Effect of calcium hydroxide alone or in combination with ibuprofen and ciprofloxacin on postoperative pain and periapical prostaglandin E2 level: A randomized clinical study.

AIM: The aim of the present study was to compare pure Ca(OH)2, Ca(OH)2 + ibuprofen and Ca(OH)2 + ciprofloxacin in terms of postoperative pain and prostaglandin E2 (PGE2) level in previously treated teeth with periapical lesions. MATERIALS AND METHODS: Sixty-six patients were randomly assigned into 3 groups according to the intracanal medication (Ca(OH)2, Ca(OH)2 + ibuprofen and Ca(OH)2 + ciprofloxacin). After removing gutta-percha from the root canals, the PGE2 sample collection was obtained by introducing three sterile paper points into the root canals through the root apex (2 mm). Selected intracanal medicament was placed into the root canal and the participants were told to record postoperative pain levels at 24, 48, and 72 h and on 1 week after treatment using visual analog scale (VAS). At the second appointment, the medicaments were removed and second sampling was performed using the same method. The PGE2 levels measured by enzyme-linked immunosorbent assay kits, and the data were statistically analyzed. RESULTS: All the tested Ca(OH)2 pastes were found to be significantly effective in lowering the preoperative PGE2 levels. However, intergroup analyses revealed that the Ca(OH)2 + ciprofloxacin group had the highest effectiveness in lowering PGE2 with a significant difference when compared with the pure Ca(OH)2 group. There was no statistically significant difference among the groups in terms of pre- and post-operative pain levels. CONCLUSION: The Ca(OH)2 + ciprofloxacin medication is more effective than the pure Ca(OH)2 medication in lowering periapical PGE2 level. However, addition of ibuprofen or ciprofloxacin to the Ca(OH)2 paste does not provide extra benefit in terms of post-operative pain relief.

Immune modulatory and antioxidant effects of locally administrated vitamin C in experimental periodontitis in rats.

Background: Vitamin C is an important water-soluble vitamin with antioxidant and immune-modulatory actions. The aim of this study was to investigate the effects of locally applied vitamin C on alveolar bone resorption in rats with experimental periodontitis.Methods: Twenty-one male Sprague-Dawley rats divided into three groups with seven animals in each group: (1) control, (2) experimental periodontitis and 3) experimental periodontitis-local vitamin C treatment group. After ligature was removed, 50 µL vitamin C was locally administered into the subperiosteum of the buccal gingiva of periodontitis vitamin C (PvitC) group rats for three times in intervals of 2 days. At the end of the study, the animals were scarified, and serum and gingival samples were collected for analysis of serum IL-1ß, oxidative stress index (OSI), CTX and malondialdehyde (MDA) levels and gingival MMP-8 immunostaining. Alveolar bone loss and attachment loss were determined based on measurements on histological sections obtained from rat mandibles.Results: Serum MDA and OSI levels which are related to the oxidative stress were significantly lower in the PvitC group as compared with those in the P group (p < .05). Serum CTX levels which are related to the bone resorption were significantly lower in the PvitC group as compared with those in the P group (p < .05). The numeric density of MMP-8-positive cells was significantly lower in the PvitC group compared to P group (p < .05). Alveolar bone loss and attachment loss were significantly lower in the PvitC group compared to P group (p < .05)Conclusions: The local vitamin C administration provided protection against inflammation-induced alveolar bone resorption by decreasing oxidative stress and inflammation-induced tissue breakdown vitamin C may be a therapeutic agent that can be used in periodontitis treatment.

Effects of Autogenous Tooth Bone Graft and Platelet-Rich Fibrin in Peri-Implant Defects: An Experimental Study in an Animal Model.

The aim of this study was to evaluate the effect of autogenous tooth bone graft (ATBG) combined with platelet-rich fibrin (PRF) on bone healing in rabbit peri-implant osseous defects. Eighteen New Zealand rabbits were divided into 3 groups. Bone defects were prepared in each rabbit, and then an implant cavity was created in the defects. Dental implants were placed, and the peri-implant bone defects were treated with the following 3 methods: no graft material was applied in the control group, bone defects were treated with ATBG in the ATBG group, and bone defects were treated with ATBG combined with PRF in the ATBG+PRF group. After 28 days, the rabbits were sacrificed, and the dental implants with surrounding bone were removed. New bone formation and the percentage of bone-to-implant contact (BIC) were determined with histomorphometric evaluations. New bone formation was significantly higher in the ATBG+PRF group than the control and ATBG groups (P < .05). In addition, BIC was significantly higher in the ATBG+PRF group than in the control and ATBG groups (P < .05). The combination of ATBG with PRF contributed to bone healing in rabbits with peri-implant bone defects.

N-glycan profiling of papillary thyroid carcinoma tissues by MALDI-TOF-MS.

Papillary thyroid carcinoma (PTC) is a type of thyroid cancer whose incidence rate has increased recently all over the world. Glycosylation is a crucial post-translational modification (PTM) for the regulation of thyroid hormone synthesis in thyroid glands. However, our knowledge regarding the N-glycosylation change in PTC is limited. To the best of our knowledge, this is the first study to profile glycans in PTC tissues by mass spectrometry. Herein, we have analyzed the N-glycans of formalin-fixed paraffin-embedded (FFPE) tissues of patients diagnosed with PTC in a matched case-control study. Using MALDI-TOF(/TOF)-MS, 35 enzymatically released N-glycan compositions were characterized. The statistical analyses showed significant differences including six N-glycan compositions (p < 0.001) between patients and controls. It was determined that four of them (H5N4E1, H5N4F1E1, H5N4F1L1E1 and H5N4F1E2, E: α2,6-linked sialic acid; L: α2,3-linked sialic acid) were up-regulated in PTC tissues, whereas two N-glycans (H8N2 and H9N2) found to be down-regulated. Besides, a significant difference was found in six different N-glycan traits. Variants of PTC (follicular, classical, hurtle cell) were also studied to define specific N-glycan change for each variant.

Determination of olanzapine for therapeutic drug monitoring in schizophrenia patients by LC/MS method.

Olanzapine is an atypical antipsychotic drug from the thienobenzodiazepine family which displays efficacy in patients with schizophrenia and related psychoses. A novel LC/MS method was developed and validated for determination of olanzapine in schizophrenia patients' plasma. A liquid-liquid extraction procedure was carried out using 5 mL diethyl ether-diisopropyl ether mixture (1:1, v/v). Average recovery of the extraction procedure was 94.8%. Chromatographic separation was performed on reversed-phase C18 column (250 × 2.0 mm, 5 µm) using mixture of deionized water (trifluoro acetic acid 0.1%)-acetonitrile (20:80, v/v) as mobile phase at a flow rate of 1 mL/min. Irbesartan was used as internal standart and total run time was 2.5 min. Mass spectrometric analysis were carried out in selective-ion montoring mode, and detected olanzapine at m/z 313.1 and IS at m/z 429.4 in all forms of the ions. The calibration curve of olanzapine was linear in the range 2-300 ng/mL (r2 > 0.9993). The interday and intraday precisions (RSD) were <7.55%, and accuracy was >7.59% (n = 6). The proposed study was successfully validated with respect to the US Food and Drug Administration guidelines.

A novel, rapid and sensitive UPLC-MS/MS method for the determination of macitentan in patients with pulmonary arterial hypertension.

Macitentan is an endothelin receptor antagonist commonly used in the treatment of pulmonary arterial hypertension (PAH). A novel, rapid, simple and sensitive UPLC-MS/MS method was developed and validated for pharmacokinetic study and the determination of macitentan in PAH patients. Macitentan and bosentan, which are used as internal standards, were detected using atmospheric pressure chemical ionization in positive ion and multiple reaction monitoring mode by monitoring the mass transitions m/z 589.1 → 203.3 and 552.6 → 311.5, respectively. Chromatographic separation was performed on a reverse-phase C18 column (5 µm, 4.6 × 150 mm) with an isocratic mobile phase, which consisted of water containing 0.2% acetic acid-acetonitrile (90:10, v/v) at a flow rate of 1 mL/min. Retention times were 1.97 and 1.72 min for macitentan and IS, respectively. The calibration curve with high correlation coefficient (0.9996) was linear in the range 1-500 ng/mL. The lower limit of quantitation and average recovery values were determined as 1 ng/mL and 89.8%, respectively. This method is the first UPLC-MS/MS method developed and validated for the determination of macitentan from human plasma. The developed analytical method was fully validated for linearity, selectivity, specificity, accuracy, precision, sensitivity, stability, matrix effect and recovery according to US Food and Drug Administration guidelines. The developed method was applied successfully for pharmacokinetic study and the determination of macitentan in PAH patients.

Effect of intracanal medicaments on matrix metalloproteinase-9 and vasoactive intestinal peptide secretion in periapical lesions of re-treated canals: a randomized controlled clinical study.

OBJECTIVE: The aim of this study was to evaluate the effect of calcium hydroxide (Ca[OH]2) and chlorhexidine (CHX) gel on matrix metalloproteinase-9 (MMP-9) and vasoactive intestinal peptide (VIP) secretion in periapical lesions. MATERIALS AND METHODS: A total of 60 patients were randomly divided into two groups that were to receive different medications. Pre-and post-treatment samples were collected from the interstitial fluid of periapical lesions using sterile paper points. VIP and MMP-9 levels were measured by enzyme-linked immunosorbent assay kits, and the data were statistically analyzed. RESULTS: Gender and smoking habits had no effect on the pre- and post-treatment VIP and MMPs levels. Intragroup analyses revealed that in the Ca(OH)2 group, the post-treatment VIP level was found to be significantly higher than the pre-treatment VIP level. In the CHX group, the post-treatment MMP-9 level was significantly higher than the pre-treatment MMP-9 level. CONCLUSION: According to the results of the present study, the type of the medication affected the amount of periapical VIP and MMP-9 secretion. CLINICAL RELEVANCE: VIP is a neuropeptide that promotes new bone formation. Thus, intracanal Ca(OH)2 medication may accelerate the repair process of bone tissue.

Simple high-performance liquid chromatography method for formaldehyde determination in human tissue through derivatization with 2,4-dinitrophenylhydrazine.

A simple high-performance liquid chromatography method has been developed for the determination of formaldehyde in human tissue. FA Formaldehyde was derivatized with 2,4-dinitrophenylhydrazine. It was extracted from human tissue with ethyl acetate by liquid-liquid extraction and analyzed by high-performance liquid chromatography. The calibration curve was linear in the concentration range of 5.0-200 µg/mL. Intra- and interday precision values for formaldehyde in tissue were <6.9%, and accuracy (relative error) was better than 6.5%. The extraction recoveries of formaldehyde from human tissue were between 88 and 98%. The limits of detection and quantification of formaldehyde were 1.5 and 5.0 µg/mL, respectively. Also, this assay was applied to liver samples taken from a biopsy material.

Anti-oxidant and anti-inflammatory effects of apigenin in a rat model of sepsis: an immunological, biochemical, and histopathological study.

OBJECTIVE: We hypothesize that apigenin may inhibit some cellular process of sepsis-induced spleen injury and simultaneously improve inflammation and oxidative stress. Therefore, the aim of this study was to investigate the potential protective effects of apigenin in a polymicrobial sepsis rat model of by cecal ligation and puncture. MATERIALS AND METHODS: 64 female Wistar albino rats were divided into 8 groups. The pro-inflammatory (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta) and anti-inflammatory (tumor growth factor-beta and interleukin-10) cytokine levels were measured by enzyme-linked immunosorbent assay. CD3, CD68, and nuclear factor kappa B (NF-κB) positivity rates were detected by immunohistochemical methods. Oxidative stress parameters were measured by tissue biochemistry. RESULTS: Sepsis caused a significant increase in TNF-alpha, IL-1-beta, IL-6, and TGF-beta levels whereas it reduced IL-10 level. Additionally, it led to an increase in CD3, CD68, and NF-κB positivity rates as well as oxidative stress parameters levels. However, apigenin inhibited the inflammation process, increased the IL-10 level and normalized the oxidative stress parameters. DISCUSSION AND CONCLUSION: Pretreatment with apigenin results in a significant reduction in the amount of inflammatory cells. The beneficial effect of apigenin on spleen injury also involved inhibition of NF-κB pathway, suppression of proinflammatory cytokines, and induction of anti-inflammatory cytokine production. Additionally, it led to a decrease in oxidative stress in spleen tissue. Taking everything into account, apigenin may be an alternative therapeutic option for prevention of sepsis-induced organ.

Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer.

BACKGROUND: The primary objective of the study was to evaluate the association between the minimum apparent diffusion coefficient (ADCmin) and Ki-67, an index for cellular proliferation, in non-small cell lung cancers. Also, we aimed to assess whether ADCmin values differ between tumour subtypes and tissue sampling method. METHODS: The patients who had diffusion weighted magnetic resonance imaging (DW-MRI) were enrolled retrospectively. The correlation between ADCmin and the Ki-67 index was evaluated. RESULTS: Ninety three patients, with a mean age 65 ± 11 years, with histopathologically proven adenocarcinoma and squamous cell carcinoma of the lungs and had technically successful DW-MRI were included in the study. The numbers of tumour subtypes were 47 for adenocarcinoma and 46 for squamous cell carcinoma. There was a good negative correlation between ADCmin values and the Ki-67 proliferation index (r = -0.837, p < 0.001). The mean ADCmin value was higher and the mean Ki-67 index was lower in adenocarcinomas compared to squamous cell carcinoma (p < 0.0001). There was no statistical difference between tissue sampling methods. CONCLUSIONS: Because ADCmin shows a good but negative correlation with Ki-67 index, it provides an opportunity to evaluate tumours and their aggressiveness and may be helpful in the differentiation of subtypes non-invasively.

Acute effect of moderate and high-intensity interval exercises on asprosin and BDNF levels in inactive normal weight and obese individuals.

This study aimed to examine the acute effects of moderate-intensity aerobic and high-intensity interval exercise protocols on Asprosin and Brain-Derived Neurotrophic Factor (BDNF) levels in inactive normal weight and obese individuals. A total of 20 male individuals aged 18-65 years, ten normal weight (NW) (Body Mass Index (BMI): 18.5-24.99 kg/m2) and 10 obese (Ob) (BMI: 24.99-35.00 kg/m2) participated in this study, voluntarily. Moderate aerobic exercise (AE) (main circuit 30 min, between 40 and 59% of Heart Rate Reserve: HRR) and High-Intensity Interval exercise (HIIE) running protocols (main circuit 20 min, between 75 and 90% of the HRR for 1 min*10 times, and 1-min active rest at 30% of the HRR) was applied to the volunteer participants in the morning hours (08.00-10.00 a.m.), following the night fasting (at least 8-10 h) for at least 3 days between each other. Blood samples were collected from the participants before and immediately after each exercise protocol, and serum asprosin and BDNF hormone levels were determined by Enzyme-Linked Immunosorbent Assay" method. Basal serum asprosin was found to be significantly higher in the Ob group compared to the NW group (p < .001), while the basal serum BDNF hormone was found to be lower (p < 0.05). It was observed that the serum asprosin level of both groups decreased significantly after both AE and HIIE protocols (p < 0.05). In addition, there was a significantly higher decrease in serum asprosin level in the Ob group compared to the NW group after HIIE protocol. For the Ob group, serum BDNF level increased considerably after HIIE protocol compared to AE protocol (p < 0.05). Serum asprosin was found to be higher in the Ob group, while the serum BDNF was found to be lower. In addition, the acute exercises of different intensity significantly affected hormones that regulate appetite metabolism. In particular, it was observed that the HIIE protocol had a greater effect on the regulation of appetite (hunger-satiety) in the Ob group. This result can be taken into account when planning training programs for these individuals.

Determination and pharmacokinetic study of riociguat by UPLC-MS/MS in human plasma.

Pulmonary hypertension (PH) is frequent in the general population and is linked to an increased risk of death. Riociguat is a kind of endothelin receptor antagonist that is often used to treat PH. For pharmacokinetic studies and the determination of riociguat in PH patients, a new, quick, easy, and sensitive UPLC-MS/MS approach was designed and validated. Riociguat and irbesartan (IS) were detected using ESI in positive ion and multiple reaction monitoring mode, respectively, by monitoring the mass transitions m/z 423.0 â†’ 391.0 and 429.1 â†’ 206.9. A reverse-phase C18 column (5 µm, 4.6 × 150 mm) was used with an isocratic mobile phase of water containing 0.1 % formic acid-acetonitrile (25:75, v/v) at a flow rate of 1 ml/min for chromatographic separation. In the range of 5-400 ng/ml, the calibration curve was linear and had a good correlation coefficient (0.9972). This is the first UPLC-MS/MS technique that has been developed and validated for determining riociguat from human plasma. The developed analytical method was extensively validated for linearity, selectivity, specificity, accuracy, precision, sensitivity, stability, matrix effect and recovery, according to FDA criteria. The devised approach was successfully used for a pharmacokinetic research and riociguat determination in PH patients.

Differential N-glycosylation profiling of formalin-fixed paraffin-embedded (FFPE) invasive ductal carcinoma tissues using MALDI-TOF-MS.

Invasive ductal carcinoma (IDC) is the most common type of breast cancer. As dynamic changes of the glycome are closely associated with complex diseases, they have become a focal point of cancer research involving predictive and prognostic markers. Formalin-fixed paraffin-embedded (FFPE) clinical specimens are representative of the tumor environment and are thus utilized in studies on cancer related research and biomarker discovery. Further studies on differential N-glycosylation profiling of IDC cancer tissues are necessary in order to understand the biological role of glycans in cancer and to evaluate their predictive ability. In this study, matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS)-based analyses were conducted for determining differential N-glycosylation patterns of IDC. Two different derivatization methods, namely, 2-aminobenzoic acid (2-AA) labeling and linkage-specific sialic acid esterification, were used for the analysis of N-glycans. Forty-seven 2-AA labeled and fifty ethyl esterified N-glycans were identified by MALDI-MS. In statistical analyses conducted for 2-AA-labeled N-glycans, the relative amounts of 32 N-glycans and prevalence of 15 N-glycan traits showed significant (p < 0.05) differences between cancer and normal tissues; and in such analyses for the ethyl-esterified N-glycans, the relative amounts of 27 N-glycans and prevalence of 17 N-glycan traits showed significant (p < 0.05) differences between them. It was found that mainly high mannose N-glycans, including H5N2, H6N2, and H7N2, and two fucosylated compositions (H3N3F1 and H5N5F1) showed strong discrimination between IDC and controls. In addition, compared with the controls, high mannose N-glycans were observed to be up-regulated in IDC whereas bisecting N-glycans were down-regulated.

A Sensitive UPLC-MS/MS Method for the Determination of Flurbiprofen in Rat Plasma: Application to Real Sample.

For the quantification of flurbiprofen in rat plasma, a simple UPLC-MS/MS method with high sensitivity and short retention time for flurbiprofen was developed and validated using specific parameters. Etodolac was used as internal standard. The transitions (precursor to the product) of flurbiprofen and internal standard were obtained using the electrospray ionization in the negative ion multiple reaction monitoring mode, 243.2 â†’ 199.2, 286.2 â†’ 212.1, respectively. For chromatographic separation, C18 column was used for the stationary phase and gradient elution was used for the mobile phase. This mobile phase consisted of a methanol (A) and a 5 mM ammonium formate solution (B), which varied at a flow rate of 0.4 mL/min. For flurbiprofen, LLOQ was determined as 5 ng/mL. Quantification of flurbiprofen in the rat plasma with a linear calibration curve of 5-5000 ng/mL (r > 0.9991 for plasma) is possible with a retention time of 1.89 min. The total analysis time of the method was 3 min. The proposed method was validated. The intraday and inter-day precision (RSD%) and accuracy (RE%) were within 10% in all cases for flurbiprofen. The stability of flurbiprofen was evaluated under conditions such as short-term, long-term, autosampler and freeze/thaw. After method validation, flurbiprofen was succesfully quantified in real rat plasma samples.

The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats.

OBJECTIVES: Sepsis model was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or concomitantly, on the response of the activity of the nuclear factor kappa B (NF-kappaB) and the oxidative response in kidney. SUBJECTS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Diabetes was induced in female rats using administration of alloxan. The rats were divided into five groups: sham control (group 1), ovariectomy (group 2), ovariectomy + sepsis (group 3), ovariectomy + diabetes (group 4), and ovariectomy + diabetic + sepsis (group 5). RESULTS: In kidney tissues, the levels of lipid peroxidation (LPO) and glutathione (GSH) and the activity of catalase (CAT) were higher for groups 3, 4, 5 than the control groups. Superoxide dismutase (SOD) activity was lower for groups 3, 4, 5 than the control groups. We determined that CLP produced injury evident in the kidneys of rats when compared to the control group, whereas the severity of the injury was higher in the diabetes + ovariectomy + CLP group when compared to the CLP group. In immunohistochemical staining, we determined that CLP operation increased NF-kappaB activation. In the ovariectomized, septic, and diabetic group, NF-kappaB activation was significantly higher than other groups. CONCLUSIONS: Hyperglycemia and ovariectomy severely increased NF-kappaB activation and oxidant levels with the stages of our sepsis model. Ovariectomy resulted in general changes in metabolism, which are seen in the kidney with diabetes under sepsis conditions.

Effects of vitamin C local application on ligature-induced periodontitis in diabetic rats.

OBJECTIVE: This study evaluated the effects of local vitamin C treatment on tissue advanced glycation end products (AGE), interleukin (IL)-6, 8-hydroxy-2-deoxyguanosine (8-OHdG), and matrix metalloproteinases (MMP)-8 in tissues; serum C-terminal telopeptide fragments (CTX); and alveolar bone loss (ABL) in rats. METHODOLOGY: 35 male Sprague Dawley rats were divided equally into five groups: 1) control (C), 2) experimental periodontitis (P), 3) experimental diabetes (D), 4) experimental diabetes and experimental periodontitis (D + P), and 5) experimental diabetes-experimental periodontitis-locally applied vitamin C (D + P + LvitC). Diabetes was induced in rats with alloxan monohydrate, after which periodontitis was induced by ligature placement in the right mandibular first molar teeth for 11 days. In the treatment group, vitamin C was administered locally three times with two-days interval after ligature removal. The animals were sacrificed, and the samples were analyzed histometrically and immunohistochemically. RESULTS: CTX, 8-OHdG, and AGE values significantly decreased in the treatment group compared to the D + P group. IL-6 and MMP-8 values decreased in the treatment group compared to the D + P group, but this is not significant. ABL was significantly reduced by the local delivery of vitamin C. CONCLUSION: This study reveals that vitamin C treatment may be beneficial to reduce serum CTX and gingival MMP-8 levels, oxidative stress, inflammation, and AGE accumulation in periodontal tissue. Vitamin C may be an immunomodulator and antioxidant locally applied in the treatment of periodontitis to reduce the adverse effects of diabetes in periodontal tissues.

A biochemical and immunohistochemical study of the effects of caffeic acid phenethyl ester on alveolar bone loss and oxidative stress in diabetic rats with experimental periodontitis.

Caffeic acid phenethyl ester (CAPE) is used as a therapeutic agent to prevent bone loss. We determined the effects of systemically administered CAPE on alveolar bone loss and oxidative stress in diabetic rats with experimental periodontitis. Forty male rats were divided into four equal groups: control, experimental periodontitis (EP), EP-diabetes mellitus (EP-DM) and EP-DM-CAPE. DM was induced by streptozotocin, then lipopolysaccharide was injected to induce periodontitis. CAPE was administered to the EP-DM-CAPE group daily for 15 days. Then, serum samples were taken and the rats were sacrificed for histological analyses. Serum interleukin (IL-1ß) and oxidative stress also were evaluated. Alveolar bone loss was assessed histomorphometrically. Alveolar bone loss and IL-1ß levels were significantly less in the EP-DM-CAPE and EP groups compared to the EP-DM group. Oxidative stress was significantly less in the EP-DM-CAPE group compared to the EP and EP-DM groups. Receptor activator of nuclear factor kappa-B ligand (RANKL) levels were significantly higher in the EP-DM group compared to the disease groups. CAPE significantly reduced RANKL levels in the EP-DM-CAPE group compared to the EP-DM group. We found that CAPE treatment significantly inhibited DM induced oxidative stress and RANKL induced osteoclastogenesis and alveolar bone loss in diabetic rats with periodontitis.

Investigation of the efficacy of daidzein in experimental knee osteoarthritis-induced with monosodium iodoacetate in rats.

BACKGROUND: Osteoarthritis (OA) is a degenerative chronic illness that most frequently occurs in the knee joint. Daidzein (DZ) an isoflavone has anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effectiveness of DZ as a treatment for experimental knee OA (KOA) in rats. METHOD: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. Thereafter, 49 Wistar albino male rats (250-300 g, 12-16 weeks old) were randomly divided into 7 groups: C (healthy control); DC (KOA + saline); hyaluronic acid (HA); HA+ intraarticular (ia) DZ; oral (po) DZ; ia DZ; HA + po DZ groups. DZ and/or HA were administered intraarticularly to the rats as 50 µL on days 1, 7, 14, and 21. Alternatively, the DZ was administered orally as 0.5 mL twice daily for 21 days. After the treatment, rats were sacrificed by decapitation under general anesthesia. Serum samples were analyzed to determine the total oxidant status (TOS) and total antioxidant status (TAS) and the levels of TNF-α, IL-1ß, MMP-13, and DZ. Knee joint samples underwent histopathological examination, and TNF-α, IL-1ß, NOS2, and MMP-13 were analyzed with immunohistochemical methods. RESULTS: HA, DZ, and DZ + HA effectively reduced the levels of TNF-α, IL-1ß, and MMP-13 in the serum of the DC group (p < 0.001). In groups that received HA, DZ, or DZ + HA, the serum TAS increased compared with the DC group (p < 0.05). When the DZ + HA combination was used, a more pronounced reduction in the levels of TNFα, NOS2, IL-1ß, and MMP-13 was observed in knee joints. In addition, the cracks on the cartilage surface and fibrillation were completely improved in the groups that received HA, DZ, or DZ + HA compared with the DC group. CONCLUSION: DZ had anti-inflammatory and antioxidant effects in a rat OA model. Therefore, DZ, as monotherapy or especially in combination with HA, may be a promising and beneficial therapy for OA. Key Points •DZ has been shown to reduce TNF-α, IL-1ß, and MMP-13 both in serum and in tissue samples taken from the knee-joints. •The cracks on the cartilage surface and fibrillation in KOA were completely improved by using DZ and DZ + HA combination. •DZ may be useful to eliminate/reduce/ameliorate inflammation and oxidative damage in the pathogenesis of KOA. •DZ, alone or in combination with HA, may be a promising natural compound with beneficial effects in the treatment of KOA.

Effect of Calcium Hydroxide Alone or in Combination with Ibuprofen and Ciprofloxacin on Nuclear Factor Kappa B Ligand and Osteoprotegerin Level in Periapical Lesions: A Randomized Controlled Clinical Study.

INTRODUCTION: The aim of the present study was to evaluate the effects of calcium hydroxide (Ca[OH]2), Ca(OH)2 + ibuprofen, and Ca(OH)2 + ciprofloxacin in terms of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) levels in asymptomatic periapical lesions. METHODS: Sixty-six patients were randomly divided into 3 groups using a Web program according to the medication selected: Ca(OH)2, Ca(OH)2 + ibuprofen, and Ca(OH)2 + ciprofloxacin. After removing gutta-percha from the root canals, the RANKL and OPG samples were taken from the interstitial fluid of the apical tissues using 3 paper points. At the second appointment, medicaments were removed, and second sampling was performed using the same method. The RANKL and OPG levels were measured by the enzyme-linked immunosorbent assay, and the RANKL/OPG ratio was calculated. RESULTS: According to the intragroup analysis, there were no statistically significant differences between the preoperative and postoperative levels of the RANKL/OPG ratio in any of the groups. Intergroup analyses showed that there were no statistically significant differences among the Ca(OH)2, Ca(OH)2 + ibuprofen, Ca(OH)2 + ciprofloxacin groups in terms of the percentage change in RANKL/OPG levels before and after treatment. CONCLUSIONS: Within the limitations of the present study, it can be concluded that addition of ibuprofen or ciprofloxacin to Ca(OH)2 paste does not provide any extra benefit in terms of lowering RANKL and OPG levels.

Therapeutic effects of caffeic acid phenethyl ester on alveolar bone loss in rats with endotoxin-induced periodontitis.

BACKGROUND/PURPOSE: Caffeic acid phenethyl ester (CAPE) is an antioxidant which is decreases the bone resorption and enhances the bone healing. The aim of this study was to investigate the effects of administering systemic CAPE on alveolar bone loss in rats with experimental periodontitis. MATERIALS AND METHODS: Thirty male Sprague Dawley rats were divided into three groups: control, endotoxin-induced periodontitis (EP), and EP treated with CAPE (EP-CAPE). Endotoxin was injected into the gingiva of test rats on days 1, 3, and 5, whereas saline was injected into the control rats. The EP-CAPE group received 10 mmol/kg/day CAPE intraperitoneally for 28 consecutive days. Saline was given in the control and EP groups in the same manner. At the end of the study, intracardiac blood samples were obtained, and the rats were sacrificed. Alveolar bone loss was analyzed with histometric measurements. The oxidative stress index (OSI) was used to evaluate the oxidative stress. The receptor activator of the nuclear factor kappa B ligand (RANKL) level was analyzed stereologically. RESULTS: CAPE administration significantly decreased the serum OSI and interleukin-1ß levels. Alveolar bone loss was statistically higher in the EP group compared with the EP-CAPE group (P < 0.05). Immunohistochemical analyses of the RANKL were significantly lower in the EP-CAPE group than in the EP group (P < 0.05). CONCLUSION: This experimental study revealed that CAPE administration significantly prevented alveolar bone loss and stimulated periodontal tissue healing.