Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?

Clinical and laboratory evaluation of the effectiveness of therapy of psoriasis vulgaris in 78 HIV-infected patients using the two treatment regimens is presented. Peculiarities of clinical course of psoriasis depending on the number of CD4+lymphocytes in the peripheral blood are shown. Histological and histochemical studies of biopsy samples from psoriatic skin lesions and apparently healthy skin in 15 people were performed. The dynamics before and after treatment of CD4+ and CD8+ lymphocytes in biopsies of skin and blood, their relationship with the index of severity of psoriasis (PASI) are presented. This study is of theoretical and practical interest in understanding the value and role of CD4+ and CD8+ lymphocytes in the formation of inflammatory reactions in the skin of patients with psoriasis as a possible option for treatment of psoriasis in HIV-infected patients.

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Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment

British Journal of Dermatology ◽

10.1046/j.1365-2133.2000.03826.x ◽

2000 ◽

Vol 143 (5) ◽

pp. 950-956 ◽

Cited By ~ 14

Author(s):

C. Miracco ◽

M. Pellegrino ◽

M.L. Flori ◽

R. Vatti ◽

M. Materno ◽

...

Keyword(s):

Cyclin D1 ◽

Skin Lesions ◽

Psoriatic Skin ◽

Cell Turnover ◽

Cyclosporin Treatment ◽

Before And After

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Interleukin-17A blockade with secukinumab results in decreased neutrophil infiltration in psoriasis: minimally-invasive measurement by tape stripping

Advances in Precision Medicine ◽

10.18063/apm.2016.02.003 ◽

2016 ◽

Vol 1 (1) ◽

Cited By ~ 4

Author(s):

Christian Loesche ◽

Frank Kolbinger ◽

Marie-Anne Valentin ◽

Philip Jarvis ◽

Melanie Ceci ◽

...

Keyword(s):

Minimally Invasive ◽

Immunohistochemical Analysis ◽

Neutrophil Infiltration ◽

Skin Lesions ◽

Psoriatic Skin ◽

Tape Stripping ◽

Neutrophil Accumulation ◽

Interleukin 17A ◽

Before And After ◽

Invasive Method

Psoriasis is a well characterized interleukin (IL)-17A-driven skin disease with neutrophil infiltration and epidermal hyperkeratosis. Several biomarkers, most prominently β-defensin-2 (BD-2), have been identified using local and systemic invasive measurements as responsive markers of IL-17A-driven skin pathology. We sought to determine whether measurements of epidermal proteins by tape stripping could offer a minimally-invasive method to assess treatment responses. We compared the expression of 170 proteins in the epidermis (tape stripping) and dermis (open flow microperfusion) of 8 psoriatic subjects before and after administration of a single dose of subcutaneous (s.c.) antiIL-17A mAb secukinumab. Proteomic analyses of tape strips revealed a >3-fold decrease in 32 epidermal and inflammatory cell proteins in response to secukinumab. The epidermal proteins with the largest (>10-fold) decreases were: matrix metalloproteinase-8 (MMP-8, 15.68-fold, p<0.05); myeloperoxidase (MPO, 14.72-fold, p<0.005); IL-8 (11.93-fold, p<0.05); MMP-9 (10.81-fold, p<0.005); and IL-1β (10.35-fold, p<0.05). For these proteins, greater-fold protein changes were detected in the epidermis compared to dermis. Immunohistochemical analysis confirmed that neutrophils are the predominant cell type in psoriatic skin lesions that express MPO, MMP-8 and MMP-9, and that secukinumab treatment dramatically decreases neutrophil accumulation. Thus, tape stripping may be used to assess epidermal neutrophils, and protein biomarker responses to anti-IL-17A therapy in psoriasis.

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BESTIMMUNG DER INSULINAKTIVITÄT IM MENSCHLICHEM SERUM NACH GLUKOSEBELASTUNG ALS PRÜFUNG DER FUNKTIONSFÄHIGKEIT DES PANKREAS

Acta Endocrinologica ◽

10.1530/acta.0.0420437 ◽

1963 ◽

Vol 42 (3) ◽

pp. 437-452 ◽

Cited By ~ 8

Author(s):

H. Daweke

Keyword(s):

Blood Sugar ◽

Pancreatic Insufficiency ◽

Normal Subjects ◽

Insulin Binding ◽

Epididymal Adipose Tissue ◽

Moderate Increase ◽

Glucose Loading ◽

Before And After ◽

Oral Hypoglycaemic Drugs ◽

Severity Of The Disease

Using the method of glucose-1-14C oxydation to 14CO2 on the rat epididymal adipose tissue, the insulin-like activities (ILA) in the serum have been compared before and after oral loading with glucose in normal subjects, in maturity-onset diabetics and in insulin-requiring diabetics. In maturity-onset diabetics mean fasting values were found to be 30% below normal while in insulin-requiring diabetics they were 85% above normal. In normal subjects there was observed, 30 minutes after glucose loading, a moderate increase in blood sugar together with an increase of ILA of 222% above the starting value; in maturity-onset diabetics the increase in ILA was only 106% while the blood sugar was markedly increased. After glucose loading in maturity-onset diabetics, the total amount of insulin detected during the period of the experiment was, on the average, only 45% of that found in normal subjects. In insulin requiring diabetics there was no increase but, on the contrary, a steady decrease of the ILA values, while the blood sugar excessively increased. In general ILA values were higher than those in maturity-onset diabetics. No difference in response was found between maturity-onset diabetics treated with diet alone and those treated with diet and oral hypoglycaemic drugs. In contrast to the absolute ILA values, the index of insulin reserve, is of value in assessing the functional capacity of the pancreas. This index decreases progressively with the severity of the disease and reaches a maximum of 54% of the normal in maturity-onset diabetics, which can satisfactorily be explained by pancreas insufficiency. Only in some cases of insulin-requiring diabetics was an insulin reserve still detectable. The biological inactivity of the insulin circulating in the blood can be deduced from the increased ILA-values, as compared with those found in maturity-onset diabetics. Obviously some of this insulin can be released by the addition of glucose. It is likely that, in addition to pancreatic insufficiency, insulin-binding or insulin-inactivating antibodies play a part in the pathogenesis of insulin-requiring diabetes.

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The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration

Cell Death and Disease ◽

10.1038/s41419-021-03774-w ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Chenliang Gou ◽

Wenkai Ni ◽

Panpan Ma ◽

Fengbo Zhao ◽

Zhou Wang ◽

...

Keyword(s):

Physiological Role ◽

Neutrophil Infiltration ◽

Proper Function ◽

Psoriatic Skin ◽

Epidermal Keratinocytes ◽

Keratinocyte Proliferation ◽

Proliferation And Differentiation ◽

Long Time ◽

Chronic Skin ◽

Upregulated Genes

AbstractPsoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.

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TNFα and its Receptors in Psoriatic Skin, before and after Treatment with Etanercept

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200902200411 ◽

2009 ◽

Vol 22 (4) ◽

pp. 961-966 ◽

Cited By ~ 14

Author(s):

G. Caldarola ◽

C. De Simone ◽

A. Carbone ◽

A. Tulli ◽

P. Amerio ◽

...

Keyword(s):

Psoriatic Skin ◽

Before And After

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Botulinum toxin injection changes resting state cerebellar connectivity in cervical dystonia

Scientific Reports ◽

10.1038/s41598-021-87088-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Pavel Hok ◽

Lenka Hvizdošová ◽

Pavel Otruba ◽

Michaela Kaiserová ◽

Markéta Trnečková ◽

...

Keyword(s):

Functional Mri ◽

Resting State ◽

Cervical Dystonia ◽

Botulinum Neurotoxin ◽

Botulinum Toxin Injection ◽

Clinical Severity ◽

Before And After ◽

Positive Correlations ◽

Using Data ◽

The Right

AbstractIn cervical dystonia, functional MRI (fMRI) evidence indicates changes in several resting state networks, which revert in part following the botulinum neurotoxin A (BoNT) therapy. Recently, the involvement of the cerebellum in dystonia has gained attention. The aim of our study was to compare connectivity between cerebellar subdivisions and the rest of the brain before and after BoNT treatment. Seventeen patients with cervical dystonia indicated for treatment with BoNT were enrolled (14 female, aged 50.2 ± 8.5 years, range 38–63 years). Clinical and fMRI examinations were carried out before and 4 weeks after BoNT injection. Clinical severity was evaluated using TWSTRS. Functional MRI data were acquired on a 1.5 T scanner during 8 min rest. Seed-based functional connectivity analysis was performed using data extracted from atlas-defined cerebellar areas in both datasets. Clinical scores demonstrated satisfactory BoNT effect. After treatment, connectivity decreased between the vermis lobule VIIIa and the left dorsal mesial frontal cortex. Positive correlations between the connectivity differences and the clinical improvement were detected for the right lobule VI, right crus II, vermis VIIIb and the right lobule IX. Our data provide evidence for modulation of cerebello-cortical connectivity resulting from successful treatment by botulinum neurotoxin.

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PAROXYSMAL NOCTURNAL HEMOGLOBINURIA IN CHILDHOOD AND ADOLESCENCE

PEDIATRICS ◽

10.1542/peds.39.5.675 ◽

1967 ◽

Vol 39 (5) ◽

pp. 675-688

Author(s):

Denis R. Miller ◽

Robert L. Baehner ◽

Louis K. Diamond

Keyword(s):

Fetal Hemoglobin ◽

Normal Activity ◽

Glycolytic Enzyme ◽

Clinical Severity ◽

Childhood And Adolescence ◽

Red Cell ◽

Red Cell Membrane ◽

Severity Of The Disease ◽

Increased Activity ◽

Aldolase A

Two cases of PNH in adolescence and childhood are reported. The first presented at age 7½ years with aplastic anemia and improved after splenectomy performed at age 14. The second, a 15-year-old girl, presented with a Coombs-positive hemolytic anemia and has had a course complicated by multiple peripheral thromboses. The clinical and laboratory manifestations, complications, and certain therapeutic aspects of PNH are discussed. Anticoagulant therapy appears indicated in the presence of multiple thrombotic episodes. Erythrocyte metabolic studies revealed normal glycolysis, ATP stability, and GSH content in the cells of a child with a normal reticulocyte count. Mild elevations of glycolysis, noted in the child with a reticulocytosis, was ascribed to a younger mean red cell population since further elevations found in the "top" reticulocyte-rich layer after centrifugation. Heparin, the anticoagulant used in these studies, had no adverse effect on glycolysis but did inhibit hemolysis and minimize ATP instability when compared to cells suspended in defibrinated serum. Erythrocytes fractionated by centrifugation revealed increased glycolytic enzyme activities of hexokinase, G3PD, PGK, TPI, PK, LDH, G6PD, and 6PGD in the reticulocyte-rich layer. Normal, rather than increased activity of aldolase, a membrane enzyme, may reflect damage to the red cell membrane. PFK, known to be decreased in the erythrocyte of neonates, showed normal activity, but it was lowest in the reticulocyte-rich layer. Fetal hemoglobin was elevated in this layer. AChE deficiency and increased suceptibility to hydrogen perioxide and acid hemolysis confirmed previous reports and were most marked in the young cell layer. The level of increased glycolytic rates and enzyme activity, AChE deficiency, acid hemolysis and peroxide hemolysis were related to the clinical severity of the disease.

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