Evaluation of RANK, RANKL and OPG Levels in Gingival Crevicular Fluid After Surgically Assisted Rapid Maxillary Expansion.

Objectives: Maxillary transverse deficiency is one of the most common skeletal problems. Patients who have completed skeletal maturity, maxillary transverse deficiency can be treated with surgically assisted rapid maxillary expansion. Orthodontic forces affect the cells in the periodontium to form biologically active substances responsible for remodeling. These substances can be detected in the content of the gingival crevicular fluid (GCF). This study aimed to investigate changes in RANK, RANKL and OPG in the gingival crevicular fluid after surgically assisted rapid maxillary expansion. Materials and Methods: A total of 16 patients with a maxillary transverse deficiency were included in the study. Gingival crevicular fluid samples were collected from the mesiobuccal regions of the upper left central, lateral incisors, first and second premolar teeth before the operation (T0), after activation period (T1) and at the 4th month (T2) after the retention period. Changes in RANK, RANKL and OPG levels of gingival crevicular fluid samples were investigated. Results: RANK and RANKL amounts were found to be significantly increased in the first and second premolar teeth after expansion, and OPG amounts were significantly decreased in central incisor and first premolar teeth. RANKL was also significantly higher in the first premolar teeth than in the second premolar after retention. Conclusion: According to the results of the study, RANK, RANKL and OPG levels are changed in the gingival crevicular fluid after surgically assisted rapid maxillary expansion. Clinical Relevance: Using tooth-borne appliances for SARME operations alters the biological content of the GCF. For avoiding these interactions, bone-borne appliances may be used for SARME procedures.

Hydroxychloroquine Attenuates Acute Inflammation (LPS)-Induced Apoptosis via Inhibiting TRPV1 Channel/ROS Signaling Pathways in Human Monocytes.

Acute inflammation (INF) and apoptosis are induced in monocytes by the generation of several factors, including the products of cytosolic oxygen free radicals (cROS) and the excessive influx of Ca2+ via the stimulation of TRPV1. These are main factors in the etiology of monocyte activation-induced inflammatory and neurodegenerative diseases. Importantly, the protective action of hydroxychloroquine (HCQ) treatment via the inhibition of TRPV1 on the levels of inflammatory factors, cROS, and apoptosis in acute INF (lipopolysaccharide, LPS)-exposed neuronal cells was recently reported. However, the relationships between acute INF via TRPV1 activation and HCQ in monocytes have not been fully clarified yet. The cell membrane of U937 human monocytes contains natural TRPV1. In the study plan, we used U937 cells in four main groups, namely control, HCQ (60 µM for 48 h), INF (1 µg/mL LPS for 16 h), and HCQ + INF. The current data indicate that LPS-induced acute INF caused the upregulation of excessive cytosolic Ca2+ accumulation via the stimulation of TRPV1 in the cells. The treatment of INF additionally upregulated the levels of apoptosis and cytokines (IL6, IL1ß, and TNFα), due to upregulated cROS and lipid peroxidation levels as well as upregulated generation of caspase -3 (CAS3) and -9 (CAS9) but a decrease in glutathione and glutathione peroxidase. The expression levels of TRPV1, Bax, CAS3, and CAS9 were also upregulated by the treatment of LPS. However, treatment with HCQ and TRPV1 blocker (capsazepine) modulated the levels of cytokines, caspases, cROS, Ca2+ influx, and apoptosis through the modulation of TRPV1 in the U937 that were stimulated with LPS. In summary, the present data suggest TRPV1 activation through the acute INF (LPS)-induced inflammatory, oxidant, and apoptotic adverse actions in monocyte cells, whereas HCQ prevented adverse actions via the modulation of TRPV1. The results may be significant in the modulation of monocyte activation-caused inflammatory and neurodegenerative diseases.

Diagnostic and early prognostic value of serum CRP and LDH levels in patients with possible COVID-19 at the first admission.

INTRODUCTION: COVID-19 is the infection caused by the new coronavirus. Specific treatment for COVID-19 has not been established, yet. It is important to determine the disease severity of the patients at the first admission. Therefore, the exploration of biomarkers is deemed necessary. We aimed to assess the diagnostic and early prognostic value of CRP and LDH levels in possible COVID-19 patients presenting with a severe clinical picture. METHODOLOGY: We evaluated the correlations of relevant routine laboratory test results with disease severity in COVID-19 patients admitted to our infectious diseases clinic. Patients were divided into severe and non-severe disease groups based on clinical findings, oxygen saturation levels in the arterial blood, biochemical test results, and radiological findings. Differences in the findings between the two disease severity groups were examined to determine potential biomarkers. RESULTS: Median age and the CRP and LDH levels in the severe disease group were statistically significantly higher compared to the nonsevere group (p < 0.0001). No other parameters statistically significant differences have been observed between the two groups (P > 0.05). CONCLUSIONS: CRP and LDH levels were positively correlated with lung lesions in early-stage COVID-19, potentially reflecting disease severity. Because LDH and CRP levels can potentially reflect the pulmonary function, they can be potential predictors of COVID-19- related respiratory failure. For avoiding poor prognosis; LDH and CRP should be considered as potential predictors for identifying the need for thoracic CT scans, close monitoring of pulmonary function, and aggressive supportive therapy early in the course of COVID-19.

Diagnostic values of HNP 1-3 and procalcitonin levels in synovial fluid aspirates in the differential diagnosis between septic arthritis and noninfectious arthritis.

INTRODUCTION: Although early diagnosis of septic arthritis may reduce mortality rates, and limit unnecessary surgical interventions, clinical parameters alone are not adequate for making the diagnosis of septic arthritis. Therefore, relevant laboratory parameters are used to enhance diagnostic sensitivity. The aim of our study was to assist in making the diagnosis of septic arthritis, and prevent delays in the diagnosis. For this purpose; we aimed to determine the diagnostic values of human neutrophil peptides 1-3 (HNP 1-3) and procalcitonin (PCT) in synovial fluids of patients with arthritis. By comparing the HNP 1-3 and procalcitonin levels, as well as CRP, in synovial fluid aspirates, we evaluated the significance of these data in the differential diagnosis of septic arthritis from noninfectious arthritis. METHODS: A total of 67 adults consisting of 37 septic arthritis and 30 noninfectious arthritis patients were included in our study. As bioindicators; levels of HNP 1-3, PCT, synovial and serum CRP levels were found to have significant ROC areas in discriminating septic arthritis patients from noninfectious arthritis patients. RESULTS: As a result, synovial fluid HNP 1-3 levels were significantly higher in septic arthritis patients compared to noninfectious arthritis patients (p < 0.001). The sensitivity, specificity, and accuracy of HNP 1-3 levels in the diagnosis of septic and noninfectious arthritis were found as 86%, 87%, and 87%, respectively (AUC of the ROC curve = 0.828). CONCLUSIONS: It was decided that the level of HNP 1-3 in the synovial fluid can be used as an alternative indicator in the diagnosis of septic arthritis.

Interferon Gamma-Mediated Oxidative Stress Induces Apoptosis, Neuroinflammation, Zinc Ion Influx, and TRPM2 Channel Activation in Neuronal Cell Line: Modulator Role of Curcumin.

Host defenses in the brain are modulated by the activation of several factors such as oxygen free radical species (ROS), Ca2+ influx, and TRPM2 activation, and they are well-known adverse factors in neurotoxicity and neurodegenerative diseases. Importantly, recent data indicated a protective action of curcumin (CRC) via inhibition of TRPM2 on the inflammation factors, ROS, and apoptosis in hypoxia-induced SH-SY5Y neuronal cells. However, the relationship between interferon gamma (IFNg) exposure and TRPM2 activation in the SH-SY5Y cells are not fully identified. The SH-SY5Y cells as a neuronal cell line model were used in several neuroinflammation studies. Hence, we used the SH-SY5Y cells in the current study, and they were divided into four main groups as control, CRC, IFNg, and IFNg+CRC. The data presented here indicate that IFNg induced excessive Ca2+ influx via activation of TRPM2. The IFNg treatment further increased cell death, cell debris amount, apoptosis, and cytokine generations (IL-1ß, IL-6, and TNF-α) which were due to increased cytosolic and mitochondrial ROS generations as well as increased activations of caspase-3 and caspase-9. The expression levels of TRPM2, PARP-1, Bax, caspase-3, and caspase-9 were increased in the cells by the IFNg treatment. However, CRC treatment reduced the increase of expression levels, cytokine generations, caspase activations, ROS release, Ca2+ influx, cell death, and apoptosis levels via inhibition of TRPM2 in the SH-SY5Y cells that were treated with IFNg. Moreover, the treatment of TRPM2 blockers (ACA and 2-APB) potentiated the modulator effects of CRC. In conclusion, these results suggest that neuroinflammation via IFNg lead to the TRPM2 activation in the SH-SY5Y cells, whereas CRC prevents IFNg-mediated TRPM2 activation, cell death, and cytokine generations.

Prevalence of Rotavirus-Associated Acute Gastroenteritis Cases in Early Childhood in Turkey: Meta-Analysis.

BACKGROUND: Rotavirus is globally the most common viral pathogen in childhood gastroenteritis. This study aimed to estimate the number of Turkish children suffering from early-childhood gastroenteritis by rotavirus by performing a meta-analysis. METHODS: Meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Following the guidelines, primary studies were found reporting the prevalence of rotavirus gastroenteritis in Turkey. We performed a computerized search of published studies in national and international databases from 1990 to 2018. We selected 38 out of 721 studies for our study. Meta-analysis was carried out using R statistical software. The Cochrane Q statistic was calculated to assess the heterogeneity of the study results. Heterogeneity among studies was evaluated using the I2 statistic. Effect-size estimate was reported with 95% confidence interval. RESULTS: On the basis of 38 selected articles, 80,113 children up to five years of age were diagnosed with symptoms of acute gastroenteritis, of whom the stool samples of 13,651 children were positive for rotavirus. The pooled prevalence of rotavirus was 19% in children younger than five years of age with acute gastroenteritis. In terms of seasonal prevalence, the highest prevalence rate was found in winter. CONCLUSION: This study supports the major prevalence of early-childhood gastroenteritis by rotavirus among Turkish children. Therefore, the decision to adopt immunization programs to prevent rotavirus infection might be helpful in Turkey.

Spinal stenosis caused by epidural and paraspinal abscess due to brucella Infection.

Human brucellosis is a common zoonotic infectious disease in the world. Spinal epidural abscess development in brucellosis is a rare but serious complication. We aimed to discuss the clinical, radiological and serological findings of the spinal stenosis caused by epidural and paraspinal abscess due to brucella infection. Treatment of the abscess usually consists of surgical drainage, decompression and antibiotherapy. In our case, since the Brucellar spinal epidural abscess was diagnosed in the early period, it was improved with medical treatment without any surgical intervention. In the early diagnosis of the disease, serology and culture as well as magnetic resonance imaging are extremely important..

Clostridium botulinum neurotoxin A induces apoptosis and mitochondrial oxidative stress via activation of TRPM2 channel signaling pathway in neuroblastoma and glioblastoma tumor cells.

BACKGROUND: The Clostridium botulinum neurotoxin A (BTX) is a polypeptide produced by the bacterium Clostridium botulinum. In addition to the therapeutic actions of BTX against pain and neuromuscular disorders, it is acted as anticancerogenic effect through excessive mitochondria reactive oxygen species (ROS) production, apoptosis, and caspase activations. The TRPM2 cation channel is activated by ROS and ADP-ribose and it is inhibited by 2-aminoethyl diphenylborinate (2-APB) and N-(p-amylcinnamoyl) anthranilic acid (ACA). The aim of this study was an investigation of involvement BTX-induced TRPM2 activation on the mitochondria ROS production and apoptosis levels in the DBTRG glioblastoma and SH-SY5Y neuroblastoma tumor cells. MATERIAL AND METHODS: The DBTRG and SH-SY5Y cells were divided into four groups as control, BTX (5 IU for 24 h), BTX + ACA (25 µM for 30 min), and BTX + 2-APB (100 µM for 30 min). RESULTS: BTX treatment increased mitochondrial membrane depolarization (JC-1), mitochondrial (MitROS), and cytosolic (DHR123 and DCFH-DA) ROS levels, neuronal death (propidium iodide/Hoechst) rate, caspase -3, and -9 levels in the BTX group, although their levels were diminished in the BTX + ACA and BTX + 2-APB groups. The ACA and 2-APB treatments also decreased BTX-induced increase of TRPM2 cytosolic free Ca2+ concentration in the glioblastoma and neuroblastoma cell death. CONCLUSIONS: BTX caused neuroblastoma and glioblastoma tumor cell death by activating the mitochondria ROS production via stimulating TRPM2 signaling pathways. BTX may serve as a potential therapeutic target via activation of TRPM2 for treating glioblastoma and neuroblastoma cells.

Corrigendum: The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels.

This corrects the article DOI: 10.1038/srep37196.

Efficacy of clarithromycin as a protective agent in the methotrexate-induced pulmonary fibrosis model.

INTRODUCTION: Methotrexate is a cytotoxic agent used in leukemia, and several other cancer types and at lower doses in auto-inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis and psoriasis. Macrolide antibiotics are effective against gram-positive and Gram-negative bacteria. They have anti-inflammatory activities as well. Clarithromycin is a macrolide with anti-inflammatory activity through blockage of the p38 MAPK signal cascade, which is involved in methotrexate-induced pulmonary toxicity. AIM: In this study, the efficacy of clarithromycin in protecting against pulmonary fibrosis was investigated in the rat model for methotrexate-induced pulmonary fibrosis. MATERIAL AND METHODS: A total of 30 female rats were divided into three groups. Group I was administered intraperitoneal and intragastric saline; group II was administered oral 3 mg/kg methotrexate; and group III was administered oral 3 mg/kg methotrexate + intraperitoneal 200 mg/kg clarithromycin for 28 days. Histopathological analyses of the lung tissues were performed under light microscopy. RESULTS: Normal histopathological changes were observed in the control group. Pulmonary fibrosis was significantly higher in the methotrexate group than in the other groups (p < 0.005). CONCLUSIONS: Clarithromycin was shown to be effective in protecting against methotrexate-induced pulmonary fibrosis; further studies should be performed to determine the dosage and safety.

Different doses of dexmedetomidine reduce plasma cytokine production, brain oxidative injury, PARP and caspase expression levels but increase liver oxidative toxicity in cerebral ischemia-induced rats.

Cerebral ischemia-induced progression of brain, liver, and erythrocyte oxidative injuries might be modulated by dexmedetomidine (DEX) as a potent antioxidant and anti-inflammatory drug. The present study was conducted to explore whether two different doses of DEX protect against plasma cytokine and brain, liver and erythrocyte oxidative toxicity and apoptosis in cerebral ischemia-induced rats. Forty-two rats were equally divided into 7 groups. The first and second groups were used as untreated and sham controls, respectively. The third (DEX4) and fourth (DEX40) groups received 4mg/kg and 40mg/kg DEX treatments. The fifth, sixth and seventh group were operated on to induce cerebral ischemia. The fifth, sixth and seventh groups are used to represent cerebral ischemia, cerebral ischemia+DEX4, and cerebral ischemia+DEX40, respectively. DEX was intraperitoneally given to the DEX groups at the 3rd, 24th and 48th hour. Brain and erythrocyte lipid peroxidation (MDA) levels and plasma IL-1ß and TNF-α levels were high in the cerebral ischemia group although they were low in the DEX4 and DEX40 groups. Decreased glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) values in the brain and erythrocyte of the cerebral ischemia group were increased by the DEX treatments, although PARP, and the caspase 3 and 9 expressions in the brain were further decreased. Conversely, the cerebral ischemia-induced decrease in the liver vitamin A, vitamin E, GSH, and GSH-Px were further decreased by the DEX treatments, although MDA level, PARP, and caspase 3 and 9 expressions were further increased by the DEX treatments. In conclusion, DEX induced protective effects against cerebral ischemia-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production. However, both doses of DEX induced oxidative toxicity and apoptotic effects in the rats' livers.

The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels.

Dexmedetomidine (DEX) may act as an antioxidant through regulation of TRPM2 and TRPV1 channel activations in the neurons by reducing cerebral ischemia-induced oxidative stress and apoptosis. The neuroprotective roles of DEX were tested on cerebral ischemia (ISC) in the cultures of rat primary hippocampal and DRG neurons. Fifty-six rats were divided into five groups. A placebo was given to control, sham control, and ISC groups, respectively. In the third group, ISC was induced. The DEX and ISC+DEX groups received intraperitoneal DEX (40 µg/kg) 3, 24, and 48 hours after ISC induction. DEX effectively reversed capsaicin and cumene hydroperoxide/ADP-ribose-induced TRPV1 and TRPM2 densities and cytosolic calcium ion accumulation in the neurons, respectively. In addition, DEX completely reduced ISC-induced oxidative toxicity and apoptosis through intracellular reactive oxygen species production and depolarization of mitochondrial membrane. The DEX and ISC+DEX treatments also decreased the expression levels of caspase 3, caspase 9, and poly (ADP-ribose) polymerase in the hippocampus and DRG. In conclusion, the current results are the first to demonstrate the molecular level effects of DEX on TRPM2 and TRPV1 activation. Therefore, DEX can have remarkable neuroprotective impairment effects in the hippocampus and DRG of ISC-induced rats.

Historical perspective of brucellosis: a microbiological and epidemiological overview.

The historical process of brucellosis extends back to humankind's first contact with animals. Although brucellosis is a sporadic disease observed in animals in certain regions of the world, it is an important disease in humans that can affect many organs and systems due to the consumption of contaminated milk or milk products. Studies have shown that the presence of Brucella dates back to 60 million years ago. In 450 BC, Hippocrates described a disease similar to brucellosis. Since Hippocrates' time, brucellosis has been characterized by fever. Our aim is to investigate selfless work undertaken by scientists on the epidemiology, diagnosis and clinical findings of brucellosis until today, and to gain a historical perspective about the disease that is as old as human history, still has importance today, causes economic losses in treated animals and harms human health.

Association between oxidative stress index and serum lipid levels in healthy young adults.

OBJECTIVES: To investigate the relationship between lipid levels and oxidative stress index in healthy young adults. METHODS: The study was camed out at the Department of Emergency Service, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey, between January 2011 and July 2012. A total of 100 healthy adult volunteers were enrolled in the study. Venous blood samples (10 ml) were collected from all individuals, and serum lipid parameters, total antioxidant capacity and total oxidative levels were studied. SPSS 15 was used for statistical analysis. RESULTS: Overall, there were 84 (84%) males and 16 (16%) females. The mean age fo the male population was 30 +/- 3 years, while that of the females was 31 +/- 3 years. Overall age ranged from 25 to 35 years. A statistically significant correlation was found between the oxidative stress index and serum cholesterol (p < 0.001; r = 0.596), triglyceride (p < 0.001; r = 0.476) and low-density lipoprotein levels (p < 0.001; r = 0.318). However, no significant correlation was found between oxidative stress index and serum high-density lipoprotein levels (p = 0.564; r = 0.058). CONCLUSION: The results showed that even at an early age, there is a direct linear correlation between oxidative stress and serum lipid levels.

Mean platelet volume is increased in patients with hypertensive crises.

Platelets may be activated in hypertension (HT). Hypertensive crisis is an extreme phenotype of HT and HT-related thrombotic complications. We aimed to assess mean platelet volume (MPV) in patients with hypertensive crises. This study included 215 hypertensive urgency (HU) patients (84 male, mean age = 66 ± 15 years) and 60 hypertensive emergency (HE) patients (26 male, mean age = 68 ± 13 years), who were admitted to the emergency department with a diagnosis of hypertensive crises. Control group was composed of age- and sex-matched 39 normotensive patients. Blood samples were withdrawn for whole blood count and routine biochemical tests. Systolic blood pressure (BP) was significantly higher in the HE group than in the HU group (p < 0.001). Median mean platelet volume (MPV) was higher in the HE group compared with HU and control groups [9.5 (Interquartile range, IQR: 8.7-10.1), 8.4 (IQR: 7.7-9.1), and 8.3 (IQR: 7.7-8.7) fl, each p < 0.001, respectively). In linear regression analysis, systolic BP (ß = 0.18, 95% confidence intervals (CI): 0.002-0.015, p = 0.007) and diabetes mellitus (ß = 0.24, 95% CI: 0.28-0.95, p < 0.001) were independently associated with MPV levels. Our findings show that MPV can be elevated in patients with HE and HU. It can be independently associated with systolic BP and diabetes mellitus. These findings imply that platelet activation contribute to the pathogenesis of thrombotic complications in hypertensive crises.

Mean platelet volume in patients with carbon monoxide poisoning.

Carbon monoxide (CO) poisoning is frequent and can lead to high morbidity and mortality. Some studies have indicated increased platelet activation and aggregation in CO poisoning. Thus, we investigated mean platelet volume (MPV), an indicator of platelet activation, in patients with CO poisoning. We included 193 (117 women) patients who presented with a diagnosis of CO poisoning between June 2011 and March 2013. Control group was composed of 39 (15 women) patients. Troponin and creatine kinase MB levels were significantly higher in the CO poisoning group. Platelet counts were significantly higher in patients with CO poisoning (281 ± 76 vs 248 ± 65 × 10(9), respectively; P = .01). Similarly, MPV was significantly higher in the CO poisoning group (8.9 ± 0.8 vs 7.9 ± 0.9 fL, respectively; P < .001). Elevated MPV values may indicate that patients with CO poisoning have a higher risk of thromboembolic and cardiovascular complications due to platelet activation.