Recent advances in the development of methyltransferase (MTase) inhibitors against (re)emerging arboviruses diseases dengue and Zika.

Emerging and/or re-emerging viral diseases such as dengue and Zika are a worldwide concern. Therefore, new antiviral therapeutics are necessary. In this sense, a non-structural protein with methyltransferase (MTase) activity is an attractive drug target because it plays a crucial role in dengue and Zika virus replication. Different drug strategies such as virtual screening, molecular docking, and molecular dynamics have identified new inhibitors that bind on the MTase active site. Therefore, in this review, we analyze MTase inhibitors, including S-adenosyl-L-methionine (SAM), S-adenosyl-l-homocysteine (SAH) and guanosine-5'-triphosphate (GTP) analogs, nitrogen-containing heterocycles (pyrimidine, adenosine, and pyridine), urea derivatives, and natural products. Advances in the design of MTase inhibitors could lead to the optimization of a possible single or broad-spectrum antiviral drug against dengue and Zika virus.

Weight loss before bariatric surgery and its impact on poor versus excellent outcomes at 2 years.

PURPOSE: To identify preoperative factors that influence the outcomes of gastric bypass surgery, in terms of excess weight loss at 24 months. METHODS: This retrospective study included two groups of patients who underwent laparoscopic gastric bypass surgery. Group A (poor outcomes) had ≤ 50%EWL or BMI ≥ 30 kg/m2; group B (excellent outcomes) had ≥ 80%EWL at 24 months. A comparative analysis of demography, anthropometry, comorbidities, and metabolic status was performed. A linear regression model was used to evaluate %EWL association; the number of preoperative and postoperative consultations were also compared. RESULTS: A total of 202 patients completed follow-up; 71 (35.1%) and 78 (38%) had poor and excellent outcomes (%EWL 44.1 ± 9.4% vs. 92 ± 10.9%), respectively. Mean age was 40.4 ± 8.9 years. Patients with poor outcomes had higher weight and BMI, lesser preoperative %EWL, higher dyslipidemia and diabetes rates with longer periods of evolution, and increased HbA1c% levels. In the linear regression analysis, preoperative %EWL and initial and preoperative BMI were statistically significant determinants of %EWL at 24 months Diabetes remission was 46.2% (group A) vs. 66.6% (group B). Group A had higher non-attendance rates after surgery. CONCLUSION: The factors independently associated with greater %EWL at 24 months between groups were higher preoperative %EWL, and lower initial and preoperative BMI.

Metabolic Surgery and Class 1 Obesity (< 35 kg/m2): a Prospective Study with Short-, Mid-, and Long-term Results Among Latinos.

INTRODUCTION: Metabolic surgery for managing class 1 obesity and type 2 diabetes mellitus has recently gained popularity. The Latino population presents high rates of these diseases. Reports on surgical outcomes in this population are scarce. METHODS: Prospective study with Mexican patients diagnosed with diabetes and class 1 obesity submitted to Roux-en-Y gastric bypass. The objective was to determine short-, mid-, and long-term outcomes (weight loss, metabolic, morbidity, and diabetes remission). Sub-analysis was included, based on preoperative usage of one (group A) or more (group B) oral hypoglycemic agents ± insulin. RESULTS: Fifty-one patients with a mean body mass index of 33.1 ± 1.9 kg/m2, and glycated hemoglobin 7.2 ± 1.7% were included. Significant improvements were observed in almost every parameter. At 24, 36, and 60 months, complete diabetes remission was achieved in 73.8%, 52.2%, and 50% of patients with glycated hemoglobin levels of 5.7% ± 0.8%, 5.8% ± 0.5%, and 6.1% ± 0.8%, respectively. At 24, 36, and 60 months, patients in group A (N=28) showed 90.9%, 69.2%, and 75% remission, respectively, versus patients in group B (N=23), who had remission rates of 50%, 30%, and 25% during the same period. Diabetes relapse was higher in patients using ≥ 2 oral hypoglycemic agents ± insulin before surgery. CONCLUSION: Gastric bypass is a safe and effective metabolic surgery that results in excellent mid- and long-term results among Mexicans. Patients using one drug preoperatively showed improved results and remission rates, which underscores the importance of intervening in the early stages of the disease. TRIAL REGISTRATION: Clinical Trials identifier: NCT04595396 ( www.ClinicalTrials.gov ).

Recent Advances in the Development of Broad-Spectrum Antiprotozoal Agents.

Infections caused by Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., Entamoeba histolytica, Giardia lamblia, Plasmodium spp., and Trichomonas vaginalis, are part of a large list of human parasitic diseases. Together, they cause more than 500 million infections per year. These protozoa parasites affect both low- and high-income countries and their pharmacological treatments are limited. Therefore, new and more effective drugs in preclinical development could improve overall therapy for parasitic infections even when their mechanisms of action are unknown. In this review, a number of heterocyclic compounds (diamidine, guanidine, quinoline, benzimidazole, thiazole, diazanaphthalene, and their derivatives) reported as antiprotozoal agents are discussed as options for developing new pharmacological treatments for parasitic diseases.

Type 2 Diabetes Mellitus Remission Models Following Laparoscopic Gastric Bypass: a 4-Model Analysis in a Latino Population.

BACKGROUND: Bariatric surgery is indicated for major weight loss and for the control of associated comorbidities, particularly type 2 diabetes. Remission prediction scores have been proposed for this end, such as: DiaRem, Ad-DiaRem, ABCD, and DiaBetter. Nevertheless, they have not been evaluated all together in a specific population. METHODS: Retrospective study with Mexican patients submitted to gastric bypass with at least 12 months follow-up. All patients had BMI > 30 kg/m2 and type 2 diabetes. The primary objective was to evaluate the remission prediction performance of scores. A baseline analysis (anthropometric, biochemical, and metabolic) and remission rates were obtained. Remission scores and cut-off values were assigned based on original descriptions. A ROC analysis was performed for sensibility and specificity. RESULTS: A total of 95 patients were included. Mean age 44 years, 85.6% female with mean BMI of 44.1 kg/m2, and mean HbA1C of 7.2%. At 12 months, complete remission was obtained in 76.8%. ROC curves were plotted showing that DiaRem had 75.3% sensitivity and 68.2% specificity (AUC 0.723 p = 0.001), Ad-DiaRem had 84.9% and 50% (AUC 0.702 p = 0.002), ABCD had 57.5% and 77.3% (AUC 0.0.690 p = 0.002), and DiaBetter had 72.6% and 77.3% (AUC 0.748 p < 0.001). CONCLUSION: In Mexican patients with obesity and type 2 Diabetes, submitted to gastric bypass, remission prediction could be assessed with any current model showing satisfactory sensibility and specificity. Among such models, DiaBetter obtained the best statistical performance in our population. Type 2 diabetes remission rate at 1 year is similar to any other race or ethnicity.

Old Antiprotozoal Drugs: Are They Still Viable Options for Parasitic Infections or New Options for Other Diseases?

Parasitic diseases, caused by helminths (ascariasis, hookworm, trichinosis, and schistosomiasis) and protozoa (chagas, leishmaniasis, and amebiasis), are considered a serious public health problem in developing countries. Additionally, there is a limited arsenal of anti-parasitic drugs in the current pipeline and growing drug resistance. Therefore, there is a clear need for the discovery and development of new compounds that can compete and replace these drugs that have been controlling parasitic infections over the last decades. However, this approach is highly resource- intensive, expensive and time-consuming. Accordingly, a drug repositioning strategy of the existing drugs or drug-like molecules with known pharmacokinetics and safety profiles is alternatively being used as a fast approach towards the identification of new treatments. The artemisinins, mefloquine, tribendimidine, oxantel pamoate and doxycycline for the treatment of helminths, and posaconazole and hydroxymethylnitrofurazone for the treatment of protozoa are promising candidates. Therefore, traditional antiprotozoal drugs, which were developed in some cases decades ago, are a valid solution. Herein, we review the current status of traditional anti-helminthic and antiprotozoal drugs in terms of drug targets, mode of action, doses, adverse effects, and parasite resistance to define their suitability for repurposing strategies. Current antiparasitic drugs are not only still viable for the treatment of helminth and protozoan infections but are also important candidates for new pharmacological treatments.

Comparative efficacy of bone anabolic therapies in women with postmenopausal osteoporosis: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis. METHODS: Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome. RESULTS: Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments. CONCLUSIONS: Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.

Development and Validation of a Copro-Enzyme-Linked Immunosorbent Assay Sandwich for Detection of Echinococcus granulosus-Soluble Membrane Antigens in Dogs.

Cystic echinococcosis (CE) is a parasitic zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus. Detection of the adult stage in the canine definitive host is essential for estimating infection rates, surveillance and monitoring of CE control programs. This study sought to develop and validate a coproantigen sandwich enzyme-linked immunosorbent assay (copro-ELISA), based on antibodies against E. granulosus-soluble membrane antigens (EGMA), that is capable of distinguishing infected and noninfected dogs. Anti-E. granulosus polyclonal immunoglobulin G antibodies were obtained from rabbit antiserum against EGMA. Optimization of the test was performed with 51 positive and 56 negative stool samples of canine echinococcosis. Specificity, sensitivity, cross-reactivity, intra- and inter-assay precision, and over time detection were evaluated. According to the receiver operating characteristic analysis, the diagnostic sensitivity and specificity were 96.1% (CI: 85.9-99.6) and 98.2% (CI: 89.5-100), respectively. Negative and positive predictive values were 96.5% (CI: 91.7-100) and 98% (CI: 94.1-100), respectively. No cross-reactivity with Taenia hydatigena, Dipylidium caninum, or Toxocara canis was observed. Intra- and inter-assay repeatability showed values of less than 15% of the variation coefficient. The over time detection was from 20 to 27 days postinfection with E. granulosus. The copro-ELISA based on EGMA detection offers a simplified in-house development of diagnostic testing. This assay showed high specificity and sensitivity and had no cross-reactivity with other parasites. Further studies and development of this test in a kit format may be useful for the detection of active infection in dogs living in CE endemic regions.

Displacements Study of an Earth Fill Dam Based on High Precision Geodetic Monitoring and Numerical Modeling.

The aim of this paper is to study the behavior of an earth fill dam, analyzing the deformations determined by high precision geodetic techniques and those obtained by the Finite Element Method (FEM). A large number of control points were established around the area of the dam, and the measurements of their displacements took place during several periods. In this study, high-precision leveling and GNSS (Global Navigation Satellite System) techniques were used to monitor vertical and horizontal displacements respectively. Seven surveys were carried out: February and July 2008, March and July 2013, August 2014, September 2015 and September 2016. Deformations were predicted, taking into account the general characteristics of an earth fill dam. A comparative evaluation of the results derived from predicted (FEM) and observed deformations shows the differences on average being 20 cm for vertical displacements, and 6 cm for horizontal displacements at the crest. These differences are probably due to the simplifications assumed during the FEM modeling process: critical sections are considered homogeneous along their longitude, and the properties of the materials were established according to the general characteristics of an earth fill dam. These characteristics were taken from the normative and similar studies in the country. This could also be due to the geodetic control points being anchored in the superficial layer of the slope when the construction of the dam was finished.

Benzoic Acid Derivatives with Trypanocidal Activity: Enzymatic Analysis and Molecular Docking Studies toward Trans-Sialidase.

Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was <0.15 µM on the NINOA strain, and LC50 < 0.22 µM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).

Dissipation kinetics of organophosphorus pesticides in milled toasted maize and wheat flour (gofio) during storage.

The dissipation/degradation of the pesticides dimethoate, terbufos, disulfoton, and pirimiphos-methyl were evaluated in milled toasted maize and wheat flour (gofio) during three months of storage. Their dissipation kinetics and residual levels were determined, as well as their possible decomposition into some of their main transformation products (disulfoton sulfoxide, terbufos sulfone and disulfoton sulfone). For this purpose, pesticide-free milled toasted maize and wheat samples were spiked with the pesticides, and they were then stored in the darkness at ambient temperature in a closed container to simulate current storage conditions of such packed food. A multiresidue analysis based on the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method was performed for the simultaneous determination of these pesticides and their metabolites. After three months of storage, the dissipation of residues ranged between 34% (pirimiphos-methyl) and 86% (disulfoton) for maize gofio and between 69% (terbufos) and 92% (disulfoton and pirimiphos-methyl) for wheat gofio. The results demonstrated that the degradation was slower in gofio than in wheat gofio and that none of the selected metabolites were detected in any of the samples. Dissipation curves of all studied pesticides fitted to a first-order decay curve in both types of cereals.

Recent developments in trans-sialidase inhibitors of Trypanosoma cruzi.

Chagas is a lethal chronic disease that currently affects 8-10 million people worldwide, primarily in South and Central America. Trypanosoma cruzi trans-sialidase is an enzyme that is of vital importance for the survival of the parasite due to its key role in the transfer of sialic acid from the host to the parasite surface and it also helps the parasite combat the host's immune system. This enzyme has no equivalent human enzyme; thus, it has become an interesting target for the development of inhibitors that combat the parasite. In this review, we summarize three classes of inhibitors (acceptor, donor and unrelated) with their inhibition values and their mode of action against this enzyme. Based on molecular docking, molecular dynamics and structure-activity relationship studies, it has been discovered that the molecules with -NH2, -OH and -COOH groups on an aromatic ring could be used as a scaffold for the development of new and potent trans-sialidase inhibitors due to their key interaction with active enzyme sites. In particular, carboxylic acid derivatives have importance over the sugar moiety due to their ease of synthesis and unique structure-activity relationship.

[Multicenter international registry to evaluate the clinical practice delivered to patients with type 2 diabetes mellitus: a sub-analysis of the experience in Mexico]. / Registro multicéntrico internacional para evaluar la práctica clínica en pacientes con diabetes mellitus tipo 2: subanálisis de la experiencia en México.

BACKGROUND: There is a lack of information on the characteristics of the medical attention delivered to Mexican patients with type 2 diabetes (T2D). Our aim was to describe the current state on the medical management of T2D in Mexico. METHODS: Among 17,232 patients included in the International Diabetes Management Practices Study (IDMPS), 2,620 (15%) corresponded to Mexico. Information regarding clinical, demographics and management characteristics, as well as the impact of T2D in the patient is clinical and social condition was registered. The metabolic control and achievement of therapeutic goals were also analyzed. RESULTS: Diagnosis of T2D was performed by the general practitioner in 76% of cases. Only about a quarter of the cohort had a blood pressure goal of < 130/80 mmHg, although 97% had anti-hypertensive treatment. Management of T2D was with diet and exercise exclusively in 5%, with oral glucose-lowering drugs (OGLD) in 66% (alone or combined), with OGLD and insulin in 18%, and with insulin alone in 11%. Only 31% of patients reached the goal of HbA1c < 7. Self-monitoring was practiced in 50% of patients and 26% received education on diabetes. The managing physician is personal impression about the quality of the metabolic control was not in accordance with HbA1c. Eight percent of patients had work absences in the last 3 months due to complications of T2D (mean of 15 days lost). CONCLUSIONS: In Mexico, quality of metabolic control of T2D patients could have important deficiencies. The personal impression of the physician on the patient is metabolic control is not consistent with objective data.

1H and 13C spectral assignment of 4-aryl-1,4,5,6,7,8-hexahydro-2,7,7,5-oxo-quinolines 3-substituted derivatives.

The 1H and 13C NMR spectroscopic data for 4-aryl-1,4,5,6,7,8-hexahydro-2,7,7,5-oxo-quinoline 3-substituted derivatives have been fully assigned by the combination of one- and two dimensional experiments (DEPT, HMBC, HMQC, COSY, NOE).

Indicadores bacterianos como herramientas para medir la calidad ambiental del agua costera / Bacterial markers as tools for coastal water environmental quality measurement

Los grupos bacterianos tales como heterótrofas totales, sulfato-reductoras y nitrato-reductoras son organismos claves en la transformación y reciclaje de nutrientes en los ambientes acuáticos, mientras que los coliformes y enterococos están asociados a la contaminación por aguas servidas. Estos dos últimos grupos son considerados bioindicadores de la calidad del agua de mar en cuanto a contenidos en materia fecal, materia orgánica y nutrientes minerales. La finalidad del presente trabajo es identificar cuáles indicadores bacterianos son los más adecuados para medir la calidad del agua y la salud ambiental, desde el punto de vista microbiológico, en dos playas del litoral caribeño venezolano. Se observó que los coliformes fecales y los enterococos son los indicadores más apropiados para determinar la presencia de contaminación de origen fecal en el cuerpo de agua. Así mismo, la detección y enumeración de los coliformes fecales en el tejido de Tivela mactroides, es un buen indicador del riesgo asociado al consumo de productos marinos crudos o poco cocinados. La enumeración de los indicadores bacterianos en los ecosistemas marinos tiene relevancia porque permite estimar su calidad bacteriológica y el potencial riesgo para la salud pública por el uso de las aguas, con fines turísticos o de extracción de los productos del mar. Se debe promover el cumplimiento de las regulaciones vigentes, y fomentar la construcción de plantas de tratamiento para las aguas servidas. Ello revertirá en la mejora de la calidad del agua y en el mejor aprovechamiento de los recursos marinos

Análisis del tratamiento quirúrgico del síndrome de Cushing en el hospital de especialidades del Centro Médico Nacional de Occidente / Analysis of surgical treatment of Cushing's syndrome in the Hospital of Medical Center of Especialities of Occident

Se revisa la experiencia del tratamiento quirúrgico del síndrome de Cushing en un periódo de 15 años en un hospital de concentración. Se incluyen 22 casos, 19 de ellos femeninos y 3 masculinos, con edades entre 17 y 49 años. Todos presentaban síndrome de Cushing. El diagnóstico se confirmó en base a determinaciones basales y funcionales anormales de cortisol, 17-hidroxicorticoesteroides y ACTH. Los estudios radiológicos de mayor utilidad fueron TAC y retroneumoperitoneo. Los diagnósticos histopatológicos indicaron 3 casos de hiperplasia simple, 2 de hiperplasia macronodular y 1 de micronodular, 10 casos de adenomas y 6 de carcinomas. De estos últimos, 4 fueron resecables. Se efectuaron 10 suprarrenalectomías bilaterales y 14 unilaterales; 21 fueron por abordaje quirúrgico anterior. No hubo mortalidad quirúrgica. La morbilidad operatoria fue del 18 por ciento. Hubo remisión total del síndrome de Cushing en 13 casos; en 2 casos de hiperplasia manejados con suprarrenalectomía bilateral, se desarrolló síndrome de Nelson. Además 11 pacientes requirieron terapia sustitutiva. De los casos con carcinoma, 5 pacientes recibieron quimioterapia con o'p'DDD por recidiva o progresión; todos fallecieron por enfermedad diseminada antes de 5 años

Biopsia endomiocárdica: resultados en los primeros 370 examenes / Endomyocardial biopsy: results in the firts 370 examination

Se presenta la experiencia obtenida en 370 biopsias del corazón realizada por el método transvascular percutáneo: 304 fueron hechas 52 receptores de un trasplante cardíaco con objeto de detectar rechazo del injerto, y las restantes en 62 con cardiopatía de origen desconocido. En 364 estudios las muestras se tomaron en el ventrículo derecho (VD) y las restantes en el izquierdo (VI). Para la biopsia del VD el bioptomo se introdujo a través de la vena femoral 360 veces y en las demás de pasó por la vena yugular interna. Para los estudios del VI el instrumento se colocó a través de uan arteria femoral. Se obtuvieron fragmentos adecuados par el examen histológico en el 98 % de los intentos y en total sólo se presentaron 8 complicaciones (2,2 %). La más importante fue el derrame pericárdico que se observó en 3 ocasiones. No hubo muerte ni necesidad de operar ningún caso a consecuencias de la biopsia. Tampoco se observó sepsis a pesar de que en los trasplantes se realizaron bajo tratamiento inmunosupresor. En el grupo de receptores el promedio de biopsias fue de 5,8 por paciente y en 17 el examen se repitió 10 veces o más. El intervalo promedio entre las biopsias fue notablemente mayor que el que emplean otros grupos de trasplantes. No obstante, ello no influyó negativamente sobre la mortalidad por rechazo del injerto. Cuando la biopsia se efectuó para precisar el diagnóstico el estudio fue útil en 48,5 % de los casos. Los autores consideran que la biopsia endomiocárdica constituye un medio de diagnóstico útil, seguro y que se puede repetir según las necesidades

Estudio comparativo entre el atenolol y el metoprolol en el tratamiento de la angina de esfuerzo estable / Coparative study between atenolol and metoprolol in the treatment of angina of stable effort

Se hizo un estudio comparativo entre el atenolol y el metoprolol en un grupo de 20 pacientes con angina de pecho estable, a una dosis diaria inicial de 100 mg, la cual fue titulada individualmente hasta alcanzar una frecuencia cardíaca cercana a 60 latidos por minuto. Los pacientes anginosos fueron seleccionados al azar y recibieron tratamiento con atenolol o metoprolol durante cuatro semanas, se cuantificaro el número de crisis anginosas y el consumo de nitroglicerina; al final de este período se realizó prueba ergométrica a las tres o cuatro horas de la ingestión del medicamento. Después recibieron placebo por espacio de dos semanas y se les continuó por otras cuatro con el fármaco restante. El número de crisis anginosas se redujo con el atenolol (p < 0,01) y el consumo de nitroglicerina disminuyó con respecto al placebo y al metropolol, el cual no modificó estas variables al compararlo con el placebo. El tiempo total de ejercicio aumentó significativamente y el infradesnivel del segmento R-ST en el mismo estadio que le máximo de la prueba basal y en la recuperación disminuyeron (p < 0,01) bajo los efectos de los beta bloqueadores. No existieron diferencias en las acciones de los medicamentos entre sí en las variables de la PE

Estudio comparativo entre el atenolol y el metoprolol en el tratamiento de la angina de esfuerzo estable / Comparative study between atenolol and metoprolol in the treatment of angina of stable effort

Se hizo un estudio comparativo entre el atenolol y el metoprolol en un grupo de 20 pacientes con angina de pecho estable, a una dosis diaria inicial de 100 mg, la cual fue titulada individualmente hasta alcanzar una frecuencia cardíaca cercana a 60 latidos por minuto. Los pacientes anginosos fueron seleccionados al azar y recibieron tratamiento con atenolol o metoprolol durante cuatro semanas, se cuantificaro el número de crisis anginosas y el consumo de nitroglicerina; al final de este período se realizó prueba ergométrica a las tres o cuatro horas de la ingestión del medicamento. Después recibieron placebo por espacio de dos semanas y se les continuó por otras cuatro con el fármaco restante. El número de crisis anginosas se redujo con el atenolol (p < 0,01) y el consumo de nitroglicerina disminuyó con respecto al placebo y al metropolol, el cual no modificó estas variables al compararlo con el placebo. El tiempo total de ejercicio aumentó significativamente y el infradesnivel del segmento R-ST en el mismo estadio que le máximo de la prueba basal y en la recuperación disminuyeron (p < 0,01) bajo los efectos de los beta bloqueadores. No existieron diferencias en las acciones de los medicamentos entre sí en las variables de la PE