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1.
Neurochem Int ; 125: 187-196, 2019 05.
Article in English | MEDLINE | ID: mdl-30825600

ABSTRACT

Neurones are dependent on their mitochondria to produce the necessary amounts of ATP for survival. Retinal ganglion cells (RGCs) have a particularly large number of mitochondria which-unlike neurones in the brain-are exposed to visual light of 400-850 nm. Here we demonstrate that short wavelength visual blue light negatively affects mitochondrial function, causing oxidative stress and decreased cell survival. In contrast, long wavelength red light enhances mitochondrial function to increase survival of cultured R28 cells and reduce the effects of blue light. Induction of retinal ischemia for 60 min in dark conditions caused a reduction in ATP levels accompanied by decreased RGC numbers in all areas of the retina. These effects were diminished when ischemia was induced with concomitant delivery of red light, and exacerbated when blue light was used. We conclude that while the levels of blue light that reach the human retina will be a fraction of those used in the present study, the chronic nature might, on a theoretical basis, be detrimental to RGC mitochondria which are already affected by conditions such as glaucoma. Our findings also show that exposing the retina to red light may be a therapeutic approach to supporting healthy mitochondrial functions as part of the treatment for retinal diseases in which these organelles are affected.


Subject(s)
Light , Mitochondria/physiology , Mitochondria/radiation effects , Retinal Ganglion Cells/physiology , Retinal Ganglion Cells/radiation effects , Animals , Cell Line , Cell Survival/physiology , Cell Survival/radiation effects , Male , Rats , Rats, Wistar , Retina/cytology , Retina/physiology , Retina/radiation effects
2.
Rev Gastroenterol Mex (Engl Ed) ; 83(4): 410-413, 2018.
Article in English, Spanish | MEDLINE | ID: mdl-29753576

ABSTRACT

INTRODUCTION AND AIMS: A strong genetic association between celiac disease (CD) and the human leukocyte antigen (HLA) has been widely demonstrated. In Europe, the HLA-DQ2 allele is predominant. However, studies in Latin America indicate that HLA-DQ8 could be more frequent. In Mexico, the frequency of those alleles has not been reported in subjects with CD. Therefore, the aim of the present study was to evaluate the distribution of HLA-DQ2 and HLA-DQ8 in Mexican individuals with CD. MATERIAL AND METHODS: An exploratory study was conducted on a cohort of 49 subjects with chronic diarrhea. Autoantibodies for CD, duodenal atrophy, and HLA haplotypes were determined. RESULTS: Thirty individuals had CD (23 women, mean age 54.2 ± 15.5 years), 24 (80%) of whom expressed HLA-DQ8, 15 (50%) expressed HLA-DQ2, and 11 (37%) presented with both alleles. However, neither the HLA-DQ2 nor the HLA-DQ8 allele was found in 5 (10%) individuals. In subjects with chronic diarrhea that did not have CD, 12 (63%) presented with HLA-DQ2, and 7 (37%) with HLA-DQ8. Individuals with CD expressed the combinations of the HLA-DQ8/DQ2 alleles (37 vs. 5%) and the HLA-DR4/DQ8 alleles (60 vs. 26%) more frequently than the subjects without CD. CONCLUSIONS: In Mexican subjects with CD, HLA-DQ8 distribution was more frequent than that of HLA-DQ2, indicating a possible similarity to the frequency reported in other Latin American countries. However, given the nature of the present study and its sample size, further conclusions could not be reached.


Subject(s)
Celiac Disease/diagnosis , HLA-DQ Antigens/analysis , Adult , Aged , Cohort Studies , Diarrhea/etiology , Female , Genotype , Haplotypes , Humans , Male , Mexico , Middle Aged
3.
Lupus ; 25(4): 364-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26466614

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the utility of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in serum and cerebrospinal fluid (CSF) as a biomarker in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty three NPSLE patients were evaluated at hospitalization and six months later. As controls, five SLE patients with septic meningitis, 51 hospitalized SLE patients without a history of neuropsychiatric (NP) manifestations and without infections, 16 SLE patients without NP manifestations (surgical-SLE), four patients with primary neuropsychiatric disorders, and 25 patients with non-autoimmune diseases were also studied. Serum and CSF samples were drawn at hospitalization, except non-NPSLE patients, in whom only serum was studied, and six months later in 19 NPSLE and 27 non-NPSLE patients. Serum and CSF TWEAK levels were measured by ELISA; values are expressed in pg/mL. RESULTS: The mean ± SD age of NPSLE patients was 31 ± 13.1 years, which was similar across study groups (p = 0.54). TWEAK levels in serum were not different across the study groups. In CSF, TWEAK levels were higher in NPSLE, surgical-SLE and primary neuropsychiatric groups than in non-autoimmune patients: median (IQR) 159.2 (94.1-374.9), 172.3 (125.3-421.9), 371.3 (143-543) vs. 122.1 (76.1-212.4), respectively; all p < 0.05. Six months later, when the neuropsychiatric manifestations were clinically in remission, serum or CSF TWEAK did not vary from baseline in NPSLE patients. CONCLUSIONS: TWEAK levels are slightly elevated in CSF in SLE patients compared with non-autoimmune controls, irrespective of the presence of NP manifestations. TWEAK levels in serum and CSF do not seem to be a useful biomarker of CNS involvement in SLE.


Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Lupus Vasculitis, Central Nervous System/diagnosis , Tumor Necrosis Factors/blood , Tumor Necrosis Factors/cerebrospinal fluid , Adolescent , Adult , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Case-Control Studies , Cytokine TWEAK , Enzyme-Linked Immunosorbent Assay , Female , Hospitalization , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/cerebrospinal fluid , Lupus Erythematosus, Systemic/therapy , Lupus Vasculitis, Central Nervous System/blood , Lupus Vasculitis, Central Nervous System/cerebrospinal fluid , Lupus Vasculitis, Central Nervous System/therapy , Male , Middle Aged , Predictive Value of Tests , Remission Induction , Time Factors , Treatment Outcome , Up-Regulation , Young Adult
4.
J Immunol Res ; 2015: 729217, 2015.
Article in English | MEDLINE | ID: mdl-26078981

ABSTRACT

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.


Subject(s)
Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Esophageal Achalasia/immunology , Esophageal Achalasia/pathology , Inflammation/immunology , Inflammation/pathology , Adult , Aged , Autoantibodies/immunology , Autoimmune Diseases/virology , Case-Control Studies , Cross-Sectional Studies , Esophageal Achalasia/virology , Female , Fluorescent Antibody Technique, Indirect/methods , Herpes Simplex/immunology , Herpesvirus 1, Human/immunology , Humans , Immunohistochemistry/methods , Inflammation/virology , Male , Middle Aged , Myenteric Plexus/immunology , Myenteric Plexus/pathology , Myenteric Plexus/virology
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