Application of gabapentinoids and novel compounds for the treatment of benzodiazepine dependence: the glutamatergic model.

BACKGROUND: Current approaches for managing benzodiazepine (BZD) withdrawal symptoms are daunting for clinicians and patients, warranting novel treatment and management strategies. This review discusses the pharmacodynamic properties of BZDs, gabapentinoids (GBPs), endozepines, and novel GABAergic compounds associated with potential clinical benefits for BZD-dependent patients. The objective of this study was to review the complex neuromolecular changes occurring within the GABAergic and glutamatergic systems during the BZD tolerance and withdrawal periods while also examining the mechanism by which GBPs and alternative pharmacological therapies may attenuate withdrawal symptoms. METHODS AND RESULTS: An elaborative literature review was conducted using multiple platforms, including the National Center for Biotechnology (NCBI), AccessMedicine, ScienceDirect, pharmacology textbooks, clinical trial data, case reports, and PubChem. Our literature analysis revealed that many distinctive neuroadaptive mechanisms are involved in the GABAergic and glutamatergic systems during BZD tolerance and withdrawal. Based on this data, we hypothesize that GBPs may attenuate the overactive glutamatergic system during the withdrawal phase by an indirect presynaptic glutamatergic mechanism dependent on the α2δ1 subunit expression. CONCLUSIONS: GBPs may benefit individuals undergoing BZD withdrawal, given that the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor current significantly increases during abrupt BZD withdrawal in animal studies. This may be a conceivable explanation for the effectiveness of GBPs in treating both alcohol withdrawal symptoms and BZD withdrawal symptoms in some recent studies. Finally, natural and synthetic GABAergic compounds with unique pharmacodynamic properties were found to exert potential clinical benefits as BZD substitutes in animal studies, though human studies are lacking.

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study.

OBJECTIVES: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). METHODS: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. RESULTS: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. CONCLUSIONS: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal.

Carcinoma sarcomatoide de laringe. ¿Un reto histológico? / Sarcomatoid carcinoma of larynx. A histological challenge?

Introducción. El carcinoma sarcomatoide puede aparecer en cualquier parte del cuerpo, siendo las glándulas salivales mayores su principal localización en cabeza y cuello, pero en la laringe representa aproximadamente un 1%. Cuenta con componentes epiteliales y mesenquimales, lo que ha llevado a plantear múltiples teorías acerca de su origen. Por esto su diagnóstico anatomopatológico puede ser un reto. Caso clínico. Presentamos un caso clínico de un varón de 76años fumador que consulta por disfonía. Se observa una lesión en cuerdas vocales sin adenopatías ni metástasis. Se le realiza microcirugía laríngea con escisión completa de la lesión, y el diagnóstico anatomopatológico es de carcinosarcoma, mostrando positividad intensa y difusa para vimentina y focal para AE1-AE3, CK5 y p63. El paciente recibe tratamiento complementario con radioterapia. Discusión. El carcinoma sarcomatoide tiende a manifestarse con síntomas obstructivos como la disfonía. Su pronóstico depende del estadio y de si hay o no metástasis. Suelen ser positivos los marcadores epiteliales citoqueratina (AE1-AE3), antígenos de membrana epitelial (EMA), Ki 67 y marcadores mesenquimales como vimentina, desmina y S-100. En cuanto al tratamiento, se recomienda de entrada una biopsia por escisión seguida o no de radioterapia complementaria, aunque la radioterapia sola también ha tenido éxito (T2-T1). En estadios T3-T4 pueden ser tratados con resección local, laringectomía parcial, total con o sin vaciamiento, seguida de radioquimioterapia concomitante (AU)

Introduction. Sarcomatoid carcinoma can occur in any part of the body; in the head and neck it occurs most frequently in the major salivary glands, with only about 1% of cases found in the larynx. As it has both epithelial and mesenchymal components, there are many theories concerning its origin and it can prove a diagnostic challenge. Case report. A 76 year old male smoker presented with dysphonia. Vocal cord injury was found on examination but no lymphadenopathy or metastases were present. Laryngeal microsurgery was performed with complete excision of the lesion. Histopathology showed it to be a carcinosarcoma which showed intense and diffuse positivity for vimentin and focal positivity for AE1-AE3, CK5 and p63. The patient underwent radiotherapy as complementary treatment. Discussion. Sarcomatoid carcinoma usually presents with obstructive symptoms such as dysphonia. Prognosis depends on the stage and the presence or not of metastases. Both epithelial markers EMA, cytokeratin (AE1-AE3), epithelial membrane antigen, Ki 67 and mesenchymal markers such as vimentin, desmin, S-100 may be positive in these tumours. Recommended treatment for T2-T1 stages is an excisional biopsy which can be followed by adjuvant radiotherapy; radiotherapy alone has also been successful. T3-T4 stages can be treated with local excision, partial laryngectomy or total laryngectomy with subsequent ganglion emptying and concomitant radio and chemotherapy (AU)

Lipoprotein(a) concentrations in rheumatoid arthritis on biologic therapy: Results from the CARdiovascular in rheuMAtology study project.

BACKGROUND: Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. OBJECTIVE: The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. METHODS: Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. RESULTS: Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (ß: -0.303, 95% confidence interval: -0.558 to -0.047; P = .02). CONCLUSIONS: RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.

Modulating Effects of Emotional Valence on Recognition Memory for High-Arousal Pictures / Efectos moduladores de la valencia emocional sobre la memoria de reconocimiento para imágenes de alto arousal

ABSTRACT The main aim of this paper was to provide new evidence on the effects of valence on recognition memory of emotional pictures, on the basis of rigorous experimental control of stimulus material. Valence was manipulated using pleasant and unpleasant pictures, keeping arousal constant at a high level. A reference condition with a neutral value in both dimensions was also included. We found greater discrimination and a more conservative response bias, as well as slower recognition decisions, for pleasant pictures. Also worthy of mention is the high positive correlation between response times and discrimination measures just for such pictures. These results would be consistent with an adaptive interpretation based on motivation and personal relevance of emotional information.

RESUMEN El principal objetivo del presente trabajo fue aportar nueva evidencia sobre los efectos de la valencia en el reconocimiento de imágenes de contenido emocional, a partir de un riguroso control experimental del material estimular. Se manipuló la valencia a niveles agradable y desagradable, manteniendo constante el arousal a un nivel alto. Se incluyó también una condición de referencia con un valor neutro en ambas dimensiones. Se encontró una mejor discriminación, un sesgo de respuesta más conservador y un reconocimiento más lento para las imágenes agradables. Además, solo para estas imágenes existió alta correlación positiva entre tiempos de respuesta y discriminación. Estos resultados serían consistentes con una interpretación de carácter adaptativo basada en la motivación y relevancia personal de la información emocional.

Successful treatment of generalized elastolytic giant cell granuloma with psoralen-ultraviolet A.

Elastolytic giant cell granuloma (EGCG) is an infrequent granulomatous skin disorder with variable response to different therapeutic regimens. Information on the benefit of phototherapy is very scarce as this therapy has seldom been tried in the affected patients. We present the results achieved in two female patients after undergoing psoralen-ultraviolet A (PUVA). Two 54-year-old otherwise healthy female patients received a course of PUVA after trying other alternatives. Complete clearance was achieved in the two patients with excellent tolerance and no adverse effects. We consider PUVA is a well-tolerated, safe, and effective treatment for patients with EGCG.

Risk factors for prediction of inadequate response to antiresorptives.

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross-sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti-osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx™) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47-8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55-9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93-0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem.

As, Hg, and Se flue gas sampling in a coal-fired power plant and their fate during coal combustion.

As, Hg, and Se are the most volatile elements in the flue gas from a coal-fired power plant. Significant amounts of these elements cause an undesired direct gaseous emission, which leads to a serious environmental health risk. The main focus of this study is to evaluate the possibility of simultaneous sampling of these volatile elements using an accurate official method for Hg (the most volatile element). A study of As, Hg, and Se emissions from a 1400 MW coal-fired power plant equipped with electrostatic precipitators (ESPs) was carried out for the combustion of a mixture of two types of coal. Simultaneous sampling of coal, bottom ash, fly ash, flue gas, and particles associated with the gas phase has been performed. Flue gas has been sampled by the Ontario Hydro Method Sampling Train, an ASTM method for Hg speciation. This sampling method was tested for As and Se sampling. As and Se determinations have been performed by HG-AAS, and Hg has been determined by CV-AAS. The results were used to examine the following: overall mass balances, relative distribution of these elements in the coal-fired power plant; As, Hg, and Se concentrations in coal and combustion residues; and predominant oxidation state for Hg in flue gas. The mass balances obtained for As, Hg, and Se were satisfactory in all cases; nevertheless, relative enrichment values in fly ash for As and Se were low; therefore, we concluded that As sampling in flue gas can be conducted by application of the Ontario Hydro Method; nevertheless Se released in the gas phase is not completely collected by this sampling train. Application of this sampling method allowed for performance of Hg speciation. The results indicated that Hg(II) was the predominant species in flue gas. It has also been proved that 24%, more than 99.8%, and 90% for As, Hg, and Se in the stack emissions, respectively, were in the gaseous phase.

Lesiones inducidas por la aplicación tópica de cocaína / Lesions of the oral mucosa in cocaine users who apply the drug topically

El uso y abuso de cocaína es un fenómeno en continuo crecimiento en nuestra sociedad y cada vez se evidencian más los problemas relacionados con la utilización de esta droga. La cocaína puede ser utilizada de varias formas y sus efectos sobre la cavidad oral varían según la vía de administración. El objetivo de este artículo es presentar las lesiones, en cuatro pacientes, que surgen como consecuencia de la aplicación tópica de cocaína sobre la mucosa alveolar y nasal con la finalidad de aliviar el dolor producido por algias faciales, tipo cefaleas en racimos. Esa práctica ha producido lesiones eritematosas en tres de estos pacientes y rápida recesión gingival y secuestro óseo en otro de ellos. El potencial vasoconstrictor de la cocaína, asociado con el efecto cáustico de la droga sobre la mucosa, son probablemente los factores responsables de estas lesiones (AU)

Características de la enfermedad de paget en una amplia serie de pacientes de ámbito hospitalario / Characteristics of Paget disease in a wide series of patients of a hospital environment

Fundamento: Se dispone de escasa información clínica sobre la enfermedad de Paget obtenida de forma sistemática a partir de fuentes originales. La hipótesis que indica que se están produciendo cambios seculares en ciertas características refuerza la necesidad de actualizar este tipo de información. Objetivo: Definir las características generales, la topografía y las manifestaciones clínicas de la enfermedad en un grupo de pacientes seguidos en una consulta monográfica. Pacientes y métodos: Cohorte constituida por 233 pacientes revisados de forma sistemática desde 1992, según un protocolo clinicoepidemiológico. Una vez codificadas, las variables se registraban en una base de datos ad hoc creada a partir del programa EPI-6. Se calculó la extensión de las lesiones (índice de Coutris) mediante las radiografías de los huesos que mostraban un depósito anómalo del trazador en la gammagrafía ósea. Se determinó la concentración de calcio, fósforo y fosfatasa alcalina total en suero (autoanalizador Hitachi 747) y de calcio y fósforo e hidroxiprolina (cromatografía líquida de alta densidad) en orina. Resultados: El 55 por ciento fueron varones; la media de edad (ñ DE) fue de 67,5 ñ 10,3 años (límites: 29-89); el 40 por ciento monostóticos. Las localizaciones más frecuentes fueron ilíaco, fémur, cráneo, vértebras lumbares y sacro. El promedio de focos fue de 3,01 ñ 3,08; extensión: 8,4 ñ 7,1. El 76 por ciento fueron sintomáticos (dolor óseo: 65 por ciento). La complicación más frecuente fue la coxopatía pagética (a menudo protrusiva). El síndrome craneal más frecuente fue la hipoacusia (49 por ciento), 34 fracturas en 30 pacientes (13 por ciento), y un caso de degeneración sarcomatosa. Fosfatasa alcalina: 905,9 ñ 800,6 U/l; hidroxiprolina: 77,2 ñ 66,5 mg/24 h. Conclusiones: La similitud entre las distintas series en cuanto a las características clínicas y topográficas de la enfermedad confieren una gran consistencia a estos datos a pesar de la diversidad de métodos empleados (AU)

Elaboración y analisis de harinas codeshidratadas de vegetales y especies de pescado subutilizadas: I. Codeshidratados de cereal-pescado / Preparation and analysis of dehydrated mixtures of vegetables and underutilized fish species flours: I. Dehydrated mixtures of cereal-fish

Con la finalidad de aportar posibles soluciones a los problemas de desnutrición que afectan a aquellas poblaciones en las que los cereales y tubérculos constituyen parte importante de la ingesta habitual diaria, se desarrollaron productos a base de cereales, codeshidratándolos con pulpa de pescado de especies subutizadas en la actualidad, pero que contienen proteína de alta calidad. Se seleccionaron dos cereales para los experimentos: arroz y maíz, y una especie marina subutilizada, curvinata de mar (Macrodom ancyclodom) para preparar harinas codeshidratadas con diferentes proporciones de pescado (0%, 5%, 10% y 15% en base seca). Luego se llevaron a cabo experimentos de alimentación en ratas Wistar, recién destetadas, y se evaluaron las características más importantes, obteniéndose un perfil de aminoácidos que refleja proteínas de alta calidad, evidenciado por los excelentes valores de PER, NPU, NPR y digestibilidad obtenidos. Los codeshidratados preparados con 5% y hasta 10% de pescado en base seca no acusaron ningún olor; a partir del nivel de 15% sí se percibía el olor a pescado. Por lo tanto, se recomienda el uso de los codeshidratados hasta con 10% de pescado en la elaboración de alimentos, ya que éstos serían de gran ayuda en la solución del problema de la excasez de proteína de buena calidad, sobre todo en los países en proceso de desarrollo