Comparison of Bretschneider HTK and Blood Cardioplegia (4:1): A Prospective Randomized Study.

BACKGROUND: We compared the effect of intermittent blood and histidine-tryptophan-ketoglutarate (HTK) solution of Bretschneider on myocardial histopathology and perioperative outcome. METHODS: Forty adult cardiac surgery patients were grouped into two (n = 20 for each): (1) Intermittent blood cardioplegia (IBC): had repeated cold 4:1 blood cardioplegia and (2) HTK: had a single dose of cold HTK for cardioprotection. Creatine kinase (CK)-MB, Troponin-I (cTn-I), pH, and lactate were studied in coronary sinus blood before and after aortic cross-clamping (AXC) and systemic blood at postoperative 6th, 24th, and 48th hours. Myocardial biopsy was performed before and after AXC for light microscopy. Vacuolation, inflammation, edema, and glycogen were graded semiquantitatively (from 0 to 3). The myocardial apoptotic index was evaluated via the terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: There were no differences in perioperative clinical outcomes between the groups. The coronary sinus samples after AXC were more acidotic (7.15 ± 0.14 vs. 7.32 ± 0.07, p = 0.001) and revealed higher CK-MB (21.0 ± 12.81 vs. 12.60 ± 11.80, p = 0.008) in HTK compared with IBC. The HTK had significantly a higher amount of erythrocyte suspension intraoperatively compared with IBC (0.21 ± 0.53 vs. 1.68 ± 0.93 U, p = 0.001). Microscopically, myocardial edema was more pronounced in HTK compared with IBC after AXC (2.25 ± 0.91 vs. 1.50 ± 0.04, p = 0.013). While a significant increase in the apoptotic index was seen after AXC in both groups (p = 0.001), no difference was detected between the groups (p = 0.417). CONCLUSION: IBC and HTK have a similar clinical outcome and protective effect, except for more pronounced myocardial edema and increased need for intraoperative transfusion with HTK.

3D Fiber Reinforced Hydrogel Scaffolds by Melt Electrowriting and Gel Casting as a Hybrid Design for Wound Healing.

Emerging biomanufacturing technologies have revolutionized the field of tissue engineering by offering unprecedented possibilities. Over the past few years, new opportunities arose by combining traditional and novel fabrication techniques, shaping the hybrid designs in biofabrication. One of the potential application fields is skin tissue engineering, in which a combination of traditional principles of wound dressing with advanced biofabrication methods could yield more efficient therapies. In this study, a hybrid design of fiber-reinforced scaffolds combined with gel casting is developed and the efficiency for in vivo wound healing applications is assessed. For this purpose, 3D fiber meshes produced by melt electrowriting are selectively filled with photocrosslinkable gelatin hydrogel matrices loaded with different growth factor carrier microspheres. Additionally, the influence of the inclusion of inorganic bioactive glass particles within the composite fibrous mesh is evaluated. Qualitative evaluation of secondary wound healing criteria and histological analysis shows that hybrid scaffolds containing growth factors and bioactive glass enhances the healing process significantly, compared to the designs merely providing a fiber-reinforced bioactive hydrogel matrix as the wound dressing. This study aims to explore a new application area for melt electrowriting as a powerful tool in fabricating hybrid therapeutic designs for skin tissue engineering.

The effect of collagenase clostridium histolyticum on adhesion reduction in a rat knee arthrofibrosis model.

OBJECTIVE: The aim of this study was to investigate whether collagenase clostridium histolyticum (CCH) reduces intra-articular fibrotic adhesion formation in a rat model of arthrofibrosis. METHODS: A total of 24 male Wistar rats (7 months old, weighing 220 -275 g) were randomly and equally assigned to one of two groups: the collagenase group and the control group (n = 12 each). In each group, a partial capsulotomy, and synovectomy were performed in knee. After a partial capsulotomy and synovectomy were performed in each group, the collagenase group received intra-articular CCH of 0.008 mg in 0.1 mL saline solution while the control group received the equal volume of intra-articular saline solution alone. After 6 weeks of surgery, the rats were sacrificed by decapitation, and the following outcome measures were collected. Knee range of motion (ROM) was measured using with a goniometer under 20 g force. Adhesion formation was rated using the macroscopic visual scoring system after the knee joint was exposed through a lateral parapatellar approach. Histological evaluation was performed on samples including connective tissue and fibrotic adhesions, and fibroblast cell numbers were measured performed per square. Levels of interleukin 1 (IL-1) and fibroblast growth factor (FGF) were assayed by ELISA from the intra-articular fluid. RESULTS: The macroscopic visual scoring system was significantly lower in the collagenasegroup (median = 1, range = 0-2) than in the control group (median = 2, range = 1-3)( < 0.001).ROMwas significantly higher in the collagenase group (102° ± 12.1°) than in the control group (77° ±8.94°) (P <0.001). The number of fibroblasts obtained from the scar tissue were considerably lower in the collagenase group (mean = 16.5 ± 2.74) compared tothe control group (mean = 30.1± 4.89) (P < 0.001). Levels of IL-1 andFGF were significantly lower in the collagenase group (mean = 18.6 ng/l ± 4.39,mean = 36.3 ng/l ± 2.03; respectively) compared to the control group (mean = 31.7ng/l ± 3.75, mean = 38.7 ng/l ± 2.19; respectively) (P < 0.001). CONCLUSION: Evidence from this study has revealed that CCH injection can inhibit the development ofarthrofibrosis, decreasing the precursor inflammatory cytokines (IL-1 and FGF-1) and histologic fibrosis in a rat knee arthrofibrosis model. LEVEL OF EVIDENCE: Level IV, Therapeutic study.

Histopathologic evaluation of saphenous vein grafts in patients with type II diabetes mellitus undergoing coronary artery bypass grafting.

INTRODUCTION: Diabetes Mellitus (DM) has been known to be a risk factor for the development of more severe form of saphenous vein graft disease after coronary artery bypass grafting (CABG). We aimed to evaluate the impact of type II-DM on histopathological features of great saphenous vein grafts of patients undergoing CABG. PATIENTS AND METHODS: Forty consecutive patients undergoing elective CABG were enrolled into the study. Patients were grouped into two; Diabetic group (n = 20); includes patients with preoperative diagnosis of type II-DM and Nondiabetic group (n = 20): those without type II-DM. In all patients, a short segment of the great saphenous vein graft at the level of medial malleolus was taken for light microscopy and transmission electron microscopy (TEM) evaluation. Moreover, immunoexpressions of Caveolin-1, Vascular cell adhesion protein 1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) were studied. RESULTS: There were no differences in the demographics of patients between two groups. The magnitude of intimal fibrosis in diabetic group was slightly higher than in nondiabetics (1.95 ± 0.99 versus 1.3 ± 0.8, P = .04). In TEM, vacuolization in endothelial cells, substance accumulation along with coarse collagen fibers and cytoplasmic degeneration with vacuolization in muscle cells were detected in diabetic group. While there were no differences in Caveolin-1 and VCAM-1 immunostaining, the intensity of positive eNOS immunostaining was significantly higher in endothelium (2.10 ± 0.64 versus 1.55 ± 0.68, P = .01) and tunica media 1.75 ± 0.63 versus 1.2 ± 0.52, P = .007) in nondiabetic group, respectively) compared with diabetic group. CONCLUSION: Type II DM might be a reason for decreased expression of eNOS and increased intimal fibrosis, vacuolization of endothelial and smooth muscle cells in saphenous vein grafts. The clinical implications of these alterations on the graft patency need to be evaluated.

Introducing Children to Anatomy: "Getting to Know Our Bodies: The First Step Toward Becoming a Scientist".

Museums are used in every discipline to collect, classify, and present information for scientific purposes. They also serve as an effective educational medium. Since the establishment of a boutique anatomy museum at Bahçesehir University, lectures, conferences, and seminars have been organized there over the past four years on the history of human anatomy and the human body. In order to raise awareness about the need to make anatomy accessible to kindergarteners and school-aged children, rather than exclusively to undergraduate students, activities that are suited to a wide range of ages have been developed at the museum and at the anatomy laboratory. Four different sessions were conducted, including activities such as lectures using plastic models as props, shaping organs out of playdough, anatomy puzzles, watching cartoons, and examining specimens through a microscope. Healthy and pathologic anatomies were chosen to match daily themes. Among the kindergarteners and elementary school children, no grading was done, nor was any questionnaire administered; however, a survey was administered in the 10-12 age group (N = 64). According to the students' written feedback, 93.75% said they "are happy with microscope activities" while 84.37% said they "had so much fun" participating in the playdough activities. However, 18.75% criticized the activities, saying they "could have been longer." In conclusion, it is believed that these "getting to know our bodies" activities that were hosted in the anatomy museum, including conferences, workshops, material preparation, and instructional movies, may play an important role in the development of a healthy society.

Effects of Algan Hemostatic Agent on bleeding time in a rat tail hemorrhage model.

BACKGROUND: Algan Hemostatic Agent (AHA) is a multi-herbal extract containing a standardized amount of Achillea millefolium, Juglans regia, Lycopodium clavatum, Rubus caesius or Rubis fruciosus, Viscum album, and Vitis vinifera, each of which is effective in hemostasis. In this study, we aimed to investigate the effects of AHA on bleeding time in a rat tail hemorrhage model. METHODS: Forty-eight Sprague Dawley rats (5-7 weeks old, 180-210 g) were randomly and equally allocated to six groups as follows: heparin plus saline (heparinized control), heparin plus AHA-soaked sponge, heparin plus liquid form of AHA, saline (non-heparinized control), AHA-soaked sponge and liquid form of AHA. Heparin (640 IU/kg) was administered intraperitoneally three times a day for three days in heparinized groups. For the bleeding model, the tail of rats was transected. According to the study group, either saline- or AHA-soaked sponge or liquid form of AHA was applied over the hemorrhage area. In AHA- or saline-soaked sponge groups, once the bleeding time had started, it was checked every 10 seconds. If the bleeding did not stop after 40 seconds, it was accepted as a failure. In liquid AHA group, the duration of bleeding was measured using a chronometer and defined as the time (seconds) from wounding until the bleeding stopped. RESULTS: Bleeding time in the heparinized and non-heparinized control groups was over 40 seconds. After applying the sponge form of AHA on the wound area, bleeding time was significantly shortened to less than 20 seconds in both heparinized and non-heparinized rats (p<0.001 for both). The liquid form of AHA stopped bleeding in 5.0±1.2 seconds and 8.0±1.3 seconds in heparinized and non-heparinized groups, respectively. CONCLUSION: AHA is a highly effective topical hemostatic agent in a rat tail hemorrhage model, thus may provide for a unique clinically effective option for control of bleeding during surgical operations or other emergencies.

Histological Comparison of Nanocomposite Multilayer Biomimetic Scaffold, A Chondral Scaffold, and Microfracture Technique to Repair Experimental Osteochondral Defects in Rats.

OBJECTIVE: We used biomimetic scaffolds, chondral scaffolds, and microfractures to repair experimentally created osteochondral defects in rat knees and then compared the results of each method. MATERIALS AND METHODS: We used a total of 56 female Wistar albino rats. The rats were grouped into 4 groups, with 14 rats each: biomimetic scaffold, chondral scaffold, microfracture, and control groups. Cylindrical full-thickness osteochondral defects 2.5 mm in diameter and 2 mm in depth were drilled into the right knees with the rats under general anesthesia. The knees of all rats were operated again after 4 weeks. Biomimetic and chondral scaffolds were classified into two groups. Microfractures 0.5 mm in diameter and 0.8 mm in depth were created in the rats of the microfracture group. The control group received no treatment. All the rats were observed for 6 weeks and then sacrificed, with samples subjected to macroscopic and histopathological examinations. RESULTS: The macroscopic and histopathological results in the biomimetic scaffold group differed significantly from those of the other treatment groups (p<0.05). When we compared the 3 treatment groups, the results of the chondral scaffold group were better than those of the microfracture group. The results of the microfracture group were somewhat better than those of the control group, but the result was not statistically significant (p>0.05). CONCLUSIONS: Nanocomposite multilayer biomimetic scaffolds were better than chondral scaffolds and microfractures when used to treat osteochondral defects.

The Effects of Corticosteroid Injection in the Healthy and Damaged Achilles Tendon Model: Histopathological and Biomechanical Experimental Study in Rats.

OBJECTIVE: To show the effects of corticosteroids on inflammatory reactions in the injured Achilles tendon in rats. MATERIAL AND METHOD: Thirty-two adult Wistar Albino rats were used in the study. The rats were divided into 4 groups. In the first group (Intact Saline), saline solution was injected to the intact Achilles tendon. In the second group (Intact Corticosteroid), corticosteroid was injected to the intact tendon. In the third group (Injured Saline), saline solution was injected to the injured Achilles tendon. In the fourth group (Injured Corticosteroid), corticosteroid was injected to the injured tendon. All groups were sacrificed on day 30 and Achilles tendons were taken and prepared for histological and biomechanical evaluation. RESULTS: According to the biomechanical test; mean load-to-failure of the Intact Saline group was significantly lower than the Intact Corticosteroid (p=0.016), Injured Saline (p=0.001) and Injured Corticosteroid) (p=0.012) groups. According to the histopathological evaluation, tenocyte mean of the Intact Saline group was statistically lower than the Injured Saline and Injured Corticosteroid groups. Tenocyte mean of the Intact Corticosteroid group was statistically significantly lower than the Injured Saline and Injured Corticosteroid groups. The ground substance mean of the Intact Saline group was significantly lower than the Injured Saline and Injured Corticosteroid groups. The ground substance mean of the Intact Corticosteroid group was significantly lower than the Injured Saline and Injured Corticosteroid groups. There was no statistically significant difference between the groups in terms of calcification. CONCLUSION: It has been found that there is biomechanical and histopathological significant benefit of intra-tendon corticosteroid administration in the experimentally generated Achilles tendon injury model.

Comparison of heat monitoring-based myocardial protection strategy with classic myocardial protection method in isolated coronary artery bypass surgery patients.

OBJECTIVE: In this study, we aimed to compare patients who have a myocardial protection strategy based on myocardial temperature monitorization with those who had myocardial protection with conventional intermittent cardioplegia. METHODS: Twenty-six patients undergoing coronary artery bypass graft surgery were included into the study. Patients were prospectively grouped into two; myocardial protection based on temperature monitoring (group 1, n = 11) and those who had cardioplegia every 20 min (group 2, n = 15) during aortic cross-clamping. In all patients, cold blood cardioplegia was used. Coronary sinus blood sampling was performed immediately before aortic cross-clamping, after 2, 20, and 40 min of aortic clamping and tumor necrosis factor-alpha, malondialdehyde, creatinine kinase-myocardial band isoenzyme (MB), troponin I, lactate, and pH were studied. In addition, myocardial biopsy was taken before and immediately after cross-clamping to evaluate cardiomyocyte apoptosis with caspase-3 tunnel immunostaining. RESULTS: There were no differences in clinical parameters like early mortality, extubation time, inotropic requirements, postoperative drainage, intensive care unit, and hospitalization time between two groups. In addition, blood and blood products were similar in two groups. In group 2, after cross-clamping, troponin I and creatinine kinase-MB values were significantly higher than the other group. In myocardial biopsies, the caspase immunostaining score, before removal of aortic cross-clamp was significantly higher in group 2 than the samples taken before aortic clamping. CONCLUSION: Our results show that there is no difference between temperature-based myocardial protection strategy with conventional intermittent cardioplegia delivery. We think that the number of patients in our study is less and that the patient population is not a homogeneous structure is the most important limiting factor of our study. Increasing the number of patients, with particularly those who have myocardial dysfunction would help augment the possible different effects of two cardioplegic techniques on myocardial protection.

Xylitol treats nasal mucosa in rhinitis medicamentosa: an experimental rat model study.

OBJECTIVE: Rhinitis medicamentosa is drug-induced rhinitis which occurs by prolonged and overdose usage of topical nasal decongestants. There is not much of treatment choice rather than nasal steroids. In this pathological study, we have been aimed to represent the healing effects of xylitol on damaged nasal mucosa due to rhinitis medicamentosa. METHOD: 30 Wistar rats were separated into 5 groups. During 2 months, oxymetazoline was given to the first group, and saline was given to second group intranasally. First and second group animals were examined at the end of 2 months and rhinitis medicamentosa was detected. Oxymetazoline was given to the third, fourth, and fifth groups during 2 months. Then xylitol solution, mometasone, and saline were applied, respectively, for 15 days. After the experiment, rats' nasal mucosas were evaluated histopathologically. RESULTS: Xylitol and mometasone were found to be more effective than the control group in terms of histopathological changes. Effectivity of xylitol and mometasone was compared and not a significant value was determined. CONCLUSIONS: According to the results, xylitol solution is effective as mometasone, usable and well-priced in the treatment of rhinitis medicamentosa. More comprehensive and ultrastructural studies on animals and human studies with rhinometric evaluation should be performed.

The effect of erythropoietin on rat rotator cuff repair model: An experimental study.

OBJECTIVES: The aim of this study was to determine whether erythropoietin (EPO) can enhance rotator cuff healing in rats as measured by histological analysis and biomechanical testing. METHODS: A total of 72 rats were included in this study. In the control group (n = 24), repair was performed without EPO injection. In the local group (n = 24) EPO was injected in the repair site. In the systemic group (n = 24) EPO was administered as an intraperitoneal injection every day for 10 days after repair. Rats were euthanized on day 10 (n = 12 from each group) and day 28 (n = 12 from each group). Histopathological (n = 6) and biomechanical examinations (n = 6) were done. RESULTS: Biomechanical results reveal that the maximum load to failure values of the early control group were statistically lower than those of the early systemic group (p = 0.006). Comparing the the total Bonar values histopathologically reveal that the early systemic group was statistically higher than those of the early local group (p = 0.043). The late control group was statistically higher than those of the late local group (p = 0.003) and the late systemic group (p = 0.034). The late systemic group was statistically higher than those of the late local group (p = 0.003). CONCLUSIONS: EPO application had a positive effect biomechanically in the early euthanized group and histopathologically in the late euthanized group.

Diagnostic value of signal peptide-CUB-EGF domain-containing protein 1 as an early and late biochemical marker in the ovarian torsion rat model.

AIMS: Signal peptide-CUB-EGF (epidermal growth factor-like protein) domain-containing protein 1 (SCUBE1) is an experimental marker of ischemia that has been previously studied both in rat models and humans. In this study, we aim to investigate the importance of SCUBE1 levels in ovarian torsion using an ovarian torsion model in rats. METHODS: A total of 18 Sprague-Dawley rats were equally divided into three groups. Group 1 (n = 6) was the Sham group and was only given a laparotomy procedure. Group 2 (n = 6) underwent bilateral ovarian torsion and ovarian ischemia lasting 8 h. Group 3 (n = 6) was subjected to bilateral ovarian torsion and ischemia lasting 24 h. Blood samples were collected from all three groups after the operations, and SCUBE1 levels were studied. Ovarian samples were collected, and microscopic evaluation was performed. The correlation of SCUBE1 levels and histopathological findings were investigated. RESULTS: The mean SCUBE1 level of group 3 was statistically higher than other groups (P < 0.01). Follicular degeneration and infiltration of inflammatory cells were, respectively, statistically significant in groups 2 and 3 (P = 0.002 and P = 0.045, respectively). CONCLUSION: SCUBE1 can be useful in diagnosing ovarian torsion during the first 24 h, but more randomized controlled studies are necessary in order to implement it in clinical settings.

Primary Pulmonary Mucinous (Colloid) Adenocarcinoma that Arose in the Cavernomyoplasty Area in a Patient with Tuberculosis: A Rare Case Report.

Primary pulmonary mucinous (colloid) adenocarcinoma is a rare type of lung cancer. Its arising in the cavernomyoplasty area has not been reported before. We here describe a sixty-year-old man with a previous history of multidrug-resistant and surgically-treated tuberculosis who was diagnosed as primary mucinous adenocarcinoma in the cavernomyoplasty site. We discuss the relevant literature on this rare entity.

Subcutaneous Toxicity of Agmatine in Rats.

OBJECTIVES: The aim of this study was to investigate the effects of repetitive agmatine administration on sensorimotor gating in rats first but, as unexpected, ulcerative necrotic cutaneous lesions appeared, thus, the study was directed primarily to clarify these results. MATERIALS AND METHODS: In the first set of experiments, we administered agmatine (40, 80 and 160 mg/kg) and saline (control group) subcutaneously to male Wistar albino rats (n=8 for each group) for 14 consecutive days. Ulcerative necrotic cutaneous lesions appeared following the third day of agmatine administration. We decided to explore the potential toxic dermal effects of agmatine and conducted second set of experiments with two groups (n=8) to compare the effects of subcutaneous vs. intraperitoneal agmatine (80 mg/kg) injection to understand if the injection route determines the toxicity. RESULTS: Our results showed that prolonged subcutaneous but not intraperitoneal administration of agmatine leads to a delayed dermal reaction in rats. Histopathologic examination of skin samples revealed cutaneous aseptic necrosis at the injection site whereas blood tests were found to be normal. CONCLUSION: This finding is important to point out the risks of prolonged subcutaneous administration of agmatine to rats within the concept of animal welfare. In addition, the results raise questions about the possible risks of over-the-counter use of agmatine among humans although the agent is taken via oral route.

Effects of 4% Icodextrin on Experimental Spinal Epidural Fibrosis.

AIM: The aim of this experimental study was to investigate whether spinal epidural 4% glucose polymer solution is effective in the prevention of postoperative fibrosis. MATERIAL AND METHODS: Twenty eight adult Wistar albino rats were randomly divided into two equal groups, including treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. Topical treatment group received 4% icodextrin. Four weeks later, epidural fibrosis was examined in both groups histologically, biochemically and macroscopically. RESULTS: Topical use of 4% icodextrin prevented significantly epidural fibrosis following the laminectomy operation. CONCLUSION: Topical 4% icodextrin application inhibits postoperative epidural fibrosis with various mechanisms and prevents adhesions by playing barrier role between tissue surfaces through flotation. Our study is first to present evidence of experimental epidural fibrosis prevention with 4% icodextrin.

Utility of Cartilage Grafts Wrapped With Amniotic Membrane in Dorsal Nasal Augmentation.

OBJECTIVES: The success of rhinoplasty may be compromised with postoperative problems like rough and rigid nasal dorsum. Biological grafts or alloplastic materials are required to hurdle and correct nasal dorsal deformities and also irregularities. The purpose of this experimental study was to compare pure cartilage graft, cartilage graft wrapped in amniotic membrane, and diced cartilage grafts wrapped in amniotic membrane for soft tissue augmentation. METHODS: All grafts were transplanted through a subcutaneous tunnel created in the nasal dorsum of 18 rats, 6 in each group. After 3 months follow-up, the histopathological changes in all groups were evaluated by light microscopy and volumetric measurements. RESULTS: With regard to cartilage viability, cartilage wrapped in amniotic membrane had a higher success rate than pure cartilage graft. Also, a further increased success rate was found in the diced group. CONCLUSIONS: In the soft tissue augmentation after rhinoplasty surgery, especially diced cartilage wrapped in amniotic membrane keeps the graft viable and adjoined.

Effectiveness of Recombinant Human Growth Hormone for Pharyngocutaneous Fistula Closure.

OBJECTIVES: In laryngeal cancer, which comprises 25% of head and neck cancer, chemotherapy has come into prominence with the increase in organ-protective treatments. With such treatment, salvage surgery has increased following recurrence; the incidence of pharyngocutaneous fistula has also increased in both respiratory and digestive system surgery. We investigated the effects of recombinant human growth hormone on pharyngocutaneous fistula closure in Sprague-Dawley rats, based on an increase in amino acid uptake and protein synthesis for wound healing, an increase in mitogenesis, and enhancement of collagen formation by recombinant human growth hormone. METHODS: This study was experimental animal study. Forty Sprague-Dawley rats were separated into two groups, and pharyngoesophagotomy was performed. The pharyngoesophagotomy was sutured with vicryl in both groups. Rats in group 1 (control group) received no treatment, while those in group 2 were administered a subcutaneous injection of recombinant human growth hormone daily. On day 14, the pharynx, larynx, and upper oesophagus were excised and examined microscopically. RESULTS: Pharyngocutaneous fistula exhibited better closure macroscopically in the recombinant human growth hormone group. There was a significant difference in collagen formation and epithelisation in the recombinant human growth hormone group compared to the control group. CONCLUSION: This study is believed to be the first in which the effect of recombinant human growth hormone on pharyngocutaneous fistula closure was evaluated, and the findings suggest the potential of use of growth hormone for treatment of pharyngocutaneous fistula.

Comparison of the effects of chronic intra-articular administration of tenoxicam, diclofenac, and methylprednisolone in healthy rats.

OBJECTIVE: Lyophilized drug manufacturing and intra-articular (IA) applications have increased to address gastrointestinal side effects resulting from chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for degenerative joint disease. Accordingly, we histologically examined joint and stomach tissues from rats to determine and compare the effects of long-term treatment with an IA corticosteroid (methylprednisolone acetate), lyophilized NSAID (tenoxicam), and non-lyophilized NSAID (diclofenac) following application to the knee joint. METHODS: One hundred Wistar albino rats were divided into 4 groups of 25 rats: control, methylprednisolone, tenoxicam, and diclofenac. Ten IA injections were administered at 1-week intervals. Rats were sacrificed at 48 h and 1, 2, 4, and 8 weeks after the tenth injection. Histomorphologically, knee joint samples were examined for osteoarthritic changes and stomach tissue samples for gastric changes. RESULTS: Unlike methylprednisolone, diclofenac and tenoxicam caused increased fibrosis and fibroblast production; furthermore, chronic methylprednisolone use had no negative effects on the synovium or cartilage. CONCLUSION: Chronic tenoxicam and diclofenac use affects joints more negatively than chronic steroid treatment.

Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord / Efeitos neurotóxicos de levobupivacaína e fentanil sobre a medula espinhal de ratos / Efectos neurotóxicos de la levobupivacaína y el fentanilo sobre la médula espinal de ratones

BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration. .

JUSTIFICATIVA: O objetivo deste estudo foi comparar os efeitos neurotóxicos da administração por via intratecal de levobupivacaína e fentanil e suas misturas sobre a medula espinhal de ratos. MÉTODOS: O experimento compreendeu quatro grupos que receberam medicamento e um grupo controle. Os ratos foram submetidos a injeção de salina (15 µL) ou fentanil (0,0005 µg/15 mL), levobupivacaína a 0,25% (15 µL) e fentanil (0,0005 µg + levobupivacaína a 0,25%/15 µL) por via intratecal durante quatro dias. O teste de placa quente foi usado para avaliar a função neurológica após cada injeção nos minutos cinco, 30 e 60. Cinco dias após a última injeção lombar, secções da medula espinhal entre os níveis vertebrais T5 e T6 foram obtidas para análise histológica. Usamos um escore com base na avaliação subjetiva do número de neurônios eosinofílicos (neurônios vermelhos), o que significa degeneração neuronal irreversível. Esses neurônios refletem o número aproximado de neurônios em degeneração presentes nas áreas neuroanatômicas afetadas da seguinte forma: 1 = nenhum; 2 = 1-20%; 3 = 21-40%; 4 = 41-60% e 5 = 61-100% neurônios mortos. Um escore neuropatológico global foi calculado para cada rato pela soma dos escores patológicos para todas as áreas examinadas da medula espinhal. RESULTADOS: Nos resultados do TPQ, comparando o grupo controle, a latência analgésica foi estatisticamente prolongada para todos os quatro grupos.Em investimento neuropatológico, os grupos fentanil e fentanil + levobupivacaína apresentaram degeneração neuronal em contagens significativamente mais altas di que os grupos controle e salina. CONCLUSÕES: Esses resultados sugerem que fentanil e levobupivacaína, quando administrados por via intratecal em ratos, se comportam de forma semelhante à ação analgésica, mas fentanil pode ser neurotóxico para a medula espinhal. Não houve degeneração significativa com levobupivacaína, mas o grupo fentanil apresentou degeneração significativa. .

JUSTIFICACIÓN: El objetivo de este estudio fue comparar los efectos neurotóxicos de la administración por vía intratecal de la levobupivacaína y el fentanilo y su mezcla sobre la médula espinal de ratones. MÉTODOS: El experimento abarcó 4 grupos que recibieron medicamento y un grupo control. Los ratones recibieron inyección de solución salina (15 µL) o fentanilo (0,0005 µg/15µL), levobupivacaína al 0,25% (15 µL) y fentanilo (0,0005 µg + levobupivacaína al 0,25%/15 µL) por vía intratecal durante 4 días. Se empleó el test de placa caliente para evaluar la función neurológica tras cada inyección en los minutos 5, 30 y 60. Cinco días después de la última inyección lumbar, se obtuvieron las secciones de la médula espinal entre los niveles vertebrales T5 y T6 para el análisis histológico. Usamos una puntuación basándonos en la evaluación subjetiva del número de neuronas eosinofílicas (neuronas rojas), lo que significa degeneración neuronal irreversible. Esas neuronas reflejan el número aproximado de neuronas en degeneración presentes en las áreas neuroanatómicas afectadas de la siguiente forma: 1 = ninguna; 2 = 1-20%; 3 = 21-40%; 4 = 41-60% y 5 = 61-100% neuronas muertas. Para cada ratón se calculó una puntuación neuropatológica global a través de la suma de las puntuaciones patológicas de todas las áreas examinadas de la médula espinal. RESULTADOS: En los resultados del test de placa caliente, comparando el grupo control, la latencia analgésica fue estadísticamente prolongada para los 4 grupos.En la inversión neuropatológica, los grupos fentanilo y fentanilo + levobupivacaína tuvieron una degeneración neuronal en recuentos significativamente más altos que los grupos control y salina. CONCLUSIONES: Esos resultados nos sugieren que el fentanilo y la levobupivacaína, cuando se administran por vía intratecal en ratones, se comportan de forma similar a la acción analgésica, pero el fentanilo puede ser neurotóxico para la médula espinal. No hubo ...

[Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord]. / Efeitos neurotóxicos de levobupivacaína e fentanil sobre a medula espinhal de ratos.

BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15µL saline or fentanyl 0.0005µg/15µL, levobupivacaine 0.25%/15µL and fentanyl 0.0005µg+levobupivacaine 0.25%/15µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups. In neuropathologic investment, the fentanyl and fentanyl+levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.