Sex differences in cytokines and adipokines in obese patients with PsA and controls undergoing a weight loss intervention.

OBJECTIVE: In this post hoc analysis of a previously published study, we compared cytokines and adipokine levels in women and men with psoriatic arthritis (PsA) at baseline (BL) and 6 months (M6) following a weight loss intervention. METHODS: Patients with PsA (n=41) between 25 and 75 years of age, with body mass index (BMI)≥33 kg/m2 were included in a weight loss intervention with a very low energy diet (VLED) for 12 or 16 weeks depending on BL BMI<40 or ≥40 kg/m2. As controls (n=39), obese individuals, already planned for VLED treatment were recruited and matched for sex, age and weight to the patients with PsA. Cytokines and adipokines were measured at BL and M6. RESULTS: At BL, serum levels of interleukin (IL)-23, leptin and high molecular weight-adiponectin were higher in women with PsA compared with men, whereas serum levels of interferon (IFN)-γ, IL-12/IL-23 p40 and IL-13 were significantly lower in women. Serum IL-23 was significantly reduced at M6 compared with BL in women but not in men with PsA. In women with PsA, the reduction in IL-23 at M6, ∆IL-23, were positively correlated with ∆Disease Activity Score 28 C reactive protein (CRP) (Spearman's correlation (rS)=0.486, p=0.016), ∆CRP (rS=0.468, p=0.021), ∆leptin (rS=0.683, p<0.001) and negatively correlated with ∆total-adiponectin (rS=-0.433, p=0.035). Also in women, ∆Disease Activity in Psoriatic Arthritis was positively correlated with ∆tumour necrosis factor-α (rS=0.417, p=0.034), ∆IL-1ß (rS=0.550, p=0.034), ∆IFN-γ (rS=0.414, p=0.035) and ∆leptin (rS=0.410, p=0.038). None of these correlations were significant in men with PsA. CONCLUSIONS: Women and men with PsA differed with regard to serum levels of cytokines and adipokines before and after weight loss.

Inhibition of PI3K/Akt and ERK signaling decreases visfatin-induced invasion in liver cancer cells.

OBJECTIVES: Visfatin is found in adipose tissue and is referred to as nicotinamide phosphoribosyltransferase (Nampt). Visfatin has anti-apoptotic, proliferative, and metastatic properties and may mediate its effects via ERK and PI3K/Akt signaling. Studies have yet to determine whether inhibition of kinase signaling will suppress visfatin-induced liver cancer. The purpose of this study was to determine which signaling pathways visfatin may promote liver cancer progression. METHODS: HepG2 and SNU-449 liver cancer cells were exposed to visfatin with or without ERK or PI3K/Akt inhibitor, or both inhibitors combined. These processes that were assessed: proliferation, reactive oxygen species (ROS), lipogenesis, invasion, and matrix metalloproteinase (MMP). RESULTS: Inhibition of PI3K/Akt and combination of inhibitors suppressed visfatin-induced viability. ERK inhibition in HepG2 cells decreased visfatin-induced proliferation. ERK inhibitor alone or in combination with PI3K inhibitors effectively suppressed MMP-9 secretion and invasion in liver cancer cells. PI3K and ERK inhibition and PI3K inhibition alone blocked visfatin's ROS production in SNU-449 cells. These results corresponded with a decrease in phosphorylated Akt and ERK, ß-catenin, and fatty acid synthase. CONCLUSIONS: Akt and ERK inhibition differentially regulated physiological changes in liver cancer cells. Inhibition of Akt and ERK signaling pathways suppressed visfatin-induced invasion, viability, MMP-9 activation, and ROS production.

Pénfigo benigno familiar de presentación atípica en paciente sin antecedente familiar / Atypical presentation of familial benign pemphigus in patient without familiar background

Resumen La enfermedad de Hailey-Hailey, también llamada pénfigo familiar benigno, corresponde a una genodermatosis debilitante que se transmite mediante un patrón autosómico dominante, con una prevalencia de alrededor de 1 en 50.000 casos. El reporte de antecedentes familiares está presente hasta en 60 % de los pacientes. Se caracteriza por la presencia de vesículas crónicas y recurrentes, erosiones y exulceraciones en zonas de flexura. El tratamiento puede representar un reto, porque a pesar del manejo con terapias tópicas, corticosteroides sistémicos, inmunomoduladores sistémicos y el empleo de láser, ninguna terapia ha logrado una remisión a largo plazo. Se presenta el caso de un paciente masculino, adulto medio, sin antecedente familiar alguno, con historia de placas de superficie descamativa y hematocostras recurrentes crónicas y presentación clínica atípica, dada la localización de lesiones predominantes en miembros superiores, con sospecha inicial de psoriasis vulgar, con posterior toma de biopsia y reporte de patología que evidencia histológia típica de PBF. Por lo cual se indica manejo con corticosteroides sistémicos, sin evidencia de reacciones adversas y con remisión a largo plazo. MÉD.UIS.2020;34(1):101-6

Abstract Hailey-Hailey disease, also called benign familial pemphigus, corresponds to a debilitating genodermatosis that is transmitted through an autosomal dominant pattern, with a prevalence of around 1 in 50,000 cases. The family history report is present in up to 60% of patients. It is characterized by the presence of chronic and recurrent vesicles, erosions and exulcerations in flexural areas. Treatment can be challenging, because despite management with topical therapies, systemic corticosteroids, systemic immunomodulators, and the use of lasers, no therapy has achieved long-term remission.We present the case of a male patient, middle adult, without any family history, with a history of scaly surface plaques and chronic recurrent hematocostras and atypical clinical presentation given the location of predominant lesions in the upper limbs, with initial suspicion of vulgar psoriasis, with subsequent biopsy and pathology report showing typical PBF histology. Therefore, management with systemic corticosteroids without evidence of adverse reactions and with long-term remission is indicated. MÉD.UIS.2020;34(1):101-6

The role of visfatin and resistin in an in vitro model of obesity-induced invasive liver cancer.

Obesity is associated with the development of liver disease and its progression to hepatocellular carcinoma. This link may be attributed to adipocytokines such as visfatin and resistin which have been shown to promote liver cancer incidence and progression. Studies have yet to determine the role of visfatin and resistin in liver cancer, specifically in the context of obesity. The objective of this study was to investigate the effect of neutralizing visfatin and resistin in obese (OB) or normal weight (NW) sera to determine the contribution of these proteins in obesity-induced invasive liver cancer. Sera from OB or NW males was used to determine the efficacy of neutralizing visfatin and resistin to reduce the obesity-induced liver cancer phenotype. HepG2 and SNU-449 cells were exposed to OB and NW sera ± antibodies for visfatin or resistin. The neutralizing antibodies differentially suppressed invasion, reactive oxygen species production, and matrix metalloproteinase-9 secretion. These changes corresponded with a decrease in phosphorylated extracellular signal-regulated kinases and protein kinase B in HepG2 cells, but differences were not observed in CAP1 or ß-catenin. In conclusion, visfatin and resistin have differential roles in obesity-associated liver cancer and may be potential targets to reverse the impact of obesity on liver cancer progression.

Characterizing the differential physiological effects of adipocytokines visfatin and resistin in liver cancer cells.

Background Obesity, a major public health concern, increases the risk of developing liver cancer which is the leading cause of cancer-related deaths worldwide. Obesity is associated with increased adiposity and macrophage infiltration both of which promote secretion of adipokines and cytokines in the tumor microenvironment. Specifically, visfatin and resistin have been detected at higher levels in the serum of obese individuals and liver tumors. However, the contribution of these adipocytokines in the progression of liver cancer remains unclear. Materials and methods The objective of this study was to characterize the effects of visfatin and resistin on HepG2, SNU-449 and HuH7 liver cancer cells. Cells exposed to visfatin and resistin were analyzed for fatty acid synthase protein, and phosphorylation of Akt and ERK tumorigenic signaling pathways, cell viability, lipogenesis, reactive oxygen species (ROS), matrix metallopeptidase 9 (MMP-9) enzyme activity and invasion. Results HepG2, SNU-449, and HuH7 liver cancer cells treated with visfatin and resistin increased cell viability, invasion, FASN protein, and Akt and ERK phosphorylation. Visfatin and resistin selectively increased ROS production in HepG2 and SNU-449 cells while there was no statistical difference in HuH7 cells. Visfatin and resistin stimulated lipogenesis in HepG2 cells while visfatin increased lipogenesis in SNU-449 cells, and visfatin nor resistin had an effect on lipogenesis in HuH7 cells. Lastly, visfatin and resistin increased MMP-9 enzyme activity in HepG2 and HuH-7 cells but only visfatin increased MMP-9 activity in SNU-449 cells. Conclusions Future studies are needed to determine if inhibition of ERK and Akt suppresses the visfatin and resistin-induced invasive liver cancer phenotype.

Effects of azithromycin and tanomastat on experimental bronchiolitis obliterans.

OBJECTIVE: Azithromycin has become a standard of care in therapy of bronchiolitis obliterans following lung transplantation. Matrix metalloprotease-9 broncho-alveolar lavage levels increase in airway neutrophilia and bronchiolitis obliterans. Interleukin-17 may play a role in lung allograft rejection, and interleukin-12 is downregulated in bronchiolitis obliterans. Whether these mechanisms can be targeted by azithromycin remains unclear. METHODS: Bronchiolitis obliterans was induced by transplantation of Fischer F344 rat left lungs to Wistar Kyoto rats. Allografts with azithromycin therapy from day 1 to 28 or 56 and mono- or combination therapy with the broad-spectrum matrix metalloprotease inhibitor tanomastat from day 1 to 56 were compared to control allografts and isografts. Graft histology was assessed, and tissue cytokine expression studied using Western blotting and immunofluorescence. RESULTS: The chronic airway rejection score in the azithromycin group did not change between 4 and 8 weeks after transplantation, whereas it significantly worsened in control allografts (P = .041). Azithromycin+tanomastat prevented complete allograft fibrosis, which occurred in 40% of control allografts. Azithromycin reduced interleukin-17 expression (P = .049) and the number of IL-17(+)/CD8(+) lymphocytes at 4 weeks, and active matrix metalloprotease-9 at 8 weeks (P = .017), and increased interleukin-12 expression (P = .025) at 8 weeks following transplantation versus control allografts. CONCLUSIONS: The expression of interleukin-17 and matrix metalloprotease-9 in bronchiolitis obliterans may be attenuated by azithromycin, and the decrease in interleukin-12 expression was prevented by azithromycin. Combination of azithromycin with a matrix metalloprotease inhibitor is worth studying further because it prevented complete allograft fibrosis in this study.

Efficiency of natural systems for removal of bacteria and pathogenic parasites from wastewater.

A combined constructed wetland formed by a facultative pond (FP), a surface flow wetland (SF) and a subsurface flow wetland (SSF) was studied from December 2004 until September 2005 in north-western Spain in order to evaluate their efficiency in the removal of pathogenic and indicator microorganisms and to determine their relationships. Microbial removal ranged from 78% for coliphages to over 99% for helminth eggs, depending on the treatment system. The highest removal of indicator bacteria (total coliforms, E. coli, faecal streptococci and Clostridium perfringens) occurred in the stabilization pond, reaching 84%, 96%, 89% and 78%, respectively. However, the greatest removal of protozoan pathogens (Cryptosporidium and Giardia) and coliphages was found in the SSF wetland, 98%, 97% and 94%, respectively. In contrast, the SF wetland was most efficient in the removal of pathogenic parasites when considering superficial removal rates. Seasonal differences in organism removal were not statistically significant during the study period. First-order removal rate constants ranged from 0.0027 to 0.71 m/d depending on the microorganism and type of wetland. Significant correlations were found between pathogenic parasites and faecal indicators in the influent of the treatment system but not in the other sampling points suggesting that such relations varied along the system due to the different survival rates of the microorganisms.

Fine needle thyroid aspiration: University Hospital Experience

El aspirado tiroideo de aguja fina (ATAF) para el diagnóstico de enfermedad tiroidea fue iniciado en el Hospital Universitario en 1983. ATAF se realizó en 54 pacientes referidos de diciembre de 1984 a diciembre de 1985. Se recomendó cirugía, siempre y cuando no hubiera contraindicación médica, para evaluar la certeza diagnóstica del aspirado. La cirugía se practicó en 34 (63%) de los pacientes. En 20 no se realizó debido a: contraindicaciones médicas en 3, abandono médico en 2, rehusaron 3, ATAF inapropiado en 7 y por razones desconocidas en 5. Ninguno tuvo complicaciones. La citología se clasificó de la siguiente manera: Clase O; inapropiada; Clase 1: benigna; Clase 2; intermedia; y Clase 3: maligna. Los casos "no benignos" fueron 14,7 intermedios (Clase 2) y 7 malignos (Clase 3). Cuatro de los últimos se confirmaron en cirugía. De los 19 casos con citología benigna (Clase 1) hubo uno con cáncer. Un paciente tuvo una muestra inapropiada (Clase O). La sensitividad fue 80%, especifidad 65% y la certeza diagnóstica 67%. Todos estos valores estadísticos están dentro del margen de lasquince series revisadas. Por lo tanto, ATAF en el UDH tiene un valor diagnóstico comparable al descrito en la literatura. Este se puede utilizar como una prueba segura y confiable junto al resto de la evaluación clínica para reducir el número de cirugía tiroideas, aumentar el porciento de casos malignos en los pacientes operados y hacer el diagnóstico de cáncer mas temprano