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1.
Curr Issues Mol Biol ; 45(11): 8755-8766, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37998727

ABSTRACT

Osteocytes play an important role as regulators of both osteoclasts and osteoblasts, and some proteins that are secreted from them play a role in bone remodeling and modeling. LPS affects bone structure because it is an inflammatory factor, despite verbascoside's potential for bone preservation and healing. Osteocytes may also be involved in the control of the bone's response to immunological changes in inflammatory situations. MLO-Y4 cells were cultured in either supplemented -MEM alone with a low serum to inhibit cell growth or media with LPS (10 ng/mL) and/or verbascoside (50 g/mL) to show the LPS effect. In our research, LPS treatment increased RANKL levels while decreasing OPG and RUNX2 expression. Treatment with verbascoside reduced RANKL expression. In our work, verbascoside increased the expression of OPG and RUNX2. In MLO-Y4 cells exposed to verbascoside, SOD, CAT, and GSH activities as well as the expression levels of bone mineralization proteins like PHEX, RUNX2, and OPG were all elevated.

2.
J Bone Miner Metab ; 41(4): 443-456, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37031330

ABSTRACT

INTRODUCTION: Osteoporosis is a major health problem that is very common worldwide and is characterized by both low bone density and deterioration in bone quality. New treatment options without side effects have become an active area of research in recent years. This study was designed to investigate the preventive effects of resveratrol on bone quality deterioration caused by ovariectomy. MATERIALS AND METHODS: Sixty rats were randomly divided into five groups (12 animals per group): Control, Sham-operated (SHAM), ovariectomized (OVX), OVX + Resveratrol-40 mg/kg/day (OVX + Res40), OVX + Resveratrol-80 mg/kg/day (OVX + Res80). Resveratrol was administered by oral gavage (40 and 80 mg/kg/day) for ten weeks. Micro-CT measurements, biomechanical testing, Raman spectroscopy analysis, and RT-PCR analysis were performed. ALP, OCN, TAS, and TOS levels were also measured from blood serum. RESULTS: Bone strength, bone volume/total volume, trabecular volume, and trabecular thickness were higher in the OVX + RES-80 group than in the OVX group. Resveratrol increased osteogenic differentiation, as the expression of osteogenic markers ALP, Col1A1, Runx2, OPG, OCN increased in both OVX + RES-80 and OVX + RES-40 groups compared to the OVX group. 80 mg/kg/day resveratrol administration decreased the levels of ALP, OCN and TOS in ovariectomized rats. Raman spectroscopy findings showed a preventive effect of resveratrol administration against ovariectomy-induced deterioration in biophysiochemical properties of bone tissue. CONCLUSION: This study revealed that administration of different doses of 80 mg/kg/day and 40 mg/kg/day of resveratrol had protective effects on bone quality deterioration caused by ovariectomy.


Subject(s)
Osteogenesis , Osteoporosis , Female , Humans , Rats , Animals , Resveratrol/pharmacology , Resveratrol/therapeutic use , Bone and Bones/metabolism , Osteoporosis/drug therapy , Osteoporosis/etiology , Osteoporosis/prevention & control , Ovariectomy/adverse effects , Bone Density
3.
J Bone Miner Metab ; 35(2): 161-170, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27038987

ABSTRACT

Inhibitors of the renin-angiotensin system used to treat several diseases have also been shown to be effective on bone tissue, suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may reduce fracture risk. The present study investigated the effects of losartan on the physicochemical and biomechanical properties of diabetic rat bone. Losartan (5 mg/kg/day) was administered via oral gavage for 12 weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Whole femurs were tested under tension to evaluate the biomechanical properties of bone. The physicochemical properties of bone were analyzed by Fourier transform infrared spectroscopy. Although losartan did not recover decreases in the BMD of diabetic bone, it recovered the physicochemical (mineral and collagen matrix) properties of diabetic rat bone. Furthermore, losartan also recovered ultimate tensile strength of diabetic rat femurs. Losartan, an angiotensin II type 1 receptor blocker, has a therapeutic effect on the physicochemical properties of diabetic bone resulting in improvement of bone strength at the material level. Therefore, specific inhibition of this pathway at the receptor level shows potential as a therapeutic target for diabetic patients suffering from bone diseases such as osteopenia.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Bone Density , Bone and Bones/drug effects , Diabetes Mellitus, Experimental/pathology , Losartan/pharmacology , Absorptiometry, Photon , Animals , Biomechanical Phenomena , Bone and Bones/physiopathology , Female , Rats , Rats, Wistar , Renin-Angiotensin System , Spectroscopy, Fourier Transform Infrared
4.
Vascular ; 25(2): 170-177, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27235843

ABSTRACT

Background The aim of the present study was to investigate the role of inflammatory markers to predict amputation following embolectomy in acute arterial occlusion. Methods A total of 123 patients operated for arterial thromboembolectomy due to acute embolism were included in the study. The patients without an extremity amputation following thromboembolectomy were classified as Group 1 ( n = 91) and the rest were classified as Group 2 ( n = 32). These groups were compared in terms of clinical and demographic characteristics, C-reactive protein, complete blood count parameters, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red cell distribution width. Results The average age was 68.0 ± 11.7 years. The most common thromboembolism localization was femoral artery. When preoperative mean C-reactive protein ( p = 0.0001), mean platelet volume ( p = 0.0001), platelet-lymphocyte ratio ( p = 0.0001), neutrophil-lymphocyte ratio ( p = 0.0001) and red cell distribution width ( p = 0.0001) were compared, a statistically significant difference was observed between groups. In univariate and multivariate regression analysis, higher levels of preoperative C-reactive protein ( p = 0.009) and mean platelet volume ( p = 0.04) were detected as independent risk factors of early extremity amputation. Conclusion We observed that preoperative mean platelet volume and C-reactive protein were predictors of amputation after thromboembolectomy in acute arterial occlusion.


Subject(s)
Amputation, Surgical , Arterial Occlusive Diseases/surgery , C-Reactive Protein/analysis , Embolectomy/adverse effects , Inflammation Mediators/blood , Mean Platelet Volume , Acute Disease , Adult , Aged , Aged, 80 and over , Area Under Curve , Arterial Occlusive Diseases/blood , Arterial Occlusive Diseases/diagnostic imaging , Biomarkers/blood , Erythrocyte Indices , Female , Humans , Limb Salvage , Logistic Models , Lymphocyte Count , Male , Middle Aged , Multivariate Analysis , Neutrophils , Odds Ratio , Platelet Count , Predictive Value of Tests , ROC Curve , Reoperation , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
5.
Heart Surg Forum ; 19(3): E099-103, 2016 May 18.
Article in English | MEDLINE | ID: mdl-27355141

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is defined as a cluster of systemic abnormalities: hyperglycemia, dyslipidemia, abdominal obesity, and hypertension. Acute kidney injury (AKI) is one of the devastating complications after cardiac surgery. Age, DM, preexisting renal dysfunction, hypertension, impaired left ventricular function, and severe arteriosclerosis of the aorta are the major risk factors for the development of AKI. The purpose of the current study was to analyze the influence of MetS on AKI occurring after coronary artery bypass grafting (CABG). METHODS: We retrospectively reviewed the prospectively collected data of 500 adult patients who underwent isolated CABG surgery with normal renal function (baseline serum creatinine value <1.4 mg/dL) from January 2011 to January 2015. The patients were divided into two groups either having the diagnosis of MetS (Group I) or not (Group II). MetS was diagnosed based on International Diabetes Federation definition. Kidney injury was interpreted according to RIFLE classification. The effect of MetS on AKI after CABG was determined using logistic regression analysis and the results were expressed as odds ratio (OR) with a 95% confidence interval (CI). A P value <.05 was considered statistically significant. RESULTS: Metabolic syndrome was diagnosed in 16.4% of all patients. Postoperative AKI occurred in 26 patients (31.7%) in Group I whereas there were 53 patients (12.7%) in Group II. On logistic regression analysis, the presence of MetS was shown to be associated with increased incidence of postoperative AKI (OR, 3.197; 95% CI, 1.850-5.526; P = .000). CONCLUSION: The presence of MetS seems to be associated with increased incidence of AKI after cardiac surgery. MetS is a modifiable issue; if its components are well controlled its dreadful effects after cardiac surgery might be controlled as well.


Subject(s)
Acute Kidney Injury/etiology , Coronary Artery Bypass/adverse effects , Metabolic Syndrome/complications , Postoperative Complications/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
6.
Heart Surg Forum ; 19(2): E084-5, 2016 Apr 11.
Article in English | MEDLINE | ID: mdl-27146238

ABSTRACT

In this report, our aim is to present a case of renal artery occlusion due to type-3 acute aortic dissection following blunt trauma. A twenty-four-year-old male patient was admitted to the emergency department of our hospital with pain in his abdomen and on his back 3 hours after a blunt abdominal trauma due to an industrial injury. After consultation with the urology department, the patient was taken to operation to be evaluated for an intervention for aortic dissection and nephrectomy.


Subject(s)
Abdominal Injuries/complications , Aortic Aneurysm, Abdominal/complications , Aortic Dissection/complications , Renal Artery Obstruction/etiology , Vascular Surgical Procedures/methods , Wounds, Nonpenetrating/complications , Abdominal Injuries/diagnosis , Aortic Dissection/diagnosis , Aortic Dissection/surgery , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/surgery , Humans , Laparotomy , Male , Renal Artery Obstruction/diagnosis , Renal Artery Obstruction/surgery , Tomography, X-Ray Computed , Wounds, Nonpenetrating/diagnosis , Young Adult
7.
Heart Surg Forum ; 19(3): E123-7, 2016 Jun 23.
Article in English | MEDLINE | ID: mdl-27355147

ABSTRACT

BACKGROUND: Acute kidney injury is a common complication of cardiac surgery that increases morbidity and mortality. The aim of the present study is to analyze the association of preoperative serum albumin levels with acute kidney injury and the requirement of renal replacement therapy after isolated coronary artery bypass graft surgery (CABG). METHODS: We retrospectively reviewed the prospectively collected data of 530 adult patients who underwent isolated CABG surgery with normal renal function. The perioperative clinical data of the patients included demographic data, laboratory data, length of stay, in-hospital complications and mortality. The patient population was divided into two groups: group I patients with preoperative serum albumin levels <3.5 mg/dL; and group II pateints with preoperative serum albumin levels ≥3.5 mg/dL. RESULTS: There were 413 patients in group I and 117 patients in group II. Postoperative acute kidney injury (AKI) occured in 33 patients (28.2%) in group I and in 79 patients (19.1%) in group II. Renal replacement therapy was required in 17 patients (3.2%) (8 patients from group I; 9 patients from group II; P = .018). 30-day mortality occurred in 18 patients (3.4%) (10 patients from group I; 8 patients from group II; P = .037). Fourteen of these patients required renal replacement therapy. Logistic regression analysis revealing the presence of lower serum albumin levels preoperatively was shown to be associated with increased incidence of postoperative AKI (OR: 1.661; 95% CI: 1.037-2.661; P = .035). Logistic regression analysis also revealed that DM (OR: 3.325; 95% CI: 2.162-5.114; P = .000) was another independent risk factor for AKI after isolated CABG. CONCLUSION: Low preoperative serum albumin levels result in severe acute kidney injury and increase the rate of renal replacement therapy and mortality after isolated CABG.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Coronary Artery Bypass/adverse effects , Hypoalbuminemia/complications , Postoperative Complications/etiology , Postoperative Complications/therapy , Renal Replacement Therapy , Acute Kidney Injury/blood , Female , Humans , Male , Middle Aged , Postoperative Complications/blood , Retrospective Studies , Serum Albumin/metabolism
8.
Postepy Kardiol Interwencyjnej ; 20(1): 45-52, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38616939

ABSTRACT

Introduction: The correlation between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease is well established. Aim: The objective of this study was to assess the short-term associations of the non-alcoholic fatty liver disease fibrosis score (NFS) with various outcomes, including mortality, severe coronary artery disease, myocardial infarction, and the need for coronary angiography, among patients who underwent coronary computed tomographic angiography (CCTA). Material and methods: In this study, we assessed 499 patients who underwent 640-slice CCTA and evaluated their liver fibrosis using the NFS. The NFS takes into account factors such as age, body mass index, impaired fasting glycemia or diabetes mellitus, aspartate aminotransferase/alanine aminotransferase ratio, platelets, and albumin. Our primary focus was myocardial infarction, the need for coronary angiography, and death. Additionally, we examined the association between NFS and severe coronary artery disease. Results: Patients with a higher NFS had a greater number of coronary angiography procedures and higher Agatston score (p < 0.001), with NFS and Agatston score emerging as independent predictors of severe coronary artery disease and the primary endpoint. An NFS value above -0.92 could predict the primary endpoint with 61% sensitivity and 63% specificity, while an NFS value above -0.88 could predict severe coronary artery disease with 62% sensitivity and 65% specificity. To analyze primary endpoints, the Kaplan-Meier method was used for survival analysis, with NFS groups compared using the log-rank test. During the follow-up period, patients with higher NFS were exposed to primary outcomes at an earlier period (p = 0.009). Conclusions: NFS is an effective predictor of major cardiovascular events such as death, myocardial infarction, severe coronary artery disease, and the need for coronary angiography. These findings underscore the importance of NFS as a valuable tool for risk assessment and early intervention in patients with suspected or confirmed coronary artery disease.

9.
Postepy Kardiol Interwencyjnej ; 19(3): 277-283, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37854961

ABSTRACT

Introduction: Even though it has been reported that femoropopliteal artery endovascular revascularization is often performed with antegrade femoral artery interventions, which are technically relatively challenging, having the advantage of better control, it has also been reported that recanalization failure may occur in approximately 20% of patients and some materials have been developed for this reason. Aim: To evaluate the safety of retrograde popliteal artery intervention and our procedural success rate for symptomatic femoropopliteal artery occlusive disease. Material and methods: A total of 95 endovascular revascularization procedures were performed for treating symptomatic occlusive peripheral artery disease in the study period. Inclusion criteria were defined as patients who underwent endovascular revascularization procedures for symptomatic femoropopliteal artery occlusive disease. Patients who underwent a percutaneous endovascular procedure for iliac artery or below-knee arterial occlusive disease in the same session and patients who had previously undergone peripheral arterial bypass grafting or endovascular treatment for existing femoropopliteal artery disease were excluded. Results: We evaluated 45 peripheral endovascular procedures performed on 39 patients with a mean age of 62.49 ±11.38 years in our hospital for chronic femoropopliteal artery occlusive disease. Twelve (26.7%) of the endovascular treatment procedures were performed with retrograde access through the popliteal artery (Group 2). In neither group were any complications of arterial rupture, distal embolism, early thrombosis, or pseudoaneurysms observed. Conclusions: We are of the opinion that the retrograde popliteal artery technique is an effective and safe intervention option in endovascular revascularization, particularly in the revascularization of the long segment and complex femoropopliteal artery occlusions.

10.
J Interv Card Electrophysiol ; 66(6): 1341-1347, 2023 Sep.
Article in English | MEDLINE | ID: mdl-35751717

ABSTRACT

BACKGROUND: Extraction of the implantable cardioverter-defibrillator (ICD) leads could be a difficult procedure due to fibrous tissue around the lead and anatomical variations. In this report, we present our experience in the radiographic predictors of failure of simple manual traction (SMT) in patients with dual-coil ICD requiring lead extraction (LE). METHODS: Between January 2017 and February 2021, 103 leads were removed in 65 consecutive patients; 65 (63.1%) were dual-coil ICD leads, 22 (21.4%) were atrial, and 16 (15.5%) were coronary sinus leads. Patient-based and procedural data were collected and analyzed retrospectively. Clinical and procedural characteristics were compared and radiographic predictors of failure of SMT of ICD leads were assessed. Projected anteroposterior (AP) lead tortuosity was measured and lead slack score was estimated on chest X-ray (CXR). RESULTS: Simple manual traction failed in 27 (42%) of the ICD leads. Ottawa slack score (odds ratio [OR] 2.368, 95% CI [1.261-4.447]; P = 0.007), AP lead tortuosity > 1.10 (OR 7.477, 95% CI [1.718-35.542]; P = 0.007), and number of previous interventions (OR 6.016, 95% CI [1.184-30.557]; P < 0.030) were found to be independently related to the failure of SMT. Receiver-operator characteristic curve analysis yielded an AP lead tortuosity cutoff value of > 1.10 for predicting the failure of SMT. The area under the curve was 0.744; the 95% confidence interval (CI) was 0.617 to 0.871 (P = 0.001), with a sensitivity of 63% and a specificity of 73%. CONCLUSION: Simple manual traction success in our study varied based on radiographic lead-related parameters. Before planning the procedure, increased AP lead tortuosity in vasculature and higher lead slack score can be easily determined on CXR and may be associated with more fibrous adherences, the complexity of the LE, and failure of SMT.


Subject(s)
Defibrillators, Implantable , Humans , Retrospective Studies , Traction , Fibrosis , Device Removal/methods
11.
Turk Kardiyol Dern Ars ; 51(3): 221-225, 2023 04.
Article in English | MEDLINE | ID: mdl-36999326

ABSTRACT

Pulmonary arterial hypertension is still a fatal disease persisting with poor prognosis, despite all the advances in treatment (new agents and new combination strategies) in recent years. Patients present with different symptoms which are not specific to the disease (dyspnea, angina, palpitation, and syncope). Angina may occur secondary to myocardial ischemia due to increased right ventricular after load (oxygen supply and demand mismatch) or external compression on the left main coronary artery. Left main coronary artery compression is associated with post-exercise sudden cardiac death in pulmonary arterial hypertension patients. It should be kept in mind in the differential diagnosis of angina in patients with pulmonary arterial hypertension and should be treated immediately. Here, we report a pulmonary arterial hypertension patient associated with secundum-type atrial septal defect presented with ostial left main coronary artery compression caused by an enlarged pulmonary artery and treated with intravascular ultrasound-guided percutaneous coronary intervention.


Subject(s)
Heart Septal Defects, Atrial , Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Coronary Vessels , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/diagnosis , Pulmonary Artery , Angina Pectoris/etiology , Angina Pectoris/therapy , Heart Septal Defects, Atrial/complications , Heart Septal Defects, Atrial/diagnostic imaging , Heart Septal Defects, Atrial/surgery
12.
Mol Med Rep ; 26(6)2022 Dec.
Article in English | MEDLINE | ID: mdl-36281920

ABSTRACT

Calcium (Ca2+) signaling is the first messenger signal exhibited by osteocytes. The present study aimed to better understand the link between Ca2+ concentration, and the levels of bone mineralization regulator proteins [phosphate­regulating neutral endopeptidase on chromosome X (PHEX), matrix extracellular phosphoglycoprotein (MEPE) and dentin matrix protein 1 (DMP1)] and the levels of oxidative stress in osteocytes. The viability of MLO­Y4 cells was determined using the live/dead assay following treatment with various Ca2+ concentrations (1.8, 6, 12, 18, 24 and 50 mM) for different durations (15 and 60 min, and 24 h). Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and NADPH oxidase (NOX) enzymes were analyzed using a colorimetric method. Apoptosis was detected by caspase­3 analysis. Furthermore, the protein expression levels of PHEX, MEPE and DMP1 were analyzed using immunoblotting, and oxidative stress was examined using the total antioxidant and total oxidant status (TOS) assay. Notably, after 15 min, there were more live cells than dead cells; however, after 60 min, the number of dead cells was increased following treatment with 24 and 50 mM Ca2+. After 24 h, there were more dead cells than live cells following treatment with 50 mM Ca2+. After 24 h of Ca2+ treatment, the highest protein expression levels of PHEX, MEPE and DMP1 were measured in cells treated with 24 mM Ca2+. In addition, as Ca2+ concentration increased, the TOS and the oxidative stress index values were also increased. In conclusion, these results suggested that 24 mM Ca2+ may trigger bone mineralization proteins, such as PHEX, MEPE and DMP1, and could be considered an applicable dosage for the treatment of bone damage in the future.


Subject(s)
Osteocytes , PHEX Phosphate Regulating Neutral Endopeptidase , Osteocytes/metabolism , PHEX Phosphate Regulating Neutral Endopeptidase/genetics , PHEX Phosphate Regulating Neutral Endopeptidase/metabolism , Calcium/metabolism , Caspase 3/metabolism , Catalase/metabolism , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Neprilysin/metabolism , Antioxidants/metabolism , Phosphoproteins/genetics , Phosphoproteins/metabolism , Glycoproteins/metabolism , Phosphates/metabolism , Glutathione/metabolism , NADPH Oxidases/metabolism , Oxidants/metabolism , Superoxide Dismutase/metabolism
13.
Am J Cardiol ; 150: 55-59, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34006373

ABSTRACT

Coronary artery bypass grafting (CABG) often causes physiological changes in patients. Although functional changes, such as lung function and exercise capacity changes, are observed in patients, there are no detailed studies examining this. The aim was to compare preoperative and postoperative pulmonary function and exercise capacity in patients undergoing on-pump CABG with a multidimensional index (BODE index). Demographic and surgical characteristics of patients were recorded. Pulmonary function test, six-minute walk test (6MWT), and modified Medical Research Council (mMRC) dyspnea score were assessed and BODE index were calculated in preoperative and at six months postoperatively. A total of 75 patients were included with a mean ± standard deviation age of 59.8±10.0 years. The male to female ratio was 57/18. There was a statistically significant decrease in the forced expiratory flow at 25-75% (FEF25-75%) value after CABG. Other pulmonary function test values were also lower in the postoperative period compared to the preoperative period, but these changes were not significant. The mean distance achieved in the 6MWT (p=0.02) and the mMRC dyspnea score (p=0.001) were significantly better postoperatively. The BODE index, which combines these parameters, had increased in the postoperative period. Age (OR 1.09; 95% CI: 1.008-1.181) and postoperative FEF25-75% (OR -0.96; 95% CI: 0.938-0.988) were the independent predictors of BODE score ≥3 in multivariate analysis. Despite the decrease in pulmonary function in patients undergoing CABG, there was an improvement in exercise capacity and dyspnea score.


Subject(s)
Coronary Artery Bypass/methods , Coronary Disease/physiopathology , Coronary Disease/surgery , Exercise Tolerance/physiology , Adult , Aged , Aged, 80 and over , Body Mass Index , Dyspnea/physiopathology , Female , Humans , Male , Middle Aged , Prognosis , Respiratory Function Tests , Severity of Illness Index , Walk Test
14.
Rev Assoc Med Bras (1992) ; 67(12): 1764-1770, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34909947

ABSTRACT

OBJECTIVE: Studies on ischemia/reperfusion injury remain the focus of interest. Ticagrelor and enoxaparin, which are antiaggregant and anticoagulant drugs developed for use in many cardiovascular pathologies, are still included in many ischemia/reperfusion studies. Remarkably, their new protective effects, especially with regard to ticagrelor, continue to be reported in the current literature. The aim of this study was to evaluate the beneficial effects of ticagrelor and enoxaparin pretreatments on the rat heart with histological and immunohistochemical markers in an ischemia/reperfusion model. METHODS: Wistar-albino rats (weighing 350-400 g) were divided into four groups as follows: Sham-Control (Group 1), Control-Saline+ischemia/reperfusion (Group 2), Ticagrelor+ischemia/reperfusion (Group 3), and Enoxaparin+ischemia/reperfusion (Group 4). The ischemia/reperfusion injury model was applied to Group 2, Group 3 and Group 4. Heart tissue sections were stained with hematoxylin and eosin for histological examinations. Caspase 3 immunostaining was evaluated to detect apoptosis in the heart tissue sections. RESULTS: Both pretreatments ameliorated the ischemic damage but especially tissue sections belonging to Group 3 were nearly similar to control levels. The results indicated that ischemia/reperfusion-induced myocardial damage was significantly increased in Group 2, whereas ticagrelor and enoxaparin pretreatments in Group 3 and Group 4 significantly decreased apoptotic scores and the histological appearance of the Group 3 close to the normal myocardium (p<0.001). CONCLUSION: As supported by histological findings in our study, ticagrelor and enoxaparin have protective properties for heart tissue in this ischemia/reperfusion injury model.


Subject(s)
Enoxaparin , Ischemia , Animals , Apoptosis , Rats , Rats, Wistar , Reperfusion , Ticagrelor
16.
Acta Biomater ; 63: 200-209, 2017 11.
Article in English | MEDLINE | ID: mdl-28890257

ABSTRACT

Flexor tendon lacerations are traditionally repaired by using non-absorbable monofilament sutures. Recent investigations have explored to improve the healing process by growth factor delivery from the sutures. However, it is difficult to conjugate growth factors to nylon or other synthetic sutures. This study explores the performance of a novel electrochemically aligned collagen suture in a flexor tendon repair model with and without platelet derived growth factor following complete tendon laceration in vivo. Collagen suture was fabricated via electrochemical alignment process. Heparin was covalently bound to electrochemically aligned collagen sutures (ELAS) to facilitate affinity bound delivery of platelet-derived growth factor-BB (PDGF-BB). Complete laceration of the flexor digitorum profundus in the third digit of the foot was performed in 36 skeletally mature White Leghorn chickens. The left foot was used as the positive control. Animals were randomly divided into three groups: control specimens treated with standard nylon suture (n=12), specimens repaired with heparinated ELAS suture without PDGF-BB (n=12) and specimens repaired with heparinated ELAS suture with affinity bound PDGF-BB (n=12). Specimens were harvested at either 4weeks or 12weeks following tendon repair. Differences between groups were evaluated by the degree of gross tendon excursion, failure load/stress, stiffness/modulus, absorbed energy at failure, elongation/strain at failure. Quantitative histological scoring was performed to assess cellularity and vascularity. Closed flexion angle measurements demonstrated no significant differences in tendon excursion between the study groups at 4 or 12weeks. Biomechanical testing showed that the group treated with PDGF-BB bound heparinated ELAS suture had significantly higher stiffness and failure load (p<0.05) at 12-weeks relative to both heparinated ELAS suture and nylon suture. Similarly, the group treated with PDGF-BB bound suture had significantly higher ultimate tensile strength and Young's modulus (p<0.05) at 12-weeks relative to both ELAS suture and nylon suture. Compared to nylon controls, heparinized ELAS with PDGF-BB improved biomechanics and vascularity during tendon healing by 12-weeks following primary repair. The ability of ELAS to deliver PDGF-BB to the lacerated area of tendon presents investigators with a functional bioinductive platform to improve repair outcomes following flexor tendon repair. STATEMENT OF SIGNIFICANCE: A high strength aligned collagen suture was fabricated via linear electrocompaction and heparinized for prolonged delivery of PDFG-BB. When it was used to suture a complete lacerated flexor tendon in a chicken model controlled release of the PDGF-BB improved the strength of treated tendon after 12 weeks compared to tendon sutured with commercial nylon suture. Furthermore, Collagen suture with affinity bound PDGF-BB enhanced the vascularization and remodeling of lacerated tendon when it compare to synthetic nylon suture. Overall, electrocompacted collagen sutures holds potential to improve repair outcome in flexor tendon surgeries by improving repair strength and stiffness, vascularity, and remodeling via sustained delivery of the PDGF-BB. The bioinductive collagen suture introduces a platform for sustained delivery of other growth factors for a wide-array of applications.


Subject(s)
Collagen/chemistry , Drug Delivery Systems , Heparin/chemistry , Lacerations/drug therapy , Proto-Oncogene Proteins c-sis/therapeutic use , Sutures , Tendons/pathology , Animals , Becaplermin , Biomechanical Phenomena , Cattle , Chickens , Lacerations/pathology , Lacerations/physiopathology , Proto-Oncogene Proteins c-sis/pharmacology , Tendons/drug effects , Tendons/physiopathology , Wound Healing/drug effects
17.
Acta Biomater ; 41: 100-9, 2016 09 01.
Article in English | MEDLINE | ID: mdl-27240725

ABSTRACT

UNLABELLED: Suturing is the standard of repair for lacerated flexor tendons. Past studies focused on delivering growth factors to the repair site by incorporating growth factors to nylon sutures which are commonly used in the repair procedure. However, conjugation of growth factors to nylon or other synthetic sutures is not straightforward. Collagen holds promise as a suture material by way of providing chemical sites for conjugation of growth factors. On the other hand, collagen also needs to be reconstituted as a mechanically robust thread that can be sutured. In this study, we reconstituted collagen solutions as suturable collagen threads by using linear electrochemical compaction. Prolonged release of PDGF-BB (Platelet derived growth factor-BB) was achieved by covalent bonding of heparin to the collagen sutures. Tensile mechanical tests of collagen sutures before and after chemical modification indicated that the strength of sutures following chemical conjugation stages was not compromised. Strength of lacerated tendons sutured with epitendinous collagen sutures (11.2±0.7N) converged to that of the standard nylon suture (14.9±2.9N). Heparin conjugation of collagen sutures didn't affect viability and proliferation of tendon-derived cells and prolonged the PDGF-BB release up to 15days. Proliferation of cells seeded on PDGF-BB incorporated collagen sutures was about 50% greater than those seeded on plain collagen sutures. Collagen that is released to the media by the cells increased by 120% under the effects of PDGF-BB and collagen production by cells was detectable by histology as of day 21. Addition of PDGF-BB to collagen sutures resulted in a moderate decline in the expression of the tendon-associated markers scleraxis, collagen I, tenomodulin, and COMP; however, expression levels were still greater than the cells seeded on collagen gel. The data indicate that the effects of PDGF-BB on tendon-derived cells mainly occur through increased cell proliferation and that longer term studies are needed to confirm whether this proliferation is outweighs the moderate reduction in the expression of tendon-associated genes. STATEMENT OF SIGNIFICANCE: A mechanically robust pure collagen suture was fabricated via linear electrocompaction and conjugated with heparin for prolonged delivery of PDFG-BB. Sustained delivery of the PDGF-BB improved the proliferation of tendon derived cells substantially at the expense of a moderate downregulation of tenogenic markers. The collagen threads were functionally applicable as epitendinous sutures when applied to chicken flexor tendons in vitro. Overall, electrocompacted collagen sutures holds potential to improve repair outcome in flexor tendon surgeries by improving cellularity and collagen production through delivery of the PDGF-BB. The bioinductive suture concept can be applied to deliver other growth factors for a wide-array of applications.


Subject(s)
Collagen/pharmacology , Drug Delivery Systems/methods , Heparin/pharmacology , Proto-Oncogene Proteins c-sis/pharmacology , Sutures , Tendons/cytology , Animals , Becaplermin , Cattle , Cell Proliferation/drug effects , Cell Shape/drug effects , Chickens , Cross-Linking Reagents/pharmacology , Delayed-Action Preparations , Real-Time Polymerase Chain Reaction , Staining and Labeling , Tensile Strength
18.
In Vivo ; 30(3): 243-9, 2016.
Article in English | MEDLINE | ID: mdl-27107082

ABSTRACT

AIM: This study aimed to analyze the effect of ticagrelor pretreatment on the prevention of lung and heart injury induced by abdominal aorta ischemia and reperfusion (I/R) and also to determine the effective dose. MATERIALS AND METHODS: Thirty-five male Sprague-Dawley rats weighing 350-400 g were randomized into five groups. The animals received ticagrelor at doses of 7.5 mg/kg, 15 mg/kg and 25 mg/kg or normal saline 0.1 ml/kg orally via gastric gavage before the ischemic period. In the control and study groups, I/R injury was induced by clamping the aorta infrarenally for 2 hs, followed by 4 h of reperfusion. After sacrifice, hearts and lungs of the animals were extracted for both histopathological and biochemical analysis. RESULTS: There was a significant difference between the animals that received 7.5 mg/kg and 25 mg/kg and 15 mg/kg and 25 mg/kg dose of ticagrelor regarding tissue malondealdehyde (MDA), and glutathione reductase levels in both lung and heart Ticagrelor treatment at 25 mg/kg led to significant cardiac remodeling activity and normal lung architecture against I/R induced injury. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells in alveolar epithelium and myocytes were increased in the sections from saline (I/R) group rats, and decreased following 25 mg/kg ticagrelor treatment. CONCLUSION: Ticagrelor dose-dependently inhibits platelet aggregation, increases cyclooxygenase-2 and also inhibits cellular uptake of adenosine all resulting in attenuation of I/R injury. Ticagrelor at 25 mg/kg was determined as the dose effective against I/R-induced injury in lung and heart in Sprague-Dawley rats in the present study.


Subject(s)
Adenosine/analogs & derivatives , Aorta, Abdominal/physiopathology , Apoptosis/drug effects , Reperfusion Injury/physiopathology , Adenosine/metabolism , Adenosine/pharmacology , Animals , Cyclooxygenase 2/metabolism , Dose-Response Relationship, Drug , Glutathione Reductase/metabolism , In Situ Nick-End Labeling , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Malondialdehyde/metabolism , Myocardium/metabolism , Myocardium/pathology , Purinergic P2Y Receptor Antagonists/pharmacology , Random Allocation , Rats, Sprague-Dawley , Ticagrelor
19.
Int J Ophthalmol ; 9(5): 677-81, 2016.
Article in English | MEDLINE | ID: mdl-27275420

ABSTRACT

AIM: To evaluate the effect of sodium tungstate on visual evoked potentials (VEPs) in diabetic rats. METHODS: Wistar rats were randomly divided into three groups as normal control, diabetic control and diabetic rats treated with sodium tungstate. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg). Sodium tungstate [40 mg/(kg·d)] was administered for 12wk and then VEPs were recorded. Additionally, thiobarbituric acid reactive substance (TBARS) levels were measured in brain tissues. RESULTS: The latencies of P1, N1, P2, N2 and P3 waves were significantly prolonged in diabetic rats compared with control group. Diabetes mellitus caused an increase in the lipid peroxidation process that was accompanied by changes in VEPs. However, prolonged latencies of VEPs for all components returned to control levels in sodium tungstate-treated group. The treatment of sodium tungstate significantly decreased brain TBARS levels and depleted the prolonged latencies of VEP components compared with diabetic control group. CONCLUSION: Sodium tungstate shows protective effects on visual pathway in diabetic rats, and it can be worthy of further study for potential use.

20.
Case Rep Surg ; 2014: 584580, 2014.
Article in English | MEDLINE | ID: mdl-25431729

ABSTRACT

Foreign body is among complications of surgery. But as a complication of varicose vein surgery it was reported extremely rarely and, to our knowledge, there is only one paper in the literature. A case with retained sponge which was detected five months after varicose vein surgery was presented.

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