ANCA vasculitis and membranoproliferative glomerulonephritis associated with Sjögren's syndrome: Case report and literature review

ANCA-associated vasculitis may occur concomitantly with primary Sjögren's syndrome (SS) or arise during its evolution. We present the case of a patient who underwent dry symptoms, a positive Schirmer test and an SS-compatible autoimmunity profile and, simultaneously, deterioration of renal function, anaemia, and dyspnoea, requiring renal biopsy and fibro-bronchoscopy. Complementary studies documented acute necrotizing glomerulonephritis with extracapillary proliferation, and membranoproliferative pattern with immune complex deposition. Bronchoalveolar lavage was compatible with alveolar haemorrhage. Kidney lung syndrome secondary to ANCA vasculitis was diagnosed and treatment with steroid and intravenous cyclophosphamide with clinical and paraclinical improvement was instituted. Mixed renal involvement found in this case is uncommon in patients with SS, and treatment changes significantly, hence the importance of differential diagnosis and reporting in the literature.

La vasculitis asociada con anticuerpos anticitoplasma de neutrófilos-ANCA puede presentarse concomitantemente con síndrome de Sjögren primario o surgir durante su evolución. Se presenta el caso de una paciente que cursó con síntomas secos, test de Schirmer positivo, perfil de autoinmunidad compatible con síndrome de Sjögren y, de forma simultánea, deterioro de la función renal, anemia y disnea, por lo que requirió biopsia renal y fibrobroncoscopia. Los estudios complementarios documentaron glomerulonefritis aguda necrosante con proliferación extracapilar y patrón membranoproliferativo con depósito de complejos inmunes. El lavado broncoalveolar fue compatible con hemorragia alveolar. Se hizo diagnóstico de síndrome de pulmón-rinón secundario a vasculitis ANCA y se instauró tratamiento con esteroide y ciclofosfamida intravenosa, con mejoría clínica y paraclínica. El compromiso renal mixto encontrado en este caso es infrecuente en pacientes con SS, y el tratamiento cambia ostensiblemente, de ahí la importancia del diagnóstico diferencial y el reporte en la literatura.

Autoimmune myelofibrosis and systemic lupus erythematosus: a case report

Bone marrow fibrosis is a rare disorder that can be associated with autoimmune diseases such as systemic lupus erythematosus (SLE), and can be confused with the manifestations of that disease. The case is presented on a patient with autoimmune myelofibrosis in the context of SLE.

La fibrosis de la médula ósea es una enfermedad rara que se puede ver asociada con enfermedades autoinmunes como el lupus eritematoso sistémico (LES) y que puede llegar a ser confundida con las manifestaciones propias de la enfermedad. Se presenta el caso de una paciente con mielofibrosis autoinmune en el contexto de LES.

El volumen medioplaquetario: su importancia en la práctica clínica / Mean platelet volume: its importance in clinical practice

Las plaquetas son fragmentos citoplasmáticos anucleados derivados de los megacariocitos que presentan función central, tanto en procesos fisiológicos como la hemostasia, así como también en procesos patológicos como la inflamación, la ateroesclerosis. El tamaño de las plaquetas, medido como volumen medio de plaquetas, es un marcador de reactividad plaquetaria, que proporciona información importante sobre el curso y pronóstico de una variedad de afecciones inflamatorias. El estudio de este marcador se ha utilizado como pronóstico en enfermedades cardiovasculares, preeclampsia y en la púrpura trombocitopénica. El objetivo de este trabajo es revisar los conceptos actuales basados en la evidencia científica relacionados con el volumen plaquetario medio e insistir en su evaluación y significado en la práctica clínica cotidiana(AU)

Platelets are enucleated cytoplasmic fragments derived from megakaryocytes, which have a central function, both in physiological processes such as hemostasis, as well as in pathological processes such as inflammation, atherosclerosis. Platelet size, measured as mean volume of platelets, is a marker of platelet reactivity, providing important information on the course and prognosis of a variety of inflammatory conditions. The study of this marker has been used as a prognostic in cardiovascular diseases, preeclampsia and in thrombocytopenic purpura. The objective of this paper is to review the current concepts based on scientific evidence related to the mean platelet volume and to insist on its evaluation and meaning in daily clinical practice(AU)

Understanding tubulointerstitial injury and repair mechanisms paves the way for renal outcome improvement in lupus nephritis / Entender la lesión tubulointersticial y los mecanismos de reparación será la vía para mejorar los desenlaces renales en nefritis lúpica

ABSTRACT Despite improvements in patient survival and quality of life, long-term renal survival has not changed significantly in the recent decades and nephritis relapses affect over 50% of patients with lupus nephritis. Renal fibrosis affecting the tubulointerstitial compartment is a central determinant of the prognosis of any kidney disease. Notwithstanding this evidence, the current 2003 ISN/RPS classification still focuses on glomerular pathology and does not include a mandatory score with clear subcategories of the tubulointerstitial injury in the biopsy. The pathogenesis, and the morphological and molecular characteristics of this process in patients with lupus nephritis will be considered, together with a discussion about the concepts the clinician needs to efficiently address in this injury during daily practice and in future clinical trials. Both tubulointerstitial inflammation and fibrosis are strongly correlated with poor renal outcomes in lupus nephritis, regardless of the extent of glomerular damage. Therefore, it is essential to develop reliable and noninvasive approaches to predict which patients are most likely to develop CKD so that appropriate interventions can be adopted before ESRD is established. Currently, no ideal method for monitoring kidney fibrosis exists, since repeated renal biopsies are invasive. Promising methods for assessing and monitoring fibrosis non-invasively include imaging techniques, such as magnetic resonance imaging or ex vivo confocal microscopy, integrated in computational and digital pathology techniques. Finally, beyond specific immunosuppressive treatment in Lupus Nephritis, identifying and treating cardiovascular risk factors should be a cornerstone of treatment in these patients.

RESUMEN A pesar de las mejoras en la sobrevida de los pacientes y su calidad de vida, la sobrevida renal en el largo plazo no ha cambiado significativamente durante las últimas décadas, y las recidivas nefríticas afectan a más del 50% de los pacientes con nefritis lúpica. La fibrosis renal, que afecta el compartimiento tubulointersticial, es un factor determinante central en el pronóstico de todas las patologías renales. A pesar de la evidencia, la actual clasificación ISN/RPS del 2003 todavía se concentra en la patología glomerular y no incluye un score obligatorio con claras subcategorías de la lesión tubulointersticial en la biopsia. Se hablará de la patogenia y las características morfológicas y moleculares de este proceso en pacientes con nefritis lúpica, así como de los conceptos que el clínico necesita para abordar esta lesión de manera eficiente en su práctica cotidiana y en los estudios clínicos a futuro. Tanto la inflamación tubulointersticial como la fibrosis se relacionan fuertemente con desenlaces renales pobres en la nefritis lúpica, con independencia de la extensión del dañío glomerular. Resulta por lo tanto esencial desarrollar sistemas confiables y no invasivos para predecir cuáles pacientes tendrán mayor probabilidad de desarrollar enfermedad renal crónica, a fin de realizar las intervenciones apropiadas antes de que se establezca la enfermedad renal terminal (ERT). En la actualidad, no existe un método ideal para monitorear la fibrosis renal, dado que las biopsias repetidas son procedimientos invasivos. Algunos de los métodos promisorios para evaluar y monitorear la fibrosis de manera no invasiva son las técnicas de imágenes, tales como la resonancia magnética o la microscopía confocal ex vivo, integradas en técnicas de patología computarizadas y digitales. Finalmente, más allá del tratamiento inmunosupresor específico para la nefritis lúpica, identificar y tratar los factores de riesgo cardiovascular deberá ser uno de los pilares de tratamiento en estos pacientes.

Prevalencia de factores de riesgo en pacientes mayores de 50 años con fracturas clásicas de fragilidad atendidos en un hospital de tercer nivel de complejidad en Boyacá / Prevalence of risk factors in patients older than 50 years with classic fragility fractures treated in a third level complexity hospital in Boyacá (Colombia)

RESUMEN Introducción: Las fracturas por fragilidad son una complicación frecuente de la osteoporosis y generan alto impacto en la calidad de vida del adulto mayor. Las fracturas de cuello femoral, radio distal, húmero proximal y vértebras toracolumbares, en el contexto de un traumatismo menor, se consideran fracturas por fragilidad. Objetivo: Identificar la prevalencia de factores de riesgo en personas mayores de 50 arios con fracturas por fragilidad atendidas en un hospital del departamento de Boyacá. Metodología: Estudio observacional, descriptivo y de corte transversal. Se incluyeron 242 pacientes que presentaron fracturas por fragilidad con diagnóstico confirmado por estudio imagenológico. Resultados: El 62,8% de la población fue femenina. La edad condiciona un aumento del número de fracturas de fémur. El 10,7% de la población tenía un antecedente de fractura, con un aumento de la prevalencia a mayor edad. La fractura de radio distal fue la más frecuente en el 36,8% de la población. Cerca del 40% de los pacientes eran hipertensos y el 7,9% tenía diabetes, en tanto que el 9,7% eran consumidores crónicos de inhibidores de la bomba de protones. El 2,4% consumía glucocorticoides previamente al evento. Conclusiones: El comportamiento poblacional de las fracturas por fragilidad en nuestra ins titución es similar al de otros lugares, tanto a escala nacional como internacional. Por tanto, es importante empezar a crear conciencia sobre la prevención secundaria de la osteoporo sis, con el fin de disminuir las complicaciones, mejorar los desenlaces y disminuir los gastos que consigo trae.

ABSTRACT Introduction: Fragility fractures are a frequent complication of osteoporosis and lead to increased morbidity and mortality, as well as decreasing quality of life of the elderly popu lation, and represents high costs for health care systems. After minor trauma, fractures of the femoral neck, distal radius, proximal humerus, and thoraco-lumbar vertebrae are associated with osteoporosis, and are considered fragility fractures. Objective: To identify the prevalence of risk factors in people over 50 years of age with fragility fractures treated at a third level hospital in the department of Boyacá, Colombia. Methodology: Observational, descriptive, retrospective cross-sectional study. An evaluation was made on 242 patients between 50 and 100 years of age with any of the previously mentioned 4 fragility fractures. Fracture diagnosis had to be confirmed by plain radiography or computed tomography. Results: The majority (62.8%) of the study population was female. Age was associated with an increase in the number of femur fractures. A history of previous fractures was observed in 10.7% of the cases, with prevalence increasing with age. Distal radius fracture was the most frequent in 36.8% of the population. About 40% of the patients had hypertension and 7.9% were diabetic. Chronic use of proton pump inhibitors was observed in 9.7%, and 2.4% consumed glucocorticoids prior to the event. Conclusions: The behaviour of fragility fractures of the population in our institution is simi lar to that of other places, both nationally and internationally. It is therefore important to start raising awareness about secondary prevention of osteoporosis, in order to reduce complications, improve outcomes, and reduce associated costs.

Evaluation of serum microRNA-30e-5p expression in systemic lupus erythematosus and its association with clinical manifestations: A cross-sectional study / Evaluación de la expresión del microARN-30e-5p sérico en el lupus eritematoso sistémico y su asociación con las manifestaciones clínicas: un estudio transversal

ABSTRACT Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally. Accumulating evidence indicates that the miR-30 family takes part in the development of multiple tissues and organs, and is a potential contributor to various dis eases, including autoimmune disorders such as systemic lupus erythematosus (SLE). The aim of this study was to evaluate the expression of miR-30e-5p, a member of the miR-30 fam ily, and investigate its potential relationship to clinical characteristics and possible disease activity in an Egyptian SLE cohort. Methods: Serum samples from 40 SLE patients and 37 age and gender matched healthy sub jects were tested for miR-30e-5p expression level using the Taqman quantitative reverse transcription-polymerase chain reaction. Analysis was performed using the 2 - AACT method. Results: The mean age of the patients was 28.7 ± 7.9 years, with a mean disease duration of 6.4 ±5.3 years. The median fold change in serum miR-30e-5p among our SLE cohort was significantly higher 1.748 (0.223-20.485) compared to the control group 0.877 (0.058-3.522) (P = 0.02). Receiver operating characteristic curve analysis revealed that miR-30e-5p expres sion level can discriminate SLE patients from controls at a cut-off value >1.06 with the area under the curve (AUC) = 0.676 (95% CI: 0.559-0.794, P = 0.02), with 64.3% sensitivity and 61.5% specificity. There was no correlation between any of the demographic features, clinical manifestations (apart from serositis, P = 0.013) or disease activity and miR-30e-5p levels. Conclusion: Our study demonstrated elevated miR-30e-5p expression levels in serum sam ples of SLE patients. Apart from serositis, it was not associated with any other disease characteristics.

RESUMEN Antecedentes: Los microARN (miRNA) son ARN no codificantes que regulan la expresión de los genes después de la transcripción. Las pruebas acumuladas indican que la familia de miR-30 participa en el desarrollo de múltiples tejidos y órganos, y es un posible contribuyente a diversas enfermedades, incluidos los trastornos autoinmunes como el lupus eritematoso sistémico (LES). El objetivo de este estudio fue evaluar la expresión del miR-30e-5p, un miembro de la familia miR-30, e investigar su posible relación con las características clínicas y la posible actividad de la enfermedad en una cohorte egipcia de LES. Métodos: Se analizaron muestras de suero de 40 pacientes con LES y 37 sujetos sanos de edad y sexo similares para determinar el nivel de expresión de miR-30e-5p, utilizando la reacción en cadena de la polimerasa de transcripción inversa cuantitativa Taqman. El análisis se llevó a cabo empleando el método 2-AACT. Los resultados: La edad media de los pacientes fue de 28,7 ± 7,9 años, mientras que la duración media de la enfermedad fue de 6,4 ± 5,3 años. La mediana del cambio de pliegue del suero miR-30e-5p entre nuestra cohorte de LES fue significativamente mayor, 1,748 (0,223-20,485), en comparación con el grupo de control, 0,877 (0,058-3,522) (p = 0,02). El análisis de la curva característica de funcionamiento del receptor reveló que el nivel de expresión del miR-30e-5p puede discriminar a los pacientes con LES de los controles en un valor de corte > 1,06, con el área bajo la curva (AUC) = 0,676 (IC del 95%: 0,559-0,794; p = 0,02), una sensibilidad del 64,3% y una especificidad del 61,5%. No hubo asociación entre ninguna de las características demográficas, manifestaciones clínicas (aparte de la serositis, p = 0,013) o actividad de la enfermedad y los niveles de miR-30e-5p. Conclusión: Nuestro estudio demostró niveles elevados de expresión de miR-30e-5p en mues tras de suero de pacientes con LES. Aparte de la serositis, no se asoció con ninguna otra característica de la enfermedad.

Tratamento odontológico de paciente com Síndrome de Singleton-Merten / Dental treatment of a patient with Singleton-Merten Syndrome

Introdução: A Síndrome de Singleton-Merten (SMS) é uma doença autossômica dominante hereditária rara caracterizada por alterações cardiovasculares, ósseas e dentais, pouco discutida na literatura em relação ao tratamento odontológico. Objetivo: O objetivo do presente estudo foi relatar o caso de uma paciente com SMS, descrevendo seus aspectos bucais e o plano de tratamento proposto, em conjunto com uma equipe multiprofissional. Relato do caso: Durante a anamnese constatou-se que o paciente apresentava alterações cutâneas decorrentes da síndrome. Os exames clínico, radiográfico e tomográfico revelaram maxila e mandíbula parcialmente edêntulas, ampla reabsorção do osso maxilar, além da maioria dos dentes permanentes incluídos e com raízes curtas. O plano de tratamento multidisciplinar incluiu a extração de dentes com formação radicular deficiente, tração ortodôntica dos caninos superiores incluídos e a confecção de próteses parciais superiores e inferiores removíveis, para reabilitação das funções mastigatória, fonética e estética. Conclusão: É importante ressaltar que durante o atendimento odontológico de pacientes com SMS, deve-se considerar o estado geral de saúde anterior, principalmente em relação às possíveis complicações cardiovasculares existentes, e a necessidade de reabilitação destes pacientes, por apresentarem perda dentária extensa.

Intoduction: Singleton-Merten Syndrome (SMS) is a rare in herited autosomaldominant disorder. Characterized by cardiovascular, bone and dental alterations, little discussed in the literature regarding dental treatment. Objective: The aim of this study was to report the case of a patient with SMS, describing her oral aspects and the proposed treatment plan, together with a multidisciplinary team. Case report: During the anamnesis it was found that the patient has alterations due to the syndrome. Clinical, radiographic and tomographic examinations revealed partially edentulous maxilla and mandible, wide resorption of maxillary bone, in addition to most of the permanent teeth included and with short roots. The multidisciplinary treatment plan included the extraction of teeth with deficient root formation, orthodontic traction of the included upper canines and the making of removable upper and lower partial dentures, for rehabilitation of masticatory, phonetic and aesthetic functions. Conclusion: It is important to emphasize that during dental care of patients with SMS, the previous general state of health should be considered, especially in relation to possible existing cardiovascular complications, and the need for rehabilitation of these patients, since they will present extensive tooth loss.

Utilização de corpo adiposo bucal em comunicação oroantral / Use of body adiposo body in oroantral communication

Introdução: A comunicação oroantral tem como principais causas etiológicas os processos patológicos, traumatismos e cirurgias, sendo comum sua ocorrência durante exodontias de elementos dentários superiores posteriores devido ao íntimo contato dos ápices radiculares com o assoalho do seio maxilar. Relato de caso: Paciente do sexo feminino, com 51 anos de idade, apresentando comunicação oroantral há 6 anos após exodontia do elemento dental 16. Realizado fechamento da comunicação oroantral sob anestesia local, com tracionamento e sutura da bola de Bichat sobre a falha óssea. Após um ano de proservação, observamos a ausência de comunicação bucosinusal bem como de sintomatologia, resultando no sucesso do tratamento. Considerações Finais: A utilização do retalho pediculado do corpo adiposo bucal é uma alternativa útil para o fechamento e tratamento de comunicações bucosinusais, sendo que o deslizamento da bola de Bichat é um método seguro para fechamento de tais comunicações e que esta é uma técnica de simples execução, com poucas complicações e limitações... (AU)

Introduction: The oroantral communication has as main etiological causes the pathological processes, traumatisms and surgeries. Its occurrence during the exodontia of posterior superior dental elements is due to the intimate contact of the root apices with the floor of the maxillary sinus. Case report: A 51-year-old female patient, presenting oroantral communication 6 years ago after the dental element 16 was extubated. The oroantral communication was closed under local anesthesia with Bichat's ball traction and suture on the bone defect. After 1 year of proservation, we observed the absence of oral communication, as well as symptomatology, resulting in the success of the treatment. Final considerations: It is concluded that the use of the pedicle flap of the buccal adipose body is a useful alternative for the closure and treatment of buco sinusal communications, and the sliding of the bichat ball is a safe method for closing such communications and that this is a technique of simple execution, with few complications and limitations... (AU)

Endoscopic Ultrasound in the Diagnosis of Pancreatoduodenal Groove Pathology: Report of Three Cases and Brief Review of the Literature

The pancreatoduodenal groove is a small area where pathologic processes involving the distal bile duct, duodenum, pancreatic head, ampulla of Vater, and retroperitoneum converge. Despite great advances in imaging techniques, a definitive preoperative diagnosis is challenging because of the complex anatomy of this area. Therefore, surgical intervention is frequently required because of the inability to completely exclude malignancy. We report 3 cases of patients with different groove pathologies but similar clinical and imaging presentation, and show the essential role of endoscopic ultrasound (EUS) in making a specific preoperative diagnosis, excluding malignancy in the first case, changing diagnosis in the second case, and confirming malignancy in the third case. EUS was a fundamental tool in this cohort of patients, not only because of its ability to provide superior visualization of a difficult anatomical region, but because of the ability to guide precise, real-time procedures, such as fine-needle aspiration.

Metformin, an Activator of AMPK, Promotes the Growth of Hair Follicles via the AMPK/β-catenin Signaling Pathway / 대한피부과학회지

BACKGROUND: AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays a pivotal role in the balance of cellular energy metabolism. Recent studies have reported that AMPK has numerous roles in physiological conditions, and dysregulation of AMPK induces pathological processes and diseases. However, the role of AMPK and its activators have not yet been studied in the context of hair growth regulation. OBJECTIVE: To investigate the effects of metformin on dermal papilla (DP) and outer root sheath (ORS) cells, as well as the role of the AMPK pathway in hair growth. METHODS: We evaluated whether metformin, a well-known AMPK activator, had any beneficial effects on hair growth. In addition, to evaluate the molecular and cellular mechanisms that were involved, protein levels of AMPK and β-catenin were analyzed. RESULTS: Metformin increased the cellular proliferation of human DP and ORS cells. Ki-67 expression was also significantly increased after metformin treatment in the ex vivo hair follicle organ culture. Furthermore, DP and ORS cells treated with metformin had a significant increase in AMPK phosphorylation, which in turn suppressed β-catenin degradation and enhanced its nuclear accumulation. CONCLUSION: We demonstrated that metformin promoted hair growth via the AMPK/β-catenin signaling pathway in vitro with DP and ORS cells. The hair-promoting effects of AMPK activators may potentially be used for the treatment of alopecia, and further investigation will be needed in the future.

Pathophysiological Role of S-Nitrosylation and Transnitrosylation Depending on S-Nitrosoglutathione Levels Regulated by S-Nitrosoglutathione Reductase

Nitric oxide (NO) mediates various physiological and pathological processes, including cell proliferation, differentiation, and inflammation. Protein S-nitrosylation (SNO), a NO-mediated reversible protein modification, leads to changes in the activity and function of target proteins. Recent findings on protein-protein transnitrosylation reactions (transfer of an NO group from one protein to another) have unveiled the mechanism of NO modulation of specific signaling pathways. The intracellular level of S-nitrosoglutathione (GSNO), a major reactive NO species, is controlled by GSNO reductase (GSNOR), a major regulator of NO/SNO signaling. Increasing number of GSNOR-related studies have shown the important role that denitrosylation plays in cellular NO/SNO homeostasis and human pathophysiology. This review introduces recent evidence of GSNO-mediated NO/SNO signaling depending on GSNOR expression or activity. In addition, the applicability of GSNOR as a target for drug therapy will be discussed in this review.

An Emerging Role for Circular RNAs in Osteoarthritis

Circular RNAs (circRNAs) are currently classed as non-coding RNAs that, unlike the better known canonical linear RNAs, form a covalently closed continuous loop without 5′ or 3′ polarities. With the development of high throughput sequencing technology, a large number of circRNAs have been discovered in many species. More importantly, growing evidence suggests that circRNAs are abundant, evolutionally conserved, and relatively stable in cells and tissues. Strikingly, recent studies have discovered that circRNAs can serve as microRNA sponges, interact with RNA-binding protein, and regulate gene transcription, as well as protein translation. Osteoarthritis (OA) is the most common chronic degenerative joint disease. CircRNAs are differentially expressed in OA cartilage. Moreover, some circRNAs are involved in multiple pathological processes during OA, mainly extracellular matrix degradation, inflammation, and apoptosis. In this review, we briefly delineate the biogenesis, characteristics, and biofunctions of circRNAs, and then, focus on the role of circRNAs in the occurrence and progression OA.

The Relationship between the Number of Manic Episodes and Oxidative Stress Indicators in Bipolar Disorder

OBJECTIVE: Bipolar disorder (BD) is a chronic mood disorder characterized by recurrent episodes that has a lifetime prevalence of 0.4–5.5%. The neurochemical mechanism of BD is not fully understood. Oxidative stress in neurons causes lipid peroxidation in proteins associated with neuronal membranes and intracellular enzymes and it may lead to dysfunction in neurotransmitter reuptake and enzyme activities. These pathological processes are thought to occur in brain regions associated with affective functions and emotions in BD. The relationship between the number of manic episodes and total oxidant-antioxidant capacity was investigated in this study. METHODS: Eighty-two BD patients hospitalized due to manic symptoms and with no episodes of depression were enrolled in the study. Thirty of the 82 patients had had their first episode of mania, and the other 52 patients had had two or more manic episodes. The control group included 45 socio-demographically matched healthy individuals. Serum total antioxidant capacity (TAC) and total oxidant capacity (TOC) measurements of the participants were performed. The oxidative stress index (OSI) was calculated by TOC/TAC. RESULTS: There were no significant differences in OSI scores between BD patients with first-episode mania and BD patients with more than one manic episode. However, OSI scores in both groups were significantly higher than in the control group. TOC levels of BD patients with first-episode mania were found to be significantly higher than TOC levels of BD patients with more than one manic episode and healthy controls. There were no significant differences in TAC levels between BD patients with first-episode mania and BD patients with more than one manic episode. TAC levels in both groups were significantly higher than in the control group. CONCLUSION: Significant changes in oxidative stress indicators were observed in this study, confirming previous studies. Increased levels of oxidants were shown with increased disease severity rather than with the number of manic episodes. Systematic studies, including of each period of the disorder, are needed for using the findings indicating deterioration of oxidative parameters.

Updated review of resistance to neuromuscular blocking agents

Since neuromuscular blocking agents (NMBAs) were introduced to the surgical field, they have become almost mandatory for the induction and maintenance of anesthesia. However, resistance to NMBAs can develop in certain pathological states, such as central nerve injury, burns, and critical illnesses. During such pathological processes, quantitative and qualitative changes occur in the physiology of acetylcholine and the acetylcholine receptor (AChR) at the neuromuscular junction. Up-regulation of AChR leads to changes in the pharmacokinetics and pharmacodynamics of NMBA. As NMBA resistance may result in problems during anesthesia, it is of utmost importance to understand the mechanisms of NMBA resistance and their associations with pathological status to maintain adequate neuromuscular relaxation. This review presents the current knowledge of pharmacokinetic and pharmacodynamic changes and pathological status associated with NMBA resistance.

The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

Up-regulation of NHE8 by somatostatin ameliorates the diarrhea symptom in infectious colitis mice model

Na⁺/H⁺ exchangers (NHEs) have been shown to be involved in regulating cell volume and maintaining fluid and electrolyte homeostasis. Pooled evidences have suggested that loss of Na⁺/H⁺ exchanger isoform 8 (NHE8) impairs intestinal mucosa. Whether NHE8 participates in the pathology of infectious colitis is still unknown. Our previous study demonstrated that somatostatin (SST) could stimulate the expression of intestinal NHE8 so as to facilitate Na⁺ absorption under normal condition. This study further explored whether NHE8 participates in the pathological processes of infectious colitis and the effects of SST on intestinal NHE8 expression in the setting of infectious colitis. Our data showed that NHE8 expression was reduced in Citrobacter rodentium (CR) infected mice. Up-regulation of NHE8 improved diarrhea symptom and mucosal damage induced by CR. In vitro, a similar observation was also seen in Enteropathogenic E. coli (EPEC) infected Caco-2 cells. Seglitide, a SST receptor (SSTR) 2 agonist, partly reversed the inhibiting action of EPEC on NHE8 expression, but SSTR5 agonist (L-817,818) had no effect on the expression of NHE8. Moreover, SST blocked the phosphorylation of p38 in EPEC-infected Caco-2 cells. Taken together, these results suggest that enhancement of intestinal NHE8 expression by SST could ameliorate the symptoms of mice with infectious colitis.

Analysis of Revision Surgery of Microsurgical Lumbar Discectomy

STUDY DESIGN: A retrospective study. PURPOSE: Our objectives were to determine the association between the pathological changes of disc herniation and the interval between primary and revision surgeries and to investigate the frequency and site of the dural laceration in the primary and revision surgeries. OVERVIEW OF LITERATURE: Among 382 patients who underwent microsurgical lumbar discectomy, we investigated 29 who underwent revision surgery to analyze recurrent herniation pathologies and complications to determine the manner in which lumbar disc herniation can be more efficiently managed. METHODS: Of 29 patients, 22 had recurrent disc herniation at the same level and site. The pathological changes associated with compression factors were classified into the following two types depending on intraoperative findings: (1) true recurrence and (2) minor recurrence with peridural fibrosis (>4 mm thickness). The sites of dural laceration were examined using video footage and operative records. RESULTS: The pathological findings and days between the primary and revision surgeries showed no statistical difference (p=0.14). Analysis of multiple factors, revealed no significant difference between the primary and revision surgery groups with regard to hospital days (p=0.23), blood loss (p=0.99), and operative time (p=0.67). Dural lacerations obviously increased in the revision surgery group (1.3% vs. 16.7%, p < 0.01) and were mainly located near the herniated disc in the primary surgery group and near the root shoulder in the revision surgery group, where severe fibrosis and adhesion were confirmed. To avoid dural laceration during revision surgery, meticulous decompressive manipulation must be performed around the root sleeve. CONCLUSIONS: We recommend that meticulous epidural dissection around the scar formation must be performed during revision surgery to avoid complications.

Male patient with C1q nephropathy and rheumatoid arthritis: A case report / Hombre con nefropatía C1q y artritis reumatoide: reporte de un caso

Abstract C1q nephropathy was first described in 1985 as a process of glomerulonephritis with mesangial C1q deposit. The histology is similar to lupus nephritis, and was initially described as being seronegative renal lupus. However, these two entities are now considered different pathological processes. Its association with rheumatoid arthritis is unusual, and there are no cases with a similar presentation reported in the literature. In this article, the case is presented of a man who developed both these conditions.

Resumen La nefropatía C1q, se describió por primera vez en 1985, como un proceso de glomerulonefritis con depósito mesangial de C1q, histológicamente similar a la nefritis lúpica, siendo inicialmente descrita como lupus renal seronegativo, sin embargo, estas dos entidades se consideran actualmente como procesos patológicos diferentes. Su asociación con artritis reumatoide es inusual y la literatura no reporta casos con presentación similar. A continuación, presentamos el caso de un hombre que desarrolla estas dos entidades.

La saturación venosa central de oxígeno es un factor predictor de mortalidad en el paciente con choque séptico / Central venous oxygen saturation is a predictor of mortality in patients with septic shock

Objetivo: determinar si la saturación venosa central de oxigeno inicial (SvCO2) anormal (alta o baja) es un factor predictor de mortalidad en los pacientes con choque séptico que ingresan al área critica de emergencia del hospital "Carlos Andrade Marín". Diseño y lugar: estudio analítico, observacional, prospectivo sobre una cohorte de pacientes que ingresaron al área crítica de emergencia de este hospital. Pacientes: 107 sujetos ingresaron en los meses de junio a septiembre del 2015, con seguimiento para la mortalidad a 28 días. Medidas y resultados: se midió la SvcO2 inicial a través de un catéter venoso central al momento del diagnóstico de choque. La mortalidad a los 28 días fue de 46,2%. Solo los valores de APACHE II (OR:1,11; IC: 1,04 a 1,19 p=< 0,01); la asistencia ventilatoria mecánica (OR:0,19; IC: 0,05 a 0,62, p=<0,01) tuvieron un valor estadístico significativo en regresión logística. APACHE II fue el factor individual más importante, en el modelo CART, el pH arterial y procalcitonina fueron útiles. Conclusiones: la saturación venosa central de O2 inicial (SvcO2) anormal alta o baja no mostró tener utilidad para predecir mortalidad a los 28 días. La medición de la SvcO2 es un método simple que refleja de manera indirecta la oxigenación tisular. El APACHE II es un predictor independiente de mortalidad a 28 días y la ventilación mecánica tuvo una relación inversa con la mortalidad. (AU)

Objective: to determine the central venous saturation of abnormal initial oxygen (SvCO2) (high or low) as a predictor of mortality in patients with septic shock admitted to the emergency area of Carlos Andrade Marín Hospital. Design and location: this is an analytical, observational, prospective study on a cohort of patients admitted to the critical area of emergency of this health unit. Subjects: 107 patients admitted in the months of June to September 2015, with a mortality follow-up of 28-day. Measurements and results: initial SvcO2 was measured by central venous catheter at the time of shock diagnosis. Mortality at 28 days was 46.2%. Only APACHE II values (OR 1.11, CI 1.04-1.19 p = <0.01) and mechanical ventilation (OR 0.19, CI 0.05-0.62, p = 0.01) had significant statistical value in the logistic regression. APACHE II was the most important single factor, in the CART model arterial pH and procalcitonin were useful. Conclusion: Central venous saturation of abnormal or high initial O2 (SvcO2) was not found to be useful in predicting mortality at 28 days of follow-up. Measurement of SvcO2 is a simple method that indirectly reflects tissue oxygenation. The APACHE II is an independent predictor of mortality at 28 days and the use of mechanical ventilation had an inverse relationship with mortality. (AU)

Animal Models of Demyelination and ¹H-Magnetic Resonance Spectroscopy

The proton magnetic resonance spectroscopy (¹H-MRS) is a tool used to detect concentrations of brain metabolites such as N-acetyl aspartate, choline, creatine, glutamate, and gamma-amino butyric acid (GABA). It has been widely used because it does not require additional devices other than the conventional magnetic resonance scanner and coils. Demyelination, or the neuronal damage due to loss of myelin sheath, is one of the common pathologic processes in many diseases including multiple sclerosis, leukodystrophy, encephalomyelitis, and other forms of autoimmune diseases. Rodent models mimicking human demyelinating diseases have been induced by using virus (e.g., Theiler's murine encephalomyelitis virus) or toxins (e.g., cuprizon or lysophosphatidyl choline). This review is an overview of the MRS findings on brain metabolites in demyelination with a specific focus on rodent models.