Fast Skeletal Muscle Troponin and Tropomyosin as a Dietary Source of Antidiabetic and Antihypertensive Bioactive Peptides: An In Silico Study / Troponina y Tropomiosina de Músculo Esquelético como Fuente Alimentaria de Péptidos Bioactivos Antidiabéticos y Antihipertensivos: Estudio In Silico

Background: The nutraceutical properties of food hydrolysates rely on multiple biochemical interactions involving the modulation of enzymes and cellular receptors. Numerous bioactive peptides released from troponin and tropomyosin digestion have been identified. Their characterization has mostly been performed by hydrolysis catalyzed by proteases unrelated to the human digestive system. Objective: This study aimed to determine the bioactive profile of beef, pork, and chicken meat by analyzing the frequency and pharmacokinetics of biopeptides released from troponin and tropomyosin. Methods:In silico digestion and biopeptide release frequency were studied by three parameters; bioactive fragments release frequency (AE), frequency percentage (W), and mean occurrence (AS), all stated on the BIOPEP-UWM platform. Further on, hydrolysis end-products were screened based on gastrointestinal-absorption probability and pharmacokinetic profiling performed on SwissADME, SwissTargetPrediction, and ADME/Tlab bioinformatics web tools. Statistical analyses were performed using a one-way ANOVA test. Results: Dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibiting biopeptides exhibited the highest release frequency. Moreover, W and ASparameters showed no significant difference (p>0.05) between the myofibrillar isoforms assessed. Seven biopeptides were classified as highly absorbable and reported optimal drug-likeness compliance. Although biopeptides hold good pharmacokinetic properties, the therapeutic potency of biopeptides showed to be lower than those of DPP-IV and ACE-inhibiting drugs. Conclusions: Troponin and tropomyosin are rich dietary sources of bioactive peptides, mainly DPP-IV and ACE inhibitors. Digestion end-products are mainly dipeptides with optimal pharmacokinetic and drug-like properties, suggesting a potential therapeutic application in hypertensive and hyperglycemic disorders

Antecedentes: Las propiedades nutracéuticas de los hidrolizados de alimentos dependen de múltiples interacciones bioquímicos que involucran la modulación de enzimas y receptores celulares. Se han identificado numerosos péptidos bioactivos liberados de la digestión de troponina y tropomiosina, pero su caracterización se ha llevado a cabo principalmente por hidrólisis catalizada por proteasas ajenas al sistema digestivo humano. Objetivo: Este estudio tuvo como objetivo determinar el perfil bioactivo de la carne de res, cerdo y pollo mediante el análisis de la frecuencia y farmacocinética de los biopéptidos liberados de la troponina y la tropomiosina. Métodos: Se estudió la digestión in silico y la frecuencia de liberación de biopéptidos mediante dos parámetros; frecuencia de liberación de fragmentos bioactivos (AE), frecuencia porcentual (W) y ocurrencia media (AS), ambos indicados en la plataforma BIOPEP-UWM. Más adelante, los productos finales de la hidrólisis se examinaron en función de la probabilidad de absorción gastrointestinal y el perfil farmacocinético realizado en las herramientas bioinformáticas SwissADME, SwissTargetPrediction y ADME/Tlab. El análisis estadístico se llevó a cabo mediante una prueba ANOVA de una vía. Resultados: Los biopéptidos inhibidores de la dipeptidil peptidasa IV (DPP-IV) y la enzima convertidora de angiotensina (ECA) exhibieron la mayor frecuencia de liberación. Además, los parámetros W y ASno mostraron diferencias significativas (p> 0.05) entre las isoformas miofibrilares evaluadas. Siete biopéptidos se clasificaron como altamente absorbibles e informaron un cumplimiento óptimo de similitud con el fármaco. Aunque los biopéptidos tienen propiedades farmacocinéticas adecuadas, su potencia terapéutica demostró ser menor que la de los fármacos inhibidores de la DPP-IV y la ACE. Conclusiones: La troponina y la tropomiosina son una fuente dietética rica en péptidos bioactivos, principalmente DPP-IV e inhibidores de la ACE. Los productos finales de la digestión son principalmente dipéptidos con propiedades farmacocinéticas óptimas y similares a la de los fármacos, lo que sugiere una aplicación terapéutica factible en trastornos hipertensivos e hiperglicémicos

La dipeptidil peptidasa 4 y su función frente a la COVID-19 / Dipeptidyl peptidase 4 and its function against COVID-19

Ante la aparición de un nuevo virus en la ciudad de Wuhan-China, llamado SARS-CoV-2, causante del conocido síndrome agudo respiratorio severo (COVID-19), muchos de científicos tratan de hallar una solución contra el virus que ha ocasionado una pandemia. En esta búsqueda, se encontró a una glicoproteína de transmembrana llamada dipeptidil peptidasa 4 o DPP-4 presente en la superficie de diferentes tipos de células y diana en la infección por el MERS-Co-V que abre una esperanza al sospechar que la DPP-4 puede ser un blanco en diferentes coronavirus al servir como estrategia terapéutica. A ello se suman resultados que encuentran la DPP-4 elevada en pacientes con complicaciones graves ante COVID-19, lo que puede ser un posible marcador de gravedad. Sin embargo, aún existe poco énfasis en la identificación y asociación de esta glicoproteína a la COVID-19. Para ello, se realizó una revisión bibliográfica sobre los aspectos más significativos de la Dipeptidil Peptidasa 4 y su función frente a la COVID-19(AU)

Given the appearance of a new virus in the of Wuhan city, China, called SARS-CoV-2, which causes the well-known severe acute respiratory syndrome (COVID-19), many scientists are trying to find a solution against the virus that has caused a pandemic. In this search, a transmembrane glycoprotein called dipeptidyl peptidase 4 or DPP-4 was found present on the surface of different types of cells and a target in MERS-Co-V infection, which opens hope by suspecting that DPP- 4 can be a target in different coronaviruses by serving as a therapeutic strategy. Added to this, there are results that find elevated DPP-4 in patients with severe complications from COVID-19, which may be a possible marker of severity. However, there is still little emphasis on the identification and association of this glycoprotein with COVID-19. To this effect, a bibliographic review was carried out on the most significant aspects of Dipeptidyl Peptidase 4 and its function against COVID-19(AU)

Prescription of DPP4 inhibitors: Indication and effect on glycosylated hemoglobin in a primary care institution of Colombia / Prescripción de inhibidores de la DPP-4: indicación y efecto sobre la hemoglobina glicosilada en un primer nivel de Colombia

Abstract Introduction and objective: In Colombia, Dipeptidyl-Peptidase IV (DPP4) inhibitors are recommended as second-best choice for type 2 diabetes mellitus treatment. However, no evaluation of the accomplishment or impact of this recommendation was performed. The objective was to determine the prescription of the DPP4 inhibitor according to the Colombian Clinicial Practice Guide regarding type 2 diabetes mellitus treatment, and its effects on glycosylated hemoglobin (HbAlc). Materials and methods: A descriptive study that included patients with type 2 diabetes mellitus who attended a first level between 2016 and 2018, had a prescription for DPP4 inhibitor and at least two control appointments. Variables included were sociodemographic, clinics, treatment and comorbidities. The unadjusted prescription was defined as the lack of accomplishment of Colombian guidelines. Descriptive statistics and X2 test were used for the comparison of categorical variables. A binary logistic regression model was applied. Results: 112 out of 207 patients accomplished inclusion criteria, of which 77 were women (68.8%). Also, 68.8% of the patients had an unadjusted prescription of the iDPP4. There was a 0.21% total reduction in HbA1c levels, with a mean of 198.2 ± 124 days between the first and second control measurement (reduction of 0.55% when the prescription was adjusted to the guidelines and 0.05% if it was unadjusted). Conclusion: There is a limited impact of DPP4 inhibitors regarding the reduction of HbA1c and metabolic control, and there is a slight follow-up to the Colombian guidelines in patients who attend a first level.

Resumen Introducción y Objetivo: En Colombia se recomiendan los inhibidores de la Dipeptidil Peptidasa-IV (iDPP4) como segunda opción para el manejo de la diabetes mellitus tipo 2. No se ha evaluado el cumplimiento e impacto de esta recomendación. Como objetivo se buscó determinar la prescripción de los iDPP4 según las recomendaciones de la Guía de Práctica Clínica colombiana, y su efecto sobre la hemoglobina glicosilada (HbA1c). Materiales y métodos: Estudio descriptivo que incluyó pacientes con diabetes mellitus tipo 2 que consultaron a un primer nivel entre 2016 y 2018, y tenían formulado un iDPP4, con al menos dos consultas de seguimiento. Se incluyeron variables sociodemográficas, clínicas, tratamiento y comorbilidades. La prescripción no ajustada se definió como la falta de cumplimento de la recomendación de la guía colombiana. Se empleó estadística descriptiva y pruebas X2 para la comparación de variables categóricas. Se aplicó un modelo de regresión logística binaria. Resultados: Hubo 207 pacientes de los cuales 112 cumplieron criterios de inclusión, 77 eran mujeres (68,8%). El 68,8% de los pacientes presentaron una prescripción no ajustada del iDPP4. Hubo una reducción total de 0,21%, con una media de 198,2±124 días entre la primera y segunda medición de HbA1c de control (reducción de 0,55% cuando la prescripción se ajustaba a la guía colombiana y 0,05% cuando no). Conclusión: Hay un limitado impacto de los iDPP4 frente a la reducción de HbA1c y poco seguimiento de la guía colombiana en pacientes de primer nivel de atención.

Gliptins vs. Milk-derived Dipeptidyl-Peptidase IV Inhibiting Biopeptides: Physicochemical Characterization and Pharmacokinetic Profiling / Gliptinas vs. Biopéptidos Inhibidores de Dipeptidil-Peptidasa IV Derivados de la Leche: Caracterización Fisicoquímica y Perfil Farmacocinético

Background: Milk-derived biopeptides have reported in vitro dipeptidyl-peptidase IV (DPP-IV) inhibition, suggesting a glycemic-regulatory effect in Type 2 Diabetes Mellitus (T2DM). Nonetheless, the therapeutic application of these nutraceuticals is limited by the scarcity of knowledge regarding their pharmacokinetic profile. Objective: This study aimed to characterize and assess the pharmacokinetics of milk-derived biopeptides. Through an in silico comparative analysis with gliptins, we expected to identify enhanced properties in food-hydrolysates and suitable DPP-IV inhibiting peptides as candidates for T2DM therapy. Methods: A comparison between gliptins and biopeptides was conducted based on in silico evaluation of drug-likeness, physicochemical properties, pharmacokinetics, and synthetic accessibility. Suitable target proteins for gastrointestinal-absorbable biopeptides were determined as well. Data collection was performed on SwissADME, ADMETlab, DrugBank, SwissTargetPrediction, ChemDes, and BIOPEP-UWM platforms. Statistical analysis was carried out using a one-way ANOVA test. Results: Drug-likeness compliance showed no significant difference between gliptins and biopeptides (p>0.05) in three out of nine assessed rules, though gastrointestinal-absorbable biopeptides exhibited no significant difference with gliptins in five drug-likeness guidelines. The physicochemical evaluation revealed a significant difference (p<0.05) between both groups, with peptides exhibiting enhanced solubility, flexibility, and polarity. Nine out of thirty-six assessed biopeptides reported being likely gastrointestinal-absorbable molecules, from which six displayed ≥30% predicted bioavailability, two reported CYP450 interactions, and all were determined to be blood confined. Biopeptides showed a slightly lower clearance than gliptins yet counteracted by a significantly lower half-life. Moreover, synthetic accessibility scores indicated higher synthetic ease for biopeptides. In addition, absorbable bioactive peptides reported a considerable binding affinity to DPP-IV and Calpain-I. Conclusions: Compared to gliptins, gastrointestinal-absorbable biopeptides exhibit superior physicochemical properties (higher solubility, flexibility, and polarity), lesser CYP450 interactions, higher synthetic ease, and some reported an important affinity for DPP-IV and Calpain-I. Only a small fraction of milk-derived biopeptides are suitable drug-like compounds and feasible candidates for T2DM therapy; yet, testing their therapeutic potency remains subject to further studies

Antecedentes: Los biopéptidos derivados de la leche han mostrado inhibir la dipeptidil-peptidasa IV (DPP-IV) en ensayos in vitro, lo que sugiere una regulación de la glicemia en la Diabetes Mellitus Tipo 2 (DM2). Sin embargo, su uso terapéutico está limitado por el escaso conocimiento de sus propiedades farmacológicas. Objetivo: Caracterizar y evaluar el perfil farmacocinético de los biopéptidos derivados de la leche. Por medio de un análisis comparativo in silico, se buscó identificar propiedades de carácter superior a las gliptinas en los biopéptidos inhibidores de DPP-IV, así como posibles candidatos a agentes terapéuticos en la DMT2. Métodos: Se llevó a cabo una comparación entre las Gliptinas y los biopéptidos basada en la evaluación in silicode las características "d r ug - li ke", propiedades fisicoquímicas, farmacocinética y accesibilidad sintética. Adicionalmente, se determinaron posibles proteínas diana para los biopéptidos de alta probabilidad de absorción gastrointestinal. Los datos se obtuvieron en SwissADME, ADMETlab, DrugBank, SwissTargetPrediction, ChemDes y BIOPEP-UWM. El análisis estadístico se basó en un análisis de varianza (one-way ANOVA test). Resultados: El cumplimiento de las reglas de "drug-likeness" no mostró diferencias significativas entre las gliptinas y los biopéptidos (p>0.05) en tres de las nueve normas evaluadas, empero, los biopéptidos absorbibles no mostraron diferencias significativas con las gliptinas en cinco de estas. La evaluación fisicoquímica reveló una diferencia significativa (p>0.05) entre ambos grupos y una mayor solubilidad, flexibilidad y polaridad para los biopéptidos. Nueve de los treinta y seis biopéptidos estudiados reportaron alta probabilidad de absorción gastrointestinal, de los cuales seis presentaron una biodisponibilidad predicha ≥30%, dos reportaron interacciones con el CYP450, y todos mostraron permanecer confinados en sangre. Los biopéptidos mostraron una tasa de aclaramiento inferior a las gliptinas, sin embargo, contrarrestado por una vida-media significativamente menor. Los valores de accesibilidad sintética indicaron una mayor facilidad de síntesis para los biopéptidos. Por último, los biopéptidos absorbibles mostraron una considerable afinidad por la DPP-IV y la Calpaína-I. Conclusiones: Frente a las gliptinas, los biopéptidos absorbibles presentan: propiedades fisicoquímicas superiores (mayor solubilidad, flexibilidad y polaridad), menores interacciones con el CYP450, mayor facilidad de síntesis y algunos una importante afinidad por la DPP-IV y la Calpaína-I. Una mínima fracción de biopéptidos derivados de la leche son candidatos viables para la terapia de DM2; sin embargo, la determinación de su efectividad terapéutica permanece sujeta a futuros estudios

Terapia complementaria a la insulina en el tratamiento de niños y adolescentes con diabetes mellitus tipo 1- (DM1) / Therapies complementaries to insulin in the treatment of children and adolescents with type 1 diabetes mellitus (T1DM)

La diabetes mellitus tipo 1 (DM1), es una enfermedad crónica caracterizada por la deficiencia de insulina debido a la pérdida de células ß pancreáticas, las alteraciones hormonales en la DM 1 no se limitan a la deficiencia de insulina; existiendo también secreción inadecuadada de glucagón en el período postprandial. Aunque el control glucémico con terapias intensivas con insulina ha reducido la incidencia de complicaciones microvascular y macrovasculares. La mayoría de las personas con DM1 tienen un control glucémico subóptimo; Por lo tanto, el uso de farmacoterapia adyuvante para mejorar el control ha sido de interés clínico. El uso de estos nuevos medicamentos brindaría la oportunidad de imitar más de cerca la fisiología pancreática normal, y contrarrestar otros mecanismos fisiopatológicos diferentes a Insulinopenia; contribuyendo a lograr un mejor control metabólico y expectativa de vida.

Type 1 diabetes mellitus (T1DM), is a chronic disease characterized by insulin deficiency due to the loss of pancreatic ß cells, the hormonal alterations in T1DM are not limited to insulin deficiency; there is also a deregulated glucagon secretion in the postprandial period. Although glycemic control with intensive therapies with insulin has reduced the incidence of microvascular and macrovascular complications, most people with T1DM1 glycemic control; therefore, the use of adjuvant pharmacotherapy to improve control has been of clinical interest. The use of these new drugs would offer the opportunity to imitate more closely the normal pancreatic physiology, and to counteract other physiopathological mechanisms different from insulinopenia; contributing to achieve better metabolic control and life expectancy.

[Use of dipeptidyl peptidase-4 inhibitors in diabetic patients in special situations]. / Uso de inhibidores de la dipeptidil peptidasa 4 en pacientes con diabetes en situaciones especiales.

Dipeptidyl peptidase-4 inhibitors form part of the group of incretin derivatives and conse-quently have a specific mechanism of action. The incretin effect avoids the adverse ef-fects of classic drugs (sulphonylureas) and provides specific benefits for their use in as-sociation with other drugs and in special situations. Because they have a low risk of pro-ducing hypoglycaemia or weight gain, these inhibitors are useful in combination with other oral antidiabetic drugs and even with insulin, although this latter combination may increase the risk of hypoglycaemia. Large studies of cardiovascular non-inferiority have reported that dipeptidyl peptidase-4 inhibitors are non-inferior to placebo, although one drug (saxagliptin) may increase the risk of hospital admission for heart failure. Because of these cardiovascular advantages, even in peripheral arterial disease, their usefulness in diabetic retinopathy, and their low risk of hypoglycaemia in renal insufficiency, dipeptidyl peptidase-4 inhibitors are the drugs of choice in elderly patients. Given the risk, although still not well defined, these drugs are not recommended in pa-tients with a history or risk of pancreatic disease, in children, in patients with type 1 diabetes, in adolescents, or in pregnant or breastfeeding women. Each of these special situ-ations is discussed in the present article.

[Recommendations of the main clinical practice guidelines]. / Recomendaciones de las principales guías de práctica clínica.

The development of new drugs to treat hyperglycemia in persons with type 2 diabetes mellitus and recent cardiovascular safety studies of these new molecules have created the need to update the various clinical practice guidelines and consensus documents on the approach and treatment of this highly prevalent disease. Metformin continues to be the first-line drug. Dipeptidyl peptidase-4 inhibitors are oral lipid-lowering drugs with specific characteristics favouring their use in primary care. Among other characteristics, these drugs have few drug-drug interactions, can be easily combined with other drugs, are well tolerated, have a neutral effect on weight, and have a low risk of producing hypoglycaemic episodes, all of which encourages their prescrip-tion. Dipeptidyl peptidase-4 inhibitors are considered as second-line drugs (and as first-line drugs if metformin is contraindicated or poorly tolerated). In some specific situa-tions, this position could be threatened by the development of new drug families, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 analogues, which have shown benefits in reducing major cardiovascular events and mortality. It is important to determine the current place of dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes mellitus, since they have been increasingly prescribed in primary care in the last few years.

Inhibidores de la dipeptidil peptidasa 4 y una nueva estrategia farmacológica en la diabetes mellitus tipo 2 / Inhibitors of dipeptidil peptidase 4 new pharmacologic strategic in the diabetes mellitus type 2

La diabetes mellitus sigue siendo una enfermedad temible. El uso adecuado de la farmacoterapia para el control metabólico, ayudaría a disminuir la incidencia de complicaciones. Actualmente se dispone de variados grupos farmacológicos para el control temporal de las cifras de glucemias de pacientes con diabetes mellitus tipo 2, entre ellos están los inhibidores de la dipeptidil peptidasa 4 caracterizados por estimular el aumento de la concentración del péptido similar a glucagón tipo 1 GLP-1 y la secreción de insulina en la célula beta del islote pancreático. La eficacia, en términos de hemoglobina glucosilada, ha mostrado ser inferior a la de la insulina, pero sin el potencial del peligro de hipoglucemia, así como el efecto neutro o la disminución del peso corporal. Se realizó esta revisión bibliográfica con el objetivo de actualizar los conocimientos sobre el papel de las sustancias con acción incretinas en el control metabólico de los pacientes con diabetes mellitus tipo 2 y específicamente la acción de los IDPP4, ya que es creciente el problema de dicha enfermedad y se requiere, cada vez más, una mejor información de los fármacos a utilizar, aunque en el futuro los datos obtenidos concluirán su efectividad(AU)

Diabetes mellitus remains a fearsome disease. Proper use of pharmacotherapy for metabolic control, would help reduce the incidence of complications. Currently there are various pharmacological groups for temporary control of blood glycemia of patients with diabetes mellitus type 2. One of them is dipeptidyl peptidase-4 inhibitor characterized by stimulating increased concentration like peptide glucagon type 1 GLP -1 and insulin secretion in pancreatic islet beta cell. The effectiveness in terms of glycosylated hemoglobin has shown to be less than that of insulin, but without the potential danger of hypoglycaemia and the neutral effect or decrease in body weight. These facts prompt this literature review which was conducted to update the knowledge on the role of substances with incretin action in the metabolic control of patients with diabetes mellitus type 2, specifically the action of IDPP4, as this disease is an growing problem requiring better information on drug use(AU)

Inhibidores de dipeptidil dipeptidasa-IV: de la teoría a la práctica / Dipeptidil dipeptidase-IV inhibidors: from the theory to the practice

Esta revisión de los inhibidores de dipeptidil peptidasa-IV busca motivar el uso racional de tal grupo farmacológico en la práctica diaria. Este grupo es una nueva opción terapéutica en monoterapia o terapia combinada para el tratamiento de los pacientes con diabetes mellitus tipo 2. En Colombia, se encuentran disponibles: sitagliptina, vildagliptina, saxagliptina y linagliptina. Si bien todas las gliptinas tienen el mismo mecanismo de acción-aumentan la vida media del péptido similar al glucagón-, esta revisión presenta las diferencias entre sus propiedades farmacológicas, eventos adversos y perfil de seguridad. Estos medicamentos son de segunda o tercera línea para el tratamiento oral de los pacientes con diabetes mellitus tipo 2, o primera línea en los pacientes intolerantes a la metformina. Además, algunas de las ventajas que tienen son que: generan menor riesgo de hipoglucemia, tienen efecto neutro sobre el peso, son seguros en adultos mayores, disminuyen la variabilidad de la glucemia y, adicionalmente, se pueden utilizar en la enfermedad renal crónica avanzada, con o sin terapia de reemplazo renal, y en la insuficiencia hepática.

This review of dipeptidyl peptidase-IV inhibitors seeks to encourage the rational use of these drugs in daily practice; this group is a new therapeutic option in monotherapy or combination therapy for the treatment of patients with diabetes mellitus type 2. Sitagliptin, vildagliptin, saxagliptin and linagliptin are available in Colombia. While all gliptins have the same mechanism of action-they increase the average life of glucagon-like peptide-, this review presents the differences among their pharmacological properties, adverse events and safety profile. These drugs are second or third-line for the oral treatment of patients with diabetes mellitus type 2, or first-line in patients intolerant to metformin. They also have some advantages like lower risk of hypoglycemia, neutral effect on weight, safety for the elderly, reduction of glycaemia variability; additionally, they can be used in advanced chronic kidney disease, with or without renal replacement therapy, and in liver failure.

[Type 2 diabetes mellitus: new treatments]. / Diabetes mellitus tipo 2: nuevos tratamientos.

The benefits and problems associated with traditional hypoglycemic drugs, such as failure of beta cells, hypoglycemia and weight gain, that lead to a worsening of diabetes, are reviewed. New hypoglycemic drugs with incretin effect (glucagon-like peptide-1 agonists and dipeptidyl peptidase 4 inhibitors), achieve, in a glucose dependent manner, an glycosylated hemoglobin reduction without hypoglycemia or increase in body weight. Recently, another group of oral hypoglycemic drugs, sodium-glucose cotransporter type 2 inhibitors, have demonstrated efficacy in diabetes control by inhibiting renal glucose reabsorption. However, long-term effects and cardiovascular prevention remain to be demonstrated. We have more and better drugs nowadays. Hypoglycemic treatment should be customized (glycosylated hemoglobin levels, risk-benefit, risk of hypoglycemia, weight changes, cardiovascular risk), with a combination of drugs being necessary in most cases. However, we do not have yet an ideal hypoglycemic drug. Moreover we must remember that an early and intensive treatment of dyslipidemia and hypertension is essential for the prevention of cardiovascular disease in patients with type 2 diabetes.

Una peptidasa ácida, insensible a inhibidores clásicos, en extractos proteicos de Trypanosoma cruzi, proveniente de una zona rural de Venezuela, endémica para la enfermedad de Chagas / Description of an acidic peptidase, insensitive to classical inhibitors, in protein extracts of Trypanosoma cruzi, from a rural area of Venezuela, where Chagas disease is endemic

Mediante dos métodos de ensayo de peptidasas, uno en fase líquida y otro en fase gel (zimografía en geles), se detectó una peptidasa, en extractos proteicos crudos de epimastigotes de Trypanosoma cruzi, provenientes de un área rural de Venezuela endémica para el mal de Chagas. La peptidasa mostró actividad en el intervalo de pH comprendido entre 2,0 y 2,9. Bajo las condiciones experimentales descritas, la peptidasa resultó insensible a concentraciones usuales de inhibidores clásicos de peptidasas de tipo: serina, cisteína, metalo-peptidasas y aspártico. No obstante, a semejanza de la pepsina porcina a pH 2,9, la peptidasa es inhibida en presencia de 5mM DTT.

Through two peptidase assay methods, one in liquid-phase and another, in gel-phase (gel zymography), an acid peptidase was detected in protein crude extracts of epimastigotes of Trypanosoma cruzi, from a rural area of Venezuela where Chagas disease is endemic. The peptidase shows activity at a pH range between 2.0 and 2.9. Under the experimental conditions described, the acid peptidase was insensitive to usual concentrations of peptidase inhibitors of the types: serine, cysteine, aspartic and metallo-peptidases. Nevertheless, like porcine pepsin at pH 2.9, the peptidase was inhibited in the presence of 5mM DTT.

Las incretinas: nueva alternativa terapéutica para el control glucometabólico de la diabetes mellitus de tipo 2 / Incretins: a new therapeutic alternative for the glycometabolic control of the type 2 diabetes mellitus

Actualmente existen tratamientos más novedosos para controlar, de forma transitoria, los niveles de glucemia de la mayoría de los pacientes con diabetes mellitus de tipo 2. Entre dichos agentes terapéuticos están aquellos que reproducen o potencian el efecto de las incretinas como los fármacos agonistas del péptido relacionado al glucagón 1 y los inhibidores de la enzima dipeptidil peptidasa 4, los cuales presentan ventajas como la eliminación de manifestaciones de hipoglucemia y el efecto neutro o la disminución del peso corporal. No obstante, con el transcurso del tiempo se aportarán datos clínicos concluyentes que demuestren su efectividad(AU)

There are now newer treatments to control temporarily the blood glucose levels of most patients with type 2 diabetes mellitus. Among these therapeutic agents are those that replicate or potentiate the effect of incretins as agonists of glucagon-related peptide-1 and dipeptidyl peptidase-4 inhibitors, which have advantages such as eliminating manifestations of hypoglycemia and neutral effect or decreased body weight. Nevertheless, conclusive clinical data that demonstrate their effectiveness will be provided over time(AU)

Nuevas terapias en diabetes: más allá de la insulina inyectable y de los antidiabéticos orales: [revisión] / New therapies for diabetes: beyond injectable insulin and oral antidiabetics: [review]

Novos medicamentos para o tratamento do diabetes tipo 1 e tipo 2 foram incorporados à lista de fármacos tradicionais: antidiabéticos orais e insulinas injetáveis. Estas alternativas de tratamento têm novos mecanismos de ação que aproveitam as propriedades antidiabéticas de certos peptídeos como é o caso da amilina ou do peptídeo similar ao glucagon (GLP-1), cujos níveis são deficientes ou insuficientes no diabetes. Isto acontece pelos análogos da amilina ou do GLP-1, embora também possa ser obtido inibindo a enzima que degrada este último. Além disso, encontra-se disponível no mercado um novo sistema para administrar insulina de maneira não-invasiva por meio de inalação. Este artigo resume os resultados mais importantes e atualizados com relação ao mecanismo de ação, eficácia, efeitos adversos e indicações destes fármacos inovadores.

New medicines for the therapy of the type 1 and type 2 diabetes have been incorporated in the list of traditional drugs: oral agents and injectable insulin. These treatment alternatives have a new mechanism of action that takes advantage of the antidiabetic properties of certain peptides such as amylin and glucagon like peptide-1 (GLP-1), whose levels are wanting or insufficient in diabetes. This is attained through amylin and GLP-1 analogues, although it can also be achieved by inhibiting the enzyme that degrades the latter. Furthermore, a new system to administer insulin in a noninvasive way through inhalation has become available in the market. This paper summarizes the most important and updated findings on the action mechanism, efficacy, adverse effects and indications of these innovative drugs.