Effects of asymmetric dimethylarginine on inflammatory cytokines (TNF-α, IL-6 and IL-10) in rats.

This study is intended to examine the effects of administration of asymmetric dimethylarginine (ADMA) on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. A total of 30 Wistar adult albino rats were used. Group I was administrated (n = 10) with 1 mg/kg/day of ADMA, group II (n = 10) was administrated with 2 mg/kg/day of ADMA and the control group was administrated (n = 10) with 0.9% sodium chloride. ADMA was intraperitoneally administrated for 7 days. The serum levels of IL-6, TNF-α and IL-10 were measured. There was a significant decrease in the levels of TNF-α, IL-6 and IL-10 in group I compared with that of the control group (p < 0.001). There was also a significant decrease in the levels of IL-10 in group II compared with that of the control group (p < 0.05) but the increase was much more distinct in the levels of IL-6 and TNF-α (p < 0.001). When comparing the groups by the doses given, no difference between the levels of IL-6 and IL-10 in groups I and II (p > 0.05) was observed; the levels of TNF-α in group II were significantly lower than those of group I (p < 0.05). A significant decrease in the serum levels of inflammatory cytokines IL-6, TNF-α and IL-10, after administration of 1 mg/kg/day and 2 mg/kg/day of ADMA, indicates that ADMA has an effect on inflammation. Increase in ADMA levels in the rats shows that the effects of inflammatory cytokines were suppressed.

Do iron chelators increase the antiproliferative effect of trichostatin A through a glucose-regulated protein 78 mediated mechanism?

Histone deacetylase (HDAC) inhibitors, such as trichostatin A (TSA), and iron chelators, including deferoxamine (DFO) and phenanthroline (PHEN), appear to have anticancer effects. We hypothesized that the HDAC inhibitors and iron chelators would be synergistic with their effect on breast cancer cell line MCF7, because the HDAC inhibitors increase glucose-regulated protein 78 (Grp78) and the iron chelators reduce its expression. Although the administration of TSA alone resulted in a dose-related decrease in the cell index, it did not have an antiproliferative effect except the 62.5 and 500 nM of TSA. However, all doses of TSA produced a cytotoxic effect from the initial hours when combined with 150 µM of DFO and 25 µM of PHEN. DFO and PHEN downregulated Grp78, Grp94, and MRP1 expressions and upregulated CHOP and HO-1 expressions. TSA upregulated all the genes in various rates when used alone but resulted in decreased expression levels when combined with DFO and PHEN. Increased HDAC-1 levels in the Grp78 promoter region indicated that DFO and PHEN either promoted binding of HDAC-1 to this region or inhibited its detachment. We determined that the reduction of increased Grp78, Grp94, HO-1, and MRP1 expressions, which appears to inhibit the chemotherapeutic effect of TSA, through the combination with DFO or PHEN will contribute to the anticancer effect.

The evaluation of serum surfactant protein D (SP-D) levels as a biomarker of lung injury in tuberculosis and different lung diseases.

BACKGROUND: To evaluate the predictive powers of serum surfactant protein D (SP-D) levels as a biomarker of lung damage in tuberculosis and lung diseases. METHODS: This study prospectively included 137 subjects who applied to our hospital. We measured serum SP-D levels from patients with active tuberculosis (TB) (n = 35), chronic obstructive disease (COPD) patients experiencing acute exacerbations (n = 30), patients with pneumonia (n = 45), and control subjects (n = 27). RESULTS: The mean age of all patients was 54.89 +/- 18.81 years (15 to 100 years); males accounted for two-thirds (70.1%) of the cases. Serum SP-D levels were higher in patients with pnemonia, tuberculosis, and COPD than in control patients (p < 0.001, p < 0.001, and p < 0.001, respectively). Serum SP-D levels in patients with pneumonia, tuberculosis, and COPD were higher than in the control group and mean serum SP-D levels were associated with pulmonary injury scores in patients with pneumonia, severity of COPD attack, and the extent of radiological lung involvement in patients with pneumonia and TB. CONCLUSIONS: Serum SP-D may be a useful biomarker of the severity of pneumonia, COPD, and tuberculosis.

The effectiveness of the serum surfactant protein D (Sp-D) level to indicate lung injury in pulmonary embolism.

BACKGROUND: Surfactant protein D (SP-D) is a biomarker specific to the lungs. Our aim was to investigate the relationship between clinical probability scores and the serum levels of SP-D to indicate the severity of lung injury that develops secondary to hypoxia in pulmonary embolism (PE). METHODS: We included three groups in the study: non-massive PE (n = 20), sub-massive PE (n = 20), and the control group (n = 20), which consisted of healthy volunteers. The modified Geneva and Wells clinical probability scoring systems were performed for PE, and the patients were classified as low risk, moderate risk, and high risk. SP-D levels were determined by the enzyme-linked immunosorbent assay. RESULTS: For risk factors, the most significant were deep vein thrombosis (DVT) and immobilization. There was no significant difference in SP-D levels between the patients identified with risk factors and those without risk factors in either the Geneva or Wells scores. Atelectasis was the most common radiographic finding, while tricuspid valve regurgitation was predominant in echocardiography. There was no significant difference between the non-massive PE group and the control group, while SP-D levels of the sub-massive group were significantly higher than the control group. CONCLUSIONS: In our study, SP-D levels were significantly higher in the sub-massive PE group overall. However, further prospective studies are required with a larger number of cases, including patients with massive PE, in order to clarify the findings.

Effect of methylphenidate treatment on appetite and levels of leptin, ghrelin, adiponectin, and brain-derived neurotrophic factor in children and adolescents with attention deficit and hyperactivity disorder.

OBJECTIVES: We aimed to explore whether the use of methylphenidate relates leptin, ghrelin, adiponectin, and brain-derived neurotrophic factor (BDNF). In addition, the relationship between methylphenidate-related weight loss in attention deficit hyperactivity disorder (ADHD) patients and these biomolecules were evaluated. METHODS: Thirty ADHD patients receiving methylphenidate and 20 healthy controls were included. Leptin, ghrelin, adiponectin, and BDNF levels were measured at baseline and after two-month treatment in both groups. RESULTS: At baseline, leptin, ghrelin, adiponectin, and BDNF levels were similar in the ADHD and control groups. The most common adverse events occurring in the ADHD group after a 2-month treatment period included loss of appetite (70%) and weight loss (66.7%). A significant difference was found in body weight, BMI, and CGI scores of the ADHD patients after the treatment. While post-treatment ghrelin and adiponectin levels were significantly higher in the ADHD group, BDNF level was significantly lower. Post-treatment decrease in leptin levels was not significant. CONCLUSIONS: Leptin and BDNF were not associated with poor appetite and/or weight loss due to methylphenidate treatment. However, ghrelin and adiponectin might be biomolecules that play a role in underlying neurobiological mechanisms of methylphenidate-related appetite or weight loss.

The relationship of T helper-2 pathway components interleukin-4, interleukin-10, immunoglobulin e, and eosinophils with prognostic markers in non-hodgkin lymphoma: a case-control study.

OBJECTIVE: Increased risk for non-Hodgkin lymphoma (NHL) is associated with infections and environmental agents. We hypothesized that these factors chronically trigger the T helper-2 (Th2) pathway and result in lymphoma. We investigated the role of the Th2 pathway by exploring the relationships between components of the Th2 pathway, interleukin (IL)-10, IL-4, immunoglobulin E (IgE), and eosinophils, and prognostic markers of NHL. MATERIALS AND METHODS: Thirty-one NHL patients and 27 healthy controls were enrolled. IL-10, IL-4, IgE, and eosinophils were measured. IL-4 and IL-10 were analyzed with the enzyme amplified sensitivity immunoassay method. RESULTS: High IL-10 levels were correlated with several poor prognostic features, short early survival, and lymphopenia. There was a positive correlation between albumin and IL-4 levels and a negative correlation between IL-10 and albumin. There was no relationship related with eosinophils and IgE. We found remnant increased IL-4, which could be a clue for the triggering of the Th2 pathway in the background. CONCLUSION: There is a need for differently designed studies to detect the place of the Th2 pathway in NHL.

Serum urotensin II levels in patients with non-dipper hypertension.

Hypertension terms "dipper" and "non-dipper" are propounded by the change that occurs during ambulatory blood pressure (BP) monitoring. The purpose of this study is to present whether the serum urotensin II levels are different in patients with dipper and non-dipper hypertension and to put forward the effects causing this difference, if there are any. Patients recently diagnosed with hypertension were included in the study. With ambulatory BP monitoring, 81 patients with high BP were divided into two groups, dipper (n = 40) and non-dipper (n = 41). Serum urotensin II levels were analyzed by ELISA method. Serum urotensin II levels were higher in patients with non-dipper hypertension than in patients with dipper hypertension (204 [106-533] vs. 140 [96-309], P = .004). There was a positive correlation between total systolic BP and serum urotensin II levels (r = 0.408 and P = .009), but the relation in the non-dipper hypertension group was not significant (r = 0.194 and P = .2). In conclusion, serum urotensin II levels were higher in non-dipper HT patients than dipper HT patients. This higher urotensin II level might be responsible for poor prognoses.

Helicobacter pylori eradication increases telomere length in gastric mucosa.

BACKGROUND/AIMS: Our purpose in this study was to analyze telomere length and telomerase activity before and after eradication treatment in gastric mucosa in patients positive for H. pylori. METHODOLOGY: There were two groups: a control group (n=17) and a study group (n=21). For H. pylori eradication, the patients were administrated proton pump inhibitor (PPI) + clarithromycin + amoxicillin or PPI + metronidazole + tetracycline + bismuth for 14 days. Telomere length was analyzed with RT-PCR and telomerase activity with PCR-ELISA on biopsy specimens from the antrum. The result p<0.05 was considered significant. RESULTS: Prior to eradication, there was no significant difference between telomere lengths of the patient and control groups (2481.2±1823 and 2958.9±1345.7 bp, p=0.11, respectively). The telomere length of the study group became longer after eradication (before 2481.2±1823bp, after 3766.3±1608.8bp, p=0.01). Telomerase activity was not detected in either the patient or the control group. CONCLUSIONS: An increase in telomere length was observed with H. pylori eradication. This finding may indicate the importance of H. pylori eradication to avoid the development of gastric cancer.

Effect of dexamethasone on unfolded protein response genes (MTJ1, Grp78, Grp94, CHOP, HMOX-1) in HEp2 cell line.

The endoplasmic reticulum (ER) is related to the various signal routes that are activated in unfolded protein response (UPR). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expressions demonstrate UPR activity. In this study, we investigated the UPR gene expressions in larynx epidermoid carcinoma (HEp2) to which dexamethasone (dex) was applied. HEp2 cells were administered for 48 h with different combinations using 0.1 microM and 1 microM dex, 1 mM phenyl butyric acid (PBA) and 100 ng/ml lipopolysaccharide (LPS). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expression was determined using quantitative RT-PCR. The Grp78, MTJ1 and HMOX1 gene expression increased with the administration of 1 microM dex. CHOP expression, on the other hand, decreased with 0.1 microM dex. When dex was combined with LPS, nearly all gene expressions decreased. The increase in Grp78, Grp94, HMOX1 and MTJ1 gene expression was greater in groups in which dex was administered in combination with PBA than in groups in which dex was administered alone. Dex in low dose (0.1 microM) caused a decrease in CHOP expression in HEp2 cells and an increase in Grp78 expression, in particular. The changes in UPR genes expressions may lead to the extended survival of the cells.

The effect of ouabain on mitochondrial DNA damage in HepG2 cell lines.

Our purpose in this study is to analyze mitochondrial DNA (mtDNA) lesion frequencies and mtDNA(4977) deletion in HepG2 cells to examine the effects of ouabain on mtDNA. HepG2 cells were treated with 0.75, 7.5, 75, and 750 nM of ouabain for 24 h in the presence and absence of 10 mM 2-deoxyglucose (2-DG). The frequency of mtDNA(4977) deletions and mitochondrial lesions were determined by real-time polymerase chain reaction. A ≥ 1.2-fold change or greater was considered significant. Ouabain doses of 750, 75, and 7.5 nM alone increased the frequency of mtDNA(4977) deletions 1.39, 1.92, and 1.44 times, respectively. The 750 and 75 nM ouabain doses combined with 2-DG increased the mtDNA(4977) deletion frequency 4.94 and 1.57 times, respectively. The 750 and 75 nM ouabain doses alone increased the mtDNA lesion frequency 2.5 and 1.5 times, respectively. The 750 nM ouabain dose combined with 2-DG increased the mtDNA lesion frequency 2.28 times. The 7.5 nM ouabain dose alone and combined with 2-DG decreased the mtDNA lesion frequency 0.67 and 0.45 times, respectively. Ouabain alone and when combined with 2-DG increases mtDNA lesion and mtDNA(4977) deletion frequencies. This supports the thesis that ouabain creates oxidative stress and induces DNA damage and apoptosis.

Infliximab attenuates activated charcoal and polyethylene glycol aspiration-induced lung injury in rats.

Aspiration is a serious complication of gastrointestinal (GI) decontamination procedure. Studies have shown that tumor necrosis factor-α (TNF-α) blockers have beneficial effects on lung injury. Therefore, the authors investigated the attenuation by infliximab (INF) on activated charcoal (AC)- and polyethylene glycol (PEG)-induced lung injury in rat model. Forty-two male Sprague-Dawley rats were allotted into 1 of 6 groups: saline (NS), activated charcoal (AC), polyethylene glycol (PEG), NS+INF treated, AC+INF treated, and PEG+INF treated. All materials were aspirated into the lungs at a volume of 1 mL/kg. Before aspiration, the rats were injected subcutaneously with INF. Seven days later, both lungs and serum specimens in all groups were evaluated histopathologically, immunohistochemically, and biochemically. Following aspiration of AC and PEG, evident histopathological changes were assigned in the lung tissue that were associated with increased expression of inducible nitric oxide synthase (iNOS), increased serum levels of oxidative stress markers (malondialdehyde [MDA], surfactant protein-D [SP-D], TNF-α), and decreased antioxidant enzyme (glutathione peroxidase [GSH-Px]) activities. INF treatment significantly decreased the elevated serum MDA and TNF-α levels and increased serum GSH-Px levels. Furthermore, the current results show that there is a significant reduction in the activity of iNOS in lung tissue and increased serum SP-D levels of AC and PEG aspiration-induced lung injury with INF treatment. These findings suggest that INF attenuates lung inflammation and prevents GI decontamination agent-induced lung injury in rats.

Analysis of the protective biochemical and pathologic effects of aminoguanidine on an experimental aspiration pneumonitis model induced by bile acids.

BACKGROUND: Gastroesophageal reflux (GER) is a common clinical pathology detected in childhood. Bile acids (BAs) are present in reflux and cause various pathologies in the esophagus, the larynx, and the lungs. OBJECTIVE: We aimed to show if aminoguanidine (AG) contributes to the biochemical and histopathologic treatment of experimental aspiration pneumonitis induced by BAs. METHODS: Twenty-eight female Sprague Dawley rats were used. There were 4 groups in the study: (1) group aspirated with 0.9% saline (n = 7), (2) group aspirated with 0.9% saline and treated with AG (n = 7), (3) group aspirated with a solution of 10 mg/kg taurocholic acid and 5 mg/kg taurochenodeoxycholate (n = 7), and (4) group aspirated with BA and treated with AG (n = 7). The saline and BA solutions were administered as 1 mL/kg intratracheally. The AG was administered intraperitoneally twice a day at a 150 mg/kg dose for 7 days. The different histopathologic and biochemical parameters were analyzed. RESULTS: Clara cell protein 16 and malondialdehyde levels were found to be significantly higher in the BA group than in the group where saline was administered; however, they were significantly lower in the BA + AG group than in the BA group. The total superoxide dismutase activity decreased significantly in the BA group compared with the group where saline was administered. A significant increase in superoxide dismutase activity was observed in the BA + AG group when compared with the group where only BA was administered. When the group where BA was administered solely was compared with the group where saline was administered, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were significantly higher in the BA group than in the saline group. When the BA + AG group was compared with the BA group, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were found to be significantly lower. CONCLUSIONS: Oxidant stress increases and antioxidant capacity decreases in pneumonitis induced by BAs. AG administration as an antioxidant helps in recovery, both biochemically and histopathologically. Consequently, AG seems to be an alternative that should be considered in a conservative approach to treating aspiration pneumonitis.

A combination of ketogenic diet and voluntary exercise ameliorates anxiety and depression-like behaviors in Balb/c mice.

The positive effects of both ketogenic diet (KD) and regular voluntary exercise on anxiety and depression behavior have been recently reported in rodent animals, but the effects of pairing a KD with exercise on depression and anxiety are unknown. In this study, we aimed to investigate the effects of combination of KD and regular voluntary exercise on anxiety and depression-like behavior in Balb/c mice. We've demostrated that anxiety and depression levels decreased in KD-exercised (KD-Ex) mice. ß-hydroxybutyrate (BHB) levels increased while glucose, insulin levels and LDL/HDL ratio decreased in KD-Ex mice. There was a negative correlation between BHB and the time spent in the closed arms of elevated plus maze (EPM) or the time spent in periphery walls of open field test (OFT) and the immobility time in forced swim test (FST) which all of them are indicators of low depression and anxiety levels. There was a positive correlation between LDL/HDL ratio and the time spent in the closed arms of EPM or the immobility time in FST. The immobility time in FST was positively correlated with insulin while the mobility time in FST was negatively correlated with glucose. In conclusion, these results suggest that decline in anxiety and depression-like behaviors resulted from KD with regular voluntary exercise may be associated with increased BHB levels and decreased LDL/HDL ratio and insulin or glucose levels. Further research is necessary for our understanding of the mechanisms by which pairing a KD with voluntary exercise influences brain and behavior.

The role of asymmetric dimethyl arginine and oxidant/antioxidant system in preeclampsia.

Preeclampsia is a syndrome characterized by hypertension and proteinuria. The aim of this study is to find the relationship between preeclampsia, asymmetric dimethyl arginine (ADMA), and the oxidant/antioxidant system. Twenty-one preeclamptic and 28 normal pregnant women were included in this study. In cord bloods, ADMA and oxidant/antioxidant parameters were measured. Asymmetric dimethyl arginine levels were significantly increased in preeclamptic pregnancies compared to the control group (p = 0.006). The activities of antioxidant enzymes and malondialdehyde levels were increased in the preeclamptic group compared to the control group (p < 0.001, p = 0.022, p < 0.001, p < 0.001, respectively). Development of endothelial dysfunction and oxidative stress may play a role in developing preeclampsia.

Cord blood and maternal serum neopterin concentrations in patients with pre-eclampsia.

BACKGROUND: Pre-eclampsia is a syndrome characterized by hypertension and proteinuria. The aim of this study was to investigate neopterin concentrations in cord blood and maternal serum in patients with pre-eclampsia and a control group. METHODS: Cord blood and maternal serum neopterin were measured in 21 patients with pre-eclampsia and in 27 control subjects. Neopterin concentrations were measured by high performance liquid chromatography. RESULTS: Cord blood neopterin concentrations were significantly increased in patients with pre-eclampsia compared to controls (54.3+/-16.8 vs. 43.4+/-8.5 nmol/L, p=0.011, respectively). Maternal serum neopterin (257.3+/-36.8 vs. 150.9+/-33.8 nmol/L, p<0.001) was also higher in patients with pre-eclampsia. CONCLUSIONS: Cord blood and maternal serum neopterin concentrations are higher in patients with pre-eclampsia. Maternal serum neopterin concentrations used may be used as a marker for the early diagnosis of pre-eclampsia.

Reliability of Pro-adrenomedullin and Interleukin 1ß in Predicting Severity of Community-Acquired Pneumonia in Pediatric Patients.

OBJECTIVES: Community-acquired pneumonia (CAP) in children is one of the most important causes of mortality and morbidity in developing countries. Therefore, it is very important for clinicians to detect the presence and severity of pneumonia. Proadrenomedullin (Pro-ADM) and Interleukin-1ß (IL-1ß) are thought to have potential for CAP evaluation in children. We sought to investigate the value of Pro-ADM and IL-1ß levels for severity assessment and outcome prediction in children with CAP. METHODS: A total of 66 hospitalized CAP patients were included in a prospective observational study. Complete blood count, serum C-reactive protein (CRP), Pro-ADM and IL-1ß levels were studied in blood samples obtained from the patients upon admission. Respiratory Clinical Score (RCS) was performed to determine the respiratory distress and severity. RESULTS: The comparison of data with laboratory-severity groups: serum CRP, Pro-ADM and IL-1ß levels increased in parallel with the disease severity. Pro-ADM was the best biomarker for severity stratification. Logistic regression analysis revealed that RCS >6 points and Pro-ADM values >1.75 nmol/L combination had the most significant results (OR: 15.38, 95% CI 1.35-166.66, p=0.027). Moreover, a relationship was found between the high serum levels of IL-1ß and requirement of intervention procedures in patients with pleural effusion. CONCLUSIONS: Serum Pro-ADM and IL-1ß levels may offer additional risk/severity stratification in children with CAP. In addition, they may be helpful in predicting the development of complications, requirements for ntensive care unit admission, and intervention procedures.

Saliva/serum ghrelin, obestatin and homocysteine levels in patients with ischaemic heart disease.

BACKGROUND: We aimed to compare ghrelin, obestatin, homocysteine (Hcy), vitamin B12 and folate levels in the serum and saliva of ischaemic heart disease patients. METHODS: Serum and saliva were collected from 33 ischaemic heart disease (IHD) patients and 28 age- and body mass index-matched healthy individuals. Levels of acylated and desacylated ghrelin, obestatin and Hcy were determined using the ELISA method. RESULTS: Acylated ghrelin, desacylated ghrelin and obestatin levels in the saliva were found to be higher than those in the serum of the control group, while acylated and desacylated ghrelin levels in the saliva were significantly lower than those in the serum. Obestatin levels were higher in IHD patients (p = 0.001). Saliva and serum vitamin B12 and folate levels in IHD patients were significantly lower than in the control group (p = 0.001). CONCLUSIONS: It was determined that serum ghrelin levels increased in ischaemic heart disease patients, while serum levels of obestatin decreased.

The Effects of Dexamethasone and L-NAME on Acute Lung Injury in Rats with Lung Contusion.

The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250-300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.

Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever.

Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended.

Genistein exerts neuroprotective effect on focal cerebral ischemia injury in rats.

Brain ischemia and treatment are one of the important topics in neurological science. Free oxygen radicals and inflammation formed after ischemia are accepted as the most important causes of damage. Currently, there are studies on many chemopreventive agents to prevent cerebral ischemia damage. Our aim is to research the preventive effect of the active ingredient in genistein, previously unstudied, on oxidative damage in cerebral ischemia. Rats were randomly divided into three groups: control group (no medication or surgical procedure), ischemia group, and artery ischemia+genistein group, sacrificed at 24 h after ischemia. The harvested brain tissue from the right hemisphere was investigated histopathologically and for tissue biochemistry. Superoxide dismutase and nuclear respiratory factor 1 values decreased after ischemia and they increased after genistein treatment, while increased malondialdehyde levels after ischemia reduced after treatment. Apoptosis-related cysteine peptidase caspase-3 and caspase-9 values increased after ischemia, but reduced after treatment. Our study revealed that genistein treatment in cerebral ischemia reduced oxidative stress and neuronal degeneration. We believe that genistein treatment may be an alternative treatment method.