Development of 3D-QSAR and pharmacophoric models to design new anti-Trypanosoma cruzi agents based on 2-aryloxynaphthoquinone scaffold.

In this work we have collected a set of 30 trypanosomicidal naphthoquinones and developed pharmacophoric and 3D-QSAR models as tools for the design of new potential anti-Chagasic compounds. Firstly, qualitative information was obtained from SAR and pharmacophoric models identifying some fragments around the 2-aryloxynaphthoquinone scaffold important for the antiparasitic activity. Then, 3D-QSAR CoMFA and CoMSIA models were developed. The models showed adequate statistical parameters where the steric, electrostatic, and hydrophobic features explain the trypanosomicidal effect. Therefore, to validate our models, we carried out the design, synthesis, and biological evaluation on T. cruzi epimastigotes of five new compounds (33a-e). According to CoMFA model, three out of five compounds showed pIC50 values within one logarithmic unit of deviation. The two compounds that did not fit the predictions were those with high lipophilicity, which agreed with the SAR and pharmacophore models. Docking and molecular dynamic studies were performed on T. cruzi trypanothione reductase, in a proposed binding site for this type of naphthoquinone. Interestingly, 33a-e showed the same interaction pattern as a naphthoquinone inhibitor (2). Finally, predicted drug-likeness properties indicated that 33a-e have optimal oral bioavailability. Thus, this study provides new in silico models for obtaining novel trypanosomicidal compounds.

A case of non-necrotising herpetic retinitis.

In developed countries, the main etiology of posterior uveitis is of infectious origin, Herpes is the most common viral agent as it has a wide spectral of ocular manifestations. These manifestations could depend on the patient's immunologic state, ranging from a mild focal form of non-necrotizing herpetic renitis (NNHR) to a severe form of Acute retinal necrosis (ARN). We present a case of NNHR by VHS 2 and the different differential diagnostics previous to its diagnosis: atypical ocular toxoplasmosis, ocular tuberculosis and ARN. During its evolution, it presented a drastic drop in the visual acuity despite of the antiviral treatment, and with systemic corticoids and the injury's clinical improvement. This event led to reevaluate the suspected entities, establishing the NNHR as a definitive diagnostic by exclusion that constituted a challenging diagnostic.

Un caso de retinitis herpética no necrosante / A case of non-necrotising herpetic retinitis

En países en vías de desarrollo la principal etiología de uveítis posterior es de origen infeccioso, siendo el herpes virus el agente viral más común, con un amplio espectro de manifestaciones oculares que puede depender del estado inmunológico del paciente: desde una forma leve focal de retinitis herpética no necrosante (RHNN) hasta una forma severa de necrosis retiniana aguda. Presentamos un caso de RHNN por VHS 2 y los diferentes diagnósticos diferenciales planteados previos a su diagnóstico: toxoplasmosis ocular atípica, tuberculosis ocular y necrosis retiniana aguda. Durante su evolución presentó una caída súbita de la agudeza visual a pesar del tratamiento antiviral y con corticoides sistémicos y de la mejoría clínica de la lesión. Este evento conllevó a replantear las entidades sospechadas, estableciendo la RHNN como diagnóstico definitivo por exclusión, lo cual constituyó un reto diagnóstico. (AU)

In developed countries, the main origin of posterior uveitis is an infection. Herpes is the most common viral agent, as it has a wide spectrum of ocular manifestations. These manifestations may depend on the immunological state of the patient, and range from a mild focal form of non - necrotising herpetic retinitis (NNHR) to a severe form of acute retinal necrosis (ARN). A case of NNHR due to Herpes simplex virus type 2 (HSV-2) is reported, along with the different differential diagnostics prior to its diagnosis: atypical ocular toxoplasmosis, ocular tuberculosis, and ARN. During its course, despite the antiviral treatment, systemic corticoids and the clinical improvement of the injury, there was a drastic drop in the visual acuity. This event led to the re-evaluation of the suspected entities, establishing the NNHR as a definitive diagnostic by exclusion, which was a diagnostic challenge (AU)

A case of non-necrotising herpetic retinitis. / Un caso de retinitis herpética no necrosante.

In developed countries, the main origin of posterior uveitis is an infection. Herpes is the most common viral agent, as it has a wide spectrum of ocular manifestations. These manifestations may depend on the immunological state of the patient, and range from a mild focal form of non - necrotising herpetic retinitis (NNHR) to a severe form of acute retinal necrosis (ARN). A case of NNHR due to Herpes simplex virus type 2 (HSV-2) is reported, along with the different differential diagnostics prior to its diagnosis: atypical ocular toxoplasmosis, ocular tuberculosis, and ARN. During its course, despite the antiviral treatment, systemic corticoids and the clinical improvement of the injury, there was a drastic drop in the visual acuity. This event led to the re-evaluation of the suspected entities, establishing the NNHR as a definitive diagnostic by exclusion, which was a diagnostic challenge.

"CLUPS": A New Culture Medium for the Axenic Growth of Entamoeba histolytica.

Amebiasis remains a major health problem in Mexico. Therefore, the search for better culture media and low-cost diagnostic and therapeutic tools is fundamental. We present a new culture medium for Entamoeba histolytica which allows the microbe to preserve its virulence factors and ability to induce hepatic abscesses in animal models. The novel CLUPS medium is an improved version of the PEHPS medium, previously designed in our laboratory. The main difference is the substitution of raw beef liver in PEHPS by raw beef lung in the CLUPS medium. To compare the performance of three-culture media (traditional TYI-S-33, PEHPS, and CLUPS), E. histolytica trophozoites were cultured in quintuplicate, followed by the evaluation of phospholipase activity and the induction of liver abscesses in golden hamsters. E. histolytica trophozoites grew significantly better in CLUPS medium than in TYI-S-33. Likewise, CLUPS-cultured trophozoites produced significantly more phospholipases than TYI-S-33-cultured trophozoites. Finally, trophozoites grown in any of the three tested media had similar potential to induce liver abscesses.

Prostatectomía simple laparascópica asistida por robot descripción de la técnica y resultados / Simple robot assisted laparoscopic prostatectomy technique description and results

Introducción: La prostatectomía simple abierta ha sido el tratamiento tradicional para el crecimiento prostático grado III sintomático. En la búsqueda de nuevas técnicas quirúrgicas menos invasivas, la cirugía robótica ha venido desempeñado un papel importante permitiendo mejorar los resultados terapéuticos en múltiples aspectos. El objetivo de este trabajo es describir la experiencia en un Hospital Público Latinoamericano de la prostatectomía simple laparoscópica asistida por robot, como alternativa de tratamiento en próstatas de gran volumen.Material y métodos. Pacientes sometidos a prostatectomía simple laparoscópica asistidas por robot mediante abordaje transperitoneal de 5 portales dispuestos en forma de W empleando la técnica de Millin.Resultados. Se realizaron 11 prostatectomías simples laparoscópicas asistidas por robot, edad promedio: 65,17±5,81 años (57-74), IMC: 26±2,06 (23,3-28,3), PSA total: 4,56±2,47 ng/ml (1,54-8,3), IPSS preoperatorio: 28,67±6,47 puntos (18-35), QoL preoperatorio: 5,33±0,82puntos (4-6), volumen prostático por ultrasonido transrectal: 94,52±18,15 (80,16-120),tiempo operatorio: 202,5±66,91 minutos (75-240), sangrado: 650±320,94cc (300-1200),complicaciones: 1 (9,09%) Clavien IIIa, tiempo de hospitalización: 3,67±1,21 días (3-6), permanencia del catéter vesical: 8,5±1,64 días (7-10). Al comparar los resultados pre y post operatorios se evidencia marcada mejoría de los síntomas urinarios obstructivos bajos (SUOB), en la calidad de vida del paciente (QoL) y de los parámetros urodinámicos. No se realizaron conversiones a cirugía abierta ni transfusiones sanguíneas.Conclusión. La prostatectomía simple laparoscópica asistida por robot es un procedimiento reproducible y seguro para el tratamiento de próstatas benignas de gran volumen con resultados quirúrgicos comparables a cualquier otro tipo de abordaje pero con las ventajas que posee la cirugía mínimamente invasiva. Palabras claves: Prostatectomía simple, cirugía robótica, Hiperplasia prostática.(AU)

Introduction: Open simple prostatectomy has being the traditional treatment for sintomatic Prostate Hiperplasia °III. In the search of new surgical techniques less invassives, the robotic surgery play an important role because let better terapeutic results in many topics. The objetive of this work is describe the initial experience in a Latinamerican Public Hospital irobot-assisted laparoscopic simple prostatectomy as an alternative treatment in high- volumen prostates.Material y Methods. Pacients under laparoscopic robot-assisted simple prostatectomy. Transperitoneal 5 ports in W form Millin technique.Results. Did it 11 laparoscopic robot-assisted. Mean age 65,17±5,81 years (57-74). ICM: 26±2,06kg/m² (23,3-28,3), PSAT: 4,56±2,47ng/ml (1,54-8,3), IPSS pre-operatory28,67±6,47 points (18-35) QoL pre-operatory: 5,33±0,82 points (4-6), ultrasound prostatevolumen 94,52±18,15 (80,16-120), surgical time 202±66,91 minutes (75-240), lost blood:650±320,94cc (300-1200), complications 1(9,09%), hospitalization time: 3,67±1,21 days (3- 6), bladder cateterization 8,5±1,64 days (7-10). When comparing the pre and post operative results marked improvement in lower urinary tract obstructive symptoms, quality of live of patients and urodynamic parameters is evident. No had convertions or transfutions around surgery.Conclusion. Robot-assisted laparoscopic simple prostatectomy is a reproducible and saved technique with surgical results similars anything other kind whit the additional ventage of minimally invasión.(AU)

Interleukin (IL)-4 and to a lesser extent either IL-13 or interferon-gamma regulate the production of eotaxin-2/CCL24 in nasal polyps.

BACKGROUND: Eotaxin-2/CCL24 is a potent eosinophil attractant that has been implicated in the recruitment of eosinophils in allergic disease. We have investigated whether the cytokines interleukin (IL)-4, IL-13, and interferon (IFN)-gamma regulate eotaxin-2/CCL24 in nasal polyps. METHODS: Nasal polyps were cultured in the presence of the cytokines described above and the concentration of eotaxin-2/CCL24 was measured in the culture supernatant. RESULTS: IL-4 was found to be the major stimulus for eotaxin-2/CCL24 production from nasal polyps followed by IL-13 and IFN-gamma. IL-4 induced eotaxin-2/CCL24 in a dose-dependent manner with concentrations as low as 0.1 ng/ml being able to induce eotaxin-2/CCL24. By immunohistochemistry, eotaxin-2/CCL24 immunoreactivity was localized to mononuclear cells in the IL-4 stimulated nasal polyp tissue. Interestingly, nasal turbinates obtained from patients suffering from nonallergic rhinitis (vasomotor rhinitis) were also found to release eotaxin-2/CCL24 both spontaneously and following cytokine stimulation with IL-4 and IFN-gamma being major inducers of this cytokine. CONCLUSIONS: All together these findings suggest that Th1 and Th2 cytokines may regulate eotaxin-2/CCL24 production in nasal polyps and nonallergic rhinits.

[Cell surface markers in patients with allergic rhinitis versus Der p and Der f challenge]. / Estudio de marcadores de superficie celular en pacientes con rinitis alérgica frente a reto con Der p y Der f.

The allergic condition is determined genetically and they affect of the general population's 20-30% in developed countries, in the last decade have been increased the prevalence. Inside the imbalance that is manifested in the atopic patients it is on one hand the antigen-presenting cells (monocytes and B cells) and on the other hand, the lymphocytes T CD4+. The association of molecules like CD80, CD 86 (co-stimulatory molecules) in monocytes and B cells and CD30, CD62L, ALL, CD11a, CD28, CD124 and CD152 in CD4+, they have shown to be of particular interest in allergic sufferings. However we don't find a difference statistically significant among patient and controls and among nasal challenges with saline solution with specific allergen. For what we suggest that the changes in the activation, proliferation and cooperation are given in the les ion place, without an apparent repercussion in cells of peripheral blood.

Angioplastía transluminal percutánea con catéter balón en coartación aórtica nativa: experiencia a largo plazo / Long term study of percutaneous angioplasty in native aortic coarctation

De agosto de 1988 a octubre de 1993, 19 pacientes portadores de coartación aórtica nativa (CoAo) fueron sometidos a angioplastía transluminal percutánea con balón (ATPB). Doce fueron hombres (63.1 por ciento) y 7 mujeres (36.9 por ciento), con edad promedio de 22 ñ 7.7 años (extr. 16-52). Todos eran portadores de hipertensión arterial al momento del procedimiento, con una presión sistólica de 190 ñ 32.3 mmHg (extr. 160-240). El gradiente de presión sistólica (GPS) fue de 77 ñ 24 mmHg (extr. 45-130), un diámetro del anillo de coartación de 4.2 ñ 0.9 mm, el diámetro promedio de los catéteres balón utilizados fue de 18.3 ñ 1.7 mm (extr. 15-20). En todos los pacientes, el procedimiento se efectuó bajo anestesia local y con la técnica habitual de Seldinger. Después de efectuar el procedimiento, el GPS así como la presión arterial descendieron a 5.0 ñ 4.1 mmHg y 130 ñ 20.6 mmHg respectivamente y la ampliación del anillo presentó un aumento de 4.2 ñ 0.9 a 14.1 ñ 1.6 mm. En ninguno de los procedimientos se presentaron complicaciones: en el seguimiento 11 pacientes se han vuelto a cateterizar en un lapso de 24.7 ñ 12.6 meses (extr. 10-48) con un GPS de 5 ñ 2 mmHg y se observó un aumento en el diámetro del anillo a 15.4 ñ 1.2 mm. En estos sujetos vueltos a estudiar no se evidenciaron aneurismas en el sitio de la dilatación; el resto de los sujetos intervenidos llevan un control por consulta externa: 17 de ellos se mantienen normotensos sin tratamiento médico y dos únicamente han requerido de terapia antihipertensiva con mejor control a dosis bajas. Nuestra experiencia sugiere que la ATPB en CoAo tipo diafragma a cualquier edad es segura y muy efectiva con mejoría sostenida a mediano y largo plazo

[Fragmentation of single biliary calculi with an electromagnetic generator]. / Fragmentación de cálculos biliares únicos con un generador electromagnético.

Extracorporeal shock wave lithotripsy is a non surgical alternative for the treatment of cholelitiasis. At present, there are three main types of shock waves generators, one of them an electromagnetic device is (lithostar plus). The aim of this work is inform results obtained using Lithostar plus machine for the treatment of patients with a single gallstone. From total of 722 patients, 98 filled criteria for lithotripsy treatment; 63 patients had a single gallstone, with a mean age of 48.83 +/- 13.89 22 were males and 41 females. Patients were divided in 5 groups in base of the number of extracorporeal shock waves used, all of them had similar a gallstones of similar size. 32 patients (50.8%) showed total fragmentation with only one session. According with the results obtained, we can conclude that using lithostar plus we can get total fragmentation in one session in 50.8% of patients with a single gallstone.

[Electromagnetic shock wave lithotripsy plus bile acids for the treatment of gallblader stones: results and perspectives from the first 57 patients]. / Litotricia electromagnética y acidos biliares para tratamiento de los cálculos de la vesícula biliar: resultados y perspectivas de los primeros 57 pacientes.

Fifty seven patients were selected from 620 cases with gallstones to be treated with an electromagnetic shock wave generator (Lithostar Plus). The machine has an overhead module with an electromagnetic generator able to produce 150-150 bar of pressure in the center of the focal zone (2 x 8 cms.) An in line ultrasound probe permits in vivo view of stone localization and fragmentations. The wide aperture of the device permits to treat patients with little pain in ambulatory basis. The mean age of the patients was 50 +/- 14 years, 57 were female and 20 were male. Stones were single in 35 cases and were multiple (2-4 gallstones) in the rest. The patients received a mean of 2620 +/- 371 shock waves. Intravenous analgesia (Fentanyl 87 +/- 40 ug p/session) was required in 26 cases. In 58.5% of the cases, fragmentation produced gallstone-rests of < 0.5 cm. Larger fragments (> 0.5 cm), were observed after an initial shock wave session in 33%. These patients underwent additional treatments sessions. Hence patients received 1.8 +/- 0.8 sessions. Minor fragmentation or no fragmentation after the first session was observed in the 14.5%. Mild biliary pain appeared in 17 patients and acute biliary colic in 2, one of these underwent emergency cholecystectomy. Overall gallstone disappearance after one year after lithotripsy, plus bile acid therapy (10-12 mg Kg day) was 72%. Patients with single gallstones were free of stones of fragments in 92% of the cases, after the same period of follow up.