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1.
J Autoimmun ; 138: 103037, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37229808

RESUMEN

Salivary secretory dysfunction in SS-patients is associated with altered proteostasis, upregulation of ATF6α and components of the ERAD complex, such as SEL1L, and downregulation of XBP-1s and GRP78. Hsa-miR-424-5p is downregulated and hsa-miR-513c-3p is overexpressed in salivary glands from SS-patients. These miRNAs emerged as candidates that could regulate ATF6/SEL1L and XBP-1s/GRP78 levels, respectively. This study aimed to evaluate the effect of IFN-γ on hsa-miR-424-5p and hsa-miR-513c-3p expression and how these miRNAs regulate their targets. In labial salivary glands (LSG) biopsies from 9 SS-patients and 7 control subjects and IFN-γ-stimulated 3D-acini were analyzed. hsa-miR-424-5p and hsa-miR-513c-3p levels were measured by TaqMan assays and their localization by ISH. mRNA, protein levels, and localization of ATF6, SEL1L, HERP, XBP-1s and GRP78 were determined by qPCR, Western blot, or immunofluorescence. Functional and interaction assays were also performed. In LSGs from SS-patients and IFN-γ-stimulated 3D-acini, hsa-miR-424-5p was downregulated and ATF6α and SEL1L were upregulated. ATF6α and SEL1L were decreased after hsa-miR-424-5p overexpression, while ATF6α, SEL1L and HERP increased after hsa-miR-424-5p silencing. Interaction assays revealed that hsa-miR-424-5p targets ATF6α directly. hsa-miR-513c-3p was upregulated and XBP-1s and GRP78 were downregulated. XBP-1s and GRP78 were decreased after hsa-miR-513c-3p overexpression, while increases in XBP-1s and GRP78 were observed after hsa-miR-513c-3p silencing. Furthermore, we determined that hsa-miR-513c-3p targets XBP-1s directly. Significant correlations were found between both miRNA levels and clinical parameters. In conclusion, IFN-γ-dependent hsa-miR-424-5p and hsa-miR-513c-3p levels affect the expression of important factors involved in cellular proteostasis that control secretory function in LSG from SS-patients.


Asunto(s)
MicroARNs , Glándulas Salivales , Síndrome de Sjögren , Humanos , Chaperón BiP del Retículo Endoplásmico , Interferón gamma/genética , Interferón gamma/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas/genética , Proteínas/metabolismo , Glándulas Salivales/metabolismo , Síndrome de Sjögren/genética , Síndrome de Sjögren/metabolismo
2.
Front Med (Lausanne) ; 10: 1118703, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37035319

RESUMEN

Introduction: Primary Sjögren's syndrome (SS) is an autoimmune exocrinopathy that affects the structure and function of salivary and lachrymal glands. Labial salivary gland (LSG) acinar cells from SS patients lose cellular homeostasis and experience endoplasmic reticulum and oxidative stress. The integrated cellular stress response (ISR) is an adaptive pathway essential for restoring homeostasis against various stress-inducing factors, including pro-inflammatory cytokines, and endoplasmic reticulum and oxidative stress. ISR activation leads eIF2α phosphorylation, which transiently blocks protein synthesis while allowing the ATF4 expression, which induces a gene expression program that seeks to optimize cellular recovery. PKR, HRI, GCN2, and PERK are the four sentinel stress kinases that control eIF2α phosphorylation. Dysregulation and chronic activation of ISR signaling have pathologic consequences associated with inflammation. Methods: Here, we analyzed the activation of the ISR in LSGs of SS-patients and non-SS sicca controls, determining the mRNA, protein, and phosphorylated-protein levels of key ISR components, as well as the expression of some of ATF4 targets. Moreover, we performed a qualitative characterization of the distribution of ISR components in LSGs from both groups and evaluated if their levels correlate with clinical parameters. Results: We observed that the four ISR sensors are expressed in LSGs of both groups. However, only PKR and PERK showed increased expression and/or activation in LSGs from SS-patients. eIF2α and p-eIF2α protein levels significantly increased in SS-patients; meanwhile components of the PP1c complex responsible for eIF2α dephosphorylation decreased. ATF4 mRNA levels were decreased in LSGs from SS-patients along with hypermethylation of the ATF4 promoter. Despite low mRNA levels, SS-patients showed increased levels of ATF4 protein and ATF4-target genes involved in the antioxidant response. The acinar cells of SS-patients showed increased staining intensity for PKR, p-PKR, p-PERK, p-eIF2α, ATF4, xCT, CHOP, and NRF2. Autoantibodies, focus score, and ESSDAI were correlated with p-PERK/PERK ratio and ATF4 protein levels. Discussion: In summary, the results showed an increased ISR activation in LSGs of SS-patients. The increased protein levels of ATF4 and ATF4-target genes involved in the redox homeostasis could be part of a rescue response against the various stressful conditions to which the LSGs of SS-patients are subjected and promote cell survival.

3.
Front Immunol ; 13: 870094, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35432384

RESUMEN

MicroRNAs (miRNAs) are small non-coding RNAs (sRNA), that alter gene expression by binding to target messenger RNAs (mRNAs) and repressing translation. Dysregulated miRNA expression has been implicated in the pathogenesis of autoimmune diseases such as Sjögren's syndrome (SS). The aim of this study was to characterize the global profile of sRNAs in labial salivary glands (LSG) from SS-patients and to validate potential miRNA candidates implicated in glandular inflammation. LSG from 21 SS-patients and 9 sicca controls were analyzed. A global next generation sequencing (NGS)-based sRNA profiling approach was employed to identify direct targets whereby differentially expressed miRNAs were predicted using bioinformatics tools. miRNA levels were validated by TaqMan and target mRNA levels were determined by quantitative real-time PCR. We also performed in vitro assays using recombinant TNF-α. NGS shows that ~30% of sRNAs were miRNAs. In comparison with samples from sicca controls, four miRNAs were found differentially expressed in LSG from SS-patients with low focus score (LFS) and 18 from SS-patients with high focus score (HFS). The miRNA with the most significant changes identified by NGS was hsa-miR-181d-5p and downregulation was confirmed by TaqMan analysis. Levels of TNF-α mRNA, a direct target of hsa-miR-181d-5p, were significantly increased and negatively correlated with hsa-miR-181d-5p presence. Moreover, positive correlations between TNF-α transcript levels, focus score, ESSDAI, and autoantibody levels were also detected. Furthermore, TNF-α stimulation decreased hsa-miR-181d-5p levels in vitro. Downregulation of hsa-miR-181d-5p in LSG from SS-patients could contribute to the glandular pro-inflammatory environment by deregulation of its direct target TNF-α. Further dissection of the pathophysiological mechanisms underlying the hsa-miR-181d-5p-mediated action in inflammatory conditions could be useful to evaluate the benefits of increasing hsa-miR-181d-5p levels for restoration of salivary gland epithelial cell architecture and function.


Asunto(s)
MicroARNs , Síndrome de Sjögren , Regulación hacia Abajo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , Síndrome de Sjögren/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
4.
Rev. méd. Chile ; 149(12)dic. 2021.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1389415

RESUMEN

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.

5.
Front Immunol ; 12: 685837, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34149728

RESUMEN

Sjögren's syndrome (SS) is an autoimmune disease that mainly affects salivary glands (SG) and is characterized by overactivation of the type I interferon (IFN) pathway. Type I IFNs can decrease the levels of hsa-miR-145-5p, a miRNA with anti-inflammatory roles that is downregulated in SG from SS-patients. Two relevant targets of hsa-miR-145-5p, mucin 1 (MUC1) and toll-like receptor 4 (TLR4) are overexpressed in SS-patients and contribute to SG inflammation and dysfunction. This study aimed to evaluate if hsa-miR-145-5p modulates MUC1 and TLR4 overexpression in SG from SS-patients in a type I IFN dependent manner. Labial SG (LSG) biopsies from 9 SS-patients and 6 controls were analyzed. We determined hsa-miR-145-5p levels by TaqMan assays and the mRNA levels of MUC1, TLR4, IFN-α, IFN-ß, and IFN-stimulated genes (MX1, IFIT1, IFI44, and IFI44L) by real time-PCR. We also performed in vitro assays using type I IFNs and chemically synthesized hsa-miR-145-5p mimics and inhibitors. We validated the decreased hsa-miR-145-5p levels in LSG from SS-patients, which inversely correlated with the type I IFN score, mRNA levels of IFN-ß, MUC1, TLR4, and clinical parameters of SS-patients (Ro/La autoantibodies and focus score). IFN-α or IFN-ß stimulation downregulated hsa-miR-145-5p and increased MUC1 and TLR4 mRNA levels. Hsa-miR-145-5p overexpression decreased MUC1 and TLR4 mRNA levels, while transfection with a hsa-miR-145-5p inhibitor increased mRNA levels. Our findings show that type I IFNs decrease hsa-miR-145-5p expression leading to upregulation of MUC1 and TLR4. Together, this suggests that type I interferon-dependent hsa-miR-145-5p downregulation contributes to the perpetuation of inflammation in LSG from SS-patients.


Asunto(s)
Interferón Tipo I/metabolismo , MicroARNs/metabolismo , Mucina-1/metabolismo , Síndrome de Sjögren/metabolismo , Receptor Toll-Like 4/metabolismo , Adulto , Regulación hacia Abajo , Femenino , Humanos , Inflamación/metabolismo , Masculino , MicroARNs/genética , Persona de Mediana Edad , Mucina-1/genética , Glándulas Salivales Menores/metabolismo , Síndrome de Sjögren/genética , Receptor Toll-Like 4/genética , Adulto Joven
6.
Autoimmun Rev ; 20(8): 102867, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34118452

RESUMEN

Relevant reviews highlight the association between dysfunctional mitochondria and inflammation, but few studies address the contribution of mitochondria and mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) to cellular homeostasis and inflammatory signaling. The present review outlines the important role of mitochondria in cellular homeostasis and how dysfunctional mitochondrion can release and misplace mitochondrial components (cardiolipin, mitochondrial DNA (mtDNA), and mitochondrial formylated peptides) through multiple mechanisms. These components can act as damage-associated molecular patterns (DAMPs) and induce an inflammatory response via pattern recognition receptors (PRRs). Accumulation of damaged ROS-generating mitochondria, accompanied by the release of mitochondrial DAMPs, can activate PRRs such as the NLRP3 inflammasome, TLR9, cGAS/STING, and ZBP1. This process would explain the chronic inflammation that is observed in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type I diabetes (T1D), and Sjögren's syndrome. This review also provides a comprehensive overview of the importance of MERCs to mitochondrial function and morphology, cellular homeostasis, and the inflammatory response. MERCs play an important role in calcium homeostasis by mediating the transfer of calcium from the ER to the mitochondria and thereby facilitating the production of ATP. They also contribute to the synthesis and transfer of phospholipids, protein folding in the ER, mitochondrial fission, mitochondrial fusion, initiation of autophagosome formation, regulation of cell death/survival signaling, and regulation of immune responses. Therefore, alterations within MERCs could increase inflammatory signaling, modulate ER stress responses, cell homeostasis, and ultimately, the cell fate. This study shows severe ultrastructural alterations of mitochondria in salivary gland cells from Sjögren's syndrome patients for the first time, which could trigger alterations in cellular bioenergetics. This finding could explain symptoms such as fatigue and malfunction of the salivary glands in Sjögren's syndrome patients, which would contribute to the chronic inflammatory pathology of the disease. However, this is only a first step in solving this complex puzzle, and several other important factors such as changes in mitochondrial morphology, functionality, and their important contacts with other organelles require further in-depth study. Future work should focus on detecting the key milestones that are related to inflammation in patients with autoimmune diseases, such as Sjögren´s syndrome.


Asunto(s)
Síndrome de Sjögren , ADN Mitocondrial/metabolismo , Retículo Endoplásmico/metabolismo , Humanos , Inflamación/metabolismo , Mitocondrias
7.
Rev Med Chil ; 149(12): 1773-1786, 2021 Dec.
Artículo en Español | MEDLINE | ID: mdl-35735345

RESUMEN

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.


Asunto(s)
Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Chile/epidemiología , Consenso , Quiste Pancreático/diagnóstico , Quiste Pancreático/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia
8.
Rheumatology (Oxford) ; 60(4): 1951-1962, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33216905

RESUMEN

OBJECTIVE: Altered homeostasis of salivary gland (SG) epithelial cells in Sjögren's syndrome (SS) could be the initiating factor that leads to inflammation, secretory dysfunction and autoimmunity. Autophagy is an important homeostatic mechanism, whose deficiency is associated with inflammation and accumulation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) components. We aimed to evaluate whether autophagy is altered in labial SG (LSG) epithelial cells from primary SS (pSS) patients and whether this contributes to inflammation through the JAK-STAT pathway. Furthermore, we investigated the anti-inflammatory effect of the JAK inhibitor tofacitinib in autophagy-deficient (ATG5 knockdown) three-dimensional (3D)-acini. METHODS: We analysed LSG biopsies from 12 pSS patients with low focus score and 10 controls. ATG5-deficient 3D-acini were generated and incubated with IL-6 in the presence or absence of tofacitinib. Autophagy markers, pro-inflammatory cytokine expression, and JAK-STAT pathway activation were evaluated by PCR or western blot, along with correlation analyses between the evaluated markers and clinical parameters. RESULTS: LSG from pSS patients showed increased p62 and decreased ATG5 expression, correlating negatively with increased activation of JAK-STAT pathway components (pSTAT1 and pSTAT3). Increased expression of STAT1 and IL-6 correlated with EULAR Sjögren's syndrome disease activity index and the presence of anti-Ro antibodies. ATG5-deficient 3D-acini reproduced the findings observed in LSG from pSS patients, showing increased expression of pro-inflammatory markers such as IL-6, which was reversed by tofacitinib. CONCLUSION: Decreased expression of ATG5 in LSG epithelial cells from pSS patients possibly contributes to increased inflammation associated with JAK-STAT pathway activation, as evidenced in ATG5-deficient 3D-acini. Interestingly, these results suggest that tofacitinib could be used as an anti-inflammatory agent in pSS patients.


Asunto(s)
Autofagia/efectos de los fármacos , Interleucina-6/metabolismo , Piperidinas/farmacología , Pirimidinas/farmacología , Adolescente , Adulto , Anciano , Western Blotting , Estudios de Casos y Controles , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Interleucina-6/antagonistas & inhibidores , Quinasas Janus/metabolismo , Masculino , Persona de Mediana Edad , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción STAT/metabolismo , Glándulas Salivales/efectos de los fármacos , Glándulas Salivales/metabolismo , Transducción de Señal/efectos de los fármacos , Síndrome de Sjögren , Adulto Joven
9.
Sci Rep ; 10(1): 3145, 2020 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-32081909

RESUMEN

Anthropic activity in Antarctica has been increasing considerably in recent years, which could have an important impact on the local microbiota affecting multiple features, including the bacterial resistome. As such, our study focused on determining the antibiotic-resistance patterns and antibiotic-resistance genes of bacteria recovered from freshwater samples collected in areas of Antarctica under different degrees of human influence. Aerobic heterotrophic bacteria were subjected to antibiotic susceptibility testing and PCR. The isolates collected from regions of high human intervention were resistant to several antibiotic groups, and were mainly associated with the presence of genes encoding aminoglycosides-modifying enzymes (AMEs) and extended-spectrum ß-lactamases (ESBLs). Moreover, these isolates were resistant to synthetic and semi-synthetic drugs, in contrast with those recovered from zones with low human intervention, which resulted highly susceptible to antibiotics. On the other hand, we observed that zone A, under human influence, presented a higher richness and diversity of antibiotic-resistance genes (ARGs) in comparison with zones B and C, which have low human activity. Our results suggest that human activity has an impact on the local microbiota, in which strains recovered from zones under anthropic influence were considerably more resistant than those collected from remote regions.


Asunto(s)
Farmacorresistencia Microbiana , Agua Dulce/microbiología , Microbiología del Agua , Animales , Regiones Antárticas , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/genética , Farmacorresistencia Bacteriana , Ambiente , Genes Bacterianos , Geografía , Humanos , Pruebas de Sensibilidad Microbiana , Microbiota/efectos de los fármacos , Reacción en Cadena de la Polimerasa , beta-Lactamasas/metabolismo
11.
Rheumatology (Oxford) ; 59(4): 742-753, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31377809

RESUMEN

OBJECTIVES: Xerostomia in SS patients has been associated with low quality and quantity of salivary mucins, which are fundamental for the hydration and protection of the oral mucosa. The aim of this study was to evaluate if cytokines induce aberrant mucin expression and whether tauroursodeoxycholic acid (TUDCA) is able to counteract such an anomaly. METHODS: Labial salivary glands from 16 SS patients and 15 control subjects, as well as 3D acini or human submandibular gland cells stimulated with TNF-α or IFN-γ and co-incubated with TUDCA, were analysed. mRNA and protein levels of Mucin 1 (MUC1) and MUC7 were determined by RT-qPCR and western blot, respectively. Co-immunoprecipitation and immunofluorescence assays for mucins and GRP78 [an endoplasmic reticulum (ER)-resident protein] were also performed. mRNA levels of RelA/p65 (nuclear factor-κB subunit), TNF-α, IL-1ß, IL-6, SEL1L and EDEM1 were determined by RT-qPCR, and RelA/p65 localization was evaluated by immunofluorescence. RESULTS: MUC1 is overexpressed and accumulated in the ER of labial salivary gland from SS patients, while MUC7 accumulates throughout the cytoplasm of acinar cells; however, MUC1, but not MUC7, co-precipitated with GRP78. TUDCA diminished the overexpression and aberrant accumulation of MUC1 induced by TNF-α and IFN-γ, as well as the nuclear translocation of RelA/p65, together with the expression of inflammatory and ER stress markers in 3D acini. CONCLUSION: Chronic inflammation alters the secretory process of MUC1, inducing ER stress and affecting the quality of saliva in SS patients. TUDCA showed anti-inflammatory properties decreasing aberrant MUC1 accumulation. Further studies are necessary to evaluate the potential therapeutic effect of TUDCA in restoring glandular homeostasis in SS patients.


Asunto(s)
Células Acinares/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Mucina-1/efectos de los fármacos , Glándulas Salivales Menores/efectos de los fármacos , Síndrome de Sjögren/metabolismo , Glándula Submandibular/efectos de los fármacos , Ácido Tauroquenodesoxicólico/farmacología , Xerostomía/metabolismo , Células Acinares/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Células Cultivadas , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/genética , Femenino , Proteínas de Choque Térmico/efectos de los fármacos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Inmunoprecipitación , Técnicas In Vitro , Interferón gamma/farmacología , Interleucina-1beta/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Proteínas de la Membrana/efectos de los fármacos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Mucina-1/genética , Mucina-1/metabolismo , Mucinas/efectos de los fármacos , Mucinas/genética , Mucinas/metabolismo , Proteínas/efectos de los fármacos , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Glándulas Salivales Menores/metabolismo , Proteínas y Péptidos Salivales/efectos de los fármacos , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/metabolismo , Síndrome de Sjögren/genética , Glándula Submandibular/citología , Glándula Submandibular/metabolismo , Factor de Transcripción ReIA/efectos de los fármacos , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Xerostomía/genética
12.
Rev Med Chil ; 147(2): 251-255, 2019 Feb.
Artículo en Español | MEDLINE | ID: mdl-31095176

RESUMEN

Liver involvement occurs in 0.2 to 3% of patients with syphilis. We report three patients with liver involvement in syphilis. A 52-year-old male presenting with erythema and malaise. Laboratory showed a gamma glutamyl transpeptidase (GGT) of 853 u/l, alkaline phosphatases of 1,010 U/L and VDRL was positive. Treatment with penicillin resolved the skin problem and normalized liver enzymes. A HIV positive 30-year-old male in peritoneal dialysis presenting with itching, malaise and markedly elevated GGT and alkaline phosphatases. VDRL was positive. He was treated with penicillin with remission of symptoms and enzyme normalization. A 43-year-old male presenting with erythema, malaise, arthralgias and elevated GGT and alkaline phosphatases. VDRL was positive and treatment with penicillin reverted symptoms and laboratory abnormalities.


Asunto(s)
Hepatitis/diagnóstico , Sífilis/diagnóstico , Adulto , Fosfatasa Alcalina/sangre , Colestasis/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Serodiagnóstico de la Sífilis , gamma-Glutamiltransferasa/sangre
13.
Rev. méd. Chile ; 147(2): 251-255, Feb. 2019. tab, graf
Artículo en Español | LILACS | ID: biblio-1004340

RESUMEN

Liver involvement occurs in 0.2 to 3% of patients with syphilis. We report three patients with liver involvement in syphilis. A 52-year-old male presenting with erythema and malaise. Laboratory showed a gamma glutamyl transpeptidase (GGT) of 853 u/l, alkaline phosphatases of 1,010 U/L and VDRL was positive. Treatment with penicillin resolved the skin problem and normalized liver enzymes. A HIV positive 30-year-old male in peritoneal dialysis presenting with itching, malaise and markedly elevated GGT and alkaline phosphatases. VDRL was positive. He was treated with penicillin with remission of symptoms and enzyme normalization. A 43-year-old male presenting with erythema, malaise, arthralgias and elevated GGT and alkaline phosphatases. VDRL was positive and treatment with penicillin reverted symptoms and laboratory abnormalities.


Asunto(s)
Humanos , Masculino , Adulto , Persona de Mediana Edad , Sífilis/diagnóstico , Hepatitis/diagnóstico , Serodiagnóstico de la Sífilis , Colestasis/diagnóstico , Diagnóstico Diferencial , Fosfatasa Alcalina/sangre , gamma-Glutamiltransferasa/sangre
14.
Clin Immunol ; 196: 85-96, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29894742

RESUMEN

Here, we determined the 5-hydroxymethylcytosine (5hmC), 5-methylcytosine (5mC), Ten Eleven Translocation (TETs), and DNA methyltransferases (DNMTs) levels in epithelial and inflammatory cells of labial salivary glands (LSG) from Sjögren's syndrome (SS)-patients and the effect of cytokines on HSG cells. LSG from SS-patients, controls and HSG cells incubated with cytokines were analysed. Levels of 5mC, 5hmC, DNMTs, TET2 and MeCP2 were assessed by immunofluorescence. In epithelial cells from SS-patients, an increase in TET2, 5hmC and a decrease in 5mC and MeCP2 were observed, additionally, high levels of 5mC and DNMTs and low levels of 5hmC were detected in inflammatory cells. Cytokines increased TET2 and 5hmC and decreased 5mC levels. Considering that the TET2 gene.promoter contains response elements for transcription factors activated by cytokines, together to in vitro results suggest that changes in DNA hydroxymethylation, resulting from altered levels of TET2 are likely to be relevant in the Sjögren's syndrome etiopathogenesis.


Asunto(s)
5-Metilcitosina/análogos & derivados , ADN (Citosina-5-)-Metiltransferasas/genética , Proteínas de Unión al ADN/genética , Proteína 2 de Unión a Metil-CpG/genética , Proteínas Proto-Oncogénicas/genética , Glándulas Salivales Menores/metabolismo , Síndrome de Sjögren/genética , 5-Metilcitosina/metabolismo , Adulto , Anciano , Citidina Desaminasa/genética , Citidina Desaminasa/metabolismo , Citocinas/inmunología , ADN (Citosina-5-)-Metiltransferasa 1/genética , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , ADN Metiltransferasa 3A , Proteínas de Unión al ADN/inmunología , Proteínas de Unión al ADN/metabolismo , Dioxigenasas/genética , Dioxigenasas/inmunología , Dioxigenasas/metabolismo , Epigénesis Genética , Femenino , Expresión Génica , Regulación de la Expresión Génica , Humanos , Inflamación/genética , Inflamación/metabolismo , Labio , Masculino , Proteína 2 de Unión a Metil-CpG/metabolismo , Persona de Mediana Edad , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/inmunología , Oxigenasas de Función Mixta/metabolismo , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas/inmunología , Proteínas Proto-Oncogénicas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Glándulas Salivales Menores/citología , Glándulas Salivales Menores/inmunología , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/metabolismo , Adulto Joven , ADN Metiltransferasa 3B
15.
Bol. latinoam. Caribe plantas med. aromát ; 15(5): 274-287, Sept. 2016. ilus, tab
Artículo en Inglés | LILACS | ID: biblio-907545

RESUMEN

The aim of this study was to assess the differences in qualitative-quantitative composition of triterpenoids and total phenolic contents, together with anti-inflammatory activity of Ugni molinae leaves obtained from ten genotypes. The ethyl acetate (EAE) and ethanol extracts (ETE) were obtained and analyzed. The plant genotypes were grown under same soil and climate conditions and under same agronomic management; the leaves were also harvested under the same conditions. Anti-inflammatory activity was evaluated by mice ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) at a single dose of 200 mg/kg BW of each extract. Composition of triterpenoids and total phenolic contents was determined by HPLC-DAD and Folin-Ciocalteu method, respectively. Ugni molinae leaves of different plant genotypes exhibited significant differences in regard to their anti-inflammatory activity, as well as in qualitative-quantitative composition of triterpenoids and total phenolic content.


El objetivo de este estudio fue establecer las diferencias en la composición cualitativa y cuantitativa de triterpenoides y en los contenidos totales de fenoles, junto con la actividad antiinflamatoria de las hojas de Ugni molinae provenientes de diez genotipos. Los extractos de acetato de etilo (EAE) y etanólicos (ETE) fueron obtenidos y analizados. Los genotipos fueron cultivados bajo las mismas condiciones edafo-climáticas y con el mismo manejo agronómico; las hojas fueron cosechadas bajo las mismas condiciones. La actividad antiinflamatoria fue evaluada en ratones a los que se les indujo un edema en la oreja mediante la aplicación del 12-O-tetradecanoilforbol-13 acetato (TPA) y los extractos fueron evaluados a una dosis única de 200 mg/kg de peso corporal. La composición en triterpenoides y los contenidos de fenoles totales fueron determinados por CLAE-DAD y por el método de Folin-Ciocalteu, respectivamente. Las hojas provenientes de los diferentes genotipos de U. molinae, exhibieron significativas diferencias en sus actividades antiinflamatorias, así como, en el contenido cualitativo y cuantitativo de triterpenoides y en el contenido de fenoles totales.


Asunto(s)
Animales , Ratones , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Edema/tratamiento farmacológico , Myrtaceae/química , Extractos Vegetales/química , Triterpenos/análisis , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales/uso terapéutico
16.
Rev. chil. dermatol ; 32(1): 8-14, 2016. tab
Artículo en Español | LILACS | ID: biblio-911483

RESUMEN

Introducción: Existe poca información de la asociación entre Psoriasis y síndrome metabólico (SM) en Chile. Objetivos: Determinar la prevalencia de SM en psoriáticos chilenos. Material y métodos: Se realizó un estudio caso-control, con 487 pacientes (238 psoriáticos y 239 controles). En ambos grupos se analizó la prevalencia de SM además del exceso de peso, hipertensión arterial, diabetes mellitus 2, hipertrigliceridemia y niveles de HDL bajo. Resultados: Los psoriáticos presentaron mayor probabilidad de padecer SM versus los controles (35,29% vs 23,29%) OR 1,8 (1,20-2,66) p<0,05. Se asoció también con circunferencia abdominal aumentada (57,14% vs 36,94) OR 2,6 (1,79 - 3,78), exceso de peso (85,99% vs 63,45%) OR 2,46 (1,62 ­ 3,73) p<0,05 y diabetes mellitus 2 (13,45% vs 4,42%) OR 3,85 (1,79 - 8,26) p<0,05. Conclusiones: Se encontró una mayor prevalencia de SM, exceso de peso, circunferencia abdominal aumentada y diabetes mellitus 2 en el grupo psoriático en comparación al grupo control.


Background: There is a paucity of information about Psoriasis and metabolic syndrome (MS) association in Chile. Aim: To determine the MS prevalence in Chilean psoriatic patients. Material and Methods: A case-control study was conducted which included 487 patients (238 psoriatic patients and 239 controls). In both groups, MS prevalence, overweight, hypertension, diabetes mellitus type 2, hypertriglyceridemia and low HDL were analyzed. Results: Psoriatic patients were more likely to present MS than controls (35.29% vs 23.29%) OR 1.8 (1.20 to 2.66) p <0.05. In addition, it was associated with increased abdominal circumference (57.14% vs 36.94) OR 2.6 (1.79 to 3.78), overweight (85.99% vs 63.45%) OR 2.46 (1.62 to 3.73) p <0.05 and diabetes mellitus type 2 (13.45% vs. 4.42%) OR 3.85 (1.79 to 8.26) p <0.05. Conclusions: There is a higher prevalence of MS, overweight, increased abdominal circumference and type 2 diabetes mellitus in the psoriatic group compared with the control group.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Psoriasis/epidemiología , Síndrome Metabólico/epidemiología , Índice de Severidad de la Enfermedad , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Comorbilidad , Chile/epidemiología , Prevalencia
17.
Bol. latinoam. Caribe plantas med. aromát ; 12(1): 108-116, ene. 2013. ilus, tab
Artículo en Inglés | LILACS | ID: lil-722513

RESUMEN

The aim of this study was to establish an analytical method to detect the presence of the responsible triterpenoids of the anti-inflammatory activity of the leaves of Ugni molinae (murtilla). Successive leaves extracts of EtOAc (EAE) and ethanol (TEE) were prepared, obtaining for the first time from TEE a triterpenoid-rich sub-fraction (TF). The topical anti-inflammatory activity of TF was assessed (43.3 percent at 1 mg/ear) by means of the TPA-induced mouse ear oedema model, which was compared to EAE (83.1 +/- 3.2 percent) and TEE (78.3 +/- 11.8 percent) activities, both previously evaluated by us. These extracts were characterized in their triterpenoids by HPLC-UV and HPLC-ESI-MS. We demonstrated that TF has triterpenoids responsible in part of the anti-inflammatory activity, among them, madecassic and maslinic acids. These two compounds have been reported for the first time for this species. ED50 for madecassic and alphitolic acids are also here reported.


El objetivo de este trabajo fue establecer un método analítico para determinar la presencia de los triterpenoides responsables de la actividad anti-inflamatoria de las hojas de Ugni molinae (murtilla). Fueron preparados los extractos seriados de EtOAc (EAE) y etanólico (TEE) desde sus hojas, obteniendo desde el TEE por primera vez una sub-fracción rica en triterpenoides (TF). Se demostró la actividad anti-inflamatoria tópica del TF por el modelo de edema de oreja de ratón inducida por TPA (43,3 por ciento a 1 mg/oreja), la cual fue comparada con las de los EAE (83,1 +/- 3,2 por ciento) y TEE (78,3 +/- 11,8 por ciento) determinadas en nuestros estudios previos. Dichos extractos fueron caracterizados en sus triterpenoides por CLAE-UV y CLAE-IES-MS. Demostramos que el TF contiene triterpenoides responsables en parte de la actividad anti-inflamatoria, entre ellos, los ácidos madecásico y maslínico, reportados por primera vez para esta especie. Se informan además las DE50 para los ácidos madecásico y alfitólico.


Asunto(s)
Animales , Ratas , Antiinflamatorios , Extractos Vegetales/farmacología , Hojas de la Planta/química , Myrtaceae/química , Triterpenos/aislamiento & purificación , Triterpenos/análisis , Chile , Cromatografía Líquida de Alta Presión , Espectrometría de Masa por Ionización de Electrospray , Triterpenos/farmacología
18.
Maturitas ; 62(3): 321-3, 2009 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-19217728

RESUMEN

BACKGROUND: Although several tools have been designed to assess quality of life (QoL) among middle-aged women their capacity to specifically assess sexual dysfunction (SD) remains uncertain. Moreover, if SD impairs QoL within this population, then sexual assessment becomes a key issue. OBJECTIVES: To evaluate the accuracy of the Menopause Rating Scale (MRS) in diagnosing SD among climacteric women. METHODS: In this cross-sectional study 370 women aged 40-59 years filled out the MRS and the Female Sexual Functioning Index (FSFI) simultaneously. SD among surveyed women was defined as those obtaining a total FSFI score of or=1 in the MRS item 8 as a cut-off value for discriminating women with SD (78% sensitivity and 62% specificity with an area below the curve of 0.70 Swett). CONCLUSIONS: The MRS was moderately accurate for diagnosing SD among climacteric women. More research is warranted in this regard.


Asunto(s)
Climaterio , Disfunciones Sexuales Fisiológicas/diagnóstico , Disfunciones Sexuales Psicológicas/diagnóstico , Encuestas y Cuestionarios , Adulto , Climaterio/fisiología , Climaterio/psicología , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Curva ROC , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
19.
Rev. méd. Chile ; 136(12): 1511-1517, dic. 2008. tab
Artículo en Español | LILACS | ID: lil-508903

RESUMEN

Background: Climacteric symptoms have a direct relationship with biological and sociocultural factors and significantly impair the quality of life of women. Aim: To assess quality of life and factors affecting it in women aged 40 to 59 years. Material and methods: The Menopause Rating Scale (MRS) was applied to 370 healthy women aged 49 ± 6 years, that accompanied patients to public hospitals in Santiago. Results: Forty four percent of women were postmenopausal and 6 percent used hormone replacement therapy. Half of the group had less than 12 years of formal education and 67 percent had a couple. The mean number of children was 2.8 ± 1.5. Total MRS score was 16.2 ± 8.5. The higher score was given by the psychological domain (7.7 + 4.4), followed by the somatic domain (5.8 ± 3.5). The urogenital domain had the lowest score (2.7 ± 2.9). Eighty percent of women had moderate to severe climacteric symptoms. A logistic regression analysis showed that the postmenopausal condition was the factor that caused the greatest derangement in quality of life, followed by her parity. Formal education had the lowest impact. Conclusions: In this sample of women, menopause significantly deteriorated quality of life and sociocultural factors such as the parity also had an impact.


Asunto(s)
Adulto , Femenino , Humanos , Persona de Mediana Edad , Menopausia/psicología , Calidad de Vida/psicología , Estudios de Cohortes , Estudios Transversales , Terapia de Reemplazo de Estrógeno , Modelos Logísticos , Menopausia/efectos de los fármacos
20.
Rev Med Chil ; 136(12): 1511-7, 2008 Dec.
Artículo en Español | MEDLINE | ID: mdl-19350167

RESUMEN

BACKGROUND: Climacteric symptoms have a direct relationship with biological and sociocultural factors and significantly impair the quality of life of women. AIM: To assess quality of life and factors affecting it in women aged 40 to 59 years. MATERIAL AND METHODS: The Menopause Rating Scale (MRS) was applied to 370 healthy women aged 49 +/- 6 years, that accompanied patients to public hospitals in Santiago. RESULTS: Forty four percent of women were postmenopausal and 6% used hormone replacement therapy. Half of the group had less than 12 years of formal education and 67% had a couple. The mean number of children was 2.8 +/- 1.5. Total MRS score was 16.2 +/- 8.5. The higher score was given by the psychological domain (7.7 + 4.4), followed by the somatic domain (5.8 +/- 3.5). The urogenital domain had the lowest score (2.7 +/- 2.9). Eighty percent of women had moderate to severe climacteric symptoms. A logistic regression analysis showed that the postmenopausal condition was the factor that caused the greatest derangement in quality of life, followed by her parity. Formal education had the lowest impact. CONCLUSIONS: In this sample of women, menopause significantly deteriorated quality of life and sociocultural factors such as the parity also had an impact.


Asunto(s)
Menopausia/psicología , Calidad de Vida/psicología , Adulto , Estudios de Cohortes , Estudios Transversales , Terapia de Reemplazo de Estrógeno , Femenino , Humanos , Modelos Logísticos , Menopausia/efectos de los fármacos , Persona de Mediana Edad
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