Homeopathy for COVID-19 in primary care: A randomized, double-blind, placebo-controlled trial (COVID-Simile study).

BACKGROUND: Different homeopathic approaches have been used as supportive care for coronavirus disease 2019 (COVID-19) cases, but none has been tested in a clinical trial. OBJECTIVES: To investigate the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A randomized, double-blind, two-armed, parallel, single-center, placebo-controlled clinical trial was conducted from June 2020 to April 2021 in São-Carlos, Brazil. Participants aged > 18 years, with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized (1:1) into two groups that received different treatments during a period of at-home-isolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo. OUTCOME MEASURES: The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures. RESULTS: Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between two groups among participants who were reporting influenza-like symptoms at the beginning of monitoring (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score ≥ 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group. CONCLUSION: Results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases. Although some secondary measures do not support the null hypothesis, the wide confidence intervals suggest that further studies with larger sample sizes and more symptomatic participants are needed to test the effectiveness of homeopathic Natrum muriaticum LM2 for COVID-19. TRIAL REGISTRATION: UMIN Clinical Trials Registry ID: JPRN-UMIN000040602.

Homeopathy for COVID-19 in primary care: A randomized, double-blind, placebo-controlled trial (COVID-Simile study) / 中西医结合学报

BACKGROUND@#Different homeopathic approaches have been used as supportive care for coronavirus disease 2019 (COVID-19) cases, but none has been tested in a clinical trial.@*OBJECTIVES@#To investigate the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19.@*DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS@#A randomized, double-blind, two-armed, parallel, single-center, placebo-controlled clinical trial was conducted from June 2020 to April 2021 in São-Carlos, Brazil. Participants aged > 18 years, with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized (1:1) into two groups that received different treatments during a period of at-home-isolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo.@*OUTCOME MEASURES@#The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures.@*RESULTS@#Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between two groups among participants who were reporting influenza-like symptoms at the beginning of monitoring (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score ≥ 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group.@*CONCLUSION@#Results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases. Although some secondary measures do not support the null hypothesis, the wide confidence intervals suggest that further studies with larger sample sizes and more symptomatic participants are needed to test the effectiveness of homeopathic Natrum muriaticum LM2 for COVID-19.@*TRIAL REGISTRATION@#UMIN Clinical Trials Registry ID: JPRN-UMIN000040602.

Homeopathy for Covid-19 in Primary Care: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: To investigate the effectiveness and safety of homeopathic medicine Natrum muriaticum (LM2) for mild cases of COVID-19 in Primary Health Care. TRIAL DESIGN: A randomized, two-armed (1:1), parallel, placebo-controlled, double-blind, clinical trial is being performed to test the following hypotheses: H0: homeopathic medicines = placebo (null hypothesis) vs. H1: homeopathic medicines ≠ placebo (alternative hypothesis) for mild cases of COVID-19 in Primary Care. PARTICIPANTS: Setting: Primary Care of São Carlos - São Paulo - Brazil. One hundred participants aged 18 years or older, with Influenza-like symptoms and a positive RT-PCR for SARS-CoV-2. Willingness to give informed consent and to comply with the study procedures is also required. Exclusion criterium: severe acute respiratory syndrome. INTERVENTION AND COMPARATOR: Homeopathy: 1 globule of Natrum muriaticum LM2 diluted in 20 mL of alcohol 30% and dispensed in a 30 ml bottle. Placebo: 20 mL of alcohol 30% dispensed in a 30 ml bottle. Posology: one drop taken orally every 4 hours (6 doses/day) while there is fever, cough, tiredness, or pain (headache, sore throat, muscle aches, chest pain, etc.) followed by one drop every 6 hours (4 doses/day) until the fourteenth day of use. The bottle of study medication should be submitted to 10 vigorous shakes (succussions) before each dose. Posology may be changed by telemedicine, with no break in blinding. Study medication should be maintained during home isolation. According to the Primary Care protocol, the home isolation period lasts until the 10th day after the appearance of the first symptom, or up to 72 hours without symptoms. MAIN OUTCOMES: The primary endpoint will be time to recovery, defined as the number of days elapsed before all COVID-19 Influenza-like symptoms are recorded as mild or absent during home isolation period. Secondary measures are recovery time for each COVID-19 symptom; score of the scale created for the study (COVID-Simile Scale); medicines used during follow-up; number of days of follow-up; number of visits to emergency services; number of hospitalizations; other symptoms and Adverse Events during home isolation period. RANDOMISATION: The study Statistician generated a block randomization list, using a 1:1 ratio of the two groups (denoted as A and B) and a web-based tool ( http://www.random.org/lists ). BLINDING (MASKING): The clinical investigators, the statistician, the Primary Care teams, the study collaborators, and the participants will remain blinded from the identity of the two treatment groups until the end of the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): One hundred participants are planned to be randomized (1:1) to placebo (50) or homeopathy (50). TRIAL STATUS: Protocol version/date May 21, 2020. Recruitment is ongoing. First participant was recruited/included on June 29,2020. Due to recruitment adaptations to Primary Care changes, the authors anticipate the trial will finish recruiting on April 10, 2021. TRIAL REGISTRATION: COVID-Simile Study was registered at the University Hospital Medical Information Network (UMIN - https://www.umin.ac.jp/ctr/index.htm ) on June 1st, 2020, and the trial start date was June 15, 2020. Unique ID: UMIN000040602. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Double-blind evaluation of homeopathy on cocaine craving: a randomized controlled pilot study.

BACKGROUND: Brazil is among the nations with the greatest rates of annual cocaine usage. Pharmacological treatment of cocaine addiction is still limited, opening space for nonconventional interventions. Homeopathic Q-potencies of opium and Erythroxylum coca have been tested in the integrative treatment of cocaine craving among homeless addicts, but this setting had not proven feasible, due to insufficient recruitment. OBJECTIVE: This study investigates the effectiveness and tolerability of homeopathic Q-potencies of opium and E. coca in the integrative treatment of cocaine craving in a community-based psychosocial rehabilitation setting. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A randomized, double-blind, placebo-controlled, parallel-group, eight-week pilot trial was performed at the Psychosocial Attention Center for Alcohol and Other Drugs (CAPS-AD), Sao Carlos/SP, Brazil. Eligible subjects included CAPS-AD patients between 18 and 65 years of age, with an International Classification of Diseases-10 diagnosis of cocaine dependence (F14.2). The patients were randomly assigned to two treatment groups: psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca (homeopathy group), and psychosocial rehabilitation plus indistinguishable placebo (placebo group). MAIN OUTCOME MEASURES: The main outcome measure was the percentage of cocaine-using days. Secondary measures were the Minnesota Cocaine Craving Scale and 12-Item Short-Form Health Survey scores. Adverse events were reported in both groups. RESULTS: The study population comprised 54 patients who attended at least one post-baseline assessment, out of the 104 subjects initially enrolled. The mean percentage of cocaine-using days in the homeopathy group was 18.1% (standard deviation (SD): 22.3%), compared to 29.8% (SD: 30.6%) in the placebo group (P < 0.01). Analysis of the Minnesota Cocaine Craving Scale scores showed no between-group differences in the intensity of cravings, but results significantly favored homeopathy over placebo in the proportion of weeks without craving episodes and the patients' appraisal of treatment efficacy for reduction of cravings. Analysis of 12-Item Short-Form Health Survey scores found no significant differences. Few adverse events were reported: 0.57 adverse events/patient in the homeopathy group compared to 0.69 adverse events/patient in the placebo group (P = 0.41). CONCLUSIONS: A psychosocial rehabilitation setting improved recruitment but was not sufficient to decrease dropout frequency among Brazilian cocaine treatment seekers. Psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca were more effective than psychosocial rehabilitation alone in reducing cocaine cravings. Due to high dropout rate and risk of bias, further research is required to confirm our findings, with specific focus on strategies to increase patient retention. TRIAL REGISTRATION: RBR-2xzcwz (http://www.ensaiosclinicos.gov.br).

Homeopathy for Perennial Asthma in Adolescents: Pilot Feasibility Study Testing a Randomised Withdrawal Design.

INTRODUCTION: Previous findings from a pragmatic trial suggest that usual care compared with usual care plus individualised homeopathy is not a feasible design to address homeopathic interventions for asthma. OBJECTIVE: The main purpose of this article was to investigate the feasibility of the randomised withdrawal design as a strategy to assess the effectiveness of a standardised clinical-pharmaceutical homeopathic protocol (Organon.modus) on perennial asthma in adolescents. METHODS: Randomised withdrawal, double-blind, parallel, placebo-controlled, 12-week study. Patients: 12 to 17 years old adolescents, with the diagnosis of perennial asthma, using inhalatory beclomethasone (plus fenoterol for wheezing episodes), who achieved 3 months of well-controlled asthma, after a variable period of individualised homeopathic treatment according to Organon.modus protocol. Setting: a secondary care medical specialist centre. Intervention: continuation with the individualised homeopathic medicine or with indistinguishable placebo during 12 weeks of beclomethasone step-down. Primary outcome: number of days of well-controlled asthma. Secondary measures: number of days of fenoterol use, number of visits to an emergency service (without hospitalisation) and percentage of patients excluded due to an exacerbation characterising a partly controlled asthma. Tolerability was assessed by Adverse Events, registered at every visit. RESULTS: Nineteen patients were randomised to continue treatment with homeopathy and 21 with placebo. Effectiveness measures for the homeopathy and placebo groups respectively were median number of days of good clinical control: 84 versus 30 (p = 0.18); median number of days of fenoterol use per patient: 3 versus 5 (p = 0.41); visits to an emergency room: 1 versus 6 (p = 0.35); percentage of exclusion due to partly controlled asthma: 36.8% versus 71.4% (p = 0.05). Few Adverse Events were reported. CONCLUSIONS: This pilot study supports the feasibility of the double-blind randomised withdrawal design in studies investigating homeopathy on teenage asthma, when performed by specialists following a standardised clinical-pharmaceutical homeopathic protocol. CLINICAL TRIAL REGISTRATION: RBR-6XTS8Z.

De Sitter symmetries and inflationary scalar-vector models / Simetrías en el espacio de De Sitter y modelos inflacionarios escalar-vector / Simetrias de De Sitter e modelos inflacionarios escalar-vetors

Abstract In this paper, we study the correspondence between a field theory in de Sitter space in D-dimensions and a dual conformal field theory in a euclidean space in (D-1)-dimensions. In particular, we investigate the form in which this correspondence is established for a system of interacting scalar and a vector fields propagating in de Sitter space. We analyze some necessary (but not sufficient) conditions for which conformal symmetry is preserved in the dual theory in (D - 1)-dimensions, making possible the establishment of the correspondence. The discussion that we address in this paper is framed on the context of inflationary cosmology. Thusly, the results obtained here pose some relevant possibilities of application to the calculation of the fields's correlation functions and of the primordial curvature perturbation Z, in inflationary models including coupled scalar and vector fields.

Resumen En este artículo se estudia la correspondencia entre una teoría de campos en el espacio de De Sitter en D-dimensiones y una teoría dual conforme en un espacio euclidiano en (D - 1)-dimensiones. En particular, se investiga la forma en la que se establece esta correspondencia para un sistema compuesto por un campo escalar y un campo vectorial acoplados propagándose en el espacio de De Sitter. Se analizan algunas condiciones necesarias (pero no suficientes) en las cuales la simetría conforme se preserva en la teoría dual en (D - 1)-dimensiones y hace posible el establecimiento de la correspondencia. La discusión presentada aquí se enmarca en el contexto de la cosmología inflacionaria, así que los resultados obtenidos plantean algunas posibilidades relevantes de aplicación en el cálculo de funciones de correlación de los campos y de la perturbación de ¡a curvatura primordial Z en modelos inflacionarios que incluyen campos escalares y vectoriales acoplados.

Resumen Neste artigo, é estudada a correspondencia entre uma teoria de campos no espaço de De Sitter em D-dimensões e uma teoria dual conforme num espaço euclidiano em (D - 1)-dimensões. Em particular, é pesquisado o caminho no qual se estabelece esta correspondência para um sistema de interação composto dum campo escalar e um vetorial, propagando-se no espaço de De Sitter. São analisadas algumas condições necessárias (mas não suficientes) para as quais a simetria conforme é preservada na teoria dual em (D-l)-dimensões, fazendo viável o estabelecimento da correspondência. A discussão apresentada aqui, está situada no contexto da cosmologia inflacionária. Portanto, os resultados obtidos representam algumas possibilidades relevantes para sua aplicacão no cálculo de funções de correlação dos campos e da perturbação da curvatura primordial Ç em modelos inflacionários incluindo campos acoplados escalares e vetoriais.

Measurement Properties of the Lower Extremity Functional Scale: A Systematic Review.

STUDY DESIGN: Systematic review of measurement properties. BACKGROUND: Many primary studies have examined the measurement properties, such as reliability, validity, and sensitivity to change, of the Lower Extremity Functional Scale (LEFS) in different clinical populations. A systematic review summarizing these properties for the LEFS may provide an important resource. OBJECTIVE: To locate and synthesize evidence on the measurement properties of the LEFS and to discuss the clinical implications of the evidence. METHODS: A literature search was conducted in 4 databases (PubMed, MEDLINE, Embase, and CINAHL), using predefined search terms. Two reviewers performed a critical appraisal of the included studies using a standardized assessment form. RESULTS: A total of 27 studies were included in the review, of which 18 achieved a very good to excellent methodological quality level. The LEFS scores demonstrated excellent test-retest reliability (intraclass correlation coefficients ranging between 0.85 and 0.99) and demonstrated the expected relationships with measures assessing similar constructs (Pearson correlation coefficient values of greater than 0.7). The responsiveness of the LEFS scores was excellent, as suggested by consistently high effect sizes (greater than 0.8) in patients with different lower extremity conditions. Minimal detectable change at the 90% confidence level (MDC90) for the LEFS scores varied between 8.1 and 15.3 across different reassessment intervals in a wide range of patient populations. The pooled estimate of the MDC90 was 6 points and the minimal clinically important difference was 9 points in patients with lower extremity musculoskeletal conditions, which are indicative of true change and clinically meaningful change, respectively. CONCLUSION: The results of this review support the reliability, validity, and responsiveness of the LEFS scores for assessing functional impairment in a wide array of patient groups with lower extremity musculoskeletal conditions.

Optimization of the sperm:oocyte ratio and sperm economy in the artificial reproduction of Rhamdia quelen using fructose as a sperm motility modulator.

This research was conducted to evaluate the effects of fructose as a modulator of sperm motility and its effects on the reduction in number of sperm cells in IVF using cryopreserved Rhamdia quelen semen. Sperm activation occurred in solutions containing fructose (0.0, 0.9, 1.8, 2.7, 3.6 and 4.5%). The sperm motility rate, velocity and duration of sperm motility were assessed by polynomial regression analysis and grouped by the principal component analysis (PCA). Then, the oocytes were mixed with semen at proportions of 1×10(4), 3×10(4), 5×10(4), 7×10(4) and 9×10(4) for the sperm:oocyte ratio and fertilization was induced by the activation of gametes with the fructose-containing solutions. The fertilization, hatching and larval normality rate were evaluated by response surface protocol and were further grouped by PCA. All sperm variables were affected by the activating solutions, and the most desirable theoretical results for the rate of sperm motility were obtained when using a solution containing 2.85% fructose. In the IVF and incubation assays, there was an interactive effect between the motile sperm:oocyte ratio and the fructose concentration on the rates of oocyte fertilization, hatching and on the clustered index for reproductive success. The results suggest the possibility of reducing the sperm cells on IVF by 17.77% when using a solution containing 2.28% fructose. In conclusion, the use of solutions containing fructose at concentrations that maximize sperm movement allow the reduction of the motile sperm:oocyte ratio, thus promoting sperm metabolic efficiencies and contributing to the feasibility of using cryopreserved semen at a large-scale in IVF.

Innermost stable circular orbits and epicyclic frequencies around a magnetized neutron star / Órbitas circulares marginalmente estables y frecuencias epicíclicas alrededor de una estrella de neutrones magnetizada / Órbitas circulares marginalmente estáveis e frequencias epicicloidais nas proximidades de uma estrela de neutrons magnetizada

El formalismo de la relatividad general es usado para calcular el radio de la órbita marginalmente estable (ROME), las frecuencias kepleriana, de Lense-Thirring, de precesion y oscilación de los movimientos radiales y verticales, de una partícula de prueba neutra que orbita el plano ecuatorial de una estrella de neutrones magnetizada. El espacio tiempo alrededor de la estrella se modela por medio de la solución seis paramétrica derivada por Pachón et al. (2012). Se concluye que la presencia del campo magnético de la fuente tiene efectos apreciables en las cantidades físicas mencionadas arriba y, por tanto, su inclusión es necesaria si se desea describir con más exactitud los procesos físicos que ocurren en la vecindad de este tipo de estrellas tales como la dinámica de discos de acreción. Los resultados presentados aquí también sugieren que la presencia de campos magnéticos intensos pueden introducir correcciones apreciables en, por ejemplo, las predicciones de la masa de estrellas de neutrones hechas con base en el modelo de precesión relativista.

A full-relativistic approach is used to compute the radius of the innermost stable circular orbit (ISCO), the Keplerian, frame-dragging, precession and oscillation frequencies of the radial and vertical motions of neutral test particles orbiting the equatorial plane of a magnetized neutron star. The space-time around the star is modelled by the six parametric solution derived by Pachón et al. (2012) It is shown that the inclusion of an intense magnetic field, such as the one of a neutron star, have non-negligible effects on the above physical quantities, and therefore, its inclusion is necessary in order to obtain a more accurate and realistic description of physical processes, such as the dynamics of accretion disks, occurring in the neighbourhood of this kind of objects. The results discussed here also suggest that the consideration of strong magnetic fields may introduce non-negligible corrections in, e.g., the relativistic precession model and therefore on the predictions made on the mass of neutron stars.

O formalismo da relatividade geral é usado para calcular o raio da órbita marginalmente estável (ROME), as frequencias keplerianas de Lense Thirring, precessao e oscilaçao de movimentos radiais e verticais, de uma partícula de prova neutra em órbita equatorial de uma estrela de neutrón magnetizada. O espaço-tempo ao redor da estrela é modelado por meio da soluçao seis paramétrica derivada por Pachón et al. (2012). Conclui-se que a presença do campo magnético da fonte tem efeitos apreciáveis nas quantidades físicas mencionadas acima e, portanto, a sua inclusão é necessária se se deseja descrever com mais exatidão os processos físicos que ocorrem na vizinhança deste tipo de estrelas tais como a dinâmica dos discos de acreção. Os resultados apresentados também sugerem que a precessão de campos magnéticos intensos podem introduzir correcções apreciáveis em, por exemplo, as predições da massa da estrela de neutróns feitas com base nos modelos de precessão relativista.

Expression of HER2 and bradykinin B1 receptors in precursor lesions of gallbladder carcinoma.

AIM: To determine the expression of HER2 and bradykinin B(1) receptors (B(1)R) in the two pathogenic models of gallbladder cancer: the metaplasia-dysplasia-carcinoma and the adenoma-carcinoma pathways. METHODS: Receptor proteins were visualized by immunohistochemistry on 5-µm sections of paraffin-embedded tissue. Expression of both receptors was studied in biopsy samples from 92 patients (6 males and 86 females; age ranging from 28 to 86 years, mean 56 years). High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridization. Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker. RESULTS: HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium. On the contrary, there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia (22/24; 91.7%) and carcinoma in situ (9/10; 90%), the lesions that displayed a significantly high proliferation index. Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene amplification. A similar result was observed in invasive carcinomas (0/12). The B(1)R distribution pattern mirrored that of HER2 except that B(1)R was additionally observed in the adenomas. The B(1)R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia (24/24; 100%) and carcinoma in situ (10/10; 100%) and in the epithelial cells of adenomas. In contrast, both HER2 (4/12; 33%) and B(1)R (1/12; 8.3%) showed a low expression in invasive gallbladder carcinomas. CONCLUSION: The up-regulation of HER2 and B(1)R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis.

New ependymal cells are born postnatally in two discrete regions of the mouse brain and support ventricular enlargement in hydrocephalus.

A heterogeneous population of ependymal cells lines the brain ventricles. The evidence about the origin and birth dates of these cell populations is scarce. Furthermore, the possibility that mature ependymal cells are born (ependymogenesis) or self-renewed (ependymal proliferation) postnatally is controversial. The present study was designed to investigate both phenomena in wild-type (wt) and hydrocephalic α-SNAP mutant (hyh) mice at different postnatal stages. In wt mice, proliferating cells in the ventricular zone (VZ) were only found in two distinct regions: the dorsal walls of the third ventricle and Sylvian aqueduct (SA). Most proliferating cells were monociliated and nestin+, likely corresponding to radial glial cells. Postnatal cumulative BrdU-labeling showed that most daughter cells remained in the VZ of both regions and they lost nestin-immunoreactivity. Furthermore, some labeled cells became multiciliated and GLUT-1+, indicating they were ependymal cells born postnatally. Postnatal pulse BrdU-labeling and Ki-67 immunostaining further demonstrated the presence of cycling multiciliated ependymal cells. In hydrocephalic mutants, the dorsal walls of the third ventricle and SA expanded enormously and showed neither ependymal disruption nor ventriculostomies. This phenomenon was sustained by an increased ependymogenesis. Consequently, in addition to the physical and geometrical mechanisms traditionally explaining ventricular enlargement in fetal-onset hydrocephalus, we propose that postnatal ependymogenesis could also play a role. Furthermore, as generation of new ependymal cells during postnatal stages was observed in distinct regions of the ventricular walls, such as the roof of the third ventricle, it may be a key mechanism involved in the development of human type 1 interhemispheric cysts.

Kinin B1 receptor activation turns on exocytosis of matrix metalloprotease-9 and myeloperoxidase in human neutrophils: involvement of mitogen-activated protein kinase family.

During neutrophil activation and degranulation, MMP-9 and MPO are released into the extracellular space to propagate inflammatory disorders. As kinin peptides are major participants in acute inflammatory responses, and the G-protein-coupled B(1)R mediates the chemotaxis of human neutrophils, we examined the release of the neutrophil enzymes MMP-9 and MPO by the B(1)R agonist LDBK and determined the signaling pathways that may regulate this cellular effect. Cytochalasin-treated and -untreated neutrophils were suspended in HBSS and stimulated with a range concentration of LDBK for 5 min. Zymography and Western blotting revealed that LDBK induced the release of MMP-9 and MPO. The use of specific signaling transduction inhibitors showed that release of MMP-9 depended on ERK1/2 and p38 MAPKs, whereas release of MPO involved only the p38 cascade. Inhibition of the key steps in these pathways showed that the release of both enzymes depended on PKC and PI3K. Stimulation of neutrophils with LDBK produced phosphorylation of ERK1/2 and p38 MAPK, which was inhibited by B(1)R antagonists. The phosphorylated ERK1/2 MAPK translocated to the neutrophil nucleus, suggesting that transcription of new genes may follow activation of B(1)R. Our results demonstrate that in human neutrophils, activation of kinin B(1)R by LDBK initiates separate signaling cascades that trigger the release of MMP-9 and MPO from tertiary and primary granules, respectively, suggesting that the B(1)R plays a pivotal role in inflammatory disorders.

Stimulation of the bradykinin B(1) receptor induces the proliferation of estrogen-sensitive breast cancer cells and activates the ERK1/2 signaling pathway.

Kinin peptides exert multiple biological effects by binding to two types of G protein-coupled receptors known as B(1) (B(1)R) and B(2) receptors. Expression of the B(1)R in human breast cancer was recently reported, but up to now the consequences of its stimulation are unknown. Our aims were (1) to investigate the capacity of B(1)R to trigger cell proliferation in breast cancer cells, (2) to explore some of the downstream events occurring after B(1)R stimulation that may be linked to cell proliferation, and (3) to determine whether human breast tumors express potentially active B(1)R assessed by the binding of a radiolabeled agonist. Breast cancer cells expressed both the mRNA and the immunoreactive protein of B(1)R that once stimulated triggered cell proliferation at nanomolar concentrations of the ligand. Inhibitor studies suggested that the proliferative effects depend on the activity of epidermal growth factor receptor and subsequent ERK1/2 mitogen-activated protein kinases phosphorylation. B(1)R binding sites, were detected in 3/4 fibroadenomas, in 4/4 ductal carcinomas in situ and in 11/13 invasive ductal carcinomas. The B(1)R-epidermal growth factor receptor crosstalk may be a key interaction that maintains tumor growth, and antagonism of B(1)R may be a valuable alternative for the treatment of breast cancer.

Tumor carcinoide apendicular: conducta terapéutica / Carcinoid appendicular tumor: terapeutic conduct

Se realizó la revisión de un caso clínico de Tumor Carcinoide apendicular, diagnosticado y tratado en el Servicio de Cirugía General del Hospital Militar "Dr. Carlos Arvelo" en julio de 1996, así como de la literatura referente a la conducta terapéutica. Los tumores apéndice son una enfermedad poco frecuente aunque importante y son difíciles de diagnosticar antes de la intervención quirúrgica. La presentación como una apendicitis es frecuente, pero incluso durante la intervención el diagnóstico pasa desapercibido. En otros casos el apéndice se observa macroscópicamente normal y el patólogo detecta la anormalidad como un hallazgo incidental. La TAC puede ayudar en el diagnóstico, aunque a veces puede imitar el aspectó de un absceso apendicular. El factor más importante para considerar el tratamiento es el tamaño del tumor. Los tumores pequeños, no agresivos y próximos a la punta del apéndice precisan como tratamiento único la apendicectomía simple. La cirugía adicional mediante hemicolectomía derecha, debe realizarse en las lesiones grandes (>2 cm), agresivas, localizadas en la base o cuando existe cualquier posibilidad de que la lesión pueda ser invasora. Si se sigue esta conducta pueden obtenerse porcentajes satisfactorios de supervivencia a largo plazo

Valoración del estado nutricional en pacientes quirúrgicos / Valoration of the nutritional state in surgical patients

La desnutrición es un problema frecuente y grave en pacientes quirúrgicos, de proporciones desconocidas en muchos hospitales de nuestro país, por lo que realizamos un trabajo prospéctivo entre febrero y septiembre de 1998, analizando 107 pacientes tratados en el Servicio de Cirugía General del Hospital Militar "Dr. Carlos Arvelo", se utilizó la evaluación por "Puntaje" de Feldtman, que consiste en asignar un valor a parámetros antropométricos (peso, pliegue del tripceps, circunferencia muscular del brazo) y a parámetros de laboratorio (albúmina, linfocitos absolutos, hierro sérico), sumando los mismos para catalogar a los pacientes en desnutrición leve, moderada, severa, o normales (sin desnutrición). Se obtuvo una desnutrición severa en el 37 por ciento, desnutrición leve en 6 por ciento desnutrición moderada en 12 por ciento y sin déficit nutricional en 45 por ciento de los pacientes al ingreso. Dicho método de evaluación es bastante objetivo pero tiene el inconveniente que no puede ser aplicado a todos los pacientes que consulten el Departamento de Cirugía General, por lo que no se usa como tamizaje para la detección de la desnutrición, alternativamente la Evaluación Global subjetiva si resulta práctica para la detección preoperatoria de este problema en vista que se basa en el interrogatorio y examen físico rápido, resultando muy eficiente para asignar a los sujetos como normales o con desnutrición severa, que son los grupos más numerosos en nuestro estudio