Boldine prevents the inflammatory response of cardiac fibroblasts induced by SGK1-NFκB signaling pathway activation.

Cardiac fibroblasts (CF) are mesenchymal-type cells responsible for maintaining the homeostasis of the heart's extracellular matrix (ECM). Their dysfunction leads to excessive secretion of ECM proteins, tissue stiffening, impaired nutrient and oxygen exchange, and electrical abnormalities in the heart. Additionally, CF act as sentinel cells in the cardiac tissue microenvironment, responding to various stimuli that may affect heart function. Deleterious stimuli induce an inflammatory response in CF, increasing the secretion of cytokines such as IL-1ß and TNF-α and the expression of cell adhesion molecules like ICAM1 and VCAM1, initially promoting damage resolution by recruiting immune cells. However, constant harmful stimuli lead to a chronic inflammatory process and heart dysfunction. Therefore, it is necessary to study the mechanisms that govern CF inflammation. NFκB is a key regulator of the cardiac inflammatory process, making the search for mechanisms of NFκB regulation and CF inflammatory response crucial for developing new treatment options for cardiovascular diseases. SGK1, a serine-threonine protein kinase, is one of the regulators of NFκB and is involved in the fibrotic effects of angiotensin II and aldosterone, as well as in CF differentiation. However, its role in the CF inflammatory response is unknown. On the other hand, many bioactive natural products have demonstrated anti-inflammatory effects, but their role in CF inflammation is unknown. One such molecule is boldine, an alkaloid obtained from Boldo (Peumus boldus), a Chilean endemic tree with proven cytoprotective effects. However, its involvement in the regulation of SGK1 and CF inflammation is unknown. In this study, we evaluated the role of SGK1 and boldine in the inflammatory response in CF isolated from neonatal Sprague-Dawley rats. The involvement of SGK1 was analyzed using GSK650394, a specific SGK1 inhibitor. Our results demonstrate that SGK1 is crucial for LPS- and IFN-γ-induced inflammatory responses in CF (cytokine expression, cell adhesion molecule expression, and leukocyte adhesion). Furthermore, a conditioned medium (intracellular content of CF subject to freeze/thaw cycles) was used to simulate a sterile inflammation condition. The conditioned medium induced a potent inflammatory response in CF, which was completely prevented by the SGK1 inhibitor. Finally, our results indicate that boldine inhibits both SGK1 activation and the CF inflammatory response induced by LPS, IFN-γ, and CF-conditioned medium. Taken together, our results position SGK1 as an important regulator of the CF inflammatory response and boldine as a promising anti-inflammatory drug in the context of cardiovascular diseases.

TGF-ß1 decreases CHOP expression and prevents cardiac fibroblast apoptosis induced by endoplasmic reticulum stress.

Transforming growth factor-beta 1 (TGF-ß1) is a cytokine with marked pro-fibrotic action on cardiac fibroblasts (CF). TGF-ß1 induces CF-to-cardiac myofibroblast (CMF) differentiation, defined by an increase in α-smooth muscle cells (α-SMA), collagen secretion and it has a cytoprotective effect against stimuli that induce apoptosis. In the Endoplasmic Reticulum (ER) lumen, misfolded protein accumulation triggers ER stress and induces apoptosis, and this process plays a critical role in cell death mediated by Ischemia/Reperfusion (I/R) injury and by ER stress inducers, such as Tunicamycin (Tn). Here, we studied the regulation of CHOP, a proapoptotic ER-stress-related transcription factor in CF under simulated I/R (sI/R) or exposed to Tn. Even though TGF-ß1 has been shown to participate in ER stress, its regulatory effect on CF apoptosis and ER stress-induced by sI/R or TN has not been evaluated yet. CF from neonatal rats were exposed to sI/R, and cell death was evaluated by cell count and apoptosis by flow cytometry. ER stress was assessed by western blot against CHOP. Our results evidenced that sI/R (8/24) h or Tn triggers CF apoptosis and an increase in CHOP protein levels. TGF-ß1 pre-treatment partially prevented apoptosis induced by sI/R or Tn. Furthermore, TGF-ß1 pre-treatment completely prevented CHOP increase by sI/R or Tn. Additionally, we found a decrease in α-SMA expression induced by sI/R and in collagen secretion induced by Tn, which were not prevented by TGF-ß1 treatment. In conclusion, TGF-ß1 partially protects CF apoptosis induced by sI/R or Tn, through a mechanism that would involve ER stress.

Polycystin-1 mitigates damage and regulates CTGF expression through AKT activation during cardiac ischemia/reperfusion.

During ischemia/reperfusion (I/R), cardiomyocytes activate pathways that regulate cell survival and death and release factors that modulate fibroblast-to-myofibroblast differentiation. The mechanisms underlying these effects are not fully understood. Polycystin-1 (PC1) is a mechanosensor crucial for cardiac function. This work aims to assess the role of PC1 in cardiomyocyte survival, its role in profibrotic factor expression in cardiomyocytes, and its paracrine effects on I/R-induced cardiac fibroblast function. In vivo and ex vivo I/R and simulated in vitro I/R (sI/R) were induced in wild-type and PC1-knockout (PC1 KO) mice and PC1-knockdown (siPC1) neonatal rat ventricular myocytes (NRVM), respectively. Neonatal rat cardiac fibroblasts (NRCF) were stimulated with conditioned medium (CM) derived from NRVM or siPC1-NRVM supernatant after reperfusion and fibroblast-to-myofibroblast differentiation evaluated. Infarcts were larger in PC1-KO mice subjected to in vivo and ex vivo I/R, and necrosis rates were higher in siPC1-NRVM than control after sI/R. PC1 activated the pro-survival AKT protein during sI/R and induced PC1-AKT-pathway-dependent CTGF expression. Furthermore, conditioned media from sI/R-NRVM induced PC1-dependent fibroblast-to-myofibroblast differentiation in NRCF. This novel evidence shows that PC1 mitigates cardiac damage during I/R, likely through AKT activation, and regulates CTGF expression in cardiomyocytes via AKT. Moreover, PC1-NRVM regulates fibroblast-to-myofibroblast differentiation during sI/R. PC1, therefore, may emerge as a new key regulator of I/R injury-induced cardiac remodeling.

[Adherence to the Ponseti method by family members as a determinant in the success of club foot treatment]. / Apego al método de Ponseti por parte de los familiares como determinante en el éxito del tratamiento del pie equinovaro.

The clubfoot is one of the most common conditions in Pediatric Orthopedics, may affect each part of the foot and ankle, equinus, varus, and internal rotation of the calcaneum, and true equinus of the ankle are common. The Ponseti method is an universally accepted treatment, consisting of three phases: manipulation and plaster, Achilles tendon tenotomy and maintenance phase. The highest percentage of relapses occurs in the maintenance phase and the deficient family member is associated in most cases. We present a clinical case of a patient with typical clubfoot treated with the Ponseti method on four occasions without the need of surgical treatment.

El pie equinovaro aducto congénito (PEVAC) es uno de los padecimientos más comunes en Ortopedia Pediátrica, el cual se compone del equino del retropié, el varo subastragalino, el aducto del antepié y el cavo del mediopié. El método de Ponseti es el tratamiento universalmente aceptado para el PEVAC; éste consta de tres fases: manipulación y enyesado, tenotomía del tendón de Aquiles y una fase de mantenimiento. El mayor porcentaje de las recaídas se presenta en la fase de mantenimiento; en la mayoría de los casos, está asociado el apego familiar deficiente. Presentamos el caso clínico de un paciente con PEVAC típico, tratado en cuatro ocasiones con el método de Ponseti y que no requirió tratamiento quirúrgico.

[Radial club hand prevalence at Shriners Hospital-Mexico and literature review]. / Prevalencia de mano zamba radial en Hospital Shriners-México y revisión de la literatura.

INTRODUCTION: Radial club hand is characterized by radial deviation of the hand, as a result of hypoplasia or absence of the radius. MATERIAL AND METHODS: A descriptive, retrospective, cross-sectional and observational study of active patients diagnosed with radial club hand at the Shriners-Mexico Hospital was carried out. RESULTS: We studied 71 patients and 92 limbs, the prevalence was 0.08%, 64.7% were men and 35.3% women. We observed 22 patients with involvement of the right thoracic extremity, 28 left and 21 bilateral. It was found that 93% of the patients had an associated syndrome. The most common type of radial longitudinal dysplasia was type 1. 58 limbs did not have a thumb. The State of Mexico is the most affected and 91.6% had a guardian with maximum high school education.

INTRODUCCIÓN: La mano zamba radial congénita se caracteriza por la desviación radial de la mano como resultado de hipoplasia o ausencia del radio. MATERIAL Y MÉTODOS: Se realizó un estudio descriptivo, retrospectivo, transversal y observacional de los pacientes activos con diagnóstico de mano zamba radial. RESULTADOS: Se estudiaron 71 pacientes y 92 extremidades, la prevalencia en nuestro hospital fue de 0.08%, 64.7% fueron hombres y 35.3% mujeres. Se observaron 22 pacientes con afectación de la extremidad torácica derecha, 28 de la izquierda y 21 pacientes bilateral. Se encontró que 93% de los pacientes presentaban un síndrome asociado. El tipo de displasia longitudinal radial más común fue la tipo I. Cincuenta y ocho extremidades no contaban con pulgar. El Estado de México es el más afectado y 91.6% contaban con un responsable tutelar con escolaridad máxima de preparatoria.

[Complex elbow fracture]. / Fractura compleja de codo.

Elbow fractures are secondary to low or high energy trauma affecting the distal humerus, olecranon, radial head or a combination of the above. Complex fractures of the elbow complicate the reduction and its subsequent fixation representing a real challenge for the orthopedic surgeon. It is essential the use of diagnostic aids such as computerized axial tomography for diagnosis and subsequent treatment. Currently new trends in the fixation of the same and the various implants with which it is counted, can improve improve the patients prognosis. We present two clinical cases of complex elbow fractures treated by osteosynthesis.

Las fracturas de codo son secundarias a traumatismos de baja y alta energía, afectan el extremo distal del húmero, olécranon, cabeza radial o una combinación de las anteriores. Las fracturas complejas de codo dificultan la reducción y su posterior fijación, lo que representa un reto para el ortopedista. Es esencial el uso de auxiliares diagnósticos como la tomografía axial computarizada para su diagnóstico y posterior tratamiento. En la actualidad, las nuevas tendencias en la fijación de las mismas y los diversos implantes con los que se cuenta pueden mejorar el pronóstico del paciente. Se presentan dos casos clínicos de fracturas complejas de codo tratadas mediante osteosíntesis.

Hernioplastias inguinales transabdominal Preperitoneal: análisis de una serie de casos / Transabdominal inguinal hernioplasties Preperitoneal: analysis of a series of cases

La hernia inguinal tiene una incidencia entre 6,3 y 23,5 hernias por 10.000 habitantes, siendo uno de los procedimientos más comunes en cirugía, con más de 20 millones de reparaciones globales por año. Una de las técnicas de abordaje por videolaparoscopía es la vía transabdominal preperitoneal (TAPP). OBJETIVOS: Describir la experiencia en una serie de casos de cirugía de hernia plastia por la vía TAPP. PACIENTES Y MÉTODO: Diseño del estudio: observacional descriptivo. Población: pacientes operados de hernioplastías inguinales por vía laparoscópica en la Clínica Universitaria Reina Fabiola, Córdoba, Argentina, durante el periodo de febrero de 2016 a febrero de 2017. RESULTADOS: Se estudiaron 47 pacientes operados; 44 (93.2 %) hombres, con un promedio de edad de 40.53 (18-65) años y de índice de masa corporal de 28.6 (24-51.2) kg/m2. Se operaron 89 hernias, 42 (89.3 %) bilaterales y 5 (10.7 %) unilaterales. Al 100 % de los pacientes se les practicó la técnica TAPP. Existieron 3 (3.33 %) recidivas. No hubo mortalidad en la serie. CONCLUSIONES: Las hernioplastías inguinales laparoscópica presentan una curva de aprendizaje rápida en cirujanos experimentados, con bajas tasas de morbilidad y recidivas. (AU)

The inguinal hernia has an incidence between 6.3 and 23.5 hernias per 10,000 inhabitants, being one of the most common procedures in surgery, with more than 20 million global repairs per year. One of the techniques of videolaparoscopy approach is the transabdominal preperitoneal (TAPP). OBJECTIVES: To describe the experience in a series of cases of hernia surgery by TAPP. PATIENTS AND METHODS: Study design: descriptive observational. Population: patients undergoing laparoscopic inguinal hernioplasty at the Clínica Universitaria Reina Fabiola, Córdoba, Argentina during the period from February 2016 to February 2017. RESULTS: 47 operated patients were studied; 44 (93.2%) men, with an average age of 40.53 (18-65) years and a body mass index of 28.6 (24-51.2) kg / m2. We operated 89 hernias, 42 (89.3%) bilateral and 5 (10.7%) unilateral. 100% of the patients underwent the TAPP technique. There were 3 (3.33%) recurrences. There was no mortality in the series. CONCLUSIONS: Laparoscopic inguinal hernioplasty has a rapid learning curve in experienced surgeons, with low morbidity and recurrence rates. (AU)

Mechanical stretch increases L-type calcium channel stability in cardiomyocytes through a polycystin-1/AKT-dependent mechanism.

The L-type calcium channel (LTCC) is an important determinant of cardiac contractility. Therefore, changes in LTCC activity or protein levels could be expected to affect cardiac function. Several studies describing LTCC regulation are available, but only a few examine LTCC protein stability. Polycystin-1 (PC1) is a mechanosensor that regulates heart contractility and is involved in mechanical stretch-induced cardiac hypertrophy. PC1 was originally described as an unconventional Gi/o protein-coupled receptor in renal cells. We recently reported that PC1 regulates LTCC stability in cardiomyocytes under stress; however, the mechanism underlying this effect remains unknown. Here, we use cultured neonatal rat ventricular myocytes and hypo-osmotic stress (HS) to model mechanical stretch. The model shows that the Cavß2 subunit is necessary for LTCC stabilization in cardiomyocytes during mechanical stretch, acting through an AKT-dependent mechanism. Our data also shows that AKT activation depends on the G protein-coupled receptor activity of PC1, specifically its G protein-binding domain, and the associated Gßγ subunit of a heterotrimeric Gi/o protein. In fact, over-expression of the human PC1 C-terminal mutant lacking the G protein-binding domain blunted the AKT activation-induced increase in Cav1.2 protein in cardiomyocytes. These findings provide novel evidence that PC1 is involved in the regulation of cardiac LTCCs through a Gißγ-AKT-Cavß2 pathway, suggesting a new mechanism for regulation of cardiac function.

Experimental analysis of the air velocity and contaminant dispersion of human exhalation flows.

Human exhalation flow is a potential source of pathogens that can constitute a cross-infection risk to people in indoor environments. Thus, it is important to investigate the characteristics of this flow, its development, area of influence, and the diffusion of the exhaled contaminants. This paper uses phase-averaged particle image velocimetry together with a tracer gas (CO2 ) to study two different exhalation flows over time: the exhalation of an average male (test M) and an average female (test F), using a life-sized thermal manikin in a supine position. The exhalation jets generated for both tests are similar in terms of symmetrical geometry, vorticity values, jet opening angles, and velocity and concentration decays. However, there is a difference in the penetration length of the two flows throughout the whole exhalation process. There is also a time difference in reaching maximum velocity between the two tests. It is also possible to see that the tracer gas dispersion depends on the momentum of the jet so the test with the highest velocity decay shows the lowest concentration decay. All these results are of interest to better understand cross-infection risk.

Heterogeneous size datasets of broiler intestinal microbial communities can be analyzed without normalization.

Next-generation sequencing technologies have become a powerful tool for the analysis of microbial communities. Sequencing of the hypervariable regions of the 16S ribosomal RNA gene following the amplitag amplification process has allowed the study of the diversity of samples of diverse origin. According to previous reports, the number of sequences required for the correct determination of the composition of a given sample may vary with the degree of diversity of that sample. In this paper, we investigate the correctness of comparing heterogeneous size datasets of bird intestinal microbial communities obtained from pyrosequencing data (Roche 454 technology) without prior normalization. We conclude that the differences observed between samples are due mainly to individual differences, not to differences in the number of readings in each sample, which makes data normalization unnecessary with the conditions described here.

Effects of feed additives on ileal mucosa-associated microbiota composition of broiler chickens.

The effects of dietary supplementation with 2 recently developed feed additives on the composition of the mucosa-associated microbiota of the ileum were studied in growing broiler chickens. A total of 48 male 1-d-old broiler chickens of the Cobb 500 strain were distributed in 4 treatments with 2 replicates of 6 birds each. The 2 additives tested were a di-d-fructose dianhydride­enriched caramel (FC) and the garlic derivative propyl propane thiosulfonate (PTS-O). Dietary treatments were a control (commercial diet with no additive), INU (20 g inulin/kg diet), CAR (20 g FC/kg diet), and GAR (90 mgPTS-O/kg diet). As a result of this study, inulin supplementation resulted in lower (P < 0.05) and FC feeding resulted in higher (P < 0.05) Blautia coccoides/Eubacterium rectale log10 number of copies respect to controls. Higher (P < 0.05) bifidobacteria log10 number of copies with respect to the controls was determined in the ileal mucosa of birds fed the PTS-O­supplemented diet. Denaturing gradient gel electrophoresis and PCR analysis on Bifidobacterium spp. revealed the presence of Bifidobacterium longum, Bifidobacterium pseudolongum, and Bifidobacterium pseudocatenulatum in samples from chickens fed the control and the PTS-O­supplemented diet. Bifidobacterium longum was exclusively found in poultry fed the control diet, whereas B. pseudocatenulatum was found only in poultry fed the PTS-O­supplemented diet. This study showed that both PTS-O and FC were able to modulate the composition of the ileal mucosa-associated microbiota of growing broiler chickens. Finally, in addition to B. pseudolongum, the presence of B. longum and B. pseudocatenulatum, species not previously described in intestinal samples of broilers, was also demonstrated.

4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast.

Cardiac fibroblast (CF) survival is important for the maintenance of the extracellular matrix homeostasis in the heart; providing a functional support to cardiomyocytes necessary for the correct myocardial function. Endoplasmic reticulum (ER) stress causes cellular dysfunction and cell death by apoptosis; and thapsigargin is a well-known ER stress inducer. On the other hand, the chemical chaperone, 4-phenylbutyric acid (4-PBA) had showed to prevent ER stress; however, in cardiac fibroblast both the ER stress induced by thapsigargin and prevention by 4-PBA, have not been studied in detail. Neonate rat CF were treated with thapsigargin in presence or absence of 4-PBA, and cell viability was evaluated by trypan blue exclusion and apoptosis by flow cytometry; whereas CHOP, BIP, PDI, ATF4 and procollagen protein levels were assessed by western blot. In CF, thapsigargin triggered the unfolded protein response detected by early increases in ATF4, CHOP, PDI and BIP protein levels as well as, the accumulation of intracellular procollagen. Thapsigargin also stimulated CF death in a time and concentration-dependent manner. ER stress, CF death and apoptosis induced by thapsigargin were prevented by 4-PBA. Conclusion our data suggest that 4-PBA prevent ER stress, intracellular procollagen accumulation, CF death and apoptosis induced by thapsigargin.

[Intraoperative choledochoscopy usefulness in the treatment of difficult biliary stones]. / Utilidad de la coledocoscopia transquirúrgica en el tratamiento de litos biliares difíciles.

BACKGROUND: Choledocholithiasis presents in 5-10% of the patients with biliary lithiasis. Numerous treatment algorithms have been considered for this disease, however, up to 10% of these therapeutic procedures may fail. Intraoperative choledochoscopy has become a useful tool in the treatment of patients with difficult-to-manage choledocholithiasis. OBJECTIVES: To determine the usefulness of intraoperative choledochoscopy in the laparoendoscopic treatment of difficult stones that was carried out in our service. PATIENTS AND METHODS: A cross-sectional study was conducted. The case records were reviewed of the patients that underwent intraoperative choledochoscopy during biliary tree exploration plus laparoscopic choledochoduodenal anastomosis within the time frame of March 1, 2011 and May 31, 2012, at the Hospital General Dr. Manuel Gea González. Transabdominal choledochoscopies were performed with active stone extraction when necessary, followed by peroral choledochoscopies through the recently formed bilioenteric anastomosis. The data were analyzed with descriptive statistics and measures of central tendency. RESULTS: The mean age was 71 years, 57% of the patients were women, and the ASA III score predominated. Active extraction of stones with 7 to 35mm diameters was carried out in 4 of the cases and the absence of stones in the biliary tract was corroborated in all the patients. The mean surgery duration was 18 minutes (range: 4 to 45min). CONCLUSIONS: Choledochoscopy is a safe and effective minimally invasive procedure for the definitive treatment of difficult stones.

The risk of airborne cross-infection in a room with vertical low-velocity ventilation.

UNLABELLED: Downward flow ventilation systems are one of the most recommended ventilation strategies when contaminants in rooms must be removed and people must be protected from the risk of airborne cross-infection. This study is based on experimental tests carried out in a room with downward flow ventilation. Two breathing thermal manikins are placed in a room face to face. One manikin's breathing is considered to be the contaminated source to simulate a risky situation with airborne cross-infection. The position of the manikins in relation to the diffuser and the location of diffuser in the room as well as the distance between the manikins are being changed to observe the influence of these factors on the personal exposure of the target manikin. The results show that the DWF in different situations often is unable to penetrate the microenvironment generated by the manikins. The downward ventilation system can give an unexpected high level of contaminant exposure of the target manikin, when the distance between the manikins is reduced. PRACTICAL IMPLICATIONS: Several guidelines recommend the downward ventilation system to reduce the risk of cross-infection between people in hospital rooms. This study shows that this recommendation should be taken into careful consideration. It is important to be aware of people position, position to other thermal loads in the room, and especially be aware of the distance between people if the exposure to the exhaled contaminants wants to be reduced.

Distribution of exhaled contaminants and personal exposure in a room using three different air distribution strategies.

UNLABELLED: The level of exposure to human exhaled contaminants in a room depends not only on the air distribution system but also on people's different positions, the distance between them, people's activity level and height, direction of exhalation, and the surrounding temperature and temperature gradient. Human exhalation is studied in detail for different distribution systems: displacement and mixing ventilation as well as a system without mechanical ventilation. Two thermal manikins breathing through the mouth are used to simulate the exposure to human exhaled contaminants. The position and distance between the manikins are changed to study the influence on the level of exposure. The results show that the air exhaled by a manikin flows a longer distance with a higher concentration in case of displacement ventilation than in the other two cases, indicating a significant exposure to the contaminants for one person positioned in front of another. However, in all three cases, the exhalation flow of the source penetrates the thermal plume, causing an increase in the concentration of contaminants in front of the target person. The results are significantly dependent on the distance and position between the two manikins in all three cases. PRACTICAL IMPLICATIONS: Indoor environments are susceptible to contaminant exposure, as contaminants can easily spread in the air. Human breathing is one of the most important biological contaminant sources, as the exhaled air can contain different pathogens such as viruses and bacteria. This paper addresses the human exhalation flow and its behavior in connection with different ventilation strategies, as well as the interaction between two people in a room. This is a key factor for studying the airborne infection risk when the room is occupied by several persons. The paper only takes into account the airborne part of the infection risk.

[Anatomic variants of biliary ducts detected by endoscopio colangiography]. / Variantes anatómicas de la vía biliar por colangiografía endoscópica.

INTRODUCTION: The gallbladder and bile ducts originate through a complex process during the 4th gestational week; there is a wide variety in their anatomy. OBJECTIVE: To identify the type, frequency, and association with certain pathologies of anatomic variations of bile ducts in patients in which endoscopic retrograde colangiography (ERC) was performed. METHODS: Six hundred and six patients in whom ERCs were performed from 2005 to 2007 in the Endoscopio Unit at the Hospital General Dr. Manuel Gea González in Mexico City were included. Variations in bile duct anatomy seen in the X-ray taken during ERC were identified. Demographic characteristics of the patients, indications of the study, complications, treatments, and type of anatomic variant were registered. Descriptive statistics were used to analyze the information. X2 and Fisher´s exact test were also performed for the comparison between patients with and without anatomic variations. RESULTS: We identified biliary anatomic variations in 5.1% of patients in the study. Among them, seventy- seven per cent were women, with a mean age of 41 years. The anatomic variation most frequently found was a low union of the cystic duct with the common hepatic duct. The main diagnosis during ERC was choledocholithiasis in 71% of patients. Bile duct injuries were found in only 3.2% of patients with anatomic variations. CONCLUSIONS: Anatomic variations in bile ducts identified by ERC are frequent in Mexican population; nevertheless they were not associated with the occurrence of bile duct injuries.

Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice.

Gold nanoparticles (GNPs) offer a great promise in biomedicine. Currently, there is no data available regarding the accumulation of nanoparticles in vivo after repeated administration. The purpose of the present study was to evaluate the bioaccumulation and toxic effects of different doses (40, 200, and 400 microg/kg/day) of 12.5 nm GNPs upon intraperitoneal administration in mice every day for 8 days. The gold levels in blood did not increase with the dose administered, whereas in all the organs examined there was a proportional increase on gold, indicating efficient tissue uptake. Although brain was the organ containing the lowest quantity of injected GNPs, our data suggest that GNPs are able to cross the blood-brain barrier and accumulate in the neural tissue. Importantly, no evidence of toxicity was observed in any of the diverse studies performed, including survival, behavior, animal weight, organ morphology, blood biochemistry and tissue histology. The results indicate that tissue accumulation pattern of GNPs depend on the doses administered and the accumulation of the particles does not produce sub-acute physiological damage.

Hepatitis tóxica por carbimazol / Carbimazole-induced toxic hepatitis

Las tionamidas son fármacos antitiroideos que poseen habitualmente una buena tolerancia. No obstante, pueden originar toxicidad hematológica y hepática potencialmente grave. Presentamos el caso de una paciente de 45 años con hipertiroidismo por enfermedad de Graves-Basedow que, 3 semanas después de iniciar tratamiento con carbimazol (30 mg/día), presentó clínica de prurito, ictericia mucocutánea, orinas colúricas y molestias abdominales. La clínica y la analítica realizada confirmaron la existencia de colestasis y hepatólisis y fue necesario interrumpir el tratamiento antitiroideo y administrar corticoides y N-acetil cisteína. Su recuperación fue lenta y casi completa al año de evolución. La ausencia de otras causas de afección hepática y la secuencia cronológica entre el inicio del tratamiento, el comienzo de la sintomatología y la mejora tras su retirada indican que la hepatotoxicidad se debió al carbimazol

Thyonamides are antythyroid drugs usually with a good tolerance. However, these drugs can produce a potencially serious hepatic and hematologic toxicity. A file case report of a 45-year-old-woman with severe hyperthyroidism caused by Graves-Basedow illness, which was treated with carbimazole (30 mg daily) is provided. Three weeks later, the patient presented itch, icterus, intense choluria and abdominal discomfort. Clinic and analysis confirm cholestasis and hepatolysis, making it neccesary to interrupt the antythyroid therapy and administer corticoids and n-acetyl-cisteine. The recovery of this patient was slow and almost complete within one year. The absense of other causes of hepatic injury, chronology at the beginning of therapy, appearance of symptons and improvement after discontinuing use, leads us to believe that this response is due to carbimazole