Innate immune and chronic heat stress responses in sturgeons: Advances and insights from studies on Russian sturgeons.

Chronic stress deteriorates the immune function of fish, thereby increasing their vulnerability to infections. However, the molecular and cellular mechanisms underlying stress-mediated immunosuppression and infection susceptibility in fish remain largely unknown. Understanding these mechanisms will contribute to improving fish welfare and their farm production. Herein, we review the challenges of sturgeon aquaculture in subtropical countries, where current climate change has giving rise to significant temperature increments during summer. This leads to the exposure of fish to stressful conditions during these months. Chronic heat stress deserves attention considering the rapid warming rate of the planet. It is already affecting wild fish populations, with disastrous consequences for sturgeons, which are one of the most endangered fish species in the world. In this context, we discuss the most recent advances through the studies on the effects of chronic heat stress on the innate immune components of sturgeons. To this end, we summarise the findings of studies focusing on the aquaculture of Russian sturgeons and observations made on other Acipenser species. Special attention is given to acute-phase proteins, as they might be valuable biomarkers of heat stress and infection, with applicability in monitoring the fish health status in farms.

Infecciones asociadas al cuidado de salud en la unidad de quemados durante la pandemia SARS-CoV-2 / Healthcare-associated infections in the burn unit during the SARS-CoV-2 pandemic

Introducción: a partir de la pandemia por Covid19 se reportó variabilidad en la incidencia de las infecciones asociadas al cuidado de la salud (IACS). Con el objetivo de describir y comparar las tasas de IACS en la Unidad de Quemados de un hospital pediátrico de tercer nivel, antes y después del inicio de la pandemia se llevó a cabo este estudio. Material y métodos: estudio de cohorte, retrospectivo, descriptivo, de vigilancia epidemiológica. Se registraron todos los eventos de IACS en la Unidad de Quemados desde el 01/07/2018 hasta el 31/06/2021. Se compararon las tasas de las IACS entre el período I (PI) previo a la pandemia (07/2018-12/2019) y el período II (PII) posterior al inicio de la misma (01/2020- 06/2021). Resultados: se registraron 74 episodios de IACS, en un total de 8232 pacientes-día. Se registró una tasa global de IACS similar en ambos períodos, 10,08 ‰ pacientes-día (PI) vs 7,34 ‰ pacientes-día (PII), sin encontrarse diferencias estadísticamente significativas en las tasas de bacteriemia asociada a catéter venoso central (BSI-CVC) 3,32 ‰ días uso de CVC (PI) vs 3,20 ‰ (PII), neumonía asociada a ARM 1.43 ‰ días de uso de ARM (PI) vs un 2.02 ‰ (PII), ni infección urinaria asociada a sonda vesical (SV) 7,36 ‰ días de uso de SV (PI) vs 3,64 ‰ (PII). Conclusiones: no se observaron diferencias estadísticamente significativas en las tasas de IACS entre ambos períodos, lo cual podría justificarse con el estricto protocolo en control de infecciones implementado previo al inicio de la pandemia (AU)

Introduction: since the start of the Covid19 pandemic, variability in the incidence of healthcare-associated infections (HAIs) has been reported. This study was conducted to describe and compare the rates of HAIs in the burn unit of a tertiary pediatric hospital before and after the onset of the pandemic. Material and methods: a retrospective, descriptive, epidemiological surveillance cohort study was conducted. All HAI events in the burn unit from 01/07/2018 to 31/06/2021 were recorded. HAI rates between the pre-pandemic period I (PI) (07/2018- 12/2019) and post-pandemic period II (PII) (01/2020-06/2021) were compared. Results: 74 episodes of HAI were recorded in a total of 8232 patient-days. There was a similar overall rate of HAIs in both periods, 10.08 ‰ patient-days (PI) vs 7.34 ‰ patient-days (PII), with no statistically significant differences found in the rates of central venous catheter-related bloodstream infections (CVC-BSI) 3.32 ‰ days CVC use (PI) vs 3.20 ‰ (PII), ventilator-associated pneumonia 1. 43 ‰ days MV use (PI) vs a 2.02 ‰ (PII), or catheter-associated urinary tract infection 7.36 ‰ days catheter use (PI) vs 3.64 ‰ (PII). Conclusions: no statistically significant differences were observed in the rates of HAIs between both periods, which may be explained by the strict infection control protocol implemented prior to the onset of the pandemic (AU)

Efficacy of an organically modified bentonite to adsorb 2,4-dichlorophenoxyacetic acid (2,4-D) and prevent its phytotoxicity.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used due to it selective action, and preferential control of dicotyledonous weeds affecting cereal crops. Physiological responses of sensitive dicotyledonous plants to 2,4-D include growth retardation, senescence, and cell death. Due to soil and water contamination by agricultural practices, 2,4-D constitutes a potential risk to non-target plant species. In this work, the potential advantage of using organic modified bentonite (Bent) to adsorb 2,4-D and therefore mitigate damage produced by this herbicide on sensitive not-target vegetable species was investigated. Dodecylamine (DDA) was used as an organic modifier to change the hydrophilic nature of Bent into an organophilic matrix. The adsorption performances of 2,4-D by Bent-DDA were analyzed. The maximum adsorptions of 2,4-D (22.1 mg/L) from aqueous solution containing 1.0 or 2.5 mg/mL Bent-DDA were 40 and 80 %, respectively. The physical interaction of Bent-DDA with 2,4-D was characterized by Wide Angle X-ray Scattering (WAXS) and thermogravimetric analysis (TGA). The biological functionality of Bent-DDA matrix as 2,4-D adsorbent was tested in a bioassay in the Arabidopsis thaliana plant model system. The primary root growth of Arabidopsis seedlings is strongly inhibited by low concentrations of 2,4-D. Arabidopsis seedlings submitted to Bent-DDA pre-treated herbicide aqueous solution showed similar root growth than 2,4-D non-treated seedlings. Finally, the ability of Bent-DDA to prevent 2,4-D phytotoxicity was exploratory investigated in lettuce plants. Lettuce plants pre-treated with 20 µg/mL Bent-DDA showed reduced sensitivity to 2,4-D including an increment on chlorophyll content and biomass compared with non-treated plants. Our findings revealed a promising scenario for the application of Bent-DDA as an effective adsorbent of 2,4-D at productive scale.

Design of magnetic hybrid nanostructured lipid carriers containing 1,8-cineole as delivery systems for anticancer drugs: Physicochemical and cytotoxic studies.

The development of versatile carriers to deliver chemotherapeutic agents to specific targets with establishing drug release kinetics and minimum undesirable side effects is becoming a promising relevant tool in the medical field. Magnetic hybrid nanostructured lipid carriers (NLC) were prepared by incorporation of 1,8-cineole (CN, a monoterpene with antiproliferative properties) and maghemite nanoparticles (MNPs) into a hybrid matrix composed of myristyl myristate coated with chitosan. Hybrid NLC characterized by DLS and TEM confirmed the presence of positively charged spherical nanoparticles of around 250 nm diameter and +10.2 mV of Z-potential. CN encapsulation into the lipid core was greater than 75 % and effectively released in 24 h. Modification of the crystalline structure of nanoparticles after incorporation of CN and MNPs was observed by XRD, DSC, and TGA analyses. Superparamagnetic NLC behavior was verified by recording the magnetization using a vibrating scanning magnetometer. NLC resulted in more cytotoxic than free CN in HepG2 and A549 cell lines. Particularly, viability inhibition of HepG2 and A549 cells was increased from 35 % to 55 % and from 38 % to 61 %, respectively, when 8 mM CN was incorporated into the lipid NPs at 24 h. Green fluorescent-labeled NLC with DIOC18 showed an enhanced cellular uptake with chitosan-coated NLC. Besides, no cytotoxicity of the formulations in normal WI-38 cells was observed, suggesting that the developed hybrid NLC system is a safe and good potential candidate for the selective delivery and potentiation of anticancer drugs.

Emerging responses to the COVID-19 crisis from family farming and the agroecology movement in Latin America - A rediscovery of food, farmers and collective action.

CONTEXT: In Latin America, the so-called informal sector associated with family farming and the agroecology movements were instrumental at coping with and adapting to the COVID-19 challenges. OBJECTIVE: To assess the nature and extent of the early initiatives (first three months) deployed by this informal sector to cope with and adapt to the impacts of the COVID-19 pandemic on food production and consumption in several countries of the region. METHODS: We used key used informant consultation (n = 168), an online survey (n = 125) and the detailed characterisation of regional case studies (n = 4). Textual data was analysed and categorised using Reinert's method, combined with similarity analysis. RESULTS AND CONCLUSIONS: 65% of the initiatives were 'local' in terms of geographic reach, 30% of them started within the first month after the pandemic and most of them were urban or urban-rural, whereas only 29% of them were exclusively rural. The analysis of the textual information captured through the survey revealed four major types of initiatives that were deployed or adapted in response to COVID-19:1.Direct producer-to-consumer food sales, generally existing before the COVID-19 crisis but adapted/strengthened to cope with it;2.Short value chains that linked rural and urban organisations and individuals supported by national or local governments, readapted through new health and safety protocols;3.Newly developed support and training programs on sustainable food production for self-consumption or local commerce, in rural, urban or peri-urban settings;4.Food assistance and aid initiatives focusing on vulnerable populations, relying on solidarity networks associated with the agroecological movement. SIGNIFICANCE: The pandemic highlighted the key role played by local food systems and value chains and the need to strengthening them through public policies, as a way to build food resilience in times of crisis.

Nanoparticulated Systems Based on Natural Polymers Loaded with Miconazole Nitrate and Lidocaine for the Treatment of Topical Candidiasis.

People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300 nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12 mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24 h.

Lumbar degenerative spondylolisthesis II: treatment and controversies.

There are various approaches and surgical techniques with the objective of nerve root decompression, restrict mobility, and fusion of the listhesis. Among the techniques, posterior interbody fusion combines direct and indirect root decompression with the fusion between vertebral bodies, placing an autologous bone graft between transverse apophysis and vertebral bodies. Transforaminal lumbar and posterior interbody fusion, on the same way, look to decompress and fuse but with a different approach to the spine. The anterior approach for interbody fusion provides a better fusion rate. Lateral lumbar interbody fusion is considered less invasive, with an anterolateral transpsoas approach. The lumbar fusion technique in degenerative spondylolisthesis must be individualized. Non-fusion decompression is considered a less invasive procedure. Various studies suggest that decompression has better results when fusion is added. Surgery had several potential benefits and greater improvement in those patients who fail conservative management. An optimal technique is not conclusively identified.

El tratamiento de la espondilolistesis degenerativa lumbar es específico para cada etapa de la enfermedad y el manejo quirúrgico no debe de ser la primera elección en la mayoría de los casos. El manejo conservador está basado en el uso de antiinflamatorios no esteroideos, control de peso y rehabilitación. En caso de falla después de cuatro a seis semanas, el siguiente paso es la infiltración facetaria. En caso de dolor persistente, alteraciones neurológicas o claudicación neurogénica el siguiente paso es la cirugía. Existen varios abordajes y técnicas quirúrgicas con el objetivo de descomprimir las raíces nerviosas, restringir la movilidad y fusionar la listesis. Entre las técnicas quirúrgicas, la fusión posterior combina la descompresión directa e indirecta con artrodesis entre los cuerpos vertebrales, colocando injerto entre las apófisis transversas y los cuerpos vertebrales. La artrodesis intersomática transforaminal y posterior buscan de la misma manera la descompresión y fusión, pero con un abordaje distinto. El abordaje anterior para artrodesis intersomática provee la mejor tasa de fusión. La artrodesis intersomática lateral se considera un procedimiento menos invasivo, con un abordaje anterolateral transpsoas. La técnica de artrodesis lumbar en la espondilolistesis debe ser individualizada. La descompresión sin artrodesis se considera un procedimiento menos invasivo; varios estudios sugieren que la descompresión tiene mejores resultados cuando se agrega una artrodesis. La cirugía tiene múltiples beneficios posibles en pacientes en quienes el tratamiento conservador ha fallado. No se ha identificado una técnica óptima de tratamiento.

Degenerative spondylolisthesis I: general principles.

Lumbar degenerative spondylolisthesis is the result of the progression from degenerative changes in the intervertebral disc and facet joints that lead to destabilizing one or more vertebral segments. It is characterized by the anterior sliding of the vertebral body secondary to the sagittalization of the facet joints. Wiltse, Newman, and Macnab classified it as type III. It is a pathology typical of elderly patients that predominate in women with a ratio of 5:1 compared to men; the most affected segment is L4-L5, the listhesis rarely exceeds 30% slip. It may or may not generate clinical manifestations, and the severity of these does not always correlate with the degree of sliding. The cardinal symptom is lumbar pain with or without radicular pain. Neurogenic claudication occurs in 75% of patients; it is caused by blood hypoperfusion secondary to the compression of the nerve roots, manifesting as pain in the lower limbs with variable walking distances. For the diagnosis of degenerative spondylolisthesis, comprehensive evaluation with static, dynamic radiographic studies in a standing position and magnetic resonance imaging are essential. The conservative treatment is the first-line therapy; it includes analgesics, anti-inflammatories, physiotherapy.

La espondilolistesis degenerativa lumbar es el resultado de la progresión de los cambios degenerativos en el disco intervertebral y las articulaciones facetarias que termina por inestabilizar uno o varios segmentos vertebrales. Se caracteriza por el deslizamiento anterior del cuerpo vertebral secundario a la sagitalización de las facetas articulares, Wiltse, Newman y Macnab la clasifican como tipo III. Es una patología propia de los pacientes de la tercera edad, predomina en mujeres con una relación de 5:1 respecto a los varones, el segmento más afectado es L4-L5, el desplazamiento rara vez supera el 30% de deslizamiento. Puede o no generar manifestaciones clínicas y la severidad de éstas, no siempre correlaciona con el grado de listesis. El síntoma cardinal es el dolor lumbar con o sin dolor radicular; mientras que la claudicación neurogénica se presenta en 75% de los pacientes, es causada por la hipoperfusión sanguínea secundaria a la compresión de las raíces nerviosas y se manifiesta como dolor en los miembros inferiores, con la deambulación a distancias variables. Para el diagnóstico de la espondilolistesis degenerativa es indispensable una evaluación integral con estudios radiográficos estáticos, dinámicos en posición de pie y resonancia magnética. La primera línea de tratamiento es el manejo conservador, este incluye analgésicos, antiinflamatorios, fisioterapia.

Silicon sources for studies of rice plants in nutrient solutions / Fontes de silício para estudos com a cultura do arroz em solução nutritiva

The objective of this work was to evaluate the effects of various Si sources currently used in studies of Si doses in nutrient solutions on dry matter yield and the accumulation of nutrients and Si in rice plants. Treatments of rice plants with three sources of Si (monossilicic acid, sodium metasilicate, potassium metasilicate) and a treatment without Si were allocated in a randomized block design with ten replications. After 39 days in the nutrient solution, the following traits were evaluated: leaf area, leaf specific mass, dry matter yield of roots and shoots, and levels of K, Na, and Si in leaves and roots. Si increased leaf area, leaf specific mass, and dry matter yield of shoots and roots regardless of the Si source. Levels of Si in leaves and roots were significantly higher in relation to the control treatment but no significant difference among Si sources was identified. It was also observed that K and Na were adequately balanced across the treatments. Thus, a cheaper and easier to obtain Si source, such as sodium metasilicate and potassium metasilicate, may be chosen to carry out studies of Si additions to nutrient solutions.

O objetivo deste trabalho foi avaliar fontes de Si utilizadas atualmente nos estudos com Si em solução nutritiva, na produção de massa seca e acúmulo de nutrientes e Si em plantas de arroz. Foram avaliadas fontes de Si (ácido monossilícico, metassilicato de sódio, metassilicato de potássio) e um tratamento sem aplicação desse elemento, em delineamento em blocos casualizados, com dez repetições, utilizando a cultura do arroz. Após 39 dias em solução nutritiva com os tratamentos foram avaliadas a área foliar, massa foliar específica, produção de matéria seca das raízes e da parte aérea, teores de K, Na e Si nas folhas e nas raízes. O Si aumentou a área foliar, a massa foliar específica e produção de massa seca da parte aérea e raízes, independentemente da fonte utilizada. Os teores de Si nas folhas e nas raízes foram significativamente maiores em relação à testemunha e não houve diferença entre as fontes utilizadas. Observou-se também que o balanceamento de K e Na entre os tratamentos foi adequado. Desse modo, pode-se escolher uma fonte de menor custo e mais fácil obtenção como o metassilicato de sódio e o metassilicato de potássio para a execução de trabalhos que avaliem a adição de Si à solução nutritiva.

Osteomielitis fúngica en niños quemados / Fungal osteomyelitis in burned children

Introducción: En pacientes pediátricos quemados la osteomielitis fúngica es una complicación infrecuente que conduce a una significativa morbilidad. La información en la literatura está limitada a unos escasos reportes de casos. Objetivo: Describir las características clínicas, epidemiológicas y de evolución de niños quemados con osteomielitis fúngica. Métodos: Se llevo a cabo un estudio retrospectivo y descriptivo de pacientes mayores de 1 mes y menores de 18 años quemados con osteomielitis fúngica internados en el hospital Juan P. Garrahan, un hospital terciario en Buenos Aires, Argentina. Resultados: entre enero del 2007 y enero del 2017, de 600 niños quemados, 9 pacientes presentaron diagnóstico confirmado de osteomielitis fúngica. La mediana de edad fue de 42.5 meses (RIC, 27-118 meses) y la mediana de superficie quemada fue de 33.5% (RIC, 18.5-58%). La osteomielitis fue diagnosticada con una mediana de 30 días luego de la quemadura. Las localizaciones más frecuentes de osteomielitis fueron los miembros superiores y a nivel de calota. Los microorganismos aislados a partir del cultivo de hueso fueron: Fusarium spp. en tres pacientes, Mucor spp. en un paciente; Trichosporon asahii en un paciente; Cándida albicans en dos pacientes y Candida parapsilosis en dos pacientes. En dos casos la infección fúngica fue asociada con aislamientos bacteriano concomitante. Todos los pacientes presentaron hallazgos histopatológicos compatibles con osteomielitis. La mediana de tiempo de tratamiento fue de 44.5 días (RIC, 34.5- 65.5 días). Seis pacientes (67%) presentaron secuela motora. Conclusión: La osteomielitis fúngica fue infrecuente Candida spp. y Fusarium spp. fueron los hongos más comúnmente identificados. La secuela funcional fue frecuente (AU)

Introduction: In pediatric burn patients fungal osteomyelitis is a rare complication that leads to significant morbidity. Data in the literature are limited to sporadic case reports. Objective: To describe the clinical and epidemiological features and outcome in burned children with fungal osteomyelitis. Methods: A retrospective descriptive study was conducted in burn patients older than 1 month and younger than 18 years admitted to Hospital Juan P. Garrahan, a tertiary hospital in Buenos Aires, Argentina. Results: Between January 2007 and January 2017, of 600 burned children, nine had a confirmed diagnosis of fungal osteomyelitis. Median age was 42.5 months (IQR, 27-118 months) and median burn surface was 33.5% (IQR, 18.5-58%). Osteomyelitis was diagnosed at a median of 30 days after the burn. The most common location of osteomyelitis were the upper limbs and skull. The microorganisms isolated form bone cultures were Fusarium spp. in three patients, Mucor spp. in one patient; Trichosporon asahii in one patient; Candida albicans in two patients; and Candida parapsilosis in two patients. In two cases the funal infection was associated with concomitant bacterial isolation. In all patients, the histopathological findings were compatible with osteomyelitis. Median duration of treatment was 44.5 days (IQR, 34.5-65.5 days). Six patients (67%) had motor sequelae. Conclusion: Fungal osteomyelitis is a rare disease. Candida spp. and Fusarium spp. were most frequently identified fungi. Functional sequelae were common (AU)

Hybrid Ofloxacin/eugenol co-loaded solid lipid nanoparticles with enhanced and targetable antimicrobial properties.

In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiate antimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol (Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24 h. Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300 nm and Ofx entrapped in amorphous state. The SLN exhibited an enhanced bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0 µg/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3-30.0 µg/ml and showed no toxicity up to 3.0 µg/ml Ofx in human cell models (A549 and Wi-38) at 24 h and 48 h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.

Effect of platform subway depth on the presence of Airborne PM2.5, metals, and toxic organic species.

PM2.5 that have been related to public health risks, were collected during two seasons with High-Vol samplers in platforms of a Mexican subway station, which interconnects through transfers three lines having different depths. The objective was to study the influence of depth on the PM2.5 concentrations and their species. PM2.5 concentrations in cold-dry and warm-dry seasons presented statistical differences, being in average 57 and 66 µgm-3 respectively, in the shallower line 9; 90 µgm-3 and 111 µgm-3 in line 1; and 104 and 122 µgm-3in the deepest line 7. During the cold-dry season and warm-dry season PM2.5concentrations in the subway environment were respectively up to 3.5 times and up to 5 times greater than in the ambient air. Like PM2.5, metals analyzed with an OES-ICP presented higher concentrations in deeper lines as well as PAHs quantified with CG-MS, which ranged from 4.5 to 11.7 ngm-3. High PM2.5, metals and organic toxic concentrations found in deeper lines of the subway environment represent a risk for commuters endorsing the need for ventilation systems to reduce them. Zn, Pb, V and Ni in subway particles presented the highest solubility in artificial lysosomal fluid suggesting high bioavailability in the lung fluids.

Hipotiroidismo refractario idiopático: un caso clínico / Idiopathic refractory hypothyroidism: case report

Introducción: El hipotiroidismo constituye una patología frecuente, y su tratamiento habitual es el suplemento de levotiroxina (LT4) oral (VO). Sin embargo, existen casos inhabituales donde no es posible corregir esta condición a pesar de la utilización de LT4 en dosis alta. El hipotiroidismo refractario se define como la persistencia del hipotiroidismo a pesar del uso de LT4 > 1,9 ug/kg/día. La prevalencia del hipotiroidismo refractario no ha sido suficientemente documentada hasta ahora. Descripción del caso: Mujer de 53 años con antecedentes de hipotiroidismo, obesidad, dislipidemia, hipertensión arterial e insulinorresistencia. Fue derivada desde APS a nivel terciario por hipotiroidismo persistente a pesar del uso de LT4 800 ug/día y liotironina 80 ug/día. En forma ambulatoria se descartaron distintas causas, como mala adhesión al tratamiento, pseudo-malabsorción, síndromes de malabsorción; interacciones farmacológicas o interacciones alimentarias. Ante esto, y manteniéndose en su condición, se decide hospitalizar. Durante la hospitalización se prueban distintas fórmulas de administración. Finalmente, se logra respuesta adecuada con LT4 por vía rectal 100 ug/día asociado a 100 ug c/12 horas VO. Discusión: A pesar de no contar con herramientas óptimas para enfrentar este caso, se logró aplicar una estrategia sistemática especializada, que permitió un buen manejo de la paciente. Luego de probar distintas formulaciones de hormonas tiroideas, se logró respuesta mediante la administración por vía rectal, lo cual sugiere que esta paciente presentaba algún trastorno celular/bioquímico intestinal alto, que impedía la absorción óptima de LT4 VO. Conclusiones: La principal fortaleza de este trabajo consiste en la demostración de la utilidad práctica, en un contexto de recursos limitados, de una estrategia de estudio y tratamiento sistemático del hipotiroidismo refractario, lo cual ha sido escasamente publicado en la literatura internacional. Además, se recalca la importancia de una intervención especializada oportuna para evitar los riesgos sistémicos asociados a dosis altas de hormonas tiroideas.

Introduction: Hypothyroidism is a common condition, and its usual treatment is the supplement of oral levothyroxine (po). However, there are unusual cases where it is not possible to correct this condition despite the use of high-dose levothyroxine. Refractory hypothyroidism is defined as the persistence of hypothyroidism despite the use of levothyroxine > 1.9 ug/kg/ day. The prevalence of refractory hypothyroidism has not been sufficiently documented so far. Case description: 53 year old woman with a history of hypothyroidism, obesity, dyslipidemia, hypertension and insulin resistance. She was sent from primary care to tertiary level due to persistent hypothyroidism despite the use of 800 ug/day levothyroxine and liothyronine 80 ug/ day. On an outpatient basis, different causes were excluded as poor adherence to treatment, pseudo-malabsorption, malabsorption syndromes; drug interactions or food interactions. Given this, and staying on her condition, it was decided to hospitalize. Different forms of administration were tested during hospitalization. Finally, got adequate response with levothyroxine rectally 100 ug/day associated with 100 ug po bid. Discussion: Despite not having optimum tools to deal with this case, it was succeeded thanks to the implementation of a specialized systematic strategy. After testing different formulations of thyroid hormones, a positive response by rectal administration was achieved, which suggests that this patient presented any high intestinal cell/biochemist disorder that prevented the optimal absorption of levothyroxine po. Conclusions: The main strength of this work consists in demonstrating the practical utility, in a context of limited resources, of a study and systematic treatment strategy of refractory hypothyroidism, which has barely been published in the international literature. It is also highlighted the importance of an early specialized intervention to prevent the systemic risks associated with high doses of thyroid hormones.

Composite Microparticles Based on Natural Mucoadhesive Polymers with Promising Structural Properties to Protect and Improve the Antifungal Activity of Miconazole Nitrate.

Oropharyngeal candidiasis is a recurrent oral infection caused by Candida species. Gel formulation containing miconazole nitrate is the most common approach for treating oral candidiasis. However, traditional oral topical antifungal therapies have many limitations, including short contact time with the oral mucosa and the necessity to administrate various doses per day. Thus, the aim of this work was to formulate composited microparticulated systems based on combinations of mucoadhesive cationic, anionic, and nonionic polymers that could protect and modify the drug release rate and therefore avoid a fast dilution of the drug by saliva. Microparticulated systems were prepared by the spray drying method employing chitosan, gelatin, and hydroxypropyl methylcellulose. The morphology of the systems was investigated by scanning electron microscopy; drug crystallinity was studied by X-ray, while interactions between polymers were analyzed by infrared spectroscopy. Drug release and halo zone test were employed to analyze the release and activity of the systems loaded with miconazole against Candida albicans cultures. The most appropriate microparticulated system was the one based on chitosan and gelatin which showed homogeneous morphology (mean size of 1.7 ± 0.5 µm), a protective effect of the drug, and better antifungal effect against Candida culture than miconazole nitrate and the other assayed systems. Taking into account these results, this approach should be seriously considered for further evaluation of its safety and in vivo efficacy to be considered as an alternative therapeutic system for the treatment of oral candidiasis.

Bacterial cellulose hydrogel loaded with lipid nanoparticles for localized cancer treatment.

The use of hybrid materials, where a matrix sustains nanoparticles controlling the release of the chemotherapeutic drug, could be beneficial for the treatment of primary tumors prior or after surgery. This localized chemotherapy would guarantee high drug concentrations at the tumor site while precluding systemic drug exposure minimizing undesirable side effects. We combined bacterial cellulose hydrogel (BC) and nanostructured lipid carriers (NLCs) including doxorubicin (Dox) as a drug model. NLCs loaded with cationic Dox (NLCs-H) or neutral Dox (NLCs-N) were fully characterized and their cell internalization and cytotoxic efficacy were evaluated in vitro against MDA-MB-231 cells. Thereafter, a fixed combination of NLCs-H and NLCs-N loaded into BC (BC-NLCs-NH) was assayed in vivo into an orthotopic breast cancer mouse model. NLCs-H showed low encapsulation efficiency (48%) and fast release of the drug while NLCs-N showed higher encapsulation (97%) and sustained drug release. Both NLCs internalized via endocytic pathway, while allowing a sustained release of the Dox, which in turn rendered IC50 values below of those of free Dox. Taking advantage of the differential drug release, a mixture of NLCs-N and NLCs-H was encapsulated into BC matrix (BC-NLCs-NH) and assayed in vivo, showing a significant reduction of tumor growth, metastasis incidence and local drug toxicities.

Effect of drug incorporation technique and polymer combination on the performance of biopolymeric antifungal buccal films.

Numerous films with a dissolved or dispersed active principle within a polymeric matrix have been described in literature. However, the incorporation of solid crystals into the films may influence several relevant properties. Additionally, it has been reported that different polymeric matrices lead to films presenting a different performance. The aim of this work was to evaluate the effect of the combination of chitosan with carrageenan (κ-, λ-, and ι-) as matrices, and of the miconazole nitrate incorporation method, on the films behavior. Mechanical properties, drug release and antifungal activity were evaluated. The state of the drug in the films was analyzed by different techniques. Films showed a homogeneous surface and a thermal protective effect on the drug. The combination of chitosan and λ-carrageenan leads to films with the highest values of tensile and mucoadhesive strength. Films with solubilized drug displayed slightly higher elongation at break, tensile and mucoadhesive strength and faster drug release than those with suspended miconazole nitrate. However, no differences were found regarding the antifungal activity of the different formulations including time-to-kill curves.