scholarly journals Μελέτη της επίπτωσης της χορήγησης βλαστοκυττάρων από λιπώδη ιστό στην βιωσιμότητα ολικού πάχους μοσχευμάτων δέρματος σε διαβητικούς και μη διαβητικούς επίμυες και ο συσχετισμός της όποιας επιδράσεως με την έκφραση των παραγόντων VEFG και TGFb3

2012 ◽  
Author(s):  
Αγγελική Ζωγράφου
Keyword(s):  
Growth Factor ◽  
Graft Survival ◽  
Skin Graft ◽  
Skin Grafts ◽  
Group 4 ◽  
Thickness Skin ◽  
Group 3 ◽  
Group 2 ◽  
Graft Necrosis ◽  
Group 1

Background: Skin grafts are frequently used for a variety of indications in plastic andreconstructive surgery. heir necrosis is a common complication while differenttherapies have been proposed. Currently, adipose-derived stem cells (ASCs) holdgreat promise for their angiogenic potential and role during tissue repair. In this study,autologous transplantation of ASCs was usedin skin grafts in diabetic and nondiabeticrats to determine if it increases angiogenesis, skin graft survival and woundhealing.Methods: ASCs were isolated, cultured, labeled with fluorescent dye and injectedunder full thickness skin grafts in twenty rats (group 1 and group 3, non-diabetic anddiabetic respectively, ten rats in each group), while twenty others served as controls(group 2 and group 4, non-diabetic and diabetic respectively, ten rats in each group).immunohistochemistry. Additionally, immunohistochemical staining intensity ofvascular endothelial growth factor (VEGF) and transforming growth factor b3(TGFb3) was assessed in all grafts.Results: Mean area of graft necrosis was significantly less in group 1 than group 2(6.12% vs. 32.62%, p<0.01). Statistically significant increase of microvessel density,collagen density, VEGF and TGFb3 expression was noted in group 1 compared withgroup 2 (all: p<0.01). Additionally, mean area of graft necrosis was significantly lessin group 3 than group 4 (7.49% vs. 39.67%, p<0.001). Statistically significant30increase of capillary density, collagen intensity, VEGF and TGFb3 expression wasnoted in group 3 compared with group 4.Conclusions: These findings suggest that autologous ASCs transplantation increasesfull-thickness skin graft survival and shows promise for use in skin graft surgery. Thismight be both due to in situ differentiation of ASCs into endothelial cells and ASCsincreased secretion of growth factors such as VEGF and TGFb3 that enhanceangiogenesis and wound healing. This might represent a novel therapeutic approach inskin graft surgery which is particularly useful for diabetic wounds.

scholarly journals Modulation of transforming growth factor beta2 (TGF-beta2) by inositol hexaphosphate in colon carcinogenesis in rats

2006 ◽  
Vol 21 (suppl 4) ◽  
pp. 51-56 ◽  
Author(s):  
Guido Marks ◽  
Ricardo Dutra Aydos ◽  
Djalma José Fagundes ◽  
Elenir Rose Jardim Cury Pontes ◽  
Luiz Carlos Takita ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Colon Carcinogenesis ◽  
Male Rats ◽  
Right Colon ◽  
Inositol Hexaphosphate ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

PURPOSE: To evaluate modulation in the expression of Transforming growth factor beta2 (TGF-beta2) in short-term colon carcinogenesis. METHODS: 64 male rats was used, comprising 4 groups of 16 animals each: group 1 received Inositol hexaphosphate (IP6) and azoxymethane (AOM); group 2, AOM alone; group 3, IP6 alone; group 4 was used as control. Groups 1 and 3 were given 1% IP6 in drinking water for 6 weeks. AOM was administered subcutaneously at weeks 3 and 4 of the experiment at 20 mg/kg of body weight each week. Immunohistochemical processing was performed with the use of anti-TGF-beta2 primary antibodies in right colon samples and quantitation of TGF-beta2 as percentage of expression, through computer-assisted image processing. RESULTS: mean values of TGF-beta2 expression were 9.0 ± 3.9% for group 4 (control), 12.7 ± 4.0% for group 3 (IP6), 19.3 ± 6.2% for group 2 (AOM), and 13.1 ± 5.3% for group 1 (IP6+AOM). The value of p was calculated as 0.0001 for a 5% or lower significance level. CONCLUSION: the experiment revealed a significant increase in TGF-beta2 expression in right colon with the administration of AOM, and a significant decrease in TGF-beta2 expression when IP6 was administered with AOM.

Zinc-Mediated Reduction of Apoptosis in Cardiac Allografts

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Murray H. Kown ◽  
Tim Van der Steenhoven ◽  
Francis G. Blankenberg ◽  
Grant Hoyt ◽  
Gerald J. Berry ◽  
...  
Keyword(s):  
Graft Survival ◽  
Caspase 3 ◽  
Annexin V ◽  
Survival Group ◽  
Group 4 ◽  
Group 3 ◽  
Cardiac Allografts ◽  
Group 2 ◽  
Dose Dependent ◽  
Group 1

Background —Apoptosis is thought to occur during immune-mediated acute rejection of cardiac allografts. In vitro studies have shown that zinc inhibits the activity of the proapoptotic enzyme caspase-3. We hypothesized that ZnCl 2 would reduce acute cardiac rejection in vivo via the blockade of caspase-3–dependent apoptosis. 99m Tc-labeled annexin V was used to measure apoptosis in cardiac allografts through nuclear imaging. Annexin V binds to phosphatidylserines, which are externalized to the outer membrane of apoptotic cells. Methods and Results —Twenty-seven PVG rat hearts were transplanted heterotopically into the abdomen of untreated ACI rats as controls (group 1). Fifteen were scanned and euthanized on postoperative day 4, and 12 were assessed for graft survival. Group 2 and 3 rats (n=15 each) received 1 and 5 mg/kg ZnCl 2 BID IP, respectively. Nine of each of these groups were scanned and euthanized on postoperative day 4, and 6 were studied for allograft survival. Group 4 rats (n=3) received isografts. Region-of-interest analysis demonstrated a dose-dependent reduction in 99m Tc annexin uptake in ZnCl 2 -treated allografts: 2.43±0.37% for group 1, 1.97±0.41% for group 2, 1.21±0.47% for group 3, and 0.55±0.19% for group 4 (ANOVA, P =0.001). Graft survival times of 6.4±1.7, 9.3±3.0, and 11.5±3.4 days for groups 1, 2, and 3, respectively, were also observed (ANOVA, P =0.001). Caspase-3 activity in the allografts showed a 3.7-fold reduction in group 3 animals compared with group 1 animals ( P =0.004). Conclusions —Apoptosis that occurs in acute cardiac allograft rejection is reduced with ZnCl 2 in a dose-dependent manner via caspase-3 inhibition.

133 Effect of cytokines on the quality bovine oocytes matured invitro

2021 ◽  
Vol 33 (2) ◽  
pp. 174
Author(s):  
G. N. Singina ◽  
E. N. Shedova ◽  
T. E. Taradajnic
Keyword(s):  
Growth Factor ◽  
Leukaemia Inhibitory Factor ◽  
Control Group ◽  
Group 4 ◽  
First Polar Body ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Bovine Oocytes ◽  
Group 1

As has been shown previously, fibroblast growth factor 2 (FGF2), leukaemia inhibitory factor (LIF), and insulin-like growth factor 1 (IGF1) in combination play a positive role in maintaining the quality of mammalian oocytes maturing invitro. In the present work, we studied the effects of these cytokines in optimal concentrations when added in combination to IVM medium on the nuclear status and development competence of bovine oocytes. Slaughterhouse-derived cumulus–oocyte complexes (COC) (n=1107 COC) were cultured for 22h in either IVM medium [TCM-199 supplemented with 10% fetal calf serum (FCS), 0.2mM sodium pyruvate, 10μgmL−1 porcine FSH, and 10μgmL−1 ovine LH] (Control) or the same IVM medium supplemented with FGF2, LIF, and IGF1. The eight combinations of cytokines tested during maturation were (1) 20ngmL−1 LIF/10ngmL−1 IGF1/10ngmL−1 FGF2 (Group 1); (2) 20ngmL−1 LIF/10ngmL−1 IGF1/40ngmL−1 FGF2 (Group 2); (3) 20ngmL−1 LIF/20ngmL−1 IGF1/10ngmL−1 FGF2 (Group 3); (4) 20ngmL−1 LIF/20ngmL−1 IGF1/40ngmL−1 FGF2 (Group 4); (5) 5ngmL−1 LIF/10ngmL−1 IGF1/10ngmL−1 FGF2 (Group 5); (6) 5ngmL−1 LIF/10ngmL−1 IGF1/40ngmL−1 FGF2 (Group 6); (7) 5ngmL−1 LIF/20ngmL−1 IGF1/10ngmL−1 FGF2 (Group 7); and (8) 5ngmL−1 LIF/20ngmL− 1 IGF1/40ngmL−1 FGF2 (Group 8). After IVM, matured and denuded oocytes were activated by culturing in 5μM ionomycin solution for 5min followed by 4h in 2mM 4-dimethylaminopyridine (DMAP) and 10mgmL−1 cyclohexamide. Activated oocytes were cultured in CR1aa medium until Day 5 and then transferred to the same medium supplemented with 5% FCS and cultured until Day 7. All cultures were performed at 38.5°C and 5% CO2 in humidified air. At Days 2 and 7 after activation, the cleavage and blastocyst rates were determined. The data from 6 to 7 replicates (122–181 oocytes per treatment) were analysed by ANOVA. The rate of MII oocytes, assessed by the presence of the first polar body, did not differ between the groups and reached 67.1 to 84.5%. Cleavage rate was higher (84.5±2.9%, P&lt;0.05) in Group 1 compared with Control (68.9±2.7%), Group 4 (67.1±4.9%) and Group 7 (66.6±2.0%), but not compared with Group 2 (76.5±4.8%), Group 3 (76.6±4.8%), Group 5 (78.2±3.1%), or Group 8 (79.9±3.1%). The percentage of blastocyst formation relative to the total number of MII oocytes in the control group was 19.6±2.4%. The culture of COC in Group 1 (20 ngmL−1 LIF/10ngmL−1 IGF1/10ngmL−1 FGF2) and Group 2 (20ngmL−1 LIF/10ngmL−1 IGF1/40ngmL−1 FGF2) caused the blastocyst yield to increase to 33.0±3.8 and 31.2±4.3%, respectively (P&lt;0.05), whereas the culture COC in other cytokine-treated groups had no effect. In Groups 3 to 8, the blastocyst rates were 22.9±4.6, 19.2±3.0, 24.2±3.2, 27.8±1.7, 21.6±1.8, and 25.5±9.0%, respectively, and did not differ (except Group 4) compared with those of Group 1 and Group 2. In conclusion, LIF, FGF2, and IGF1 in optimal combinations can maintain competence for parthenogenetic development of bovine COC during their maturation invitro. This research was supported by RFBR (projects No. 18-29-07089) and the Ministry of Science and Higher Education of Russia.

In-vivo evaluation of the effect of cyanoacrylate on prosthetic vascular graft infection – does cyanoacrylate increase the severity of infection?

VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin
Keyword(s):  
Vascular Graft ◽  
Graft Infection ◽  
Vascular Graft Infection ◽  
Group 4 ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Prosthetic Vascular Graft Infection ◽  
Group 1

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.

Does Perioperative Hemoglobin A1c Level Affect the Incidence, Pattern and Mortality of Lower Extremity Amputation?

2019 ◽  
Vol 17 (4) ◽  
pp. 354-364
Author(s):  
Hassan Al-Thani ◽  
Moamena El-Matbouly ◽  
Maryam Al-Sulaiti ◽  
Noora Al-Thani ◽  
Mohammad Asim ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Lower Extremity ◽  
Hazard Ratio ◽  
Lower Extremity Amputation ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Extremity Amputation ◽  
Group 1

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.

Association between cervical disc disease and lesions of multiple sclerosis

2021 ◽  
pp. 197140092098356
Author(s):  
Marwan Alkrenawi ◽  
Michael Osherov ◽  
Azaria Simonovich ◽  
Jonathan Droujin ◽  
Ron Milo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cervical Disc ◽  
Cervical Disc Disease ◽  
Disc Disease ◽  
Group 4 ◽  
Demyelinating Lesions ◽  
Grade Ii ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. Methods Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1–C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher’s exact test was used to test the association between demyelinating lesions and disc pathology. Results Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease ( p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). Conclusion Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.

scholarly journals Association between serum oestradiol level on the hCG administration day and neonatal birthweight after IVF-ET among 3659 singleton live births

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Wanyu Zhang ◽  
Yihong Guo
Keyword(s):  
Birth Weight ◽  
Ovarian Stimulation ◽  
Group 4 ◽  
Group 6 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
The Impact ◽  
Ivf Et ◽  
Group 1

AbstractOestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.

scholarly journals Control of Vulval Competence and Centering in the Nematode Oscheius sp. 1 CEW1

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 133-146 ◽  
Author(s):  
Sophie Louvet-Vallée ◽  
Irina Kolotuev ◽  
Benjamin Podbilewicz ◽  
Marie-Anne Félix
Keyword(s):  
Germ Line ◽  
Specific Mechanism ◽  
C Elegans ◽  
Group 4 ◽  
Cell Ablation ◽  
Group 3 ◽  
Group 2 ◽  
P Cells ◽  
Large Category ◽  
Group 1

Abstract To compare vulva development mechanisms in the nematode Oscheius sp. 1 to those known in Caenorhabditis elegans, we performed a genetic screen for vulva mutants in Oscheius sp. 1 CEW1. Here we present one large category of mutations that we call cov, which affect the specification of the Pn.p ventral epidermal cells along the antero-posterior axis. The Pn.p cells are numbered from 1 to 12 from anterior to posterior. In wild-type Oscheius sp. 1 CEW1, the P(4-8).p cells are competent to form the vulva and the progeny of P(5-7).p actually form the vulva, with the descendants of P6.p adopting a central vulval fate. Among the 17 mutations (defining 13 genes) that we characterize here, group 1 mutations completely or partially abolish P(4-8).p competence, and this correlates with early fusion of the Pn.p cells to the epidermal syncytium. In this group, we found a putative null mutation in the lin-39 HOM-C homolog, the associated phenotype of which could be weakly mimicked by injection of a morpholino against Osp1-lin-39 in the mother’s germ line. Using cell ablation in a partially penetrant competence mutant, we show that vulval competence is partially controlled by a gonadal signal. Most other mutants found in the screen display phenotypes unknown in C. elegans. Group 2 mutants show a partial penetrance of Pn.p competence loss and an abnormal centering of the vulva on P5.p, suggesting that these two processes are coregulated by the same pathway in Oscheius sp. 1. Group 3 mutants display an enlarged competence group that includes P3.p, thus demonstrating the existence of a specific mechanism inhibiting P3.p competence. Group 4 mutants display an abnormal centering of the vulval pattern on P7.p and suggest that a specific mechanism centers the vulval pattern on a single Pn.p cell.

scholarly journals Hypertrophy of unaffected cardiomyocytes correlates with severity of cardiomyopathy in female patients with Fabry disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Cristina Chimenti ◽  
Romina Verardo ◽  
Andrea Frustaci
Keyword(s):  
Fabry Disease ◽  
Wall Thickness ◽  
Left Ventricular ◽  
Female Patients ◽  
Maximal Wall Thickness ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.

scholarly journals THU0227 CAFFEINE INTAKE MODULATES DISEASE ACTIVITY AND CYTOKINES LEVELS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 340.2-341
Author(s):  
V. Orefice ◽  
F. Ceccarelli ◽  
C. Barbati ◽  
R. Lucchetti ◽  
G. Olivieri ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Caffeine Intake ◽  
Caffeine Consumption ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

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