Dexpanthenol ameliorates lipopolysaccharide-induced cardiovascular toxicity by regulating the IL-6/HIF1α/VEGF pathway.

Introduction: Lipopolysaccharide (Lps) is an essential component responsible for the virulence of gram-negative bacteria. Lps can cause damage to many organs, including the heart, kidneys, and lungs. Dexpanthenol (Dex) is an agent that exhibits anti-oxidative and anti-inflammatory effects and stimulates epithelialization. In this study, we aimed to investigate the effects of Dex on Lps-induced cardiovascular toxicity. Methods: Rats were divided into four groups: control, Lps (5 mg/kg, intraperitoneal), Dex (500 mg/kg, intraperitoneal), and Lps + Dex. The control group received saline intraperitoneally (i.p.) once daily for three days. The Lps group received saline i.p. once daily for three days and a single dose of Lps i.p. was administered on the third day. The Dex group received Dex i.p. once daily for three days and saline on the third day. The Lps + Dex group received Dex i.p. once daily for three days and a single dose of Lps i.p. on the third day. Heart and aortic tissues were taken for biochemical, histopathological, immunohistochemical, and genetic analysis. Results: Lps injection caused histopathological changes in both heart and aortic tissues and significantly increased total oxidant status and oxidative stress index levels. Interleukin-6, and Tumor necrosis factor-α mRNA expressions were significantly altered in heart and aorta, likely do to the anti-inflammatory and antioxidative effects of Dex. Furthermore, Dex affected Caspase-3 and Hypoxia-inducible factor 1-α staining patterns. Conclusions: Our results show that Dex treatment has a protective effect on Lps-induced cardiac and endothelial damage in rats by reducing inflammation, oxidative stress, and apoptosis.

The beneficial effects of vortioxetine on BDNF, CREB, S100B, ß amyloid, and glutamate NR2b receptors in chronic unpredictable mild stress model of depression.

BACKGROUND: Depression, one of the most significant mental disorders, is still poorly understood in terms of its pathogenetic mechanisms despite its well-recognized association with stress. OBJECTIVES: The current study's goal was to ascertain how the novel antidepressant drug vortioxetine (VOR) affected the BDNF (brain-derived neurotrophic factor), S100, amyloid ß (Aß), CREB (cAMP response element-binding protein), and NR2B, as well as its impact on depression-like behaviors, and tissue damage in an experimental rodent model of depression caused by chronic unpredictable stress. METHODS: We employed twenty-eight Wistar albino male rats, and we randomly divided them into four groups, each consisting of 7 rats: control, CUMS (chronic unpredictable mild stress), CUMS+vortioxetine (CUMS+VOR), and CUMS+fluoxetine (CUMS+FLU). Sucrose preference and forced swimming tests (SPT and FST, respectively), PCR, ELISA, and histopathological and immunohistochemical evaluation were made on brains. RESULTS: The behaviors of reduced immobility in the FST and increased sucrose preference were observed in the CUMS group and they improved in the groups treated with VOR and FLU. Compared with the control group, the group exposed to CUMS showed increased Aß and decreased BDNF, CREB, and S-100 expressions, as well as neuronal degeneration (p<0.001). VOR and FLU treatment ameliorate the findings. CONCLUSIONS: This study demonstrated significant ameliorative effects of VOR in an experimental model of chronic unpredictable depression to reduce brain tissue damage and depression-like behaviors in rats. Effects of CUMS on the brain and possible effects of VOR.

Immunochemical identification of the mammalian peptide hormone obestatin from tea plant (Camellia sinensis).

This study determines obestatin-like substances from the young shoots of the tea plant [Camellia sinensis (L.) O. Kuntze (Theaceae)]. Proteins were extracted from the vegetative tea leaves using the QB (Quick Buffer) buffer as an extraction buffer. Obestatin-like substances in tea extract were investigated using an indirect home-made enzyme-linked immunosorbent assay (ELISA). Human obestatin-like immunoreactive substances from tea extract were isolated and characterized by tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (tricine-SDS-PAGE) and immunoblotting techniques. Immunochemical results showed that there are strong human obestatin-like immunoreactive substances (0.048±0.0064ng/mg protein) in vegetative tea leaves. This finding was completely unexpected since this hormone was considered to be present solely in animals. Furthermore, a single obestatin-like immunoreactive protein band of 13kDa was identified by tricine-SDS-PAGE and Western blotting of extract of vegetative tea leaf proteins. Present investigation is the first report of presence of obestatin-like immunoreactive substances in plants. It is concluded that obestatin-like bioactive peptides derived from plants can affect gastrointestinal tract structures as endogenous obestatin does and hence play a role in appetite regulation and body weight gain.

Does puberty affect oxidative stress levels and antioxidant activity of saliva in patients with fixed orthodontic appliances?

PURPOSE: To evaluate and compare patients' oxidative stress parameters and antioxidant status with fixed orthodontic appliances during the pubertal and postpubertal growth periods. METHODS: Saliva samples of 20 pubertal (mean age: 12.94 ± 0.34 years) and 20 postpubertal (mean age: 16.34 ± 0.45 years) patients were collected just before the application of fixed orthodontic appliances (T0), 4-5 h (T1), and 7 days (T2) after the initial orthodontic activation. Myeloperoxidase (MPO), nitric oxide (NO), 8­hydroxydeoxyguanosine (8-OHdG) levels, and superoxide dismutase (SOD) activity in the saliva were examined. Repeated measures analysis of variance (ANOVA), least significant difference (LSD) pairwise comparison, and independent sample t­tests were used to analyze the differences between the time points and growth periods, respectively. RESULTS: MPO levels in the saliva of patients in the pubertal period showed a significantly higher increase within the first days of treatment (T2-T1) than in patients in the postpubertal period (p < 0.05). The SOD antioxidant enzyme activity decreased in the samples from T0 to T1 in the patients in the pubertal and postpubertal groups and returned to baseline values (T0) at T2 (p < 0.01). No significant differences in the other biochemical parameters between groups were observed. CONCLUSIONS: Comparing the pubertal and postpubertal groups, orthodontic force application with fixed orthodontic appliances did not change the final levels (on day 7) of antioxidant status or oxidative stress markers, except for MPO in saliva.

Ramelteon and mechanism of its restorative effect in an experimental lung disease model.

Methotrexate (MTX) is an anticancer agent widely used in clinical practice for various oncological, rheumatological, autoimmune, and inflammatory diseases. However, the side effects of MTX limit its usage for treatment. In addition, diffuse alveolar damage, interstitial pneumonia, fibrosis, and pleural reactions may be encountered in MTX-induced pulmonary toxicity. Ramelteon (RML), a melatonin receptor agonist, has antioxidant, anti-inflammatory, and protective effects are shown by several studies. This study aimed to show the antioxidant, anti-inflammatory, and antiapoptotic effects of RML and its effect on the airway surface liquid volume homeostasis via aquaporins (AQP) in MTX-induced lung injury. Thirty-two female Wistar Albino rats were grouped into four groups as control, MTX (20 mg/kg, intraperitoneally, a single dose), MTX + RML, and RML (10 mg/kg, via oral gavage, for seven days) groups. Once the experiment ended, the rats' lung tissues were taken for biochemical, genetic, histopathological, and immunohistochemical examinations. MTX significantly increased oxidative stress index and total oxidative status, and decreased total antioxidant status levels by 202.0%, 141.4%, 20.2%, respectively, relative to the control (p ˂ 0.001 for all). AQP-1/5, which is an indicator of lung damage, was also found to decrease significantly (p ˂ 0.001). In addition, a significant increase was observed in interleukin-1ß, interferon-beta, and caspase-8 expressions and histopathological changes as a result of immunohistochemical and histochemical examinations (p ˂ 0.001). RML treatment ameliorated all these changes and significantly regressed lung damage. Our results suggest that RML might be used as a lung-protective agent in various models of lung and tissue injury.

Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity.

Objectives: Methotrexate (MTX) is a widely used chemotherapeutic agent that, however, is known to have serious side effects such as neurotoxicity. In the present study, we aimed to evaluate the possible favorable effects of ramelteon (RMLT) on MTX-induced cerebral toxicity. Materials and Methods: Thirty-two male Wistar albino rats were divided into four groups: Control group, MTX group (20 mg/kg MTX, IP, single dose), MTX+RMLT group (20 mg/kg MTX, IP, single dose + 10 mg/kg RMLT, by gavage, 7 days), and RMLT group (10 mg/kg RMLT, by gavage, 7 days). Results: In the MTX group, increased levels of total oxidant status (TOS) and oxidative stress index (OSI) levels and decreased levels of total antioxidant status (TAS) level were observed. RMLT significantly reversed oxidative stress parameters. Real-time PCR analysis revealed that MTX increased the expressions of Beclin-1 and autophagy-related gene 12 (ATG12). These expressions were significantly decreased by RMLT. Vacuolar changes, apoptotic cells, and inflammatory cell infiltration induced by MTX were ameliorated by RMLT treatment. Increased tumor necrosis factor-α (TNF- α) and Caspase-3 activities induced by MTX were returned to their normal levels by RMLT. Conclusion: All our results demonstrate that RMLT alleviates the harmful effects of MTX on the cerebral cortex tissue. Therefore, RMLT may be considered for supportive therapy for preventing side effects of MTX in patients needing MTX therapy.

Hypothalamic NR3C1 DNA methylation in rats exposed to prenatal stress.

BACKGROUND: Human and animal studies have indicated that maternal prenatal stress (PS) has molecular and behavioral effects during pregnancy and early life. The present study aimed to evaluate the epigenetic changes of the NR3C1 gene involved in the HPA axis in the hypothalamic tissues of rats exposed to PS induced by chronic unpredictable mild stress (CUMS). Behavioral and molecular effects of these changes on the next generation were also assessed. METHODS AND RESULTS: CUMS protocol was used to generate stress in pregnant Wistar rats. To determine the effects of stress on anhedonia and movement, sucrose preference test, forced swimming test, and open field test were performed. Following these behavioral experiments, bisulfite sequencing PCR for DNA methylation levels of the NR3C1 gene, RT-qPCR for mRNA levels, and Western blot techniques for protein analysis were used in the hypothalamic tissue of sacrificed rats. Depression-like behaviors were evident in the behavioral tests of stress-exposed mothers and pups. In PS-exposed pups, hypothalamic NR3C1 promoter methylation was higher, and NR3C1 mRNA levels and NR3C1 protein levels were lower compared with controls, regardless of sex. CONCLUSION: Our results confirm the relationship between PS and epigenetic changes of HPA axis-related genes and show that NR3C1 gene methylation status in pups is sensitive to PS during pregnancy. Environmental maternal stress may have transgenerational effects that are potentially associated with adverse outcomes in the pups.

Serum Claudin-5, but not Zonulin, May Be Associated with Obsessive-Compulsive Disorder.

BACKGROUND: The aim of this research was to assess serum zonulin and claudin-5 concentrations to show whether or not their eventual changes in patients with obsessive-compulsive disorder (OCD) could have etiopathogenetic importance. There was no research in the literature assessing serum zonulin and claudin-5 levels in OCD to the best of our understanding. SUBJECTS AND METHODS: In this study, we assumed that there may be a deterioration in serum zonulin and claudin-5 levels in OCD patients and this may affect the severity of the disease. Thirty-six OCD patients and 35 healthy controls were included in this study. The patients were administered Hamilton Depression Rating Scale (HDRS) and Yale-Brown Obsession Compulsion Scale (Y-BOCS) to determine the severity of depression and OCD, respectively. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured. RESULTS: The mean serum claudin-5 level was significantly higher without a significant difference between age, sex, and body mass index, whereas serum zonulin level was not different from the control group in OCD patients. CONCLUSIONS: In conclusion, the current research indicates that claudin-5 is enhanced in OCD patients and this finding may contribute to the role of blood-brain barrier in the pathogenesis of OCD.

Maternal prenatal stress and depression-like behavior associated with hippocampal and cortical neuroinflammation in the offspring: An experimental study.

Prenatal stress can negatively impact neonatal health, growth, and bonding with the mother. However, molecular basis of these modifications is not completely understood. The aim of this experimental study was to test the hypothesis that intrauterine stress exposure may contribute to subsequent depression-like comorbidities associated with neuroinflammation. Wistar Albino nulliparous female rats were divided into two groups (each, n = 6): controls and pregnancy stress (Days 1 through 21). Two live rat pups (one female and one male) from each term delivery were randomly selected, and depression-like behavior tests were performed on Postpartum Days 30-34, followed by euthanasia on Day 35. NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) pathway gene expressions in the hippocampus and immunohistochemical caspase 3 (cas-3), mammalian target of rapamycin (mTOR), and transient receptor potential melastatin (TRPM) staining in the temporal and prefrontal cortices were evaluated. Compared with controls, exposure to prenatal stress was associated with increased depression and anxiety-like behavior, hippocampal NLRP3 inflammasome activation (p = 0.022 and p = 0.035 for female and male pups, respectively), neuronal degeneration and increased cas-3, mTOR, and TRPM immunostaining in the prefrontal and temporal cortices of both female and male offspring (p < 0.05 for all comparisons except p < 0.01 for cas-3 in the male cortex and female temporal cortex). Exposure to antenatal stress can lead to depression-like behavior in the infant, mainly driven by hippocampal NLRP3 inflammasome activation, cortical neuroinflammation, and neurodegeneration. Future perspectives include NLRP3-targeted therapies with anti-inflammatory and anti-apoptotic effects against adverse prenatal effects of maternal stress.

The role of oxidant status on the etiopathogenesis of unexplained infertility and intracytoplasmic sperm injection - embryo transfer success: a case-control study.

The present study aims to evaluate the role of follicular fluid (FF) and serum (s) total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) on the etiopathogenesis of unexplained infertility (UI) and intracytoplasmic sperm injection-embryo transfer (ICSI-ET) success. Twenty UI patients and 20 controls with male factor undergoing an ICSI-ET cycle were recruited. FF samples aspirated from mature follicles and blood samples collected just before the oocyte retrieval were stored until analysis. Embriyo quality and implantation, clinical pregnancy and living birth rates were evaluated.FF-TOS and FF-OSI of the UI patients were higher than the control group. s-TOS and s-OSI were significantly increased in the UI group compared to the control group. However, only s-TOS was positively associated with UI diagnosis after age-adjustment. FF-OSI was negatively associated with embryo quality in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI on implantation, clinical pregnancy and live birth rate was observed. In conclusion, especially s-TOS can have a partial role in the etiopathogenesis of UI. High FF-OSI can decrease the quality of embryo in patients with UI.Impact statementWhat is already known? Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), which is the ratio of TOS to TAS, provide a broad overview of redox status.What do the results of this study add? An elevated serum TOS (s-TOS) was associated with UI after age-adjustment. Follicular fluid OSI (FF-OSI) was negatively associated with embryo quality and embryo score in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI was observed on implantation, clinical pregnancy, and live birth rate.What are the implications of these findings for clinical practice and/or further research? Evaluation of FF-OSI in women with unexplained infertility can be considered to predict embryo quality. Further studies that evaluate antioxidant agents to decrease oxidative stress in UI and its' clinical implications are warranted.

Salivary glands of fetuses are adversely affected by artificial food colorings in rats.

OBJECTIVE: Artificial food colorings, as types of food additives, are widely used at present in daily life. We aimed to investigate the effects of exposure to artificial food colorings during the intrauterine period on the salivary glands in adulthood. METHODS: A total of 30 Wistar albino female pregnant rats were included in this study. The treatment group was given a mixture of nine artificial food colorings at no observed adverse-effect-level doses. Neither mothers nor offspring were fed with food colorings after delivery. When the offspring became adults, they were sacrificed, and the possible histopathological and immunohistochemical effects of artificial food colorings on the salivary glands were investigated. In these glands, anti-matrix metallopeptidase 2 (anti-MMP2), anti-MMP9, anti-tissue inhibitor of metalloproteinases (TIMP) metallopeptidase inhibitor 1 (anti-TIMP1), anti-TIMP2, and anti-TIMP3 were examined. RESULTS: The expressions of anti-MMP2, anti-TIMP1, anti-TIMP2, and anti-TIMP3 parameters were found to be higher in treatment groups (p<0.05). CONCLUSION: It was suggested that intrauterine exposure of synthetic food colorings may lead to deterioration of the tissue structure of the salivary glands in adulthood, thereby increasing susceptibility to chronic illnesses including malignancy and chronic inflammation. Therefore, pregnant women should give importance to their nutrition in terms of foods containing synthetic colorings.

Serum zonulin levels in type 2 diabetes patients with diabetic kidney disease.

INTRODUCTION: Recent data have shown that diabetic kidney disease (DKD) is associated with abnormal gut microbiota composition. Zonulin is a physiological tight junction modulator and an intestinal permeability marker. In this study we aimed to investigate serum levels of zonulin and interleukin 6 (IL-6) in patients with type 2 diabetes mellitus (T2DM) and different levels of albuminuria. MATERIAL AND METHODS: Ninety patients with T2DM and 30 healthy controls (HC) aged between 18 and 65 years were enrolled in the study. T2DM patients were divided into three groups as patients with normoalbuminuria (n = 30), microalbuminuria (n = 30), and macroalbuminuria (n = 30). Serum zonulin and IL-6 levels were measured by ELISA method. RESULTS: There was no significant difference between groups in terms of age, gender, serum ALT, LDL-C, HDL-C, and zonulin levels (p > 0.05). Significant differences between groups were present for the duration of diabetes (p < 0.001), body mass index (p < 0.001), fasting blood glucose (p < 0.001), creatinine (p < 0.001), uric acid (p = 0.037), triglyceride (p = 0.003), total cholesterol (p < 0.001), glycated haemoglobin (p < 0.001), and IL-6 (p < 0.001) levels. IL-6 levels were significantly increased in the microalbuminuria and macroalbuminuria groups compared to the HC group, but no significant difference was determined between the HC and normoalbuminuria group. In patients with diabetic kidney disease, a significant positive correlation was found between zonulin with IL-6 and proteinuria (rho = 0.296, p = 0.008; rho = 0.190, p < 0.047, respectively). The serum IL-6 level was positively correlated with microalbuminuria and proteinuria (rho = 0.451, p < 0.001; rho = 0.425, p < 0.001, respectively). CONCLUSIONS: We suggest that the serum zonulin level is not a promising biomarker to assess the severity of DKD in patients with long-standing T2DM.

Salivary glands of fetuses are adversely affected by artificial food colorings in rats

SUMMARY OBJECTIVE: Artificial food colorings, as types of food additives, are widely used at present in daily life. We aimed to investigate the effects of exposure to artificial food colorings during the intrauterine period on the salivary glands in adulthood. METHODS: A total of 30 Wistar albino female pregnant rats were included in this study. The treatment group was given a mixture of nine artificial food colorings at no observed adverse-effect-level doses. Neither mothers nor offspring were fed with food colorings after delivery. When the offspring became adults, they were sacrificed, and the possible histopathological and immunohistochemical effects of artificial food colorings on the salivary glands were investigated. In these glands, anti-matrix metallopeptidase 2 (anti-MMP2), anti-MMP9, anti-tissue inhibitor of metalloproteinases (TIMP) metallopeptidase inhibitor 1 (anti-TIMP1), anti-TIMP2, and anti-TIMP3 were examined. RESULTS: The expressions of anti-MMP2, anti-TIMP1, anti-TIMP2, and anti-TIMP3 parameters were found to be higher in treatment groups (p<0.05). CONCLUSION: It was suggested that intrauterine exposure of synthetic food colorings may lead to deterioration of the tissue structure of the salivary glands in adulthood, thereby increasing susceptibility to chronic illnesses including malignancy and chronic inflammation. Therefore, pregnant women should give importance to their nutrition in terms of foods containing synthetic colorings.

Serum zonulin and claudin-5 levels in patients with schizophrenia.

The aim of this research was to assess whether or not changes in the concentrations of serum zonulin and claudin-5 in patients with schizophrenia could have etiopathogenetic importance. In previous studies, the data regarding the relationship between intestinal and blood-brain barrier (BBB) permeability and the etiology of schizophrenia have been limited. In this study, we assumed that there may be a difference in serum zonulin and claudin-5 levels in patients with schizophrenia, which may affect the severity of the disease. Fifty schizophrenia patients and 50 healthy controls were included in this study. The patients were administered the Positive Symptoms Assessment Scale (SAPS) and Negative Symptoms Assessment Scale (SANS) to determine the severity of symptoms. Venous blood samples were collected, and the serum zonulin and claudin-5 levels were measured. The mean serum zonulin levels were significantly increased in patients with schizophrenia when compared to the control group. Serum claudin-5 levels were decreased in the schizophrenia patients when compared to the controls. The present study indicates that zonulin is increased and claudin-5 is decreased in patients with schizophrenia. These findings extend the existing knowledge on the dysregulation of intestinal permeability, especially zonulin, and BBB, especially claudin-5, and show that both proteins may be involved in the etiopathogenesis of schizophrenia.

Prenatal exposure to artificial food colorings alters NMDA receptor subunit concentrations in rat hippocampus.

Exposure to artificial food color additives (AFCAs) has been implicated in the etiology of certain childhood hyperactivity and learning disabilities. N-methyl-D-aspartate receptors and alpha-7 nicotinic acetylcholine receptor (α7 nAChR) are involved in learning and memory. We administered a mixture of AFCAs (erythrosine, ponceau 4R, allura red AC, sunset yellow FCF, tartrazine, amaranth, brilliant blue, azorubine, and indigotine) to female rats during gestation to investigate the effects of prenatal exposure to AFCAs on neurobehavior, spatial learning, and memory in their offspring. We also investigated whether AFCAs modulate NR2A, NR2B, and α7 nAChR protein levels in their offsprings' hippocampi. Although spatial learning and memory were not altered, the offspring of rats exposed to AFCAs exhibited decreased motivation and increased despair-related behavior. NR2A and NR2B protein levels were significantly reduced in female offspring in the experimental group (p < 0.05), whereas α7 nAChR level was not significantly altered. Our results suggest that prenatal exposure to AFCAs may lead to sex-dependent alterations in glutamatergic signaling which may continue into adolescence.

Serum zonulin and claudin-5 levels in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study aimed to investigate serum zonulin and claudin-5 levels of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and healthy controls by controlling the parameters such as age, sex and body mass index (BMI) percentile which are known to affect these parameters. METHOD: A total of 80 treatment-naive children and adolescents with ADHD and 40 healthy volunteer controls aged 8-12 years were enrolled in this study. The severities of ADHD symptoms were assessed via parent- and teacher-rated questionnaires. The severity of anxiety and depression symptoms of the children were assessed by the self-report inventories. Serum levels of zonulin and claudin-5 were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the serum zonulin and claudin-5 levels, an effect that was independent of age, sex and BMI percentile. Significant differences were found between the study groups in terms of serum log-claudin-5 levels. However, there was no significant difference between the study groups in terms of serum zonulin levels. CONCLUSION: These findings provide additional evidence for dysregulation of the blood-brain barrier, especially abnormalities in claudin-5 function, which may be involved in the aetiology of ADHD.Key pointsADHD is one of the most common neurodevelopmental disorders of childhood. Although ADHD is quite common, its aetiology has yet to be fully explained.In recent years, studies on the relationship between intestinal and blood-brain brain barrier permeability and psychiatric disorders have increased.In our study, serum claudin-5 levels were higher in the ADHD group compared to the control group, while serum zonulin levels did not differ between the groups.

Diagnostic value of serum pentraxin 3 level in children with acute appendicitis.

BACKGROUND: Appendicitis is one of the most common surgical emergencies. Early diagnosis of appendicitis is important in children because any delay in treatment substantially leads to complicated appendicitis. In this study, we aimed to test the diagnostic value of pentraxin 3 (PTX3) level in children with acute appendicitis and to investigate whether there is a relationship between the progression of the disease and PTX3 level. METHODS: This prospective study included 70 children. They were divided into three groups as follows: group 1 (appendicitis; n=37), group 2 (abdominal pain; n=25), group 3 (control; n=8). Demographic data, medical history, the time from the onset of symptoms to blood sampling, operative and pathological findings of the patients were noted, and white blood cell (WBC), C-reactive protein (CRP) and PTX3 values were measured. RESULTS: The mean WBC, CRP and PTX3 values were found to be significantly increased in the appendicitis group (p<0.001). PTX3 has the highest diagnostic value (AUC=0.828), specificity (88%) and positive predictive value (90%) in the appendicitis group. WBC values did not show a significant correlation with the time periods (p=0.999). The mean CRP level of the appendicitis group in 24-48 hours was found to be higher than in 0-24 hours, but this was marginally significant (p=0.068). On the other hand, PTX3 value was significantly correlated with the time periods (p<0.05). CONCLUSION: This study showed that PTX3 is a valuable inflammatory biomarker in the diagnosis of acute appendicitis and also documented that PTX3 is useful for predicting the progression of the disease.

Assessment of the effect of pulsed electromagnetic field application on the healing of bone defects in rats with heparin-induced osteoporosis.

Osteoporosis is a systemic skeletal disease characterized by an increase in bone fragility and fracture risk due to low bone mass and deterioration of bone tissue. Application of pulsed electromagnetic fields (PEMF), a non-invasive method with a low complication risk, is known to stimulate bone formation. The present study examines the histomorphometric and biochemical effects of PEMF application on the healing of bone defects in rats with heparin-induced secondary osteoporosis. Briefly, 12-month-old male Sprague-Dawley rats were examined in a prospective, randomized, single-blind study. Osteoporosis was induced by administering a daily dose of 2 IU/g heparin for 33 days. Bone defects were created on the right femur on Day 35. PEMF of an average intensity of 0.8 ± 0.2 mT and a frequency of 7.3 Hz, was applied for 1 h/day, for 28 days following surgery. Bone healing was evaluated by histomorphometric and biochemical analyses. The heparin + PEMF group displayed the largest amount of new bone area (P = .002) and the lowest mean CTx on Day 63 (P = .05). This study demonstrates that heparin administration leads to bone loss and osteoporosis, whereas the application of PEMF decreases this effect.

Serum zonulin and claudin-5 levels in patients with bipolar disorder.

BACKGROUND: The etiology in bipolar disorder has not been fully understanding. There are limited data regarding the relationship between the permeability of intestinal and blood-brain barrier (BBB), and bipolar disorder etiology. Zonulin is regarded as a non-invasive biomarker for intestinal permeability. Claudin-5 is an important part of BBB permeability. In this study, we assumed that there may be a deterioration in serum zonulin and claudin-5 levels in patients with bipolar disorder and this may affect the severity of the disease. METHODS: Forty-one bipolar disorder patients (21 patients in remission and 20 patients with manic episodes) and 41 healthy controls were included in this study. The patients were administered Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) to determine the severity of manic and depressive symptoms, respectively. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured. RESULTS: The mean serum zonulin and claudin-5 levels in patients were significantly higher than healthy controls. There is no difference zonulin and claudin-5 levels between patients with manic episodes and patients in remission. LIMITATION: This study's small sample size limits the generalization of these outcomes to a larger population. Also, a major limitation of our study is lack of evaluations of gut microbiota in patients with bipolar disorder and controls. CONCLUSION: In conclusion, the current research indicates that zonulin and claudin-5 are increased in patients with bipolar disorder and this finding may contribute to the role of intestinal permeability or BBB in the pathogenesis of bipolar disorder.