WNK kinase is a vasoactive chloride sensor in endothelial cells.

Endothelial cells (ECs) line the wall of blood vessels and regulate arterial contractility to tune regional organ blood flow and systemic pressure. Chloride (Cl-) is the most abundant anion in ECs and the Cl- sensitive With-No-Lysine (WNK) kinase is expressed in this cell type. Whether intracellular Cl- signaling and WNK kinase regulate EC function to alter arterial contractility is unclear. Here, we tested the hypothesis that intracellular Cl- signaling in ECs regulates arterial contractility and examined the signaling mechanisms involved, including the participation of WNK kinase. Our data obtained using two-photon microscopy and cell-specific inducible knockout mice indicated that acetylcholine, a prototypical vasodilator, stimulated a rapid reduction in intracellular Cl- concentration ([Cl-]i) due to the activation of TMEM16A, a Cl- channel, in ECs of resistance-size arteries. TMEM16A channel-mediated Cl- signaling activated WNK kinase, which phosphorylated its substrate proteins SPAK and OSR1 in ECs. OSR1 potentiated transient receptor potential vanilloid 4 (TRPV4) currents in a kinase-dependent manner and required a conserved binding motif located in the channel C terminus. Intracellular Ca2+ signaling was measured in four dimensions in ECs using a high-speed lightsheet microscope. WNK kinase-dependent activation of TRPV4 channels increased local intracellular Ca2+ signaling in ECs and produced vasodilation. In summary, we show that TMEM16A channel activation reduces [Cl-]i, which activates WNK kinase in ECs. WNK kinase phosphorylates OSR1 which then stimulates TRPV4 channels to produce vasodilation. Thus, TMEM16A channels regulate intracellular Cl- signaling and WNK kinase activity in ECs to control arterial contractility.

Routine postdilation after 23 mm Sapien 3 Ultra implantation in the aortic position.

BACKGROUND: Residual transprosthetic gradient (TG) after transcatheter aortic valve replacement (TAVR) with balloon-expandable valves (BEV) may be due to suboptimal valve expansion. AIMS: To compare hemodynamics after TAVR with small BEV according to postdilation strategy. METHODS: This observational, retrospective cohort study included 184 consecutive patients from a single center treated with 23 mm Sapien 3 Ultra (Edwards Lifesciences) BEV implantation in the aortic position and enrolled between January 2020 and April 2023. Patients treated with routine postdilation (RP, n = 73) were compared to patients treated according to local standard practice (SP, n = 111). Primary endpoint was 30-day mean TG. Secondary endpoints were incidence of 30-day prosthesis-patient mismatch (PPM), technical success and device success. RESULTS: Thirty-day mean TG was lower in RP versus SP (12.3 ± 4.6 mmHg vs. 14.1 ± 5.7 mmHg, p = 0.031), and incidence of PPM was less common with RP versus SP (47.3% vs. 71.0%, p = 0.006). Technical success (98.6% vs. 99.1%, p = 0.637) and device success (93.1% vs. 90.1%, p = 0.330) did not differ between groups. Differences in 30-day mean TG were driven by patients at normal flow (12.1 ± 4.0 mmHg vs. 15.0 ± 5.5 mmHg, p = 0.014), while no differences were evident among patients at low flow (12.5 ± 5.5 mmHg vs. 11.7 ± 5.5 mmHg, p = 0.644). RP decreased height and increased width of BEV, and a linear regression established that final BEV width could predict 30-day mean TG (r = -0.6654, p < 0.0001). CONCLUSIONS: RP after TAVR with small BEV was associated with more favorable forward-flow hemodynamics than SP.

Reduced PaxillinB localization to cell-substrate adhesions promotes cell migration in Dictyostelium.

Many cells adhere to extracellular matrix for efficient cell migration. This adhesion is mediated by focal adhesions, a protein complex linking the extracellular matrix to the intracellular cytoskeleton. Focal adhesions have been studied extensively in mesenchymal cells, but recent research in physiological contexts and amoeboid cells suggest focal adhesion regulation differs from the mesenchymal focal adhesion paradigm. We used Dictyostelium discoideum to uncover new mechanisms of focal adhesion regulation, as Dictyostelium are amoeboid cells that form focal adhesion-like structures for migration. We show that PaxillinB, the Dictyostelium homologue of Paxillin, localizes to dynamic focal adhesion-like structures during Dictyostelium migration. Unexpectedly, reduced PaxillinB recruitment to these structures increases Dictyostelium cell migration. Quantitative analysis of focal adhesion size and dynamics show that lack of PaxillinB recruitment to focal adhesions does not alter focal adhesion size, but rather increases focal adhesion turnover. These findings are in direct contrast to Paxillin function at focal adhesions during mesenchymal migration, challenging the established focal adhesion model.

Plasma sodium during the recovery of renal function in critically ill adult patients: Multicenter prospective cohort study.

BACKGROUND: Sodium increases during acute kidney injury (AKI) recovery. Both hypernatremia and positive fluid balances are associated with increased mortality. We aimed to evaluate the association between daily fluid balance and daily plasma sodium during the recovery from AKI among critical patients. METHODS: Adult patients with AKI were enrolled in four ICUs and followed up for four days or until ICU discharge or hemodialysis initiation. Day zero was the peak day of creatinine. The primary outcome was daily plasma sodium; the main exposure was daily fluid balance. RESULTS: 93 patients were included. The median age was 66 years; 68% were male. Plasma sodium increased in 79 patients (85%), and 52% presented hypernatremia. We found no effect of daily fluid balance on plasma sodium (ß -0.26, IC95%: -0.63-0.13; p = 0.19). A higher total sodium variation was observed in patients with lower initial plasma sodium (ß -0.40, IC95%: -0.53 to -0.27; p < 0.01), higher initial urea (ß 0.07, IC95%: 0.04-0.01; p < 0.01), and higher net sodium balance (ß 0.002, IC95%: 0.0001-0.01; p = 0.05). CONCLUSIONS: The increase in plasma sodium is common during AKI recovery and can only partially be attributed to the water and electrolyte balances. The incidence of hypernatremia in this population of patients is higher than in the general critically ill patient population.

Applications of three-dimensional printing in percutaneous closure of aortic-to-right ventricle fistula after transcatheter aortic valve replacement: a case report.

Background: Percutaneous closure of aortic-to-right ventricle (ARV) fistula has emerged as an alternative to surgical management in selected cases. The use of three-dimensional (3D) printing in interventional planning for structural heart disease provides a concrete understanding, and it is useful in diagnostic assessment and to guide treatment approaches and to simulate procedures. Case summary: We report a case of a 70-year-old male presenting in cardiogenic shock due to severe aortic stenosis and reduced left ventricular ejection fraction. The patient had several comorbidities and was deemed not eligible for cardiac surgery. After transcatheter aortic valve replacement (TAVR), an ARV fistula was discovered on the TTE. Due to complex anatomical considerations, a 3D printed model of the patient's anatomy was employed to supplement the decision-making process and technical planning of percutaneous ARV closure. Successful closure of the fistula with the use of the Amplatzer atrial septal occluder was subsequently performed. Discussion: Three-dimensional printing improves the understanding of complex structures of cardiac diseases, allowing for enhanced planning and simulation of the procedure. This case, demonstrating the effective percutaneous closure of a TAVR-related ARV fistula facilitated by the use of 3D printed anatomical models in the pre-procedural phase, highlights the technology's potential in advancing patient-specific treatment approaches.

Acute Hemodynamic Compromise After Transcatheter Aortic Valve Replacement Due to Dynamic Left Ventricle Obstruction: A Systematic Review.

Acute hemodynamic compromise after transcatheter aortic valve replacement (TAVR) because of dynamic left ventricle (LV) obstruction (LVO), also known as suicide LV, is an infrequent but severe complication of TAVR that is poorly defined in previous studies. Understanding this complication is essential for its prompt diagnosis and optimal treatment. We conducted a systematic literature review using PubMed, Embase, Web of Science, and Medline databases for studies describing acute hemodynamic compromise after TAVR because of dynamic LVO or suicide LV. Each study was reviewed by 2 authors individually for eligibility, and a third author resolved disagreements. From a total of 506 studies, 25 publications were considered for the final analysis. The majority of patients with this condition were women demonstrating a hypertrophic septum, a small ventricle, and hyperdynamic contractility on pre-TAVR echocardiographic assessment. An intraventricular gradient before TAVR was found in half of the cases. Acute hemodynamic compromise after TAVR because of dynamic LVO manifested mainly as significant hypotension and occurred most often immediately after valve deployment. The LV outflow tract was the most common site of obstruction. Advanced therapies were required in nearly 65% of the cases. In conclusion, acute hemodynamic compromise after TAVR because of dynamic LVO occurred almost invariably in women. Echocardiography before TAVR may offer essential information to anticipate this complication. LV outflow tract obstruction appears to carry the highest risk of developing this phenomenon. Advanced therapies should be promptly considered as a bailout strategy in patients with hemodynamic collapse refractory to medical therapy.

Uso de balón subacromial en lesión masiva irreparable del manguito rotador

La lesión del manguito rotador es una causa importante de dolor y disfunción del hombro. El tratamiento de las roturas masivas e irreparables del manguito rotador sigue siendo un gran reto para los ortopedistas por su complejidad y severidad. Una de las alternativas prometedoras para su manejo es el uso del balón subacromial. Presentamos el caso de una mujer de 67 años con diagnóstico de rotura masiva e irreparable del manguito rotador en el hombro derecho (grado III de Patte, grado IV Goutallier y grado II de Hamada) sin artrosis glenohumeral, tenosinovitis del bíceps y subescapular íntegro. La escala de constant preoperatorio fue de 40 puntos. Se realizó una reparación parcial artroscópica del tendón supraespinoso e infraespinoso asociado a una tenodesis suprapectoral del bíceps y la colocación del balón subacromial. La paciente realizó rehabilitación con mejoría de los arcos de movilidad, disminución del dolor e incremento de la fuerza del hombro derecho. La escala de constant postoperatorio fue de 80 puntos a la semana doce. El balón subacromial es una buena alternativa de tratamiento para las lesiones irreparables del manguito rotador con resultados óptimos a corto plazo en cuanto a dolor y función.

The rotator cuff injury is a significant cause of shoulder pain and dysfunction. Treating massive and irreparable rotator cuff tears remains a major challenge for orthopedists due to their complexity and severity. One promising alternative for managing these cases is the use of subacromial balloons. In this study, we present the case of a 67-year-old woman diagnosed with a massive and irreparable rotator cuff tear in her right shoulder (Grade III Patte, Grade IV Goutallier, and Grade II Hamada), without glenohumeral arthritis, intact biceps tenosynovitis, and subscapularis. The preoperative Constant score was 40 points. The patient underwent partial arthroscopic repair of the supraspinatus and infraspinatus tendons, along with a suprapectoral biceps tenodesis and subacromial balloon placement. Postoperative rehabilitation led to improved range of motion, reduced pain, and increased strength in the right shoulder. The postoperative Constant score reached 80 points at the twelve-week mark. The subacromial balloon proves to be a promising treatment alternative for irreparable rotator cuff injuries, providing optimal short-term results in terms of pain relief and functionality.

Reconstrucción del ligamento cruzado posterior en un paciente adulto mayor con lesión multiligamentaria de rodilla

Las lesiones multiligamentarias de rodilla son traumatismos complejos de alta energía cuyo pronóstico puede ser devastador. Esta lesión es infrecuente en adultos mayores cuyo tratamiento es controversial. El tratamiento quirúrgico en adultos mayores puede presentar resultados funcionales similares que en pacientes jóvenes. Presentamos el caso de una mujer de 75 años, quien presentó ruptura total del ligamento cruzado posterior (LCP), ruptura total del ligamento colateral medial (LCM) y ruptura parcial del ligamento cruzado anterior (LCA) con < 50% de espesor en la rodilla derecha. La cirugía realizada fue una reconstrucción artroscópica del LCP con aloinjerto de tibial posterior y reparación del LCM superficial. El score KOS-ADL preoperatorio fue de 42,9% y el postoperatorio fue de 81,4% a los 18 meses de seguimiento. Por tanto, la cirugía reconstructiva en lesiones multiligamentarias de rodilla es clínicamente factible en pacientes adultos mayores con un resultado clínico aceptable y satisfactorio.

The multiligamentary knee injuries are complex high-energy trauma with a devastating prognosis. This injury is rare in older adults whose treatment is controversial. Surgical treatment in older adults may present similar functional results as in younger patients. Present the case of a 75-year-old woman with total posterior cruciate ligament (PCL) rupture, total medial collateral ligament (MCL) rupture and partial anterior cruciate ligament (ACL) rupture with <50% thickness in the right knee. The surgery performed was an arthroscopic reconstruction of the PCL with a posterior tibial allograft and repair of the superficial MCL. The preoperative KOS-ADL score was 42.9% and the postoperative was 81.4% at 18 months of follow-up. The reconstructive surgery in multiligamentary knee injuries is clinically feasible in older adult patients with an acceptable and satisfactory clinical outcome.

Reconstrucción anatómica del ligamento patelofemoral medial con aloinjerto en la luxación patelar recurrente / Medial patellofemoral ligament anatomic reconstruction with allograft in recurrent patellar dislocation

La técnica de reconstrucción del ligamento patelofemoral medial es eficaz, segura, reproducible y con baja morbilidad para el tratamiento de la luxación patelar recurrente. Los pasos a seguir son: 1) Paciente en decúbito dorsal. 2) Artroscopía diagnóstica con liberación del retináculo lateral y valoración de lesiones asociadas. 3) Incisión de 2 a 3 cm sobre el borde superomedial de la patela. 4) Realización de dos túneles de 20 a 22 mm de profundidad y 4 mm de diámetro a través del grosor de la patela bajo fluoroscopia. 5) Fijar dos anclas desde el borde medial de la patela y anudar al aloinjerto con sutura de alta resistencia. 6) Identificar el punto de Schöttle bajo fluoroscopia. 7) Incisión de 2 a 3 cm a nivel del epicóndilo medial. 8) Colocar un Kirschner de 2 mm de medial a lateral, de posterior a anterior y de distal a proximal. 9) Medir la longitud, el grosor y la tensión final deseada del aloinjerto. 10) Realizar el túnel femoral con broca canulada, 1 mm mayor al grosor del aloinjerto. 11) Utilizar el clavo con ojal para pasar la sutura y traccionar el aloinjerto de medial a lateral. 12) Fijar el aloinjerto con un tornillo biodegradable con la rodilla a 30° de flexión valorando la tensión final deseada. 13) Realizar el lavado y cierre por planos. Nivel de Evidencia: IV

The medial patellofemoral ligament reconstruction technique is effective, safe, reproducible and with low morbidity in the treatment of recurrent patellar luxation. The steps in this technique: 1) Patient in supine position. 2) Diagnostic arthroscopy with release of the lateral retinaculum and assessment of associated lesions. 3) 2 to 3 cm incision on the supero - medial border of the patella. 4) Make two tunnels 20 to 22 mm deep and 4 mm in diameter through the thickness of the patella under fluoroscopy. 5) Fix two anchors from the medial edge of the patella and tie to the allograft with high strength suture. 6) The Schöttle's point is identified under fluoroscopy. 7) 2 to 3 cm incision in the medial epicondyle. 8) A 2 mm Kirschner is placed from medial to lateral, posterior to anterior, and distal to proximal. 9) The length, thickness and desired final tension of the allograft are measured. 10) The femoral tunnel is made with a cannulated drill, 1 mm greater than the thickness of the allograft. 11) The eyelet nail is used to pass the suture and pull the allograft from medial to lateral. 12) The allograft is fixed with a biodegradable screw with the knee at 30 ° flexion, assessing the desired final tension. 13) The washing and closing are carried out by planes up to the skin. Level of Evidence: IV

Instrumentos de viento y su relación con el sistema estomatognático / Relationship between wind musical instruments and the stomatognatic system

Por la importancia que reviste ampliar los conocimientos del odontólogo en esta área, la presente revisión bibliográfica propone como objetivo resumir las modificaciones del sis-tema estomatognático que se presentan en músicos que practican instrumentos de viento. Dentro de las anomalías bucales que más abundan en la literatura se encuentran distonía focal, xerostomía, faringitis, queilitis angular, herpes labial y maloclusiones de una gran prevalencia e impacto, dentro de las más frecuentes registradas en este tipo de músicos se encuentran: el resalte aumentado, el apiñamiento y la adaquia. El resalte aumentado es consecuencia de la presión que ejerce la boquilla en la cara palatina de los incisivos superiores, esto provoca que aumente la distancia entre la cara vestibular de los incisivos inferiores y la cara palatina de los incisivos superiores, en sentido anteroposterior (con las arcadas en oclusión). Se concluye que las presiones anormales que generan los instrumentos de viento sobre el aparato estomatognático, provocan una serie de alteraciones que pueden afectar la mucosa oral, los músculos implicados en la práctica instrumental y la oclusión dentaria. Palabras clave: Cavidad bucal, Factores de riesgo; Maloclusiones.

This bibliographical review proposes as an objective to summarize the stomatognathic system modifications that occur in musicians who play wind instruments. Among the oral anomalies that abound most in the literature are focal dystonia, xerostomia, pharyngitis, angular cheilitis, cold sores and malocclusions but the impact and high prevalence among this type of musicians are: the increased teeth protrusion, crowding and adaquia. The increased teeth protrusion is a consequence of the pressure exerted by the mouthpie-ce on the palatal surface of the upper incisors, increasing the anteroposterior distance between the upper and lower incisors (with arcades in occlusion). It is concluded that the abnormal pressures generated by wind instruments on the stomatognathic apparatus cause alterations that may affect the oral mucosa, the muscles involved in the instrumen-tal playing and dental occlusion. Keywords: Malocclusions; Oral cavity; Risk factors.

Alteraciones estomatológicas en estudiantes de viola, violín e instrumentos de vientos Amadeo Roldán. Habana 2011 / Odontologic disorders in students of viola, violin and instruments of wind Amadeo Roldan. Havana. 2011

Introducción: las fuerzas anormales que ejercen el violín y la viola sobre la rama mandibular, así como la boquilla de los instrumentos de viento sobre los dientes, producen una serie de alteraciones bucomaxilofaciales, pues cada instrumento requiere una técnica específica, una posición concreta y el movimiento de determinados músculos. Objetivo: se propuso como objetivo identificar la relación entre tocar violín, viola e instrumentos de viento con la presencia de maloclusión y signos clínicos de Trastornos Temporomandibulares (TTM). Método: se realizó un estudio descriptivo inferencial, de corte transversal en el Conservatorio de Música Amadeo Roldán, de enero a febrero del 2011. De un universo de 130 estudiantes que tocan instrumentos de viento, violín y viola, se seleccionó una muestra conformada por 52 estudiantes, mediante un muestreo aleatorio simple. Se utilizó el Estadístico X2, con la corrección de Yates para continuidad, con una p < 0.005 (probabiblidad de error) y se aplicó el Indicador de Riesgo OR. Resultados: presentaban resalte aumentado 25 pacientes (48.1%), y ruidos articulares 42 pacientes (80.8%); 27 pacientes que tocaban instrumentos de viento (51.9%) presentaban maloclusión; 21 pacientes que tocaban violín y viola (40.4%), presentaban signos clínicos de trastornos temporomandibulares. El Chi Cuadrado para determinar la asociación entre instrumentos musicales y la maloclusión es X² =22.36, y entre instrumentos musicales y los signos clínicos de trastorno temporomandibular es X² =18.39, con p< 0.005. Conclusiones: los estudiantes que tocaban instrumentos de viento fueron más propensos a presentar maloclusiones, mientras que los estudiantes que tocaban violín y viola, fueron más propensos a presentar signos clínicos de trastornos temporomandibulares.

Introduction: the violin and the viola cause an abnormal force upon the jaw and wind instruments upon teeth. Because instruments require a specific technique, a concrete position and the abnormal movement of some muscles. Objective: this investigation proposes to identify the relation among play the violin, viola and instruments of wind with malocclusions and clinic signs of temporomandiblular joint disorders (TMJ). Method: this investigation was descriptive and inferencial. The study was at the Academy of Music: Amadeo Roldan, since January until February of the 2011. It used X² p < 0.005 and OR , with 50 patients. Results: 42 patients (80, 8 %) showed noises in the temporomandiblular joint (TMJ); 27 patients play instruments of wind (51, 9 %) and they showed malocclusions. 21 patients play the violin and viola (40, 4 %), and they showed clinic signs of temporomandiblular joint (TMJ) disorders. The association among to play musical instruments and the maloclusión was: X² =22.36 and among to play musical instruments and clinic signs of temporomandiblular joint (TMJ) disorders was: X²= 18.39, with p<0,005. Conclusions: the students that were touching instruments of wind, were prone to show malocclusions, while the students that were playing violin and viola, were prone to show clinical signs of temporomandibular disorders.

Trastornos temporomandibulares en pacientes con maloclusiones / Temporomandibular disorders found in patients with malocclusions

Existe una prevalencia de trastornos oclusales en gran medida relacionados con la presencia de disfunción temporomandibular. Objetivo: determinar el grado de disfunción temporomandibular según el Índice de Maglione en correspondencia con la prevalencia de maloclusiones en el área de salud del policlínico "Turcios Lima". Métodos: se realizó un estudio observacional descriptivo, de corte transversal, en la consulta de ortodoncia, de junio del 2008 a junio del 2009. De un universo constituido por los 280 pacientes que acudieron al servicio de ortodoncia en el período señalado con presencia de maloclusiones, se seleccionó una muestra de 84 pacientes por muestreo aleatorio simple, teniendo en cuenta los criterios de inclusión y exclusión realizados por criterios de expertos. Resultados: presentaban disfunción temporomandibular 74 pacientes y dentro de ellos 44 (52,4 por ciento) tenían disfunción grado II (Moderada). El 97 por ciento de los pacientes con relación molar de clase II, presentaban disfunción temporomandibular. El 42,9 por ciento de los pacientes con una maloclusión, presentaban disfunción grado I. El 60 por ciento de los pacientes con dos maloclusiones presentaban disfunción grado II y el 66,7 por ciento de los pacientes con tres maloclusiones, presentaban disfunción grado III. La mayor cantidad de pacientes tuvieron disfunción grado II (Moderada). Conclusiones: el mayor por ciento de los pacientes con disfunciones presentó una clase II molar y a medida que aumentó el número de maloclusiones aumentó también la severidad de la disfunción(AU)

Prevalence of occlusal disorders are mostly related with temperomandibular dysfunction. Objective: to determine the level of temperomandibular dysfunction according to Maglione's index in correspondence with prevalence of malocclusions in the health area under Turcios Lima polyclinics. Methods: cross-sectional. observational and descriptive study was conducted in the orthodontics service from June 2008 to June 2009. Of a universe of 280 patients that went to the orthodontics service with maloclussions, a sample of 84 patients was randomly selected according to the inclusion and exclusion criteria set by experts. Results: seventy four patients presented with temporomandibular joint dysfunction and 44 of them (52.4 percent) had moderate dysfunction (Grade II). Ninety seven percent of the patients with Class II molar relationship, also presented temporomandibular joint dysfunction whereas 42.9 percent with malocclusion presented Grade I dysfunction; 60 percent of patients with two malocclusions presented Grade II dysfunction and 66.7 percent with three malocclusions, presented Grade III dysfunction. The majority of patients had Grade II dysfunction (moderate). Conclusions: the highest percent of patients with dysfunctions presented a Class II molar relation and the severity of dysfunction increased as the number of malocclusions increased(AU)

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

Chemical composition of essential oils of Piper jacquemontianum and Piper variabile from Guatemala and bioactivity of the dichloromethane and methanol extracts

The essential oils from two native species from Guatemala were studied for their chemical composition and the dichloromethane and methanol extracts for their biological activity. A GC-MS analysis of the essential oil from Piper jacquemontianum Kunth, Piperaceae, showed 34 constituents, consisting mainly of linalool (69.4 percent), while Piper variabile C. DC. essential oil had 36 constituents, camphor (28.4 percent), camphene (16.6 percent) and limonene (13.9 percent) being the major components. Dichloromethane extracts of both species were cytotoxic against MCF-7, H-460 and SF-268 cell lines (<7 µg/mL). Dichloromethane extract of P. jacquemontianum was slightly active against bacteria (0.5 mg/mL), was active against promastigotes of Leishmania (20.4-61.0 µg/mL), and epimastigotes of Trypanosoma cruzi (51.9 µg/mL). The methanol extract of P. variabile showed antimalarial activity against Plasmodium falciparum F32 (4.5 µg/mL), and the dichloromethane extract against Leishmania (55.8-76.3 µg/mL) and T. cruzi (45.8 µg/mL). None of the extracts from the two species was active against Aedes aegypti larvae and Artemia salina nauplii.