Browsing by Author "Borzutzky, Arturo"
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- ItemAltered Sensory and Stress Responses in Atopic Dermatitis: Effects of Acute Stress on Lesional and Non-Lesional Skin(WILEY, 2025) Tejos Bravo, Macarena; Cid, Dixon; Espinoza, Fernanda; Rojas Thomas, Felipe; Torres, Gustavo; Cossio, Maria Laura; Borzutzky, Arturo; Calvo, MargaritaItch and pain are both mediated by small sensory fibres. Atopic dermatitis (AD) patients usually report stress-induced flares, but the impact of stress on sensory fibres in lesional and non-lesional skin remains inconclusive. This observational study assessed the effect of acute stress on sensory profiles in subjects with AD (n = 18) and healthy controls (HC, n = 21). Participants completed clinical and psychological questionnaires, and quantitative sensory testing was performed on lesional and non-lesional skin in AD and healthy skin in HC. Assessments were done before and after the Montreal Imaging Stress Task, an acute stress protocol. Stress responses were evaluated by anxiety ratings, heart rate (HR) and salivary cortisol (CORT). Cortisol binding globulin (CBG) was quantified as an indirect measure for circulating CORT. AD participants reported higher anxiety, depression and stress perception than HC. HR was similar between groups, but AD participants showed a blunted CORT response post-stress and lower CBG levels, suggesting altered stress regulation. Acute stress reduced cold sensitivity in HC and non-lesional AD skin but had no effect on lesions. These findings indicate that the effects of stress on small fibres depend on the condition of the skin and emphasise the sensory alterations experienced by AD patients.
- ItemAltered Sensory and Stress Responses in Atopic Dermatitis: Effects of Acute Stress on Lesional and Non-Lesional Skin(HUMANA PRESS INC, 2025) Tejos Bravo, Macarena; Cid, Dixon; Espinoza, Fernanda; Rojas Thomas, Felipe; Torres, Gustavo; Cossio, Maria Laura; Borzutzky, Arturo; Calvo, MargaritaItch and pain are both mediated by small sensory fibres. Atopic dermatitis (AD) patients usually report stress-induced flares, but the impact of stress on sensory fibres in lesional and non-lesional skin remains inconclusive. This observational study assessed the effect of acute stress on sensory profiles in subjects with AD (n = 18) and healthy controls (HC, n = 21). Participants completed clinical and psychological questionnaires, and quantitative sensory testing was performed on lesional and non-lesional skin in AD and healthy skin in HC. Assessments were done before and after the Montreal Imaging Stress Task, an acute stress protocol. Stress responses were evaluated by anxiety ratings, heart rate (HR) and salivary cortisol (CORT). Cortisol binding globulin (CBG) was quantified as an indirect measure for circulating CORT. AD participants reported higher anxiety, depression and stress perception than HC. HR was similar between groups, but AD participants showed a blunted CORT response post-stress and lower CBG levels, suggesting altered stress regulation. Acute stress reduced cold sensitivity in HC and non-lesional AD skin but had no effect on lesions. These findings indicate that the effects of stress on small fibres depend on the condition of the skin and emphasise the sensory alterations experienced by AD patients.
- ItemChanges in Treatments and Outcomes After Implementation of a National Universal Access Program for Juvenile Idiopathic Arthritis(J RHEUMATOL PUBL CO, 2021) Concha, Sara; Morales, Pamela S.; Talesnik, Eduardo; Borzutzky, ArturoObjective. To evaluate the clinical and demographic characteristics of patients with juvenile idiopathic arthritis (JIA) in Chile and compare treatments and outcomes before and after the introduction in 2010 of the Explicit Health Guarantees (GES) for JIA, a national universal access program for diagnosis and treatment of this condition. Methods. The clinical records of 280 patients with JIA followed at a private tertiary academic health network between 2007 and 2018 were reviewed. Results. Seventy percent of patients with JIA were female, mean age at diagnosis was 8.5 +/- 4.8 years and mean follow-up was 4.0 +/- 3.7 years. After GES implementation (post-GES), time to evaluation by pediatric rheumatologist and diagnostic delay were significantly reduced (15.0 +/- 4.5 vs 9.0 +/- 4.2 months, P = 0.004). In addition, use of magnetic resonance imaging significantly increased post-GES (P < 0.001). In terms of JIA treatments, before GES implementation, no patients received biologics. Of the 67 patients diagnosed before 2010 with continued follow-up at our center, 34% began biologic treatment after GES implementation. Of 196 patients diagnosed post-GES, 46% were treated with biologics. JIA remission rates were significantly higher in patients diagnosed post-GES compared to pre-GES (43% vs 29%, P = 0.02). Post-GES, we observed a significant decrease in uveitis complications among JIA patients (45% vs 13%, P = 0.04). Conclusion. The implementation of a national government-mandated universal access program for guaranteed JIA diagnosis and treatment led to earlier access to a pediatric rheumatologist and JIA diagnosis, increased rates of treatment with biologic drugs, higher rates of clinical remission, and lower rates of uveitis complications in Chilean children with JIA.
- ItemClinical and genetic features of hereditary periodic fever syndromes in Hispanic patients: the Chilean experience(2012) Vergara, Cristian; Borzutzky, Arturo; Gutierrez, Miguel A.; Iacobelli, Sergio; Talesnik, Eduardo; Martinez, Maria E.; Stange, Lilith; Basualdo, Javier; Maluje, Viviana; Jimenez, Renato; Wiener, Roberto; Tinoco, Javier; Jarpa, Elena; Arostegui, Juan I.; Yaguee, Jordi; Alvarez-Lobos, ManuelHereditary periodic fever syndromes (HPFS) are rare genetic diseases characterized by recurrent episodes of inflammation. Little information is available concerning HPFS in Latin American Hispanic population. The purpose of this study was to determine the clinical and genetic features of HPFS in Chilean population. A multicenter retrospective study of Hispanic Chilean patients with genetically confirmed HPFS was performed. We included 13 patients, 8 with familial Mediterranean fever (FMF) and 5 with TNF receptor-associated periodic syndrome (TRAPS), evaluated at rheumatology or pediatric rheumatology clinics between January 2007 and December 2010. Median age of symptoms onset was 8 years (range 1-35) and 8 years (range 0.3-21) for FMF and TRAPS, respectively. Median duration of fever was 3 days (range 2.5-15) for FMF and 21 days (range 9.5-30) for TRAPS. Genotyping of the MEFV gene in FMF patients revealed a homozygous M694V missense mutation in one patient, and heterozygous missense mutations in seven patients: M694V (n = 3), E148Q, R717H, A744S, and A511V. Sequencing of the TNFRSF1A gene in TRAPS patients revealed heterozygous missense mutations in four patients: T50M, C30R, R92Q, and IVS3+30:G -> A, and a two-base pair deletion (IVS2-17_18del2bpCT) in one patient. Mutation in MEFV R717H and mutations in TNFRSF1A IVS2-17_18del2bpCT and IVS3+30:G -> A are novel and have not been described previously. This study reports the largest series of genetically confirmed HPFS in Latin America, and adds evidence regarding the clinical and genetic characteristics of patients with FMF and TRAPS in Hispanic population. Mutations identified in MEFV and TNFRSF1A genes include defects reported in other ethnicities and novel mutations.
- ItemIncreasing food allergies in Chile, a developing country post-epidemiological transition(WILEY, 2020) Hoyos Bachiloglu, Rodrigo; Escobar, Juan J.; Cifuentes, Camila; Aguilera Insunza, Raquel; Morales, Pamela S.; Borzutzky, Arturo
- ItemMaternal obesity is associated with a higher number of regulatory-T-cells in newborns without affecting suppression(2023) Arroyo-Jousse, Viviana; Borzutzky, Arturo; Rosa Bono, Maria; Casanello, PaolaBackgroundMaternal obesity (MO) is associated with a higher risk of immune-mediated diseases in the offspring and higher leptin levels in cord blood (CB). This study evaluates the number and function of lymphocyte subtypes in CB related to MO and its relationship with leptin concentration and leptin receptor expression. MethodsPregnant women with (n = 32) or without obesity (n = 41) were enrolled at delivery. Cord blood mononuclear cells were separated with Ficoll-Hypaque. B and CD4+, regulatory and effector T cells were quantified by Flow Cytometry. Cord blood leptin concentration was measured by ELISA, and the leptin receptor (sLepR) on Treg cells was determined by Flow Cytometry. ResultsMO was associated with higher numbers of CD4+, Treg and effector T cells in the CB of their offspring, without differences in the suppressive function of Tregs. Female offspring had a higher number of these cells and a higher cord leptin concentration. Tregs expressed higher levels of sLepR than effector T cells, without differences between groups. ConclusionsMO is associated with changes in the newborn's immune profile, more evident in female newborns with higher leptin concentrations. More studies are needed to identify the mechanisms by which the high levels of cord leptin in the newborn of women with obesity could affect the offspring's immune system.
- ItemOsteoporosis in children with severe congenital neutropenia: Bone mineral density and treatment with bisphosphonates(LIPPINCOTT WILLIAMS & WILKINS, 2006) Borzutzky, Arturo; Reyes, Maria Loreto; Figueroa, Valeria; Garcia, Cristian; Cavieres, MirtaA high incidence of decreased bone mineral density (BMD) has been described in patients with severe congenital neutropenia (SCN). The objectives of the study are to describe changes in BMD in children with SCN treated with granulocyte colony-stimulating factor and evaluate the response to treatment with bisphosphonates in those two had osteoporosis. A prospective open-label study was performed evaluating BMD and metabolism in 9 Chilean patients with SCN, administrating bisphosphonates in those with osteoporosis. Follow-up ranged between 7 months and 3.5 years. Six out of 9 patients had reduced BMD on initial assessment: 3 had osteoporosis (z score < - 2) and 3, had osteopenia (z score < - 1). Four children presented vertebral fractures. Two presented osteopenia on follow-up without Clinical Symptoms. Five patients were treated with biphosphonates, increasing their BMD z Score (mean increase 1.2. range 0.27 to 2.62). z Score of hydroxyproline/ creatinine ratios, which was elevated in 4 patients with osteoperosis, decreases during treatment (mean decrease 2.18, range 1.56 to 2.53). Four patients remodeled and reexpanded fractured vertebrae during treatment. No side effects of bisphosphonate were seen on follow-up. Osteoporosis is an important comorbidity in SCN patients probably due to an increased bone resorption. Bisphosphonates seem to be an effective treatment for osteoporosis in these patients.
- ItemPediatric Chronic Nonbacterial Osteomyelitis(AMER ACAD PEDIATRICS, 2012) Borzutzky, Arturo; Stern, Sara; Reiff, Andreas; Zurakowski, David; Steinberg, Evan A.; Dedeoglu, Fatma; Sundel, Robert P.BACKGROUND AND OBJECTIVES: Little information is available concerning the natural history and optimal treatment of chronic non-bacterial osteomyelitis (CNO). We conducted a retrospective review to assess the clinical characteristics and treatment responses of a large cohort of pediatric CNO patients.
- ItemSafety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-& alpha;2b in Healthy Adults: The (INCOVID)-C-2 Phase I Randomized Trial(2023) García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Perez-Mateluna, Guillermo; Fajuri, Paula; Severino Cuevas, Nicolás Felipe; Urzua, Marcela; Fraga, Juan Pablo; Cruz, Javiera de la; Poli, Cecilia; Castro Rodríguez, José Antonio; Fish, Eleanor; Borzutzky, ArturoBackground and ObjectivesInterferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-& alpha;2b (IFN)-& alpha;2b in healthy adults.MethodsA double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-& alpha;2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-& alpha;2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFN & alpha; concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments.ResultsExposure to inhaled IFN-& alpha;2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-& alpha; concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons).ConclusionsInhaled IFN-& alpha;2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects.
- ItemWeekly Vitamin D Supplementation to Prevent Acute Respiratory Infections in Young Children at Different Latitudes: A Randomized Controlled Trial(2024) Reyes, Maria Loreto; Vizcaya, Cecilia; Le Roy, Catalina; Loureiro, Carolina; Brinkmann, Karin; Campos, Laura; Arancibia, Monica; Iturriaga, Carolina; Perez-Mateluna, Guillermo; Rojas-McKenzie, Maite; Dominguez, Gonzalo; Camargo Jr, Carlos A.; Borzutzky, ArturoObjective: To evaluate the effectiveness of weekly vitamin D supplementation in reducing the number of acute respiratory infections (ARI) in preschool children. Study design: Randomized, double-blind, placebo-controlled trial in 303 children aged 1.5-3.5 years from 2014 to 2105 in 3 Chilean cities at different latitudes: Santiago (33 degrees S, n = 101), Talcahuano (37 degrees S, n = 103), and Punta Arenas (53 degrees S, n = 99). Participants were allocated (1:1:1) to receive placebo, cholecalciferol (vitamin D3 (VD3)) 5600 IU/week (low-dose), or 11 200 IU/week (high-dose) for 6 months. Primary outcome was parent-reported number of ARI; secondary outcomes included number of ARI hospitalizations, change of serum 25-hydroxyvitamin D (25(OH)D) and LL-37/cathelicidin levels, and adverse events. Results: The mean age of participants was 26 +/- 6 months; 45% were female. Baseline 25(OH)D was 24.9 +/- 6.1 ng/ml, with 23% having 25(OH)D <20 ng/ml. No significant baseline clinical or laboratory differences were observed among groups. Overall, 64% (n = 194) completed study participation, without baseline differences between subjects lost to follow-up vs those completing participation or differences in completion rates across groups. After 6 months, a dose-dependent increase in serum 25(OH)D was observed from the VD3 intervention (P < .001), with a higher proportion of subjects ending the trial with 25(OH)D <20 ng/ml in the placebo group (30.8%) vs the low-dose (7.4%) and high-dose groups (5.1%). However, no group differences were observed in number of ARI (P = .85), ARI hospitalizations (P = .20), LL-37/cathelicidin change (P = .30), or adverse events (P = .41). Conclusions: While weekly VD3 supplementation, in doses equivalent to 800 IU and 1600 IU daily, was associated with improved 25(OH)D levels in preschoolers, we did not find a reduced number of ARI in this sample.