Curvature-induced stabilization and field-driven dynamics of magnetic hopfions in toroidal nanorings.

Three dimensional magnetic textures are a cornerstone in magnetism research. In this work, we analyze the stabilization and dynamic response of a magnetic hopfion hosted in a toroidal nanoring with intrinsic Dzyaloshinskii-Moriya interaction simulating FeGe. Our results evidence that unlike their planar counterparts, where perpendicular magnetic anisotropies are necessary to stabilize hopfions, the shape anisotropy originated on the torus symmetry naturally yields the nucleation of these topological textures. We also analyze the magnetization dynamical response by applying a magnetic field pulse to differentiate among several magnetic patterns. Finally, to understand the nature of spin wave modes, we analyze the spatial distributions of the resonant mode amplitudes and phases and describe the differences among bulk and surface modes. Importantly, hopfions lying in toroidal nanorings present a non-circularly symmetric poloidal resonant mode, which is not observed in other systems hosting hopfions.

[Inflammatory bowel disease during pregnancy]. / Embarazo en enfermedad inflamatoria intestinal: no solo 9 meses de cuidado.

The prevalence of inflammatory bowel disease (IBD) increased in the last decades. Thus, the number of pregnant women with the condition is also increasing. Given that active disease itself is the main risk factor for complications during pregnancy, it is necessary to achieve a complete remission before planning a pregnancy. Also, pregnant women with IBD must be monitored noninvasively and be treated proactively, including escalated therapies, if needed, to prevent potential flares during pregnancy. Patients can undergo vaginal delivery in most forms of IBD. However, cesarean delivery is still preferable in women with a history of ileal pouch-anal anastomoses (IPAA) or active perianal disease.

[Implementation of diagnosis related groups methodology in a university hospital]. / Experiencia en el desarrollo e implementación de la metodología de grupos relacionados por diagnóstico en un hospital universitario chileno. Evaluación a diez años de funcionamiento.

Background The Diagnosis Related Groups (DRG) constitute a method of classifying hospital discharges. Aim To report its development and implementation in a Chilean University Hospital and global results of 10 years Material and Methods We included 231,600 discharges from 2007 to 2016. In the development we considered the physical plant, clinical record flow, progressively incorporated human resources and computer equipment for coding and analysis to obtain results. The parameters used were: average stay, average DRG weight, mean of diagnosis and codified procedures, behavior of upper outliers, hospital mortality, distribution by severity and its relationship with other variables. Results The global complexity index was 0.9929. The average of diagnoses coded was 4.35 and of procedures was 7.21. The average stay was 4.56 days, with a downward trend. The top outliers corresponded to 2.25%, with stable hospital days and average DRG weight. The median of hospital mortality was 1.65% with a tendency to decrease and stable DRG mean weight. Seventy two percent had a grade 1 severity, with low median hospital stay. They occupied 40% of bed days. Nine percent had a grade 3 severity with high median hospital stay and accounting for 31.5% of bed days. Conclusions DRG methodology is a valuable information tool for decision making and result assessment in hospital management.

Expression, functionality, and localization of apurinic/apyrimidinic endonucleases in replicative and non-replicative forms of Trypanosoma cruzi.

Trypanosoma cruzi is the etiological agent of Chagas disease. The parasite has to overcome oxidative damage by ROS/RNS all along its life cycle to survive and to establish a chronic infection. We propose that T. cruzi is able to survive, among other mechanisms of detoxification, by repair of its damaged DNA through activation of the DNA base excision repair (BER) pathway. BER is highly conserved in eukaryotes with apurinic/apirimidinic endonucleases (APEs) playing a fundamental role. Previous results showed that T. cruzi exposed to hydrogen peroxide and peroxinitrite significantly decreases its viability when co-incubated with methoxyamine, an AP endonuclease inhibitor. In this work the localization, expression and functionality of two T. cruzi APEs (TcAP1, Homo sapiens APE1 orthologous and TcAP2, orthologous to Homo sapiens APE2 and to Schizosaccaromyces pombe Apn2p) were determined. These enzymes are present and active in the two replicative parasite forms (epimastigotes and amastigotes) as well as in the non-replicative, infective trypomastigotes. TcAP1 and TcAP2 are located in the nucleus of epimastigotes and their expression is constitutive. Epimastigote AP endonucleases as well as recombinant TcAP1 and TcAP2 are inhibited by methoxyamine. Overexpression of TcAP1 increases epimastigotes viability when they are exposed to acute ROS/RNS attack. This protective effect is more evident when parasites are submitted to persistent ROS/RNS exposition, mimicking nature conditions. Our results confirm that the BER pathway is involved in T. cruzi resistance to DNA oxidative damage and points to the participation of DNA AP endonucleases in parasite survival.

DNA repair BER pathway inhibition increases cell death caused by oxidative DNA damage in Trypanosoma cruzi.

Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas disease, an endemic and neglected pathology in Latin America. It presents a life cycle that involves a hematophagous insect and man as well as domestic and wild mammals. The parasitic infection is not eliminated by the immune system of mammals; thus, the vertebrate host serves as a parasite reservoir. Additionally, chronic processes leading to dysfunction of the cardiac and digestive systems are observed. To establish a chronic infection some parasites should resist the oxidative damage to its DNA exerted by oxygen and nitrogen free radicals (ROS/RNS) generated in host cells. Till date there are no reports directly showing oxidative DNA damage and repair in T. cruzi. We establish that ROS/RNS generate nuclear and kinetoplastid DNA damage in T. cruzi that may be partially repaired by the parasite. Furthermore, we determined that both oxidative agents diminish T. cruzi cell viability. This effect is significantly augmented in parasites subsequently incubated with methoxyamine, a DNA base excision repair (BER) pathway inhibitor, strongly suggesting that the maintenance of T. cruzi viability is a consequence of DNA repair mechanisms.

Motion-induced inertial effects and topological phase transitions in skyrmion transport.

When the skyrmion dynamics beyond the particle-like description is considered, this topological structure can deform due to a self-induced field. In this work, we perform Monte Carlo simulations to characterize the skyrmion deformation during its steady movement. In the low-velocity regime, the deformation in the skyrmion shape is quantified by an effective inertial mass, which is related to the dissipative force. When skyrmions move faster, the large self-induced deformation triggers topological transitions. These transitions are characterized by the proliferation of skyrmions and a different total topological charge, which is obtained as a function of the skyrmion velocity. Our findings provide an alternative way to describe the dynamics of a skyrmion that accounts for the deformations of its structure. Furthermore, such motion-induced topological phase transitions make it possible to control the number of ferromagnetic skyrmions through velocity effects.

Safety and efficacy of a mesenchymal stem cell intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis.

Although, antibiotics are effective in the treatment of bovine mastitis, they do not address the regeneration of mammary glandular tissue and have been associated to the increment in antimicrobial resistance worldwide. Considering the necessity of alternative therapies for this disease of high economic impact and the reported regenerative and antibacterial effects of mesenchymal stem cell (MSCs), we evaluated the safety and efficacy of an allogenic MSC-based intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis. In a safety trial, heifers were inoculated intramammarily with a 2.5 × 107-suspension of bovine fetal AT-MSCs on experimental days 1 and 10. Animals were evaluated clinically on a daily basis during a 20-day experimental period and blood samples were collected for hemogram determination and peripheral blood leukocytes (PBLs) isolation. In an efficacy trial, Holstein Friesian cows were inoculated with S. aureus and treated intramammarily with vehicle (NEG; days 4 and 10), antibiotics (ATB; days 4 and 5) or a suspension of 2.5 × 107 AT-MSCs (MSC; days 4 and 5). Cows were clinically evaluated daily and milk samples were collected for somatic cell count (SCC) and colony forming units (CFU). Blood samples were collected for serum haptoglobin and amyloid A determination. Intramammary administration of two doses of bovine fetal AT-MSCs in healthy cows did not induce changes in clinical or hematological variables, and gene expression profiles in PBLs associated to activation (CD4, CD8, CD25, CD62L and CD69) and proinflammatory cytokines (CCL2, CCL5, IL2, CXCL3, IFNγ, and TNFα). Quarters of MSC group of cows had similar SCC log/mL in milk compared to infected quarters of ATB or NEG cows. However, quarters of MSC cows had lower CFU log/mL in milk compared to quarters of NEG cows. Intramammarily inoculation of repeated doses of 2.5 × 107 allogenic AT-MSCs did not induce clinical or immunological response in healthy cows. Moreover, MSC-intramammary treatment reduced bacterial count in milk of cows with S. aureus clinical mastitis compared to untreated cows. This work provides initial evidence for the safety and efficacy of an allogenic MSC-based intramammary therapy for the treatment of bovine mastitis.

Comparative genomic hybridization of oocytes and first polar bodies from young donors.

Chromosome abnormalities are common in oocytes derived from patients undergoing IVF treatment. The proportion of oocytes displaying aneuploidy is closely related to maternal age and may exceed 60% in patients over 40 years old. However, little information currently exists concerning the incidence of such anomalies in oocytes derived from young fertile women. A total of 121 metaphase II oocytes and their corresponding first polar bodies (PB) were analysed with the use of a comprehensive cytogenetic method, comparative genomic hybridization (CGH). The oocytes were donated from 13 young women (average age 22 years) without any known fertility problems. All oocytes were mature at the time of retrieval and were unexposed to spermatozoa. A low aneuploidy rate (3%) was detected. These results clearly indicate that meiosis I segregation errors are not frequent in oocytes of young fertile women. The higher aneuploidy rates reported in embryos derived from donor oocytes could be due to aggressive hormonal stimulation, in combination with male factors. However a definite contributing factor remains to be elucidated. The data obtained during this study also illustrate that CGH accurately and efficiently detects aneuploidy, confirming that it is suitable for application in a clinical setting for the assessment of oocytes, via PB analysis.

Sertoli cell-mediated differentiation of bovine fetal mesenchymal stem cells into germ cell lineage using an in vitro co-culture system.

In vitro gamete derivation based on differentiation of germ cells (GC) from stem cells has emerged as a potential new strategy for the treatment of male infertility. This technology also has potential applications in animal reproduction as an alternative method for dissemination of elite animal genetics, production of transgenic animals, and conservation of endangered species. Mesenchymal stem cells (MSC) are multipotent progenitor cells defined by their ability to differentiate into mesodermal lineages. Under the effect of selected bioactive factors, MSC upregulate expression of pluripotent and GC specific-markers revealing their potential for GC differentiation. In addition to the effect of trophic factors, cell-to-cell interaction with Sertoli cells (SC) may be required to guide the sequential differentiation of MSC into GC. Thus, the aim of the present study was to investigate the effect of coculture with SC on the potential for in vitro GC differentiation of bovine fetal MSC (bfMSC) derived from bone marrow (BM-MSC) and adipose tissue (AT-MSC). bfMSC were isolated from male bovine fetuses and SC were collected from adult bull testes. The effect of SC interaction with BM-MSC or AT-MSC was analyzed on the expression of pluripotent factors OCT4 and NANOG, GC genes FRAGILLIS, STELLA and VASA and male GC markers DAZL, PIWIL2, STRA8 and SCP3 at Day 14 of coculture. Flow cytometry analyses detected that the majority (95,5% ±â€¯2.5; P < 0.05) of the isolated population of SC cultures were positive for SC-specific marker WT1. Levels of mRNA of WT1 in BM-MSC and AT-MSC were lower (P < 0.05) compared to SC; whereas, WT1 expression was not detected in bovine fetal fibroblasts (FB). Cocultures of BM-MSC and AT-MSC with SC had higher (P < 0.05) OCT4 mRNA levels compared to monocultures of BM-MSC, AT-MSC and SC. Moreover, cocultures of BM-MSC with SC had higher (P < 0.05) proportion of cells positive for Oct4 and Nanog compared to monocultures of BM-MSC and SC. Levels of mRNA of DAZL, PIWIL2 and SCP3 were upregulated in cocultures of AT-MSC with SC compared to monocultures of AT-MSC and SC. Accordingly, the proportion of cells positive for Dazl were higher (P < 0.05) in cocultures of AT-MSC with SC compared to monocultures of AT-MSC and SC. Changes in gene expression profiles during coculture of SC with AT-MSC suggest that cell-to-cell interaction or bioactive factors provided by SC may induce progression of AT-MSC into early stages of GC differentiation.

Mielitis transversa aguda asociada a Covid-19. Reporte de caso

Desde el inicio de la pandemia por COVID-19 (coronavirus disease), en el 2019, se han descrito numerosas manifestaciones clínicas de la enfermedad causada por este virus, destacando el compromiso respiratorio, hematológico, cardiovascular y neurológico. Dentro de las manifestaciones y/o complicaciones neurológicas, se encuentra la mielitis aguda transversa por COVID-19(1), cuyo diagnóstico se ha realizado principalmente clínico-imagenológico y PCR (reacción de polimerasa en cadena), o serología (+) para COVID-19, con manejos y resultados no siempre afortunados. Presentamos el caso de un paciente con mielitis aguda transversa longitudinalmente extensa en relación a COVID-19, tratada con éxito clínico con rituximab.

Since the beginning of the COVID-19 pandemic in 2019, numerous clinical manifestations of the disease caused by this virus have been described, highlighting respiratory, hematological, cardiovascular, and neurological compromise. Among the neurological manifestations and/or complications, there is acute transverse myelitis due to COVID-19(1), whose diagnosis has been made mainly clinical-imaging and PCR or serology (+) for COVID-19, with management and results not always lucky. We present the case of a patient with longitudinally extensive acute transverse myelitis in relation to COVID-19, treated with clinical success with rituximab.

Factores asociados al control de síntomas nucleares en pacientes pediátricos con trastorno de déficit de atención e hiperactividad, en un centro especializado de Medellín entre 2018 y 2019 / Factors associated with the control of nuclear symptoms in pediatric patients with Attention Deficit Hyperactivity Disorder in a specialized center in Medellín between 2018 and 2019 / Fatores associados ao controle de sintomas nucleares em pacientes pediátricos com transtorno de déficit de atenção e hiperatividade, em um centro especializado em Medellín entre 2018 e 2019

Objetivo: el trastorno de déficit de atención e hiperactividad (TDAH) ha sido descrito como el trastorno del neurodesarrollo más común en la infancia. Esta condición se asocia a un significativo deterioro en calidad de vida, múltiples comorbilidades y, a largo plazo, a menores logros académicos y laborales. A pesar de que se ha evidenciado que en los pacientes de ascendencia latina se presenta un posible subdiagnóstico, que en Colombia se han estimado prevalencias mayores a las descritas en el planeta, y que los efectos de la pandemia por Covid-19 han podido exacerbar esta problemática, el volumen de estudios con estimaciones reproducibles sobre las características, tratamientos recibidos y control de síntomas de estos pacientes aún requiere ampliarse. Este estudio busca establecer los factores sociodemográficos, clínicos y del tratamiento asociados al control de los síntomas nucleares de este trastorno, que consisten en patrones persistentes y generalizados de inatención, impulsividad e hiperactividad. Metodología: estudio descriptivo con intención analítica en una cohorte retrospectiva de pacientes pediátricos con trastorno de déficit de atención e hiperactividad seguidos durante seis meses en un centro especializado de Medellín, Colombia, entre 2018 y 2019. Resultados: se identificó una incidencia de control de síntomas de 46,7% que se asoció de manera significativa con la adherencia al tratamiento y con historia familiar de TDAH. Conclusiones: puede afirmarse que, en pacientes pediátricos con TDAH, estos factores podrían aumentar la probabilidad de lograr el control de los síntomas nucleares.

Objective: Attention Deficit Hyperactivity Disorder (ADHD) has been described as the most common neurodevelopmental disorder in childhood. This condition is associated with significant deterioration in the quality of life, multiple comorbidities and, in the long term, lower academic and work achievements. Despite the fact that it has been shown that patients of Latin descent present a possible underdiagnosis, that in Colombia higher prevalence has been estimated than those described worldwide, and that the effects of the Covid-19 pandemic have been able to exacerbate this problem, the volume of studies with reproducible estimates on the characteristics, treatments received, and symptom control of these patients still needs to be expanded. This study seeks to establish the sociodemographic, clinical and treatment factors associated with the control of the core symptoms of this disorder, which consist of persistent and generalized patterns of inattention, impulsivity and hyperactivity. Methodology: Descriptive study with analytical intent in a retrospective cohort of pediatric patients with attention deficit hyperactivity disorder followed up for 6 months in a specialized center in Medellín, Colombia, between 2018 and 2019. Results: An incidence of symptom control of 46.7% was identified, which was significantly associated with adherence to treatment and with a family history of ADHD. Conclusions: It can be affirmed that, in pediatric patients with ADHD, these factors could increase the probability of achieving control of nuclear symptoms.

Objetivo: o transtorno dedéficit de atenção e hiperatividade (TDAH) tem sido descrito como o transtorno do neurodesenvolvimento mais comum na infância. Esta condição está associada a uma deterioração significativa na qualidade de vida, múltiplas comorbidades e, a longo prazo, menores rendimentos acadêmicos e profissionais. Apesar de ter sido demonstrado que os pacientes de ascendência latina apresentam um possível subdiagnóstico, e que na Colômbia foram estimadas prevalências mais altas do que as descritas no planeta e que os efeitos da pandemia de Covid-19 foram capazes de exacerbar esse problema, o volume de estudos com estimativas reprodutíveis sobre as características, tratamentos recebidos e controle de sintomas desses pacientes ainda precisam ser ampliados. Este estudo busca estabelecer os fatores sociodemográficos, clínicos e de tratamento associados ao controle dos sintomas centrais desse transtorno, que consistem em padrões persistentes e generalizados de desatenção, impulsividade e hiperatividade. Metodologia: estudo descritivo com intenção analítica em uma coorte retrospectiva de pacientes pediátricos com transtorno de déficit de atenção e hiperatividade acompanhados por seis meses em um centro especializado em Medellín, Colômbia, entre 2018 e 2019.Resultados: identificou-se uma incidência de controle dos sintomas de 46,7%, signifi-cativamente associada à adesão ao tratamento e ao histórico familiar de TDAH.Conclusões: Pode-se afirmar que, em pacientes pediátricos com TDAH , esses fatores podem aumentar a probabilidade de controle dos sintomas nucleares.

Vitamina d: su implicancia en la infección por SARS-CoV-2 y su rol en el desarrollo y prevención de la enfermedad / Vitamin d: the implications in SARS-CoV-2 infection and its role in the development and prevention of the disease

Introducción: La pandemia del SARS-CoV-2 ha sido un desafío para la medicina en estos últimos años por su alta tasa de contagios y muertes asociadas. Progresivamente los investigadores han ido dilucidando vías de transmisión y manifestaciones clínicas más frecuentes, que han facilitado la detección el virus. Con el objetivo de optimizar la prevención y tratamiento en pacientes infectados, investigadores de todo el mundo han evaluado la importancia de la respuesta inmune frente al virus, destacando la acción de algunos inmunomoduladores, como por ejemplo, la vitamina D. Desarrollo: Tras invadir el organismo, el SARS-CoV-2 se une a receptores de las células epiteliales del tracto respiratorio, específicamente en el neumocito tipo II, disminuyendo la producción de surfactante y provocando una producción desregulada de citocinas proinflamatorias, principal responsable de los casos más severos. Se ha demostrado que la Vitamina D puede modular la respuesta inmune tras unirse a su receptor VDR, disminuyendo la liberación de citocinas proinflamatorias. Algunos estudios han determinado que el uso de suplementos de vitamina D en dosis altas pudieran producir efectos protectores frente a infecciones respiratorias agudas. Conclusión: Finalmente, pese a los estudios realizados que relacionan el déficit de vitamina D con casos más severos de COVID-19, aún se requiere más evidencia para recomendar suplementación.

Introduction: The SARS-CoV-2 pandemic has been a challenge for medicine in recent years, due to its high contagion rate and associated deaths. Researchers have progressively elucidated transmission methods and most frequent clinical manifestations, that helps the virus detection. With the objective of optimizing prevention and treatment of infected patients, researchers all over the world have evaluated the importance of the immune system response against the virus, highlighting some immunomodulators, such as vitamin D. Body: After SARS-CoV-2 invades the organism, it binds to the receptor located on the respiratory tract epithelial cells, specifically type 2 pneumocyte, decreasing surfactant production and increasing the production of pro inflammatory cytokines, being the main reason for severe cases. Vitamin D has been shown to modulate the immune response after binding to its receptor, decreasing the release of proinflammatory cytokines. Some studies have shown that vitamin D supplementation in high doses may produce protective effects against acute respiratory infections. Conclusion: Finally, even the studies that correlate vitamin D deficiency and COVID-19 severe cases, we still need more evidence to recommend Vitamin D supplementation.

Colgajo giratorio retroauricular / Retroauricular flip-flop flap

Resumen El colgajo retroauricular en isla (flip-flop flap) fue descrito por Masson en 1972 y consiste en tejido dermoepidérmico irrigado por un pedículo de patrón aleatorio subcutáneo de ramas de la arteria auricular posterior. Proviene de la región mastoidea y retroauricular y aporta buena cobertura para la región anteromedial del pabellón auricular. Se describen dos casos, en que se realizó cobertura inmediata secundario a un defecto de la concha auricular posterior a resección neoplásica, obteniendo resultados satisfactorios y sin complicaciones.

Abstract The retroauricular island flap (flip-flop flap), was described by Masson in 1972 and consists on dermoepidermal tissue irrigated by a random subcutaneous pedicle of branches of the posterior auricular artery. It comes from the mastoid and retroauricular region and provides a good coverage for the anteromedial region of the pinna. Two cases are described, in which immediate coverage was performed secondary to a defect in the auricular concha after a neoplastic resection, obtaining satisfactory results without complications.

Embarazo en enfermedad inflamatoria intestinal: no solo 9 meses de cuidado

The prevalence of inflammatory bowel disease (IBD) increased in the last decades. Thus, the number of pregnant women with the condition is also increasing. Given that active disease itself is the main risk factor for complications during pregnancy, it is necessary to achieve a complete remission before planning a pregnancy. Also, pregnant women with IBD must be monitored noninvasively and be treated proactively, including escalated therapies, if needed, to prevent potential flares during pregnancy. Patients can undergo vaginal delivery in most forms of IBD. However, cesarean delivery is still preferable in women with a history of ileal pouch-anal anastomoses (IPAA) or active perianal disease.

In vivo fluorescence microscopy for the assessment of microvascular reperfusion injury in small bowel transplants in rats.

With the use of in vivo fluorescence microscopy we have analyzed microvascular reperfusion injury of small bowel isograft transplants in rats. Following 1 hr cold storage in University of Wisconsin solution, the small bowel was transplanted heterotopically, and the intestinal microcirculation was quantitatively analyzed 20-60 min after onset of reperfusion. The intestinal grafts' capillary perfusion of both the mucosa and the circular and longitudinal muscles was not found altered when compared with the intestinal capillary perfusion of sham-operated controls. In contrast, leukocyte-endothelial cell interaction, including leukocyte rolling (40 +/- 5%) and sticking (280 +/- 100 mm-2) in submucosal postcapillary venules, was significantly increased when compared with nontransplanted controls (12 +/- 8% and 20 +/- 10 mm-2, P < 0.01 and P < 0.05, respectively). Leukocyte-endothelial cell interaction was associated with a marked alteration of lymphatic capillary drainage, as indicated by the low functional density of lymphatic microvessels of 10.2 +/- 6.1 cm-1 (P < 0.01 vs. sham-operated controls (39.2 +/- 6.1 cm-1)). From these results we propose that leukocyte-endothelial cell interaction, not capillary "no-reflow," is the primary step in the manifestation of microvascular reperfusion injury following a short period of cold ischemia in small bowel grafts.

Frequency and type of electrocardiographic abnormalities in cocaine abusers (electrocardiogram in cocaine abuse).

Electrocardiographic abnormalities of 200 asymptomatic, chronic cocaine abusers (aged < or = 45 years, 69% black) admitted for rehabilitation (group 1) were compared with 38 cocaine abusers treated in the emergency room (group 2), 21 cocaine abusers who died suddenly (group 3), and 425 control subjects from the general population. In group 1, 39% of electrocardiograms were abnormal: Increased QRS voltage was noted in 27%, ST elevation in 22%, ST-T changes in 17%, and prior myocardial infarction in 3%. Increased QRS voltage (35% vs 10%, p = 0.00007) and ST elevation (26% vs 13%, p = 0.0278) were more prevalent in blacks than in whites. With use of Minnesota coding, electrocardiograms in group 1 were compared with those of 141 black and 284 white men (aged < 40 years) from the general population. ST elevation was more prevalent in both black (22% vs 8%, p = 0.00073) and white (15% vs 1%, p < 0.00001) cocaine abusers than in the general population. Compared with group 1, group 2 had higher prevalence of sinus tachycardia (16% vs 1%, p = 0.0002), supraventricular tachycardia (5% vs 0%, p = 0.024), ST-T changes (34% vs 17%, p = 0.0164), and QTc > 440 ms (26% vs 4%, p = 0.00003); mean QTc was also greater among group 2 subjects (427 +/- 38 vs 404 +/- 19 ms, p < 0.0001). In group 3, QTc was > 440 ms in 6 of 8 subjects (75%) with 12-lead electrocardiograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Progesterone interaction with eosinophils and with responses already induced by oestrogen in the uterus.

Progesterone pretreatment decreases oestrogen-induced uterine eosinophilia and other non-genomic responses that are possibly mediated by eosinophils. To investigate the mechanisms of this interaction, the present study describes the effects of progesterone on oestrogenic responses already induced by oestrogen treatment and the in-vivo and in-vitro effects of progesterone on blood eosinophils. Progesterone treatment of oestrogen-pretreated animals potentiated uterine eosinophilia 24 h after progesterone treatment but decreased it at later times and increased eosinophil degranulation in vivo. In addition, progesterone degranulated blood eosinophils in vitro. These findings demonstrate interaction of progesterone with oestrogenic responses mediated by eosinophils. Progesterone interaction with other oestrogenic responses was analysed for comparison; evidence is shown suggesting a role of eosinophils in oestrogen-induced uterine luminal fluid accumulation.

Increased activity of lecithin:cholesterol acyltransferase during short-term oral estrogen progestin replacement therapy in a group of postmenopausal women.

The aim of the study was to assess the short-term effect of estrogen-progestin therapy on the plasma level of lecithin: cholesterol acyltransferase ([LCAT] EC 2.3.1.43), a key enzyme in the cholesterol reverse-transport process. The trial included 21 women with at least 6 months of menopause, which was confirmed by anamnesis, physical evaluation, and follicle-stimulating hormone (FSH) determination. Women receiving pharmacological treatment or who had any kind of endocrine disorder were excluded. In addition, we evaluated and confirmed normal Papanicolaou and mammography tests in all 21 women included in the trial. They received conjugated equine estrogen 0.625 mg daily, plus cyclic medroxyprogesterone acetate (5 mg daily) for 12 days each month. Plasma levels of LCAT, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apoB, and apoAI were evaluated before and after 1 and 3 months of therapy. Pretherapy and posttherapy results were analyzed statistically by Wilcoxon's rank-sum test for paired samples. No significant changes were observed either for body mass index or for blood pressure. A significant increase in plasma LCAT activity was found at the first and third month posttherapy (P < .005). In addition, after 3 months of therapy, HDL-C significantly increased (P < .005), in contrast to the significant decrease detected in total cholesterol (P < .025), LDL-C (P < .005), cholesterol to HDL-C and LDL-C/HDL-C ratios (P < .005). Triglyceride levels did not show significant modification. In conclusion, our results indicate that short-term estrogen-progestin therapy produces a significant increase in plasma LCAT activity, as well as beneficial changes in the lipid profile, in postmenopausal women.

Effect of diet and disulfiram on acetaldehyde blood levels after ethanol in UChA and UChB rats.

Acetaldehyde (AcH) levels in blood samples taken from different zones of the vascular system 2 h after a p.o. dose of ethanol (2.76 g/kg) were studied in UChA (low ethanol consumer) and UChB (high ethanol consumer) rats fed a diet devoid of animal products, diet 1 (D1), and a diet containing fish meal, diet 2 (D2), and in rats pretreated with disulfiram (600 mg/kg p.o.). The results showed that, while there is no significant difference between UChA and UChB rats fed D1 with respect to blood AcH levels and the basal activity of the hepatic mitochondrial high-affinity aldehyde dehydrogenase (AIDH), a significant strain difference was observed in rats fed D2, which induced high blood AcH levels in UChA rats but not in UChB ones. No strain differences were observed in blood ethanol levels in the two groups of rats. When rats fed D1 were pretreated with disulfiram, the raising of AcH blood levels induced by ethanol after disulfiram was significantly higher in UChA than in UChB rats in suprahepatic vein, femoral vein, and tail blood. This difference was concomitant with a greater inhibition of the hepatic mitochondrial high-affinity ADH activity in UChA rats than in UChB ones, whether disulfiram was administered in vivo or in vitro, which excluded the possibility that the strain difference would be caused by a different bioavailability of disulfiram.

In-vitro evaluation of sustained release ibuprofen microspheres.

Microspheres for oral use have been employed to target and to sustain the release of the drug. The objective of this study was to use the melt dispersion technique and aqueous vehicle to entrap ibuprofen into wax carrier (carnauba wax) with the aid of surfactant (Pluronic L-62). The effects of different levels of Pluronic L-62, stirring speed, and ibuprofen levels, as well as the in-vitro release rate of ibuprofen were evaluated. The in-vitro dissolution of ibuprofen in phosphate buffer pH 7.2 showed that microspheres prepared with low amount of drug (1.5 g) released 58.1% of ibuprofen after 6 hours, while microspheres prepared with high amount of drug (6.0 g) released only 38.9% of ibuprofen. Microsphere formulations prepared by using aqueous vehicle were spherical and of smooth surface. In general the melt dispersion technique was a successful method for preparing sustained release ibuprofen microspheres.