Intracerebroventricular administration of the exercise hormone irisin or acute strenuous exercise alleviates epileptic seizure-induced neuroinflammation and improves memory dysfunction in rats.

BACKGROUND: Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels. RESULTS: Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 - 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01-0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 - 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 - 0.01) and upregulated cerebral BDNF expression (p < 0.05). CONCLUSION: In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.

Early Prediction of Bloodstream Infection with Complete Blood Count Parameters: an Ex-Vivo Human Whole Blood Model.

BACKGROUND: Despite the advanced laboratory technologies available today, blood culture is the gold standard method in the diagnosis of bloodstream infections. Automated blood culture devices give blood culture results for laboratories approximately in 2 - 3 days up to 7 days. Moreover, some microorganisms like nonreproducible bacteria, fungi or viruses cannot be produced in culture. Among all samples taken for blood culture on suspicion of infection approximately 10% are determined as positive whereas the false positive rate due to contamination is 5%. Especially in life-threatening severe conditions such as sepsis early diagnosis and prompt treatment are crucial. Based on this the aim of this study is to investigate complete blood count parameters as potential early markers in Escherichia coli, Staphylococcus aureus and Candida albicans bloodstream infections using an ex vivo whole blood model. METHODS: Blood samples collected from healthy donors (n = 10) were treated with suspensions containing a certain concentration of microorganisms (107 CFU/mL for both E. coli ATCC 25922 and S. aureus ATCC 29213, 106 CFU/mL for C. albicans ATCC 14053). After bacteremia and candidemia were induced, complete blood count parameters were analyzed hourly in the samples until the end of the 4th hour with a Mindray BC-6800 hematology analyzer. Statistical analysis was performed by Tukey-Kramer post-hoc multiple comparison test and statistical significance was accepted as p < 0.05. RESULTS: When platelet derived parameter baseline values were compared to hourly values in E. coli and S. aureus induced whole blood samples, it was found that the decrease in PLT, P-LCC and the increase in IPF% was significant from the first hour whereas the increase in IMG% was found to be significant only from the 3rd hour onward. In the experiments with C. albicans, it was observed that the increase in IPF% and IMG% was significant from the 2nd and 3rd hour onward, respectively. There was no relationship between MPV, P-LCR, and NLR baseline and hourly results in any microorganism induced model. CONCLUSIONS: IPF% can guide clinicians in the early diagnosis and management of treatment of infections caused by S. aureus, E. coli, and C. albicans.

Neuropeptide W protects against ovarian oxidative injury and reinforces ovarian steroidogenic activity via the upregulation of ERα expression.

OBJECTIVES: The aim of this study was to investigate the protective effect of neuropeptide W (NPW) on ovarian ischemia-reperfusion-induced oxidative injury and ovarian steroid metabolism. METHODS: Rats were randomly divided into control and ischemia groups that received either saline or NPW (0.1 or 5 µg/kg/day). Bilateral ovarian ischemia was performed for 3 h followed by a 72-h reperfusion. Blood, ovary, and uterus samples were collected for biochemical and histological assessments. KEY FINDINGS: Treatment with either dose of NPW alleviated oxidative injury of the ovaries with a significant suppression in free radical formation and decreased histopathological injury in both the ovarian and uterine tissues, along with reduced lipid peroxidation and neutrophil accumulation in the uterus. Moreover, NPW treatment reversed the decrease in aromatase expression with a concomitant reduction in the expression of the inactivity enzyme estrogen sulfotransferase. Also, downregulation of estrogen receptor-α (ERα) expression in the injured ovarian tissue was abolished by NPW treatment, which implicates that the protective effect of NPW on the female reproductive system may involve the upregulation of the ERα-mediated signaling pathway. CONCLUSIONS: Our study demonstrated for the first time that NPW protects against ovarian oxidative injury and reinforces ovarian steroidogenic activity, which is accompanied by the upregulation of ERα expression in the ovaries.

Gilaburu (Viburnum opulus L.) fruit extract has potential therapeutic and prophylactic role in a rat model of acetic acid-induced oxidant colonic damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) which has a global impact on the health care system with its recurrent and incompletely curable characteristics, affects the patients' quality of life. Gilaburu (GB; Viburnum opulus L.) is a fruit with rich polyphenol ingredient which is used ethnobotanically in Türkiye for medicinal purposes (for example, to pass kidney stones, to treat stomach, heart, and liver diseases, hemorrhages, hypertension, ulcers, common cold, tuberculosis, rheumatic and menstrual pain, and diabetes). On the other hand, the effects of GB in the experimental UC model have not been studied. AIM OF THE STUDY: This study aimed to explore the potential antioxidant and anti-inflammatory effects of GB fruit extract in improving acetic acid (AA)-induced UC. MATERIALS AND METHODS: Starting immediately after (AA + GB group) or 1 week before (GB + AA + GB group) the colitis induced by intrarectal AA (5%; v/v) administration, the rats orally received GB (100 mg/kg) once per day for 3 days. The control and AA groups were administered orally saline (1 ml), while the AA + SS group were administered sulfasalazine (SS; 100 mg/kg; orally) as a positive control once per day for 3 days. Distal colonic tissue specimens were obtained for the histological and biochemical [myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), chemiluminescence (CL), caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-ß1, smad-3 and cytokine (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, interferon (IFN)-γ), measurements] evaluations on the 3rd day. RESULTS: Elevated macroscopic and microscopic damage scores, high tissue wet weight values, increased tissue-associated MPO, MDA, CL, caspase-3, 8-OHdG, cytokines (TNF-α, IL-1ß, IL-6, IL-8), MMP-9, TGF-ß1, smad-3 levels, and decreased GSH values of the AA group were all reversed by GB treatments (AA + GB and GB + AA + GB groups) (p < 0.05-0.001). However, sulfasalazine treatment (AA + SS group) did not change the IL-8, 8-OHdG, MMP-9, and TGF-ß1 measurements significantly. CONCLUSIONS: Gilaburu shows both anti-inflammatory and antioxidant effects against AA-induced colonic damage by suppressing neutrophil infiltration, regulating inflammatory mediators, inhibiting reactive species production, lipid peroxidation, and apoptosis, conserving endogenous antioxidant glutathione, and ameliorating oxidative DNA damage. Since the current ulcerative colitis drugs display limited benefits and adverse side effects, potential therapeutic and/or prophylactic role of gilaburu can be evaluated in ulcerative colitis.

Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels. .