Is increased activator protein 1 in cerebrospinal fluid as a potential biomarker that distinguishes idiopathic intracranial hypertension from multiple sclerosis?

OBJECTIVES: To distinguish whether idiopathic intracranial hypertension (IIH) is a condition predisposing to multiple sclerosis (MS) or an isolated disease, the current gene transcription factor Activator Protein-1 (AP-1) was evaluated with its potential to differentiate both diseases. BACKGROUND: The aim of this study was to investigate the use of AP-1 as biomarkers for the discrimination of IIH and MS. METHODS: AP-1, TNF-α, and IL-6 protein values in the CSF of the cases were evaluated by the ELISA method. The numerical measures of the groups and the ability of AP-1 to distinguish the groups were analyzed with the ROC curve. RESULTS: There was no difference between the groups in CSF TNF-α, IL-6, CSF, and serum biochemistry analyses. However, it was determined that the AP-1 concentration (pg/ml) was significantly higher in the IIH group, the sensitivity of AP-1 in separating those with IIH was 75%, and the specificity in separating those with MS was 60% in those with an AP-1 concentration of 606.5 and above. CONCLUSION: According to our results, the fact that CSF TNF-α and IL-6 values did not differ in IIH compared to MS revealed that IIH could not methodologically control MS, and AP-1 was a supportive parameter in differentiating both diseases (Tab. 2, Fig. 1, Ref. 31).

Evaluation of the dynamic thiol/disulfide homeostasis in patients with chronic venous insufficiency.

OBJECTIVE: There is no study in the literature evaluating the dynamic thiol/disulfide homeostasis in patients with chronic venous insufficiency. Thus, we designed this study to evaluate the dynamic thiol/disulfide homeostasis as a novel indicator of oxidative stress in patients with chronic venous insufficiency. METHODS: This was a prospective case-control study performed at the department of cardiovascular surgery of a tertiary referral hospital in Turkey. A total of 80 (CEAP C3-C6) patients with lower extremity chronic venous insufficiency (as the study group) and 80 healthy subjects (as the control group) were enrolled to the study. The participants' basic demographic and clinical characteristics as well as serum levels of some laboratory parameters including albumin, ferroxidase, myeloperoxidase, native thiol, total thiol, disulphide, native thiol/total thiol, disulphide/native thiol, and disulphide/total thiol were determined, and then compared between the groups. RESULTS: In terms of basic demographic and clinical characteristics, both groups were statistically similar, and there were no significant differences between the groups. When the laboratory parameters were considered, serum ferroxidase and myeloperoxidase levels were detected to be significantly higher, whereas albumin, native thiol, total thiol, and disulphide levels were detected to be significantly lower in the study group than in the control group. CONCLUSIONS: Dynamic thiol/disulphide homeostasis could be considered as an indicator reflecting the oxidative stress status in patients with chronic venous insufficiency.

Electrophysiologic and anti-inflammatorial effects of cyclooxygenase inhibition in epileptiform activity.

The aim of our study is to investigate the electrophysiological and anti-inflammatory effects of diclofenac potassium on epileptiform activity, which is the liquid form of diclofenac, and frequently used clinically for inflammatory process by inhibiting cyclooxygenase enzyme (COX). Wistar rats aged 2-4 months were divided into Epilepsy, Diazepam, Diclofenac potassium, and Diazepam+diclofenac potassium groups. Diazepam and diclofenac potassium were administered intraperitoneally 30 min after the epileptiform activity was created with penicillin injected intracortically under anesthesia. After the electrophysiological recording was taken in the cortex for 125 min, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by the ELISA in the serums. No change was observed between the groups in serum IL-1ß, IL-6, and TNF-α values. It was observed that the co-administration of diclofenac potassium and diazepam at 51-55, 56-60, 61-65, 111-115, and 116-120 min was more effective in reducing spike amplitude than diclofenac potassium alone (p < 0.05). Single-dose diclofenac potassium did not have an anti-inflammatory effect in epileptiform activity but both diazepam and diclofenac potassium reduced the epileptiform activity.

The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats.

BACKGROUND: The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. OBJECTIVE: To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. METHODS: Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1ß, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. RESULTS: During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1ß (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. CONCLUSION: Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

ANTECEDENTES: O fato de a inflamação desencadear crises epilépticas traz à mente as propriedades antiepilépticas dos anti-inflamatórios. OBJETIVO: Investigar os efeitos eletrofisiológicos e anti-inflamatórios do fingolimode em um modelo experimental de crise epiléptica aguda induzida por penicilina em ratos. MéTODOS: Trinta e dois ratos Wistar machos foram divididos em quatro grupos: controle (penicilina), controle positivo (penicilina + diazepam [5 mg/kg]), droga (penicilina + fingolimode [0,3 mg/kg]) e grupo sinergia (penicilina + diazepam + fingolimode). Os animais foram anestesiados com uretano, e a atividade epileptiforme foi induzida por injeção intracortical de penicilina (500.000 UI). Após registro eletrofisiológico por 125 minutos, IL-1ß, TNF-α e IL-6 foram avaliados por ELISA no soro dos animais sacrificados. RESULTADOS: Durante o experimento, ocorreram mortes de animais no grupo sinérgico devido ao efeito cronotrópico negativo sinérgico do diazepam e do fingolimode. Embora não seja estatisticamente significativo, o fingolimode causou uma ligeira diminuição na atividade pico-onda e nas amplitudes pico no modelo de convulsão aguda induzida pela penicilina (p > 0,05). O fingolimode diminuiu a IL-1ß sérica (p < 0,05); fingolimode e diazepam juntos reduziram a IL-6 (p < 0,05), mas não foi observada alteração nos valores séricos de TNF-α. CONCLUSãO: Pensa-se que o efeito anticonvulsivante leve de uma dose única de fingolimode será mais proeminente em aplicações crônicas e em avaliações de tecidos centrais. Além disso, o uso concomitante de fingolimode e diazepam é considerado contraindicado devido ao efeito inotrópico negativo sinérgico.

The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats / Os efeitos antiinflamatórios e eletrofisiológicos do fingolimode em ratos induzidos pela penicilina

Abstract Background The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. Objective To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. Methods Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1β, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. Results During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1β (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. Conclusion Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

Resumo Antecedentes O fato de a inflamação desencadear crises epilépticas traz à mente as propriedades antiepilépticas dos anti-inflamatórios. Objetivo Investigar os efeitos eletrofisiológicos e anti-inflamatórios do fingolimode em um modelo experimental de crise epiléptica aguda induzida por penicilina em ratos. Métodos Trinta e dois ratos Wistar machos foram divididos em quatro grupos: controle (penicilina), controle positivo (penicilina + diazepam [5 mg/kg]), droga (penicilina + fingolimode [0,3 mg/kg]) e grupo sinergia (penicilina + diazepam + fingolimode). Os animais foram anestesiados com uretano, e a atividade epileptiforme foi induzida por injeção intracortical de penicilina (500.000 UI). Após registro eletrofisiológico por 125 minutos, IL-1β, TNF-α e IL-6 foram avaliados por ELISA no soro dos animais sacrificados. Resultados Durante o experimento, ocorreram mortes de animais no grupo sinérgico devido ao efeito cronotrópico negativo sinérgico do diazepam e do fingolimode. Embora não seja estatisticamente significativo, o fingolimode causou uma ligeira diminuição na atividade pico-onda e nas amplitudes pico no modelo de convulsão aguda induzida pela penicilina (p > 0,05). O fingolimode diminuiu a IL-1β sérica (p < 0,05); fingolimode e diazepam juntos reduziram a IL-6 (p < 0,05), mas não foi observada alteração nos valores séricos de TNF-α. Conclusão Pensa-se que o efeito anticonvulsivante leve de uma dose única de fingolimode será mais proeminente em aplicações crônicas e em avaliações de tecidos centrais. Além disso, o uso concomitante de fingolimode e diazepam é considerado contraindicado devido ao efeito inotrópico negativo sinérgico.

Does alpha-1-acid glycoprotein determine for infertility in polycystic ovary syndrome?

OBJECTIVES: The underlying cause of metabolic abnormalities and ovarian dysfunction in PCOS is thought to be chronic low-grade inflammation. This study aimed to show whether alpha-1-acid glycoprotein (AGP), an inflammatory marker, predicts the risk of infertility in fertile and infertile women with PCOS. Our study had a cros-sectional case-control design. STUDY DESIGN: A total of 20 fertile and 50 infertile patients with PCOS who wanted a child were in the early follicular phase were included in our study. Among the study groups (fertil (n = 20) and infertile (n = 50), AGP, CRP, NLR, BMI, FAI, VAI, triglyceride, HDL-cholesterol, fasting blood sugar, HOMA-IR, SHBG, testosterone values and waist circumference were measured. RESULTS: Among the inflammatory markers compared in the fertile and infertile groups included in the study, only the difference between the AGP variable was statistically significant (p = 0.011). The mean AGP was found to be higher at a statistically significant level in the infertile group (p < 0.05). Age, BMI, waist circumference and AGP were weakly positive and CRP was moderately positive in the infertile group (p < 0.05). CONCLUSION: AGP can be a good indicator of inflammation in PCOS, especially in infertility.Revealing the risk of infertility in PCOS with AGP measurement may contribute to the correct management of the reproductive process.

Anti-inflammatory potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in rats with peripheral acute inflammation.

The present study aimed to explore the possible anti-inflammatory actions of liraglutide (LRG), a glucagon-like peptide-1 (GLP-1) receptor agonist, and to compare with tramadol (TR) or LRG, and TR combination treatment by investigating the inflammatory signs such as pain hypersensitivity, edema, and fever in carrageenan (CG)-induced acute peripheral inflammation model in rats. The levels of several biomarkers for inflammatory status, angiogenesis, and oxidative stress were also measured in inflamed tissues. CG induced inflammation in the paws of rats identified by hypersensitivities, redness, edema and fever. LRG, significantly improved the hypersensitivity to mechanical (from 4 to 35.5 g) or cold (from 5 to 44.2 s) stimuli, reduced the edema (paw mass, from 2.54 to 1.85 g), and fever (paw temperature, from 33.6 to 27.3 °C). LRG dramatically suppressed the inflammatory signs when compared to those of TR. In addition, co-administration of TR and LRG resulted in further reduction of sensitivity to mechanical and cold stimuli. Anti-inflammatory potential of LRG altered depending on their inhibitory effects in the biomarkers of inflamed paws. Consequently, the suppressive actions of LRG in the inflammation induced hypersensitivities, edema, and fever, indicating that these drugs have significant anti-inflammatory potential with anti-hypersensitivities, anti-edema, and anti-pyretic effects. LRG with anti-inflammatory actions may be a highly promising therapeutic option for the management of inflammatory conditions or inflammatory-related various diseases.

Association between vitamin D levels and lower-extremity deep vein thrombosis: a case-control study.

BACKGROUND: Vitamin D has relationships with pathogenesis and inflammation pathways in many diseases. Its deficiency may make clinicians think not only of supplementation but also of presence of other diseases. OBJECTIVE: To investigate the relationship between vitamin D levels and deep vein thrombosis (DVT), given that reduced levels are related to increased risk of cardiovascular diseases. DESIGN AND SETTING: Case-control study conducted in the cardiovascular surgery and family medicine departments of a hospital in Turkey. METHODS: A total of 280 participants were included: 140 each in the DVT and control groups. Basic clinical characteristics, comorbidities and serum 25-hydroxyvitamin D (25(OH)D) levels were recorded and then compared between the groups. Serum 25(OH)D levels were also evaluated separately in three subgroups (sufficient, insufficient and deficient). RESULTS: Serum 25(OH)D levels were significantly lower in the DVT group than in the controls (P < 0.001). Females in the DVT group had lower 25(OH)D levels than those in the control group (P = 0.002). Nonetheless, the median 25(OH)D level (16.41 ng/ml) of the control group was still below the reference value. Logistic regression analysis showed that 25(OH)D was a significant predictor of DVT. Weight, height and body mass index, which all presented interaction, were significant in the logistic regression analysis but not in individual analyses. CONCLUSION: The serum vitamin D levels of DVT patients were lower than those of controls. If the results obtained from our study are supported by further large-scale randomized controlled trials, vitamin D replacement may be brought into the agenda for protection against DVT.

Association between vitamin D levels and lower-extremity deep vein thrombosis: a case-control study

ABSTRACT BACKGROUND: Vitamin D has relationships with pathogenesis and inflammation pathways in many diseases. Its deficiency may make clinicians think not only of supplementation but also of presence of other diseases. OBJECTIVE: To investigate the relationship between vitamin D levels and deep vein thrombosis (DVT), given that reduced levels are related to increased risk of cardiovascular diseases. DESIGN AND SETTING: Case-control study conducted in the cardiovascular surgery and family medicine departments of a hospital in Turkey. METHODS: A total of 280 participants were included: 140 each in the DVT and control groups. Basic clinical characteristics, comorbidities and serum 25-hydroxyvitamin D (25(OH)D) levels were recorded and then compared between the groups. Serum 25(OH)D levels were also evaluated separately in three subgroups (sufficient, insufficient and deficient). RESULTS: Serum 25(OH)D levels were significantly lower in the DVT group than in the controls (P < 0.001). Females in the DVT group had lower 25(OH)D levels than those in the control group (P = 0.002). Nonetheless, the median 25(OH)D level (16.41 ng/ml) of the control group was still below the reference value. Logistic regression analysis showed that 25(OH)D was a significant predictor of DVT. Weight, height and body mass index, which all presented interaction, were significant in the logistic regression analysis but not in individual analyses. CONCLUSION: The serum vitamin D levels of DVT patients were lower than those of controls. If the results obtained from our study are supported by further large-scale randomized controlled trials, vitamin D replacement may be brought into the agenda for protection against DVT.