Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3-/-/C57BL/6N Knockout and WT (C57BL/6N) Control Mice.

High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3-/- gene knockout mice (Tff3-/-/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3-/- and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3-/--HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3-/- mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins' expression and Tff3 depletion, but HS diet did not increase the stroke volume, which is related to proteome modification and upregulation of genes involved mainly in cellular antioxidative defense. In conclusion, Tff3 depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet.

Hyperbaric oxygenation and 20-hydroxyeicosatetreanoic acid inhibition reduce stroke volume in female diabetic Sprague-Dawley rats.

NEW FINDINGS: What is the central question of this study? Is there a beneficial effect and what are the mechanisms of acute and multiple hyperbaric oxygenation (HBO2 ) exposures on the outcome of cerebral tissue injury induced by a transient middle cerebral artery occlusion model in diabetic female rats? Are 20-hydroxyeicosatetreanoic acid and epoxyeicosatrienoic acids involved? What is the main finding and its importance? Equal reduction of cortical and total infarct size in rats treated with HBO2 and HET0016 (20-hydroxyeicosatetreanoic acid production inhibitor) and significant mRNA upregulation of epoxyeicosatrienoic acid-producing enzymes (Cyp2J3 and Cyp2C11) in treated groups suggest that HBO2 and HET0016 are highly effective stroke treatments and that cytochrome P450 metabolites are involved in this therapeutic effect. We evaluated the effects of acute and repetitive hyperbaric oxygenation (HBO2 ), 20-hydroxyeicosatetreanoic acid (20-HETE) inhibition by N-hydroxy-N'-(4-butyl-2methylphenyl)-formamidine (HET0016) and their combination on experimental stroke outcomes. Streptozotocin-induced type 1 diabetic Sprague-Dawley female rats (n = 42; n = 7 per group), were subjected to 30 min of transient middle cerebral artery occlusion (t-MCAO)-reperfusion and divided into the following groups: (1) control group, without treatment; and groups exposed to: (2) HBO2 ; (3) multiple HBO2 (HBO2 immediately and second exposure 12 h after t-MCAO); (4) HET0016 pretreatment (1 mg kg-1 , 3 days before t-MCAO) combined with HBO2 after t-MCAO; (5) HET0016 treatment (1 h before, during and for 6 h after t-MCAO); and (6) HET0016 treatment followed by HBO2 after t-MCAO. Messenger RNA expression of CYP2J3, CYP2C11, CYP4A1, endothelial nitric oxide synthase and epoxide hydrolase 2 was determined by real-time qPCR. Cortical infarct size and total infarct size were equally and significantly reduced in HBO2 - and HET0016-treated rats. Combined treatment with HET0016 and HBO2 provided no significant additive effect compared with HET0016 treatment only. Messenger RNA of Cyp2J3 was significantly increased in all study groups, and mRNA of Cyp2C11 was significantly increased in the multiple HBO2 group and the HET0016 treatment followed by HBO2 group, compared with the control group. Expression of endothelial nitric oxide synthase was significantly increased after HBO2 treatments, and expression of epoxide hydrolase 2 was increased in all groups compared with the control group. In diabetic female Sprague-Dawley rats, HBO2 and HET0016 are highly effective stroke treatments, suggesting the involvement of cytochrome P450 metabolites and the NO pathway in this therapeutic effect.

Is shorter transient middle cerebral artery occlusion (t-MCAO) duration better in stroke experiments on diabetic female Sprague Dawely rats?

AIM: To determine optimal duration of transient middle cerebral artery occlusion (t-MCAO) for a stroke model in female diabetic Sprague-Dawley (SD) rats. METHODS: Streptozotocin-induced type-1 diabetic SD female rats (n = 25, 12 weeks old, five groups; n = 5 per group) were subjected to different duration of t-MCAO (20, 30, 45, 60 and 90 minutes) followed by reperfusion. A control group of rats without diabetes (n = 5) was subjected to 30 minutes of t-MCAO followed by reperfusion. Twenty-four hours after reperfusion, infarct volumes were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: Intra-ischaemic reductions of regional cerebral blood flow (rCBF) were similar in all groups (68-75% of baseline values). Reperfusion was significantly impaired in the 90-minute ischaemia group (56-62% vs 80-125% in other groups). Twenty minutes of t-MCAO induced a small infarct (3 ± 5% of ischaemic hemisphere). Thirty minutes of ischaemia produced a significantly larger infarct (46 ± 6%). In the 45 and 60 minute groups, ischaemia infarct was 52 ± 5% and 59 ± 3% of the ischaemic hemisphere, respectively. Ischaemia of 90' led to a massive stroke (89 ± 6% of ischaemic hemisphere encompassing the whole striatum (22 ± 3%) and almost the whole MCA irrigated cortex area (67 ± 6%)). Thirty minutes of t-MCAO did not produce stroke in the control group. CONCLUSION: The diabetic rat stroke model should be different from the non-diabetic, because female type-1 diabetic SD rats are highly sensitive to brain ischaemia and it is necessary to significantly shorten the duration of t-MCAO, optimally to 30 minutes.

Patient radiation doses during coronary interventions in four Croatian hospitals: 4-y comparison.

The number of coronary interventions increased substantially in the recent years. Although of great benefit to patients, these procedures can subject patients to considerable radiation doses. There is a legal framework for patient dose measurements in Croatia during radiological procedures, but in practice, it applies only occasionally. A quality control manual, established at the University Hospital Osijek, was accepted by other major cardiology centres in Croatia; besides checking the technical characteristics of the device, it provides constant measurement and analysis of patient doses in interventional cardiology. It also includes patient examination for radiation skin injuries in case of dose of >2 Gy. The aim of the study was to determine and compare patient radiation doses during cardiological interventions measured within 4 y in four major cardiology centres with the values proposed by the European Commission and other professional bodies. The local reference dose levels were also set.

[CLINICAL GUIDELINES FOR DIAGNOSING, TREATING AND MONITORING OF ADULT PATIENTS WITH GLIOMAS OF CENTRAL NERVOUS SYSTEM]. / KLINICKE UPUTE ZA DIJAGNOZU, LIJECENJE I PRACENJE ODRASLIH BOLESNIKA OBOLJELIH OD GLIOMA SREDISNJEGA ZIVCANOG SUSTAVA.

Gliomas of the central nervous system are glial cell tumors that are divided in low and high grade group. Multidisciplinary approach to treatment consists of surgery, radiotherapy and chemotherapy. The type and order of treatment depend on the characteristics of the tumor and the patient. We present the clinical guidelines for diagnostic procedures, surgical treatment, oncological treatment and follow up of patients with this type of tumor in the Republic of Croatia.