Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase.

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme's structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman's method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis.

Astenia en pacientes que asisten a la consulta externa: valoración a través de la escala de intensidad de fatiga (FSS) / Asthenia in patients attending the outpatient clinic: valuation through the rating scale fatigue

Muchos pacientes acuden a consulta externa con un conjunto inespecífico de síntomas y signos que sugieren el diagnóstico de astenia, sin encontrarse una causa orgánica que explique dichos síntomas. Se realizó un estudio prospectivo a nivel nacional para diagnosticar y cuantificar la intensidad de la astenia en estos pacientes y medir la eficacia de la sulbutiamina 400 mg/día como tratamiento farmacológicoa corto plazo de primera línea. Se realizó un estudio abierto, prospectivo y multicéntrico,en el cual se ingresaron 341 pacientes, que consultaron ambulatoriamente y que presentaban síntomas de astenia. A través de la escala de Intensidad de Fatiga (por sus siglas en inglés: Fatigue Severity Scale - FSS) se determinó la presencia de astenia en estos pacientes y se evaluó la eficacia de la sulbutiamina 400 mg/día de Laboratorios Leti S.A.V., Venezuela (Tekron®). El estudio tuvo una duración de 15 días, en los cuales el paciente fue evaluado tres veces: día 1 (inicio), día 7 y día 15. Si el paciente presentaba astenia (puntuación ≥ 36 puntos en la FSS), se le indicaba sulbutiamina400 mg/día con el desayuno por 15 días. El 74,7% de los pacientes evaluados fueron del sexo femenino, con una edad media de 43,7 ± 12,5 años y el 25,3% del sexo masculino con una edad media de 41,7 ± 13,5 años. Al inicio del estudio la media de la puntuación de la FSS fue de 49,7 ± 7,3 puntos; a los 7 días de tratamiento con 400 mg/día de sulbutiamina fue de 37,2 ± 8,8 puntos con una disminucióndel 25,2% y al día 15 fue de 28,0 ± 9,8 puntos con una disminución de 43,7% con respecto al inicio del tratamiento, resultando estadísticamente significativo (p< 0,0001 y p< 0,0001 al día 7 y día 15 vs inicio, respectivamente). El 77,7% de los pacientes respondieron al tratamiento al día 15. La sulbutiamina resultó ser un tratamiento muy bien tolerado, se reportaron eventos adversos leves en 132 pacientes (38,7%) al día 7 y en 115 pacientes(33,7%) al día 15...

Many patients attending out patient clinics with a set of nonspecific symptoms and signs that suggest the diagnosis asthenia, without organic cause to explain the symptoms. In order to determine which of was these patients confirmed the diagnosis of functional asthenia, was performed a prospective nation wide, study to diagnose and quantify the intensity of fatigue in these patients and measure the effectiveness of sulbutiamine 400 mg/day treatment short-term drug frontline. Was realized an open, prospective, multicenter study, which entered 341 outpatient patients which showed signs of fati gue. The Fatigue Severity Scale (FSS) was used as a tool for the diagnosis and evaluation of severity of fatigue and was evaluated the effectiveness of sulbutiamine 400 mg/day to Leti Laboratories, S.A.V. (Tekron®), as first line treatment.The duration of the study was 15 days, with 3 evaluations (day 1 or baseline, day 7 and day 15). The score of the FSS had to be ≥ 36 points to be enrolled. 74,7% of patients were females with a mean age of 43,7 ± 12,5 years old and 25,3% were males with a mean age of 41,7 ± 13,5 years old. At baseline, the FSS score was 49,7 ± 7,3 points; at day 7 was 37,2 ± 8,8 points with a decrease of 25,2% and at day 15 was 28,0 ± 9,8 points, with a decrease of 43,7% respective to baseline, being statistically significant (p< 0,0001 and p< 0,0001 at day 7 and day 15, respectively). The percentage of response to treatment was 77,7% at day 15. Sulbutiamine was a very well tolerated treatment, there were reported mild adverse events in 132 patients (38,7%) at day 7 and in 115 patients (33,7%) at day 15. Sulbutiamine 400 mg/day is a secure treatment, it is well tolerated and effective in improving the asthenia symptoms, as demonstrated in this clinical trial by the significant decrease in the FSS mean score and the percentage of patients with asthenia at day 15 of treatment