonorrhoeae) and non-pathogenic strains (N flava, N lactamica). The possible influence of meningococcal vaccination ...(AU)

New vaccines require potent adjuvants like AFPL1 and AFCo1.

Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative-Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen-associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non-related antigens. AFPL1 is a detergent-extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co-administrated antigens; inducing type I IFN-gamma and IL-12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4(+), TCD8(+), cross-presentation and cytotoxic T-lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1-AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co-administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.

Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin.

Twenty-one-day-old Wistar rats were fed a diet containing 0.6% cuprizone for 2 weeks. Studies carried out after withdrawal of cuprizone showed histological evidences of marked demyelination in the corpus callosum. Biochemical studies of isolated myelin showed a marked decrease in myelin proteins, phospholipids, and galactocerebrosides as well as a marked decrease in myelin yield. Treatment of these animals with a single intracranial injection of 350 ng of apotransferrin at the time of withdrawal of cuprizone induced a marked increase in myelin deposition resulting in a significantly improved remyelination, evaluated by histological, immunocytochemical, and biochemical parameters, in comparison to what was observed in spontaneous recovery. Immunocytochemical studies of cryotome sections to analyze developmental parameters of the oligodendroglial cell population at the time of termination of cuprizone and at different times thereafter showed that in the untreated animals, there was a marked increase in the number of NG2-BrdU-positive precursor cells together with a marked decrease in MBP expression at the peak of cuprizone-induced demyelination. As expected, the amount of precursor cells decreased markedly during spontaneous remyelination and was accompanied by an increase in MBP reactivity. In the apotransferrin-treated animals, these phenomena occurred much faster, and remyelination was much more efficient than in the untreated controls. The results of this study suggest that apotransferrin is a very active promyelinating agent which could be important for the treatment of certain demyelinating conditions.

[Evaluation of ventricular synchronization by fourier phase analysis in a radionuclide ventriculography]. / Evaluación de la sincronización ventricular por análisis de fase de Fourier en una ventriculografía radioisotópica.

INTRODUCTION: Radionuclide ventriculography (RNV) evaluates segmental and global ventricular contractility and also detects conduction abnormalities. OBJECTIVE: To assess the temporal parameters of ventricular synchronization in the normal heart by a third harmonic (3H) Fourier phase analysis in a RNV and introduce this technique in our center. MATERIAL AND METHODS: Thirty normal subjects (19 men and 11 women) were included. An equilibrium RNV was performed in 35 degree left anterior oblique projection with 10 degree caudal tilt. The onset (T0); mean time (T(m)); total contraction time (T(t)); final time (T(f)) and propagation time (T(p)) for right (RV) and left ventricle (LV); as well as total propagation time (T(TP)); interventricular time (T(RV-LV)) and septum-lateral wall conduction time (T(S-LW)) were measured on the 3H Fourier histogram of the time-activity curve. RESULTS: Right ventricle contraction started 5 ms before that of the left ventricle (T(0RV) = 66 +/- 38 ms; T(OLV) = 71 +/- 30 ms), with a longer total contraction time (T(tVD) = 67 +/- 28 ms vs T(tVI) = 64 +/- 38 ms). Total propagation time (T(TP)) was 69 +/- 37 ms and the interventricular time (T(RV-LV)) was 2 +/- 25 ms. Contraction progressed from septum to lateral wall, with a septum-lateral wall conduction time (T(S-LW)) of 4 +/- 22 ms. CONCLUSION: Simultaneous contraction of right and left ventricles can be quantified by RNV phase analysis, providing a useful tool for ventricular resynchronization assessment in multisite pacing.

Evaluación de la sincronización ventricular por análisis de fase de Fourier en una ventriculografía radioisotópica / Evaluation of ventricular synchronization by Fourier phase analysis in a radionuclide ventriculography

Introducción: La ventriculografía radioisotópica (VRI) permite la evaluación de la contractilidad global y segmentaria, así como la detección de trastornos de conducción. Objetivo: Se realizó el análisis de fase del tercer armónico de Fourier en una VRI con el propósito de evaluar los parámetros temporales de la sincronización ventricular en el corazón normal e introducir esta técnica en nuestro centro. Material y Métodos: Se incluyeron 30 individuos normales (19 hombres y 11 mujeres). A todos se les realizó una VRI en equilibrio en proyección oblicua anterior izquierda de 35 grados con 10 grados de angulación caudal. En el histograma del tercer armónico de Fourier de la curva actividad-tiempo se midieron: el tiempo de inicio (T0); el tiempo medio (Tm); el tiempo total (Tt); el tiempo final (Tf) y el tiempo de propagación (Tp) para cada ventrículo; así como el tiempo total de propagación (TTP); el tiempo de conducción interventricular (TVD-VI) y el tiempo de conducción septum-pared lateral (TS-PL).Resultados: El ventrículo derecho comienza a contraerse 5 ms antes que el izquierdo (T0VD = 66 ñ 38 ms; T0VI = 71 ñ 30 ms), con un tiempo de contracción total ligeramente mayor (TtVD = 67 ñ 28 ms vs TtVI = 64 ñ 38 ms). El tiempo total de propagación (TTP) fue de 69 ñ 37 ms y el tiempo interventricular (TVD-VI) fue 2 ñ 25 ms. La contracción progresó de septum a pared lateral, con un tiempo septum-pared lateral (TS-PL) de 4 ñ 22 ms. Conclusión: A través del análisis de fase en una ventriculografía radioisotópica puede cuantificarse la contracción simultánea de ambos ventrículos, lo que proporciona un instrumento que pudiera resultar de utilidad para la evaluación de la resincronización ventricular en la estimulación multisitio (AU)

[The knowledge, attitudes and practice of population groups with respect to tuberculosis. 1994-1996]. / Conocimientos, percepciones y prácticas de grupos de población respecto a la tuberculosis. 1994-1996.

The development of successful tuberculosis control programs requires the people's involvement, hence a study was performed to identify knowledge, perceptions and practices of the population regarding occurrence, transmission, treatment and control of this disease. The focal group technique was used in 6 sets of persons aged 15 years and over from 6 municipalities of the City of Havana. These groups thought that tuberculosis had declined in the last ten years but had increased again in the last 2-3 years, that it was a contagious disease presenting symptoms such as cough, hemoptysis, loss of weight, fever. They considered it as a terrible, undesirable sickness associated with poverty and caught due to malnourishment, poor hygiene of the sick person and his/her relatives and smoking. Some thought that this disease was curable and other that it was not. Several other people believed that patients should be isolated in hospital whereas others stated that they could have a normal life at home, most preferred to be informed about the disease by TV and radio. It was concluded that a quantitative study should be performed based on these results.

The cytoskeletal components of the myelin fraction are affected by a single intracranial injection of apotransferrin in young rats.

We have previously shown that in rat pups intracranially injected with a single dose of apotransferrin (aTf), there is an early oligodendroglial cell OLGc differentiation. The expression of the mRNAs of myelin basic proteins and of 2',3' cyclic nucleotide 3'-phosphodiesterase and the amount of the corresponding proteins, as well as myelin glycolipids and phospholipids, were significantly increased in these animals at 10 and 17 days of age. Microtubules and myelin basic proteins appear to be closely associated in OLGc and it has been shown that the mRNAs of myelin basic proteins are concentrated in the OLGc processes. The aim of this work was to clarify if the accelerated myelination produced by aTf could be linked to changes in certain cytoskeletal elements present in the myelin fraction such as tubulin, actin, and different microtubule-associated proteins (MAPs). A significant increase in the expression of the mRNA of tubulin and actin was observed in the brain of the aTf-treated animals. Several MAPs, particularly MAP 1B and stable tubule only peptide as well as actin and tubulin, were markedly increased in the Triton X-100 insoluble pellet obtained from the myelin fraction of these animals. The changes that we have previously described in the myelin of aTf intracranially injected rats, could be the consequence of its action on the cytoskeletal network of the OLGc. An enlargement of this structure would result in a more efficient and faster movement of the different components that are normally transported to the myelin by the cytoskeleton of this cell.

Punción aspiración con aguja fina en las lesiones palpables de mama: estudio comparativo de 3917 aspirados con los resultados clínicos e histopatológicos / Fine needle aspiration cytology in palpable breast lesions: comparative study of 3917 aspirates with the clinical and histopathological results

Introducción: La punción aspiración con aguja fina (PAAF) es un procedimiento ampliamente aceptado así como una herramienta de estimable valor en el diagnóstico y seguimiento de las lesiones mamarias. Material y métodos: En este trabajo hemos analizado un total de 3917 punciones de masas mamarias pertenecientes a 2647 pacientes, realizadas entre los años 1984 y 1997. Resultados: Los parámetros de fiabilidad fueron: sensibilidad del método 79,5 por ciento, sensibilidad de la interpretación 97,0 por ciento, especificidad 99,6 por ciento, valor predictivo positivo 96,9 por ciento, valor predictivo negativo 97,0 por ciento. La prevalencia del cáncer fue de 3,9 por ciento para las pacientes menores de 50 años y del 33,0 por ciento para las mayores de 50 años. Esta diferencia afectó principalmente a los valores predictivos positivos y negativos, que variaron entre 89,9 por ciento y 98,9 por ciento para el primer grupo y entre 99,0 por ciento y 91,6 por ciento para el segundo. Se observaron también diferencias significativas cuando se compararon los resultados entre los aspirados realizados por los clínicos y los patólogos. Estas diferencias consistieron en una disminución del material inadecuado y aumento de la sensibilidad cuando el aspirado era realizado por el patólogo que interpretó dicho aspirado. Conclusiones: Consideramos que un factor importante en el estudio de las lesiones mamarias por punción es la realización de una clasificación previa por grupos de edad para calcular los valores predictivos apropiados para cada grupo. Pensamos que el material inadecuado debe ser incluido para el cálculo de la sensibilidad del método y que es menor su proporción cuando es el patólogo el que realiza personalmente la punción, frotis y la interpretación de dicho material (AU)

Oligodendroglial cell differentiation in rat brain is accelerated by the intracranial injection of apotransferrin.

In the present paper we first studied the brain distribution and the time and dose dependent effects of apotransferrin, after its intracranial injection into young rats and at different post-natal ages. Its action upon the transferrin receptor (TfR) and upon the expression of brain transferrin, as well as its effect on the proliferation and differentiation of oligodendroglial cells (OLGc) was one of the main objectives of our investigation. Total DNA and BrdU labeling, as an index of cellularity and proliferation, respectively, were the same in the control and experimental groups of rats. A significant increase in the MBP+ and CA II+ OLGc, and a decrease in the more immature (A2B5+) OLGc were found in the aTf injected rats. At 10 and 17 days of age, Tf-mRNA decreased to around 20% of the amount present in control animals. The TfR-mRNA in the animals receiving a single dose of aTf at 3 days of age showed an increase in its expression at 10 and 17 days of age, coincident with a higher immunoreactivity of the TfR itself of neurons, choroid plexus and brain capillaries in different brain areas. Although TfR+ OLGc were present up to 7 days of age in controls and in the Tf injected rats, no positive cells were observed at 17 days of age, even in the aTf injected rats. Our results give support to the hypothesis that aTf is an important factor necessary for the maturation of the OLGc, and that the effects that it produces in the OLGc-myelin unit after its intracranial injection in young rats are not due to an increase in proliferation, but to an accelerated differentiation of Tf-sensitive OLGc.

Myelin membranes isolated from rats intracranially injected with apotransferrin are more susceptible to in vitro peroxidation.

Purified myelin obtained from 17 day old rats intracranially injected with aTf at 3 days of age was submitted to in vitro peroxidation using Fe + ascorbic acid (FeA) or Cu + H2O2 (CuH), to investigate the susceptibility of this membrane to in vitro metal catalyzed peroxidation. There was an increase in thiobarbituric acid-reactive-substances (TBARS) (60%) and in protein-associated carbonyls (PAC) (20%) in the myelin from aTf injected rats in comparison to myelin from controls, indicating a higher susceptibility to peroxidation. Desferoxamine (DFX) injected simultaneously with aTf did not change the response of myelin to aTf. CNS myelin is highly vulnerable to oxidative stress, and its susceptibility to peroxidation increases in myelin isolated from aTf injected rats. This increased liability to peroxidation as well as the previously reported aTf-dependent increment in certain myelin proteins and lipids and in the expression of specific myelin mRNAS, does not appear to be due to an increased amount of iron bound to the injected aTf. The changes in composition that we have previously reported could result in an abnormal myelin, allowing the peroxidative system to act upon the membrane more easily than in normal circumstances.