scholarly journals Application of Long-Acting VLHL PAI-1 during Sutureless Partial Nephrectomy in Mice Reduces Bleeding

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Khaled Shahrour ◽  
Rick Keck ◽  
Jerzy Jankun
Keyword(s):  
Partial Nephrectomy ◽  
Blood Clot ◽  
Treated Group ◽  
Group 4 ◽  
Final Weight ◽  
Group 3 ◽  
Group 2 ◽  
Long Acting ◽  
Pai 1 ◽  
Group 1

PAI-1 prevents lysis of blood clot by inhibiting the urokinase and tPA induced conversion of plasminogen to plasmin. VLHL PAI-1 protein mutant was created to extend half-life over 700 hours. The objective of this paper was to test VLHL PAI-1 effects on bleeding during partial nephrectomy in mice. All animals had a left partial nephrectomy after intravenous infusion of saline or tPA. The animals were divided into four groups. Group 1 was infused with saline and kidney was exposed to saline too; Group 2 was infused with saline and kidney was exposed to PAI-1. Group 3 was infused with tPA and kidney was exposed to saline, while Group 4 was infused with tPA and kidney was exposed to PAI-1. Preweighed gauze containing PAI-1 or saline was then applied to the kidney for 30 minutes. The gauze was afterward weighed and blood loss was measured by subtracting the preweight of gauze from the final weight. We have observed a statistically significant (P≤0.05) reduction of bleeding in PAI-1-treated group in comparison to saline and tPA-treated groups. Based on these results we propose that VLHL PAI-1 can be used therapeutically in limiting the flow of blood from renal wounds.

scholarly journals Pre-Existence of Prothrombotic State in Patients with Atrial Fibrillation Despite Therapy with New and Traditional Anti-Coagulant Drugs

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4731-4731 ◽  
Author(s):  
Jeffrey Paul Liles ◽  
Christopher Wanderling ◽  
Jordan Lee Liles ◽  
Debra Hoppensteadt ◽  
Jawed Fareed ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Stroke Risk ◽  
Oral Anticoagulants ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Newer Anticoagulants ◽  
Circulating Levels ◽  
Pai 1 ◽  
Group 1

Abstract Background: Oral anticoagulants such as warfarin (W) have been conventionally used for the management of atrial fibrillation (AF). Despite the effectiveness of W, its use in AF patients requiring anticoagulation is suboptimal with an even greater underuse seen in elderly patients who are at higher risk of stroke. New oral anticoagulants such as rivaroxaban (R) and apixaban (A) have been approved to manage thrombotic and cardiovascular disorders including AF. The newer anticoagulants do not require continuous monitoring like W does and are much more convenient for patients with AF. Objective: To profile the baseline level of circulating thrombogenic biomarkers von Willebrand Factor (vWF), prothrombin fragment 1.2 (F1+2), microparticle bound tissue factor (MP-TF) and plasminogen activator inhibitor (PAI-1) in patients with AF. Additionally, the effect of both newer (R and A) and traditional (W) anticoagulants on the levels of thrombogenic biomarkers in patients with AF will be assessed. Materials: Citrated blood was drawn from thirty AF patients prior to ablation surgery and spun at 3000 rpm to obtain platelet poor plasma. Normal plasma samples from healthy controls were purchased from a commercial source (George King Biomedical, Overland Park, KS). The plasma samples were analyzed using a biochip array (Randox, London, UK) for metabolic syndrome biomarkers including PAI-1 and ELISA kits for vWF, MP-TF (Hyphen BioMed, Nueville-Sur-Oise, France) and prothrombin F1+2 (Siemens, Newark, DE). Results: Circulating levels of vWF, MP-TF and PAI-1 were statistically increased in patients with AF compared to normal (P<0.0001, P<0.0001, and P=0.0014, respectively). Circulating levels of prothrombin F1+2 showed no difference between the AF and normal group (P=0.2696). AF patients (n=30) were divided into two groups based on their usage (Group 1, n=21) and non-usage (Group 2, n=9) of any anticoagulant. Furthermore, those on anticoagulants were divided based on their use of newer (R and A, Group 3, n=16) or traditional (W, Group 4, n=4) anticoagulants. A statistical increase in vWF (P<0.0001), MP-TF (P<0.0001) and PAI-1 (P=0.011) remained in Group 1 compared to normal while a statistical increase in prothrombin F1+2 (P=0.0343) and PAI-1 (P=0.0040) were noted in Group 2 compared to normal. vWF (P=0.0036) and MP-TF (P=0.0059) were elevated in Group 1 compared to Group 2 while prothrombin F1+2 (P=0.0697) and PAI-1 (P=0.4548) showed no difference between the two groups. Furthermore, there was no statistical difference in the level of any thrombogenic biomarker in AF patients between Group 3 (R and A) and Group 4 (W). (Table 1) Discussion: Elevated levels of vWF, MP-TF and PAI-1 seen in AF patients compared to normal provide insight into an additional risk of thrombogenesis associated with AF which is not targeted by current anticoagulant medications. Most patients are assessed using a stroke risk stratification scale (CHA2DS2VASc, CHADS2, CHADS-VASC, or CHADS) to determine if anti-coagulants should be used to prevent stroke associated with AF. Of the 30 patients examined in this study, 8/9 (89%) patients who were not on anticoagulants had a stroke risk stratification score of 0 while 20/21(95%) patients who were on anticoagulants had a score of >1. This data supports studies which suggest that adding levels of prothrombotic biomarkers to current risk stratification scales could be more effective in assessing the risk of stroke of patients with AF. This data also suggests that although very effective in lowering prothrombin F1+2 levels in AF, the newer anticoagulants, R and A, and the traditional anticoagulant, W, still leave additional prothrombotic biomarkers unaffected. These unaffected biomarkers could be the potential target of future drug therapies which could lower the risk of stroke in patients with AF even more than the use of newer/traditional anticoagulants alone.Table 1.Biomarkers of Thrombogenesis in AF and Normal GroupsGroupvWF (concentration %)Prothrombin F1+2 (pmol/L)MP-TF (pg/mL)PAI-1 (ng/mL)Normal4140 ± 919 n=46106.1 ± 52.7 n=500.38 ± 0.25 n=483.21 ± 4.13 n=25AF Group 1 Anticoagulant n=216616 ± 1173107.9 ± 61.20.93 ± 0.715.69 ± 4.15Group 2 Non-Anticoagulant n=94788 ± 1338162.5 ± 93.30.51 ± 0.136.49 ± 3.14Group 3 New Anticoagulants (R and A) n=166721 ± 1127103.5 ± 37.60.76 ± 0.345.68 ± 4.53Group 4 Traditional Anticoagulants (W) n=46387 ± 158075.2 ± 52.60.94 ± 0.335.63 ± 3.52 Disclosures No relevant conflicts of interest to declare.

scholarly journals Effects of a highly concentrated platelet-rich plasma on the bone repair using non-critical defects in the calvaria of rabbits

2010 ◽  
Vol 25 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Marco Antonio de Oliveira Filho ◽  
Paulo Afonso Nunes Nassif ◽  
Osvaldo Malafaia ◽  
Jurandir Marcondes Ribas Filho ◽  
Carmen Austrália Paredes Marcondes Ribas ◽  
...  
Keyword(s):  
Bone Repair ◽  
Platelet Rich Plasma ◽  
Blood Clot ◽  
Venous Blood ◽  
Control Group ◽  
Advanced Stage ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

PURPOSE: To verify the effect of highly concentrated platelet-rich plasma (hPRP) in the pathways of bone repair using non-critical defects in the calvaria of rabbits. METHODS: The hPRP was produced from collected venous blood of 21 rabbits. Four non-critical defects of 8 mm in diameter were created on the calvaria of each animal. The defects were all treated differently: autogenous particled bone (APB, group 1), autogenous particled bone associated with hPRP (APB + hPRP, group 2), isolated hPRP (group 3), and blood clot (control, group 4). Animals were submitted to euthanasia on the 2nd, 4th and 6th week postoperatively. Histological and histomorphometric analysis were carried through. RESULTS: After two weeks, groups 1 and 2 were in more advanced stage of repair than 3 and 4. At this period, comparing the groups 1 and 2, no significant differences were found between both, which also happened between the groups 3 and 4. However, after four and six weeks, the group 1 showed a more advanced stage of repair among all the other studied groups, while group 2 was in more advanced signs of bone repair than groups 3 and 4. Comparing groups 3 and 4, after four and six weeks, the least advanced stage of bone repair was found to be within group 3. CONCLUSION: The use of a highly concentrated PRP was considered prejudicial to the repair of non-critical defects in the calvaria of rabbits, either in the association of autogenous particled bone, when compared to autogenous particled bone alone, or in its isolated form, when compared to blood clot (control).

scholarly journals EFFICACY OF AMOXICILLIN (ATCOMOX®) AND/OR ALLICIN ON PERFORMANCE, HAEMATOLOGICAL, BIOCHEMICAL, AND HISTOPATHOLOGICAL CHANGES IN Clostridium perfringens INFECTED CHICKENS

2020 ◽  
Vol 57 (2) ◽  
Author(s):  
Mohamed Aboubakr ◽  
Ashraf Elkomy ◽  
Soad Belih ◽  
Mohamed Morad ◽  
Hassan Shaheen ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Broiler Chickens ◽  
Considerable Increase ◽  
Treated Group ◽  
Histopathological Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

The efficacy of amoxicillin and/or allicinin healthy and experimentally Clostridium perfringens-infected broiler chickens was investigated. The chicks were equally divided into six groups, and all medications were orally administered via drinking water for five consecutive days: Group 1: non-infected and non-treated; Group 2: infected and non-treated; Group 3: infected and amoxicillin-treated (20 mg/kg b.wt); Group 4: infected and allicin-treated (25 mg/kg b.wt); Group 5: infected and treated with amoxicillin (20 mg/kg b.wt) and allicin (25 mg/kg b.wt); Group 6: infected and treated with amoxicillin (10 mg/kg b.wt) and allicin (25 mg/kg b.wt). Growth performance,haematological andbiochemical parameters were recorded. Significant decreases in total protein, albumin, RBCs, Hb, andPCV and a considerable increase in WBCs, AST, ALT, ALP, creatinine, anduric acid in infected chickens were observed. Administration amoxicillin and/or allicin for treatment of Clostridium perfringens infection resulted in improvement in haematological and biochemical changes following infection. A dose of amoxicillin (10 mg) and allicin (25 mg)/kg bwt for treatment of Clostridium perfringens infection in broiler chickens is recommended due to great synergistic effect, reduced mortality, greater safety, and increased economic potential.Key words: amoxicillin; allicin; efficacy; broilers; biochemical; hematological VPLIV AMOXICILINA (ATCOMOX®) IN ALICINA NA PRIRAST, HEMATOLOŠKE, BIOKEMIJSKE IN HISTOPATOLOŠKE SPREMEMBE PRI PIŠČANCIH, OKUŽENIH S Clostridium perfringens Povzetek: V študiji smo ugotavljali učinkovitost amoksicilina in/ali alicinina pri zdravih pitovnih piščancih in pitovnih piščancih poskusno okuženimih z bakterijo Clostridium perfringens. Piščanci so bili razdeljeni v šest skupin in so zdravila dobivali peroralno preko vode pet dni zapored. V prvi skupini so bili neokuženi in nezdravljeni piščanci, v drugi okuženi in nezdravljeni, v tretji okuženi in zdravljeni z amoksicilinom (20 mg/kg telesne mase), v četrti skupini okuženi in zdravljeni z alicinom (25 mg/kg telesne mase) v peti skupini okuženi in zdravljeni z amoksicilinom (20 mg/kg teže) in alicinom (25 mg/kg telesne mase) in v šesti skupini okuženi in zdravljeni z amoksicilinom (10 mg/kg teže) in alicinom (25 mg/kg telesne mase). Spremljali smo prirast piščancev ter njihove hematološke in biokemične parametre. Pri okuženih piščancih smo v krvi opazili znatno znižanje skupnih beljakovin, albuminov, RBC, Hb in PCV ter znatno povečanje WBC, AST, ALT, ALP, kreatinina in sečne kisline. Uporaba amoksicilina in/ali alicina za zdravljenje okužbe s Clostridium perfringens je povzročila izboljšanje hematoloških in biokemičnih sprememb po okužbi. Odmerek amoksicilina 10 mg/kg in alicina 25 mg/kg telesne mase za zdravljenje okužbe s Clostridium perfringens pri pitovnih piščancih brojlerjih se je izkazal kot najbolj učinkovit, verjetno zaradi sinergističnega učinka obeh zdravil, in je povzročil zmanjšanje smrtnosti pitovnih piščancev. Ključne besede: amoksicilin; alicin; učinkovitost; brojlerji; biokemjski parametri; hematološki parametri

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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