Consenso de expertos sobre recomendaciones basadas en evidencia para el diagnóstico, tratamiento y seguimiento de enfermedad de Fabry en pediatría / Expert Consensus on Evidence-Based Recommendations for the Diagnosis, Treatment, and Follow-Up of Fabry Disease in Pediatric Patients / Consenso de especialistas colombianos sobre recomendações baseadas em evidências para o diagnóstico, tratamento e acompanhamento da doença de Fabry em pediatria

Antecedentes: la enfermedad de Fabry (Ef) es una enfermedad rara ligada a X secundaria al depósito lisosomal de glicoesfingolípidos, debido a la deficiencia de la enzima alfa galactosidasa A (α-Gal A). A pesar de su baja frecuencia, es una condición que afecta la calidad de vida de los pacientes y disminuye su esperanza de vida. Objetivo: generar recomendaciones informadas para el diagnóstico y tratamiento de pacientes pediátricos (menores de 18 años) con Ef. Material y Métodos: revisión de literatura en bases de datos y literatura gris a partir de 2010, incluyendo guías de práctica clínica, revisiones sistemáticas y estudios primarios. La calidad de evidencia se evaluó de acuerdo con el tipo. Las recomendaciones se sometieron a consenso de expertos a través de metodología Delphi modificada. El acuerdo se definió a partir del 80 %. Resultados: A partir del análisis de la evidencia recolectada se formularon un total de 45 recomendaciones para tamización, diagnóstico y tratamiento de paciente pediátrico con Ef. El panel revisor estuvo conformado por once expertos en el tema. Las recomendaciones fueron aprobadas con puntuaciones entre 82.3 % y 100 %. Conclusiones: las recomendaciones resultantes del consenso de expertos permitirán la toma de decisiones clínicas y estandarización de la práctica en la atención de pacientes pediátricos con Ef en el país y la región. El diagnóstico temprano y oportuno garantiza una disminución del impacto en la calidad de vida de los pacientes y sus familiares

Background: Fabry disease (fD) is a rare X-linked disease characterized by the accumulation of glyco- sphingolipids in lysosomes due to the deficiency in the production of alpha-galactosidase A (α-Gal A) enzyme. Despite its low frequency, this disease has a serious impact on the life expectancy and quality. Objective: To make evidence-based recommendations for the diagnosis and treatment of fD in pediatric patients (<18 years of age). Materials and Methods: A study of databases and gray literature was conducted in 2010, including clinical practice guidelines, systematic reviews, and primary research. The type of evidence was used to determine the quality of evidence. The recommendations were submitted to an expert consensus using the modified Delphi process. The agreement was set at 80%. Conclusions: The recommendations emerging from this expert consensus will enable the standardization of care provision for pediatric patients with fD in Colombia and Latin America and clinical decision-making for disease management. Notably, making an early diagnosis ensures a reduction in the impact of this disease on the quality of life of patients and their families

Fundamento: a doença de Fabry (Df) é uma rara doença ligada ao cromossomo X secundária à deposi- ção lisossômica de glicoesfingolipídeos devido à deficiência da enzima alfa galactosidase A (α-Gal A). Apesar de sua baixa frequência, é uma condição que afeta a qualidade de vida dos pacientes e diminui sua expectativa de vida. Objetivo: gerar recomendações baseadas em evidências para o diagnóstico e tratamento de pacientes pediátricos (com menos de 8 anos de idade) com Df. Materais e Métodos: foi realizada uma revisão da literatura em bases de dados e literatura cinza a partir de 2010, incluindo diretrizes de prática clínica, revisões sistemáticas e estudos primários. A qualidade da evidência foi avaliada de acordo com o tipo de evidência. As recomendações foram submetidas ao consenso de especialistas usando a metodologia Delphi modificada. A concordância foi definida a partir de 80%. Resultados: com base na análise das evidências coletadas, foram formuladas um total de 45 recomendações para triagem, diagnóstico e tratamento de pacientes pediátricos com doença de Fabry. O painel de revisão foi composto por onze especialistas no assunto. As recomendações foram aprovadas com pontuações entre 82,3% e 100%. Conclusões: as recomendações resultantes do consenso de especialistas permitirão a tomada de decisão clínica e a padronização da prática no cuidado de pacientes pediátricos com Df em nível nacional e regional; o diagnóstico precoce e oportuno garante a redução do impacto na qualidade de vida dos pacientes e seus familiares.

Clinical outcomes among young patients with Fabry disease who initiated agalsidase beta treatment before 30 years of age: An analysis from the Fabry Registry.

BACKGROUND: Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5-30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi). METHODS: Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database.org. Linear mixed models were conducted to assess changes over ≥2-year follow-up in the estimated glomerular filtration rate (eGFR) stratified by low (LRI) and high (HRI) renal involvement (defined by proteinuria/albuminuria levels), and changes in interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) Z-scores stratified by median age at first treatment. Self-reports ('yes'/'no') of abdominal pain, diarrhea, chronic peripheral pain (denoting neuropathic pain), and acute pain crises at baseline were compared with reports after ≥0.5-year and ≥2.5-year follow-up using McNemar's test. RESULTS: Male (n = 117) and female patients (n = 59) with LRI initiated treatment at a median age of 19.9 and 23.6 years, respectively, and were followed for a median of 6.3 and 5.0 years, respectively. The eGFR slopes were -1.18 (Pfrom 0 <0.001) and -0.92 mL/min/1.73 m2/year (Pfrom 0 = 0.040), respectively. Males with HRI (n = 23, median UPCR 1.0 g/g), who started treatment at a median age of 26.7 years, had an eGFR slope of -2.39 mL/min/1.73 m2/year (Pfrom 0 <0.001; Pdifference = 0.055, as compared with the slope of -1.18 mL/min/1.73 m2/year for LRI males) during a median follow-up of 5.6 years. Echocardiographic variables were stable among males, regardless of age, and among young females (median follow-up >5.5 years and ≥4.5 years, respectively). Older females (treatment initiation at median age 27.5 years) had a slope of LVPWT Z-scores of 0.18/year (n = 12, Pfrom 0 = 0.028), whereas IVST Z-scores remained stable (n = 13, 0.10/year, Pfrom 0 = 0.304) during a median follow-up of ≥3.7 years. These slopes did not significantly differ from slopes of younger females. Reports of chronic peripheral pain and acute pain crises by males, and of diarrhea and acute pain crises by females, significantly reduced after a median follow-up of ≥4.0 years. After a median follow-up of ≥5.4 years, reports of all four symptoms significantly decreased among males, whereas among females only reports of abdominal pain significantly decreased. CONCLUSIONS: During sustained treatment with agalsidase beta in young Fabry patients with a predicted classic phenotype or with unclassified GLA variants with similar characteristics, the decline in eGFR was modest among male and female patients with LRI. The greater decline in eGFR among older, proteinuric (i.e., HRI) males may suggest a benefit of earlier treatment. Overall, echocardiographic variables remained stable, particularly among males and younger females. Significant reductions in symptom reports occurred primarily among males after longer follow-up and were less noticeable among females. These observed trends are suggestive of an overall improvement after treatment in young patients, but warrant larger longitudinal studies.

Clinical parameters, LysoGb3, podocyturia, and kidney biopsy in children with Fabry disease: is a correlation possible?

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase enzyme deficiency. We present clinical, biochemical, and histologic findings in children with classical phenotypic presentation of Fabry disease. METHODS: A retrospective analysis was performed using charts from 14 children with confirmed diagnosis. Clinical parameters were evaluated. Globotriaosylsphingosine -lysoGb3- detection in plasma, podocyturia, and kidney biopsy were carried out in all cases. RESULTS: All patients except one demonstrated at least one symptom of Fabry disease. LysoGb3 levels were above the normal range in all patients. Podocyturia was documented in all patients. Kidney biopsy revealed glomerular, interstitial, vascular, and tubular changes on light microscopy in nearly all patients. Electron microscopy showed podocyte inclusions in all patients. CONCLUSIONS: No difference in symptomatology was discernible between boys and girls. Podocyturia was detectable in children serving as a possible early marker of kidney injury. LysoGb3 was elevated in all cases, emphasizing the importance for diagnosis especially in female patients with normal αGal A activity. A possible association between lysoGb3 and symptom severity and histological involvement in kidney biopsy should be assessed in prospective studies with enough statistical power to determine if lysoGb3 can be used to predict nephropathy in children with Fabry disease.

Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry.

BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death. METHODS: This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death. RESULTS: The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3years and 3.2years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free. CONCLUSIONS: Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies.

Time to treatment benefit for adult patients with Fabry disease receiving agalsidase ß: data from the Fabry Registry.

BACKGROUND: Agalsidase ß is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase ß cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase ß treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase ß. METHODS: The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase ß (average dose 1 mg/kg every 2 weeks) for up to 5 years. RESULTS: The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase ß was initiated. CONCLUSIONS: Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase ß 1 mg/kg every 2 weeks. TRIAL REGISTRATION NUMBER: NCT00196742.

Update on Coronary Involvement in Fabry Disease

Abstract Fabry disease is a multisystemic disorder with consequent morbidity and mortality at an early age in patients of both genders. Although renal failure has been previously described as the cause of death with the highest prevalence, recent studies, based on the analysis of the population recorded in the Fabry Registry, reported that 40% of deaths had a cardiovascular origin. Data from the same registry emphasize the high risk for these patients suffering cardiovascular events—particularly acute myocardial infarction—and to the fact that this risk is higher for those patients who need dialysis. Microvascular dysfunction is a constant in patients with Fabry disease, which affects young patients, independently from other cardiac involvement manifestations—such as left ventricular hypertrophy—and from the patient's gender.

Vertebrobasilar Dolichoectasia in Fabry Disease: The Earliest Marker of Neurovascular Involvement?

Abstract Introduction: Fabry disease (FD) is a lysosomal storage disorder associated with marked cerebrovascular involvement. Conventional magnetic resonance imaging (MRI) shows different abnormalities, like white matter lesions that may already be present at an early stage in the disease. Aim: To present observations from a series of brain MRIs performed among a cohort of patients with FD and the relationship of imaging abnormalities with the presence of cardiovascular risk factors (CVRFs). Methods: A total of 70 patients with FD (43 women) were enrolled. The cardiac, renal, ophthalmic, and peripheral nerve functioning was assessed. The MRI evaluation included assessment for evidence of ischemia, microbleeds, pulvinar sign, Arnold-Chiari type 1 malformation, and vertebrobasilar dolichoectasia (VBD). The presence or absence of CVRFs was examined for all patients. Results: Renal involvement was found in 60%, cardiac compromise in 30%, cornea verticillata in 91.4%, and acroparesthesias in 87.1% of patients. Brain MRI analysis found evidence of cerebral ischemic injury in 25.9% of men and 30.2% of women. Vertebrobasilar dolichoectasia was observed in imaging from 55.5% of men and 34.8% of women. The logistic regression analysis adjusted for cardiovascular risks factors, using ischemia or VBD as a dependent variable, showed no statistically significant results. Discussion: Our results have demonstrated cerebrovascular involvement before the third decade in many patients with FD. This study is further evidence confirming that women are not just carriers of FD and should be followed clinically and evaluated comprehensively to monitor for disease burden and progression. Although silent brain ischemias in MRI should be included as a key feature for the diagnoses of FD, VBD is an earlier and frequent sign.

Morphometric and phytochemical characterization of chaura fruits (Gaultheria pumila): a native Chilean berry with commercial potential

BACKGROUND: For the first time, a morphometric characterization of chaura (Gaultheria pumila) fruits has been conducted between natural populations growing in the Villarrica National Park, Araucania Region, Chile. Chaura is a native Ericaceae from Chile that produces aromatic and tasty fruits which could be of agricultural interest. RESULTS: To influence the decision for a further domestication of G. pumila, both the fruit sizes (indicator of productivity) and the nutritional properties of the fruits have been determined from different subpopulations. Samples were a total of 74 plants and 15 fruits per plant which were randomly harvested following its natural distribution around the Villarrica volcano. Altogether, fresh weight, shape, color, diameter in the pole and the equatorial dimensions were determined as phenotypic traits of the G. pumila fruits. Meanwhile the total soluble solids, anthocyanin and pectin contents were calculated as nutritional traits of the Chaura fruits. Results showed a high phenotypic diversity between the sampled population with three main fruit shapes and three predominant colors. The round shapes were the most abundant, whereas a significant correlation was found among fruit size with weight and color. The highest fresh weight (597.3 mg), pole diameter (7.1 mm) and equatorial diameter (6.5 mm) were estimated in the pink color fruits. CONCLUSIONS: The total amount of anthocyanin was higher in red fruits, while the maximum pectin content was obtained in the round white fruits. Overall results must pave the way for a further domestication and introduction of the Chaura species in the agro-productive system in Chile.

Enfermedad de Fabry: la importancia de la terapia de reemplazo enzimático (TRE): tratar rápida y eficazmente / Fabry Disease: the importance of the, enzyme replacement therapy (TRE): treating quickly and efficiently

La enfermedad de Fabry en un trastorno lisosomal por ausencia o deficiencia de la enzima Alfa galactosidasa A que genera un acúmulo patológico de glicoesfingolípidos principalmente en células endoteliales, musculares lisas de vasos sanguíneos y podocitos entre otras. La terapia de reemplazo enzimático es la única chance de tratamiento específico a la fecha. El creciente conocimiento de los mecanismos fisiopatológicos ha llevado a cambiar el manejo de la enfermedad y por sobretodo el momento de inicio del tratamiento. Actualmente el inicio en edades más tempranas parece ser una forma de evitar y en algunos casos revertir algunos de los signos y síntomas de la enfermedad de Fabry.

Fabry Disease is a lysosomal disorder due to the absence or deficiency of the Alpha galactosidase A enzyme that causes a pathological ac cumulation of glycosphingolipids mainly in the REVISIÓN endothelial cells, vascular smooth muscle cells and podocytes among others. Enzyme replacement therapy is the only option for a specific treatment at present. Increasing knowledge of the physiopathological mechanisms has changed the management of the disease and above all, when treatment should begin. At present, beginning treatment at an early age seems to be a way of preventing and in some cases reverting some of the signs and symptoms of Fabry disease.

[Guidelines for diagnosis, monitoring and treatment of Fabry disease]. / Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry.

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.

Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry / Guidelines for diagnosis, monitoring and treatment of Fabry disease

La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X, ocasionado por el déficit de la enzima alfa galactosidasa A. El conocimiento sobre esta patología, y en particular su manejo médico, ha progresado notablemente en la última década, incluyendo el desarrollo de su tratamiento específico. La presente guía fue desarrollada por profesionales médicos de diversas especialidades involucrados en la atención de pacientes con enfermedad de Fabry. La discusión y análisis de las evidencias científicas disponibles, sumado a la experiencia de cada uno de los participantes, ha permitido desarrollar los conceptos vertidos en esta guía con el objetivo de brindar una herramienta útil para todos los profesionales que asisten a pacientes con enfermedad de Fabry.

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.

Actividad antiviral contra el virus de la fiebre amarilla, cepa vacunal 17D, de extractos de hojas de Taraxacum officinale GH Weber ex Wiggers / Phytochemicaland antiviral activity against yellow fever virus, 17D vaccine strain, of extracts from leaves of Taraxacum officinale GH Weber ex Wiggers

Taraxacum officinale leaves were collected at two and 5 months of growth, for antiviral activity against flavivirus, using the 17D vaccine strain of yellow fever virus as a model. Using spectroscopy technique, a total of twelve (12) compounds were identified in the chloroform (C) and hexane (H) extracts of two and five months (2M and 5M) of recollection., The antiviral activity against the yellow fever 17D virus was evaluated with the plaque assay and the concentrations used (50 - 1,5 ug/mL) were no cytotoxic to Vero cells as determined using the MTT(3-(4,5-Dimetiltiazol-2yl)-2,4-difenilbromuro de tetrazolium) assay. The phytochemical composition of leaves growing for 5 months is different and more complex than leaves growing for 2 months. From the four extracts, only C5M inhibited the viral replication in a dose depend manner, with 100 percent viral inhibition at 50 ug/mL (p=0,0124) and the effective doses 50 (ED50: 10,2 +/- 8,7 ug/mL), meanwhile, ED50 of C2M extract was 93,5 +/- 23,5 ug/mL, thus, the extract C5M is 8 times more effective than extract C2M. The identified compounds in extract C5M were: Psi taraxasteryl acetate, cafeic acid, taraxasteryl acetate, taraxerol, taraxerilo acetate and Psi-taraxasterol. One of these compounds or the combinations of them is responsible for the reported high antiviral activity.

Las hojas de Taraxacum officinale fueron colectadas a dos y cinco meses de crecimiento, para determinar actividad antiviral contraflavivirus, utilizando como modelo el virus de fiebre amarilla cepa vacunal 17D. Se identificaron por métodos espectroscópicos, un total de doce (12) compuestos provenientes de los extractos de hexano (H) y cloroformo (C) a dos y cinco meses (2M y 5M) de recolección La actividad antiviral se determinó mediante un ensayo de placa y las concentraciones de extractos utilizadas (50-1,5 ug/mL) fueron no citotóxica en células Vero, determinadas por el método colorimétrico del MTT (3-(4,5-Dimetiltiazol-2yl)-2,4-difenilbromuro de tetrazolio). La composición fitoquímica de los extractos de 5 meses es distinta y más compleja que la de dos meses de crecimiento. De los cuatro extractos sólo el C5M inhibió la replicación del virus en una manera dosis dependiente, con una inhibición del 100 por ciento a 50 ug/mL (p=0,0124) y una dosis efectiva 50 (DE50) de 10,2 +/- 8,7 ug/mL, mientras que el DE50 del extracto C2M es de 93,5 +/- 23,5 ug/mL, lo que hace al extracto clorofórmico de 5 meses aproximadamente 8 veces más efectivo que el C2M. Los compuestos presentes en el extracto C5M son Psi taraxasterilo, ácido cafeíco, acetato de taraxasterilo, taraxerol, acetato de taraxerilo y Psi-taraxasterol. Uno o más de estos compuestos son responsables de alta actividad antiviral reportada.

Actividad biológica de extractos de tres plantas sobre bacterias patógenas para el humano / Biological activity of extracts from three plants over bacteria pathogenic for human beings

El objetivo de esta investigación fue determinar la actividad biológica de extractos de tres plantas sobre bacterias patógenas para el humano. Se determinó la citotoxicidad de extractos y fracciones de Parinari sprucei, Couepia paraensis y Lantana camara L. y se evaluó su actividad antibacteriana mediante el ensayo colorimétrico del 3-(4,5-dimetiltiazol-2yl)-2,4-difenilbromuro de tetrazolio (MTT), utilizando sólo concentraciones inocuas en todos los ensayos realizados. La CMI se determinó con el ensayo de micro dilución MTT y se evaluó la actividad de los posibles agentes antimicrobianos por el método de difusión en agar de Kirby-Bauer. La CMI de los extractos metanólico de C. paraensis y diclorometano/etanol de P. sprucei sobre Staphylococcus aureus fue 25 µg/mL, mientras que la CMI con el extracto etanólico de P. sprucei fue 50 µg/mL. La CMI de la fracción 19 de L. camara L. sobre Acinetobacter haemolyticus y S. aureus fue 50 µg/mL. Los halos de inhibición obtenidos con los extractos metanólico de C. paraensis, y diclorometano/etanol y etanólico de P. sprucei sobre S. aureus fueron de 8, 9 y 7 mm, respectivamente. Los extractos de la familia Verbenaceae no presentaron actividad antibacteriana, mientras que los de la familia Chrysobalanaceae inhibieron la replicación de bacterias grampositivas.

The citotoxicity of extracts and fractions obtained from three plants was determined, and their antibacterial activity was evaluated through a colorimetric assay with tetrazolium 3-(4,5-dimethilthiazol-2yl)-2,4-diphenilbromide (MTT)), using only innocuous concentrations in all the assays carried out. The MIC was determined by the MTT micro dilution assay, and the activity of the possible antimicrobial agents by the Kirby-Bauer agar diffusion test. The MIC of a methanol extract from Couepia paraensis, and a dichloromethanol/ethanol from Parinari sprucei over S. aureus was 25 µg/mL, while the MIC with the ethanol extract from P. sprucei was 50 µg/mL. The MIC of fraction 19 of Lantana camara L. over A. haemolyticus and S. aureus was 50 µg/mL. The inhibition halos obtained with the C. paraensis methanol extracts, and the P. sprucei over S. aureus dichloromethanol/methanol and ethanol extract, were 8, 9 and 7 mm respectively. The Verbenaceae family extracts did not present any antibacterial activity, while those of the Chrysobalanaceae family inhibited replication of gram positive bacteria.

Analysis of left ventricular mass in untreated men and in men treated with agalsidase-ß: data from the Fabry Registry.

PURPOSE: The aim of this study was to evaluate the progression of left ventricular hypertrophy in untreated men with Fabry disease and to assess the effects of agalsidase-ß (recombinant human α-galactosidase A) on left ventricular hypertrophy. METHODS: Longitudinal Fabry Registry data were analyzed from 115 men treated with agalsidase-ß (1 mg/kg/2 weeks) and 48 untreated men. Measurements included baseline left-ventricular mass and at least one additional left-ventricular mass assessment over ≥ 2 years. Patients were grouped into quartiles, based on left-ventricular mass slopes. Multivariate logistic regression analyses identified factors associated with left ventricular hypertrophy progression. RESULTS: For men in whom treatment was initiated at the age of 18 to <30 years, mean left ventricular mass slope was -3.6 g/year (n = 31) compared with +9.5 g/year in untreated men of that age (n = 15) (P < 0.0001). Untreated men had a 3.4-fold higher risk of having faster increases in left-ventricular mass compared with treated men (odds ratio: 3.43; 95% confidence interval: 1.05-11.22; P = 0.0415). A baseline age of ≥ 40 years was also associated with left--ventricular hypertrophy progression (odds ratio: 5.03; 95% confidence interval: 1.03-24.49; P = 0.0457) compared with men younger than 30 years. CONCLUSION: Agalsidase-ß treatment for ≥2 years may improve or stabilize left-ventricular mass in men with Fabry disease. Further investigations may determine whether early intervention and stabilization of LVM are correlated with clinical outcomes.

Daidzein-estrogen interaction in the rat uterus and its effect on human breast cancer cell growth.

Sex hormone replacement therapy provides several advantages in the quality of life for climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of cancer development in these organs. The lower incidence of mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy isoflavones, including genistein. We have previously shown that genistein induces an estradiol-like hypertrophy of uterine cells, but does not induce cell proliferation, uterine eosinophilia, or endometrial edema. It also inhibits estradiol-induced mitosis in uterine cells and hormone-induced uterine eosinophilia and endometrial edema. Nevertheless, genistein stimulates growth of human breast cancer cells in culture; therefore, it is not an ideal estrogen for use in hormone replacement therapy (HRD). The present study investigated the effect of another soy isoflavone, daidzein (subcutaneous, 0.066 mg/kg body weight), in the same animal model, and its effect on responses induced by subsequent treatment (1 h later) with estradiol-17ß (E(2); subcutaneous, 0.33 mg/kg body weight). In addition, we investigated the effects of daidzein (1 µg/mL) or E(2) on the growth of human breast cancer cells in culture. Results indicate that daidzein stimulates growth of breast cancer cells and potentiates estrogen-induced cell proliferation in the uterus. We suggest caution for the use of daidzein or formulas containing this compound in HRD. Future research strategies should be addressed in the search for new phytoestrogens that selectively inhibit cell proliferation in the uterus and breast.

Couepia paraensis: estudio fitoquímico, ensayos de citotoxicidad y de inhibición de la glucosa-6-fosfatasa / Couepia paraensis: phytochemical study, cytotoxicity assays and inhibition of glucose-6-phosphatase

From the cholroform extract of the aerial parts of Couepia paraensis the triterpenes beta-sitosterol1, betulinic acid acetate 2, and oleanolic acid acetate 3, were isolated. Six triterpenes from the chloroform-methanol, acids: oleanolic 4, pomolic 5, ursolic 6, betulinic 7, 6-beta-hydroxybetulínic 8. Additionally from the methanolic extract three flavonoids were isolated: mricetin 9, quercetin 10 y rutina 11. The chloroform and chloroform-methanol extracts were not citotoxic at concentration of 2,5 and 3,1 ug/ml respectively after 24 hours of incubation. The methanol extract was found to be harmless to a concentration of 50 ug/ml, both at 24 hours (LD50 = 10.77 ug/ml) and 120 hours (LD50 = 28.86 ug/ml) of incubation. Only the methanol extract showed significant inhibition (41 percent) of the activity of G-6-Pase in intact microsomes without affecting the activity of the enzyme in microsomes broken.

Se aislaron e identificaron tres triterpenos: beta-sitosterol 1, acetato del ácido betulínico, 2 y acetato del ácido oleanólico 3 del extracto clorofórmico. Seis triterpenos del extracto cloroformo: metanol (9:1) que fueron identificados como ácidos: oleanólico 4, pomólico 5, ursólico 6, betulínico 7, 6-beta-hidroxibetulínico 8. Mientras que del extracto metanólico se identificaron 3 flavoniodes: miricetina 9, quercetina 10 y rutina 11. Los extractos de cloroformo y cloroformo /metanol resultaron inocuos hasta las concentraciones de 2,5 y 3,1ug/ml respectivamente, después de 24 horas de incubación. El extracto metanólico es inocuo hasta una concentración de 50 ug/ml, tanto a 24 horas (LD50 = 10,77 ug/ml) como a 120 horas (LD50 = 28,86 ug/ml) de incubación. Solamente el extracto metanólico mostró una inhibición significativa (41 por ciento) de la actividad de la G-6-Pasa de microsomas intactos sin afectar la actividad de la enzima en microsomas rotos.

Genistein selectively inhibits estrogen-induced cell proliferation and other responses to hormone stimulation in the prepubertal rat uterus.

Sex hormone replacement therapy helps improve quality of life in climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk for cancer in these organs. The lower incidence of mammary cancer in Asian women than in western women has been attributed to high intake of soy isoflavones, including genistein. Our previous work in the prepubertal rat uterus model showed that genistein (0.5 mg/kg body weight subcutaneously) caused an estradiol-like hypertrophy in myometrial and uterine luminal epithelial cells and an increase in RNA content in luminal epithelium; however, it did not induce cell proliferation, uterine eosinophilia, or endometrial edema. The present study investigated, in the same animal model, the effect of genistein administration (0.5 mg/kg body weight subcutaneously) before treatment with estradiol-17ß (0.33 mg/kg body weight subcutaneously) on uterine responses that were not induced by genistein. Pretreatment with this phytoestrogen completely inhibited estradiol-induced mitoses in uterine luminal epithelium, endometrial stroma, and myometrium and partially inhibited estradiol-induced uterine eosinophilia and endometrial edema. These findings indicate that genistein protects against estrogen-induced cell proliferation in the uterus and suggest that future studies should investigate the possibility of using this agent to decrease the risk for uterine cancer after hormone replacement therapy in climacteric women.

Uso de teorías y modelos en contribuciones de la Revista de Salud Pública de la Universidad Nacional de Colombia, 1999 -2004 / Theories and models used on articles published by the Public Healt Journal of the National University of Colombia, 1999-2004

Objetivo: identificar las características del uso de teorías y modelos en las contribuciones publicadas por la Revista de Salud Pública, del Instituto de Salud Pública de la Universidad Nacional de Colombia. Método: en febrero de 2005 se consultaron los números publicados por la revista entre 1999 y 2004. Un lector entrenado registró variables de interés apoyado en instrumentos y criterios adaptados en estudios previos. Resultados: se leyeron un total de 6 volúmenes, con 21 números editados. Se identificaron 154 contribuciones, 113 en 18 números cuatrimestrales regulares y 41, en tres suplementos. Se comunicaron 66 artículos (43 por ciento), o resúmenes de investigación, 62 ensayos, revisiones o conferencias (40 por ciento) y 26 temas de actualidad y simposios (17 por ciento). Los temas predominantes fueron sistemas y políticas (26 por ciento), epidemiología (21 por ciento) y administración en salud (13 por ciento). En 34 de los 154 textos (22 por ciento) hay referencias a 9 teorías y 39 modelos; 17 de ellos (11 por ciento) usaron estos referentes en profundidad. Conclusiones: el uso de marcos, teóricos y el rigor con el que los autores orientaron temática, metodológicamente y analíticamente sus contribuciones a partir de referentes teóricos es bajo.

Objective: to identify the main features of the theories and theoretical models used in the articles published by the Revista de Salud Pública (Public Health Journal) of the National University of Colombia. Methods: in February 2005 all the numbers published by the journal from 1999 to 2004 were analyzed. A trained reader registered different variables of interest based on instruments and criteria adapted from previous studies. Results: A total amount of six volumes corresponding to 21 numbers of the journal were read, 18 of the periodical publication and 3 special numbers. A total amount of 154 contributions were classified into 66 articles or research summaries (43%), 62 essays, revisions or conferences on specific topics (40%), and 26 on up-to-date subjects or symposia (17%). The main topics were health system and policies (26%), epidemiology (21%) and health management (13%). Although 34 of 154 articles (22%) referred to 9 theories and 39 models as theoretical frameworks, only 17 (11%) involve a deep usage of them according to the criteria adopted. Conclusions: the articles published in the journal revealed a limited use of theories and models and a lack of rigor in the way the authors structured them from the point of view of subject, methodology and analysis.

Ecografía renal en 25 pacientes con enfermedad de Fabry: incidencia de patología quística renal / Renal echography in 25 Fabry disease patients: cystic renal pathology incidence

La enfermedad de Fabry (EF) es una enfermedad por depósito lisosomal, con herencia ligada al X, causada por ladeficiencia de la enzima α-galactosidasa A, lo que lleva al acúmulo de glicoesfingolípidos en diferentes célulasdel organismo. La muerte de estos pacientes se da en el contexto de insuficiencia renal, cardiaca y cerebrovascular. Otros reportes demuestran que los pacientes con EFtienen una incidencia mayor de quistes renales que la población normal.Objetivo: evaluar en un grupo de 25 pacientes con EF los hallazgos ecográficos renales. Materiales y métodos: se evaluaron 25 pacientes (16 hemicigotas), 16-50 años, con diagnóstico confirmado por test bioquímicos y genéticos, sin insuficiencia renal. Resultados: los diámetros renales fueron normales, el24% del total de los evaluados presentaron quistes renales, con un total del grupo de los hemicigotas del 24% ydel total de las heterocigotas el 22,2% afectados. Conclusión: si bien el grupo de pacientes evaluados fue pequeño, hemos encontrado una incidencia mayor a la población normal, pero menor a los valores reportados por otros autores.

glycosphingolipid catabolism caused by the deficient activity of α-galactosidase A, that results in the progressiveaccumulation of globotriaosylceramide in different cells of organism. Patiens frequently die for renal or cardiacinsufficiency. Aim: to assess 25 patients (16 hemicygotes) with confirmdiagnosis of Fabry disease without renal insufficiency. Results: renal diameter were normal, 24% ot total patientsshowed cystic abnormalities.Conclusion: although our group was small, but we found a high incidence of cystic abnormalities compared withnormal population and smaller than other reports.

Base teórica en tesis de maestría del Instituto de Salud Pública de la Universidad Nacional de Colombia, 2000-2005 / Theoretical base in masters thesis from Institute of Public Health of National University of Colombia, 2000-2005

Objetivo: explorar el uso de teorías y modelos en reportes de investigación de los posgrado del Instituto de Salud Pública (ISP) de la Universidad Nacional de Colombia (UN). Métodos: en junio de 2005, según criterios predefinidos, los trabajos finales de formación en las maestrías en salud pública o en infecciones y salud del trópico del instituto, terminados de enero de 2000 a mayo de 2005, fueron revisados por un lector entrenado en rastrear dicho uso. Resultados: se identificaron y leyeron 50 reportes, 34 en salud pública y 16 en infecciones-salud del trópico, que dedicaron 22 páginas en promedio a plantear un referente teórico. Solo cinco trabajos (10% del material), cuatro de salud pública y uno de infecciones-salud del trópico, usaron la base teórica propuesta según criterios deseables. Conclusiones: el uso de la base teórica para orientar temática, metodológica y analíticamente las investigaciones de posgrado del ISPun, terminadas entre 2000 y 2005, es bajo.

Objective: to explore theories and theoretical models used in theses in master degrees at Public Health Institute, National University of Colombia. Methods: in June 2005 the central library of National University was visited for a trained reader to review theses on public health or infections-tropical health finished from January 2000 to May 2005. Results: fifty theses, 34 on public health and 16 on infections-tropical health were evaluated, which included an average of 22 pages of theoretical framework. Only 5 (10%) theses, 4 in public health and 1 in tropical health, used theoretical basis according to the criteria previously established. Conclusions: application of theoretical basis to direct the theme, methodology and analysis of reviewed degree theses, finished between 2000 and 2005 is lower than expected.