scholarly journals Constitutive Differential Features of Type 2 Transglutaminase in Cells Derived from Celiac Patients and from Healthy Subjects

2020 ◽  
Vol 21 (4) ◽  
pp. 1231 ◽  
Author(s):  
Gaetana Paolella ◽  
Merlin Nanayakkara ◽  
Silvia Sposito ◽  
Marilena Lepretti ◽  
Salvatore Auricchio ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Dermal Fibroblasts ◽  
Autoimmune Response ◽  
Cellular Phenotype ◽  
Gliadin Peptide ◽  
Gliadin Peptides ◽  
Definition Of ◽  
Expression And Activity ◽  
In Cells

Type 2 transglutaminase (TG2) is a ubiquitous enzyme able to modify gliadin peptides introduced into the organism through the diet. By means of its catalytic activity, TG2 seems to have an important pathogenetic role in celiac disease (CD), an inflammatory intestinal disease caused by the ingestion of gluten-containing cereals. A strong autoimmune response to TG2 characterizes CD development. Anti-TG2 antibodies specifically derange the uptake of the α-gliadin peptide 31–43 by control, but not by celiac dermal fibroblasts, underlying some different constitutive features regarding TG2 in healthy and celiac subjects. Our aim was to investigate whether these differences depended on a different TG2 subcellular distribution and whether peptide 31–43 differentially regulated TG2 expression and activity in cells of the two groups of subjects. We found that TG2 was more abundantly associated with membranes of celiac fibroblasts than of control cells, in particular with the early endosomal and autophagic compartments. We also found that peptide 31–43 differentially affected TG2 expression and activity in the two groups of cells, activating TG2 more in control than in celiac cells and inducing TG2 expression in celiac cells, but not in control ones. The different TG2 subcellular localization and the different way the peptide 31–43 modulates TG2 activity and availability into control and CD cells suggested that TG2 is involved in the definition of a constitutive CD cellular phenotype, thus having an important and still undefined role in CD pathogenesis.

scholarly journals Cardiovascular disease prevalence in type 2 diabetes – an analysis of a large German statutory health insurance database

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maximilian Gabler ◽  
Silke Geier ◽  
Lukas Mayerhoff ◽  
Wolfgang Rathmann
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Health System ◽  
Cardiovascular Complications ◽  
Population Based ◽  
Stratified Sample ◽  
Icd 10 ◽  
Definition Of ◽  
Observation Period

Abstract Background The aim of this study was to determine the prevalence of cardiovascular disease in persons with type 2 diabetes mellitus (T2D) in Germany. Methods A claims database with an age- and sex-stratified sample of nearly 4 million individuals insured within the German statutory health system was used. All patients aged ≥18 years with T2D documented between 1 January 2015 and 31 December 2015 and complete retrospective documentation of ≥5 years (continuous enrollment in the German statutory health system) before 2015 were selected based on a validated algorithm. Cardiovascular disease (CVD) events were identified based on ICD-10 and OPS codes according to a previous clinical study (EMPA-REG OUTCOME trial). Results The prevalence of T2D in Germany in 2015 was 9.9% (n = 324,708). Using a narrow definition of CVD, the 6-year observation period prevalence of CVD was estimated as 46.7% [95% CI: 46.52%;46.86%]. Applying a wider CVD definition, the proportion of T2D patients who showed a history of CVD was 57.1% [95% CI: 56.9%;57.24%]. The prevalence of CVD in patients with T2D ranged from 36.3 to 57.1%, depending on the observation period and definition of CVD. Conclusions The results underline the need for a population-based registration of cardiovascular complications in T2D.

The importance of first and second ventilatory thresholds to define aerobic exercise intensity in cardiac patients and in healthy subjects: what is essential can be visible to the eyes

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
F Anselmi ◽  
L Cavigli ◽  
A Pagliaro ◽  
S Valente ◽  
F Valentini ◽  
...  
Keyword(s):  
Exercise Intensity ◽  
Healthy Subjects ◽  
Ventilatory Threshold ◽  
Cardiopulmonary Exercise Testing ◽  
Cardiac Patients ◽  
Funding Sources ◽  
Peak Vo2 ◽  
Definition Of ◽  
Very High ◽  
Sedentary Subjects

Abstract Funding Acknowledgements Type of funding sources: None. Background. Although structured exercise training is strongly recommended in cardiac patients, uncertainties exist about the methods for determining exercise intensity (EI) and their correspondence with effective EI obtained by ventilatory thresholds. We aimed to determine the first (VT1) and second ventilatory threshold (VT2) in cardiac patients, sedentary subjects and athletes comparing VT1 and VT2 with EI defined by recommendations. Methods. We prospectively enrolled 350 subjects (mean age: 50.7 ± 12.9 years; 167 cardiac patients, 150 healthy sedentary subjects, 33 competitive endurance athletes). Each subject underwent ECG, echocardiography, and cardiopulmonary exercise testing. The percentages of peak VO2, peak heart rate (HR), and HR reserve were obtained at VT1 and VT2, and compared with EI definition proposed by the recommendations. Results. VO2 at VT1 corresponded to high rather than moderate EI in 67.1% and in 79.6% of cardiac patients, applying the definition of moderate exercise by the previous recommendations and the 2020 guidelines, respectively. Most of cardiac patients had VO2 values at VT2 corresponding to very-high rather than high EI (59.9% and 50.3%, by previous recommendations and 2020 guidelines, respectively). A better correspondence between ventilatory-thresholds and recommended EI domains was observed in healthy subjects and in athletes (90% and 93.9%, respectively). Conclusions. EI definition based on percentages of peak HR and peak VO2 may misclassify the effective EI and the discrepancy between the individually determined and the recommended EI is particularly relevant in cardiac patients. A ventilatory threshold-based rather than a range-based approach is advisable in order to define an appropriate level of EI. Abstract Figure.

scholarly journals Role of Bradykinin Type 2 Receptors in Human Sweat Secretion: Translational Evidence Does Not Support a Functional Relationship

2021 ◽  
Vol 34 (3) ◽  
pp. 162-166
Author(s):  
Thad E. Wilson ◽  
Seetharam Narra ◽  
Kristen Metzler-Wilson ◽  
Artur Schneider ◽  
Kelsey A. Bullens ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Sweat Rate ◽  
Sweat Glands ◽  
Potential Therapeutic Target ◽  
Sweat Secretion ◽  
Hoe 140 ◽  
A Current

Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46–48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm<sup>2</sup>/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm<sup>2</sup>/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.

Interplay between the toxic alpha-gliadin peptide 31-43 and type 2 transglutaminase enzyme in Celiac Disease

2019 ◽  
Vol 29 (8) ◽  
pp. 873
Author(s):  
Gaetana Paolella ◽  
Marilena Lepretti ◽  
Stefania Martucciello ◽  
Lillà Lionetti ◽  
Carla Esposito ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gliadin Peptide

scholarly journals cAMP Activates The generation of Reactive Oxygen Species and Inhibits The Secretion of IL-6 in Peripheral Blood Mononuclear Cells from Type 2 Diabetic Patients

2009 ◽  
Vol 2 (5) ◽  
pp. 317-321 ◽  
Author(s):  
Camila Armond Isoni ◽  
Érica Abreu Borges ◽  
Clara Araújo Veloso ◽  
Rafael Teixeira Mattos ◽  
Miriam Martins Chaves ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
In Cells

Peripheral blood mononuclear cells (PBMNC) from patients with type 2 diabetes (DM2) have generated higher levels of reactive oxygen species (ROS) that were higher than those in cells from healthy individuals. In the presence of a cAMP-elevating agent, ROS production was significantly activated in PBMNC from DM2 patients but it was inhibited in cells from healthy subjects. Higher levels of IL-6 has been detected in the supernatant of PBMNC cultures from DM2 patients in comparison with healthy controls. When cells were cultured in the presence of a cAMP-elevating agent, the level of IL-6 decreased has by 46% in the supernatant of PBMNC from DM2 patients but it remained unaltered in controls. No correlations between ROS and IL-6 levels in PBMNC from DM2 patients or controls have been observed. Secretions of IL-4 or IFN by PBMNC from patients or controls have not been affected by the elevation of cAMP. cAMP elevating agents have activated the production of harmful reactive oxidant down modulated IL-6 secretion by these cells from DM2 patients, suggesting an alteration in the metabolic response possibly due to hyperglicemia. The results suggest that cAMP may play an important role in the pathogenesis of diabetes.

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

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