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Designing and developing inhibitors against the epigenetic target DNA methyltransferase (DNMT) is an attractive strategy in epigenetic drug discovery. DNMT1 is one of the epigenetic enzymes with significant clinical relevance. Structure-based de novo design is a drug discovery strategy that was used in combination with similarity searching to identify a novel DNMT inhibitor with a novel chemical scaffold and warrants further exploration. This study aimed to continue exploring the potential of de novo design to build epigenetic-focused libraries targeted toward DNMT1. Herein, we report the results of an in-depth and critical comparison of ligand- and structure-based de novo design of screening libraries focused on DNMT1. The newly designed chemical libraries focused on DNMT1 are freely available on GitHub.

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Graphene with defects is a vital support material since it improves the catalytic activity and stability of nanoparticles. Here, a density functional theory study was conducted to investigate the stability, energy, and reactivity properties of NinPdn (n = 1-3) clusters supported on graphene with different defects (i.e., graphene with monovacancy and pyridinic N-doped graphene with one, two, and three N atoms). On the interaction between the clusters and graphene with defects, the charge was transferred from the clusters to the modified graphene, and it was observed that the binding energy between them was substantially higher than that previously reported for Pd-based clusters supported on pristine graphene. The vertical ionization potential calculated for the clusters supported on modified graphene decreased compared with that calculated for free clusters. In contrast, vertical electron affinity values for the clusters supported on graphene with defects increased compared with those calculated for free clusters. In addition, the chemical hardness calculated for the clusters supported on modified graphene was decreased compared with free clusters, suggesting that the former may exhibit higher reactivity than the latter. Therefore, it could be inferred that graphene with defects is a good support material because it enhances the stability and reactivity of the Pd-based alloy clusters supported on PNG.

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Resumen La placenta y el hígado son los encargados del metabolismo de los carbohidratos. La glucosa es fundamental para el metabolismo cerebral. La hipoglucemia se define con valores < 47 mg/dl. La hipoglicemia que persiste más de 7 días se atribuye a problemas metabólicos o endocrinológicos y requiere un flujo de glucosa > 12 mg/kg/min para alcanzar normo-glicemia. La hipoglicemia hiperinsulinémica congénita persistente (HHCP) es poco común (1:50,000 nacidos vivos), es la causa más común de hipoglicemia persistente secundaria a una secreción inadecuada de insulina, que puede afectar el neurodesarrollo. Hay una forma difusa y una focal, con manifestaciones clínicas idénticas, pero con mecanismos patológicos diferentes. El tratamiento médico es a base de diazóxido y ocreótide. En el 95% de los casos no hay respuesta al tratamiento médico, requiriendo pancreatectomía subtotal. Se utilizó ocreótide y nifedipino. La tomografía computada con emisión de positrones (PET/TC 18F-DOPA) encontró incremento en la capación pancreática de insulina, se realizó pancreactectomía. Se egresó sin complicaciones y en seguimiento pediátrico sin alteraciones neurológicas.

Abstract The placenta and liver are responsible for the metabolism of carbohydrates. The glucose is fundamental for brain metabolism. Hypoglycaemia is defined as values < 47 mg/dl. Hypoglycaemia that persists for more than 7 days is attributed to metabolic or endocrine problems and requires glucose flow > 12 GKM to reach normoglycemia. Persistent congenital hyperinsulinemic hypoglycemia (PCHH) is uncommon (1:50,000 live births) is the most common cause of persistent hypoglycemia secondary to inadequate insulin secretion, can significantly affect neurodevelopment. There is a diffuse and a focal form, with identical clinical manifestations, but with different pathological mechanisms. The medical treatment is diazoxide and ocreotide. In 95% of cases there is no response to medical treatment, requiring subtotal pancreatectomy. Ocreotide and nifedipine were used. Positron emission computed tomography (PET/CT 18F-DOPA) found an increase in pancreatic insulin capacity, a pancreactectomy was performed. He was discharged without complications and in pediatric follow-up without neurological alterations.

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Snake envenomation by Bothrops asper is a common problem affecting cattle raising and rural workers in farms across Latin America. Control of hemorrhage must often be ensured at the site of the accident, as medical care and antivenom therapy might not be available on the premises. The aim of the present study was to investigate the effects of homeopathic medicine Phosphorus 6cH, biotherapy Bothrops asper 6cH and a homeopathic formula on hemorrhage induced by B. asper envenomation. Groups of mice received the investigated treatments before and after envenomation (minimal hemorrhagic dose) and the diameter and intensity of hemorrhage were assessed. When administered before envenomation, all 3 treatments reduced the hemorrhage diameter; the best results were achieved with formula administered 14 days before envenomation and Phos 6cH 7 days before. Among the animals treated after envenomation, Phos 6cH in 4 doses/hour exhibited the best results in terms of hemorrhage diameter and intensity. We conclude that both homeopathy and biotherapy exhibit considerable potential as alternative treatment to reduce hemorrhage induced by B. asper venom. (AU)

Acidentes por Bothrops asper afetam frequentemente o gado e trabalhadores rurais em toda a América Latina. Dado que tanto atenção médica quanto tratamento antiofídico podem não estar disponíveis no local do acidente, é necessário controlar a hemorragia in loco. O objetivo do presente estudo foi avaliar os efeitos do medicamento homeopático Phosphorus 6cH, bioterápico Bothrops asper 6cH e um complexo homeopático na hemorragia induzida por B. asper. Diferentes grupos de camundongos receberam os medicamentos testados antes e depois do envenenamento (dose hemorrágica mínima) e foram medidos o diâmetro e a intensidade da hemorragia. Quando administrados antes do envenenamento, os 3 tratamentos reduziram o diâmetro da hemorragia, obtendo-se os melhores resultados com o complexo administrado 14 dias antes e Phos 6cH 7 dias antes. Entre os animais tratados depois do envenamento, os melhores resultados em termos de diâmetro e intensidade da hemorragia foram obtidos com Phos 6cH em 4 doses/hora. Conclui-se que tanto a homeopatia quanto o bioterápico apresentam grande potencial como tratamento alternativo para reduzir a hemorragia induzida por B. asper. (AU)

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Snake envenomation by Bothrops asper is a common problem affecting cattle raising and rural workers in farms across Latin America. Control of hemorrhage must often be ensured at the site of the accident, as medical care and antivenom therapy might not be available on the premises. The aim of the present study was to investigate the effects of homeopathic medicine Phosphorus 6cH, biotherapy Bothrops asper 6cH and a homeopathic formula on hemorrhage induced by B. asper envenomation. Groups of mice received the investigated treatments before and after envenomation (minimal hemorrhagic dose) and the diameter and intensity of hemorrhage were assessed. When administered before envenomation, all 3 treatments reduced the hemorrhage diameter; the best results were achieved with formula administered 14 days before envenomation and Phos 6cH 7 days before. Among the animals treated after envenomation, Phos 6cH in 4 doses/hour exhibited the best results in terms of hemorrhage diameter and intensity. We conclude that both homeopathy and biotherapy exhibit considerable potential as alternative treatment to reduce hemorrhage induced by B. asper venom. (AU)

Acidentes por Bothrops asper afetam frequentemente o gado e trabalhadores rurais em toda a América Latina. Dado que tanto atenção médica quanto tratamento antiofídico podem não estar disponíveis no local do acidente, é necessário controlar a hemorragia in loco. O objetivo do presente estudo foi avaliar os efeitos do medicamento homeopático Phosphorus 6cH, bioterápico Bothrops asper 6cH e um complexo homeopático na hemorragia induzida por B. asper. Diferentes grupos de camundongos receberam os medicamentos testados antes e depois do envenenamento (dose hemorrágica mínima) e foram medidos o diâmetro e a intensidade da hemorragia. Quando administrados antes do envenenamento, os 3 tratamentos reduziram o diâmetro da hemorragia, obtendo-se os melhores resultados com o complexo administrado 14 dias antes e Phos 6cH 7 dias antes. Entre os animais tratados depois do envenamento, os melhores resultados em termos de diâmetro e intensidade da hemorragia foram obtidos com Phos 6cH em 4 doses/hora. Conclui-se que tanto a homeopatia quanto o bioterápico apresentam grande potencial como tratamento alternativo para reduzir a hemorragia induzida por B. asper. (AU)

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BACKGROUND: Retrocaval ureter is a rare congenital anomaly with an incidence of approx. 1/1000 live births. Recently, the laparoscopic approach has become the gold standard for treatment, relegating open surgery as a second option. CLINICAL CASE: We present the case of a 27-year-old male with a 2-year history of colicky pain in the right flank radiating to the ipsilateral thigh and genital region. The patient was initially treated with a right double-pigtail catheter stent due to obstructive uropathy as evidenced by ultrasound. He underwent laparoscopic ureteral anteposition with a successful outcome and has remained asymptomatic during a 12-month follow-up. CONCLUSIONS: Retrocaval ureter is a rare entity that requires a high grade of suspicion for initial diagnosis to provide adequate and opportune treatment that will have repercussions on kidney function and quality of life for the patient. Open surgery has traditionally been the treatment of choice; however, in recent decades laparoscopic surgery has been practiced more during this era of minimally invasive therapy, without yet displacing open surgery in our country.

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Objective. Painful physical symptoms occur frequently in patients with major depressive disorder (MDD), and although numerous studies report the effect of antidepressants on emotional aspects of depression, few focus on their effect on physical symptoms. This observational study was conducted, in a clinical practice setting, to determine antidepressant treatment decisions and their outcome on the physical and emotional symptoms of MDD. Methods. Patients with a mean score ≥2 for pain-related items on the Somatic Symptom Inventory (SSI) were classified with painful physical symptoms (PPS +) and differentiated from the remaining patients (PPS -). Severity of depression and physical pain were determined using the 17-item Hamilton Depression Rating Scale (HAMD17) and Clinical Global Impressions of Severity Scale (CGI-S), and Visual Analog Scale (VAS), respectively. Results. At baseline, 72.6% of patients were PPS+. Compared to PPS- patients, PPS +patients were, on average, significantly more depressed at baseline (mean difference [95% CI]: HAMD17 4.6 [3.6, 5.5] and CGI-S 0.3 [0.2, 0.4]; all p<0.0001), and remained more depressed and in greater pain at endpoint (HAMD17p=0.0074, CGI-S P =0.0151, and VAS P <0.0001). In addition, fewer PPS+ patients (65.8%) achieved remission (total HAMD17≤7) compared to PPS- patients (74.6%, P =0.0180). Conclusions. Painful physical symptoms are prevalent in MDD patients, highlighting the importance of addressing both the physical and emotional symptoms of depression.

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UNLABELLED: Chagas disease is caused by the flagellate protozoan T: cruzi. Seroepidemiological surveys in Chiapas, Mexico have shown seropositive individuals, therefore, we searched for people affected by the chronic form of Chagas disease which involves the heart, causing a chronic, progressive and fatal disease called Chronic Chagasic Cardiopathy (CCC). MATERIAL AND METHODS: To establish the frequency of CCC we studied 28 patients seen at the Hospital General Regional "Dr. Rafael Pascacio Gamboa" during October 2002 through October 2003 in Tuxtla Gutierrez, Chiapas, the State capital city, with diagnosis of dilated cardiomyopathy (DC), a serological survey for antibodies against T. cruzi was done. This hospital cares for people from all parts of Chiapas, Mexico. Clinical diagnosis of DC was established there and blind serological studies were performed in Mexico City. RESULTS: Fifteen out of 28 DC patients (54%) had anti T. cruzi antibodies. All of them came from poor rural villages and they had heart failure and/or arrhythmia or heart blockade on EKG. CONCLUSIONS: This observation suggest that in Chiapas were Chagas disease is endemic, there are CCC patients. Any case with a clinical diagnosis of DC should be tested for antibodies against T. cruzi. The low socioeconomic status, culture and environment in this Mexican State favour the presence and transmission of this parasitic disease.

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La enfermedad de Chagas es causada por el protozoario flagelado Trypanosoma cruzi. Encuestas seroepidemiológicas realizadas en Chiapas informan individuos seropositivos en comunidades rurales, y cabe la posibilidad de que la forma crónica de la enfermedad ocurra en el estado. La expresión clínica dominante en la enfermedad de Chagas crónica es cardíaca. Material y métodos: Con el objeto de conocer la frecuencia de cardiopatía chagásica crónica (CCC) se hizo una encuesta serológica a pacientes con miocardiopatía dilatada (MD) internados entre octubre de 2002 a octubre de 2003, en el Servicio de Cardiología del Hospital General Regional "Dr. Rafael Pascacio Gamboa" de Tuxtla Gutiérrez, Chiapas. El diagnóstico fue establecido en forma independiente y el estudio seroinmunológico fue ciego. Resultados: Quince (54%) de 28 sujetos con MD tenían anticuerpos a T. cruzi. Todos provenían de medio rural pobre, su cuadro clínico incluyó insuficiencia cardíaca y/o trastornos del ritmo o conducción. Conclusiones: Esta evidencia sugiere que en Chiapas, una zona endémica de enfermedad de Chagas, hay CCC. Dentro del estudio de la MD, la etiología chagásica, debe ser considerada, ya que las condiciones socioeconómicas, culturales y regionales favorecen su presencia.

Chagas disease is caused by the flagellate protozoan T. cruzi. Seroepidemiological surveys in Chiapas, Mexico have shown seropositive individuals, therefore, we searched for people affected by the chronic form of Chagas disease which involves the heart, causing a chronic, progressive and fatal disease called Chronic Chagasic Cardiopathy (CCC). Material and methods: To establish the frequency of CCC we studied 28 patients seen at the Hospital General Regional "Dr. Rafael Pascacio Gamboa" during October 2002 through October 2003 in Tuxtla Gutierrez, Chiapas, the State capital city, with diagnosis of dilated cardiomyopathy (DC), a serological survey for antibodies against T. cruzi was done. This hospital cares for people from all parts of Chiapas, Mexico. Clinical diagnosis of DC was established there and blind serological studies were performed in Mexico City. Results: Fifteen out of 28 DC patients (54%) had anti T. cruzi antibodies. All of them came from poor rural villages and they had heart failure and/or arrhythmia or heart blockade on EKG. Conclusions: This observation suggest that in Chiapas were Chagas disease is endemic, there are CCC patients. Any case with a clinical diagnosis of DC should be tested for antibodies against T. cruzi. The low socioeconomic status, culture and environment in this Mexican State favour the presence and transmission of this parasitic disease.

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Con el propósito de conocer la evolución de algunos componentes antioxidantes de la pulpa de arazá durante el almacenamiento de los frutos, éstos se cosecharon en su madurez fisiológica y se almacenaron durante seis días a 25 °C. Se encontró que los frutos presentan su máximo climatérico luego de dos días de almacenamiento y, al llegar al sexto día, sus características sensoriales están marcadamente deterioradas. Los contenidos de ácido ascórbico y fenólicos disminuyeron durante el almacenamiento. Los niveles encontrados de ácido ascórbico, compuestos fenólicos y la actividad anti-oxidante muestran que la contribución de la pulpa de arazá al potencial antioxidante, cuando se compara con otros alimentos, en la dieta humana es buena.

In order to know the evolution in some antioxidants from the pulp of araza fruit during its ripening, fruits were harvested in their physiological maturity and stored at 25 °C during 6 days. Fruits showed a climacteric maximum after 2 days of storage; at 6th day their sensorial characteristics were widely deteriorated. Ascorbic acid, free and bound phenolics were depleted during storage. Ascorbic acid, phenolics and antioxidant activity showed that antioxidant contribution of araza pulp to human diet is important.