Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model

Inflammation is a multi-staged process whose expansive phase is thought to be driven by acutely released arachidonic acid (AA) and its metabolites. Inhibition of cyclooxygenase (COX), lipoxygenase (LOX), or soluble epoxide hydrolase (sEH) is known to be anti-inflammatory. Inhibition of sEH stabilizes the cytochrome P450 (CYP450) products epoxyeicosatrienoic acids (EETs). Here we used a non-selective COX inhibitor aspirin, a 5-lipoxygenase activation protein (FLAP) inhibitor MK886, and a sEH inhibitor t-AUCB to selectively modulate the branches of AA metabolism in a lipopolysaccharide (LPS)-challenged murine model. We used metabolomic profiling to simultaneously monitor representative AA metabolites of each branch. In addition to the significant crosstalk among branches of the AA cascade during selective modulation of COX, LOX, or sEH, we demonstrated that co-administration of t-AUCB enhanced the anti-inflammatory effects of aspirin or MK886, which was evidenced by the observations that co-administration resulted in favorable eicosanoid profiles and better control of LPS-mediated hypotension as well as hepatic protein expression of COX-2 and 5-LOX. Targeted disruption of the sEH gene displayed a parallel profile to that produced by t-AUCB. These observations demonstrate a significant level of crosstalk among the three major branches of the AA cascade and that they are not simply parallel pathways. These data illustrate that inhibition of sEH by both pharmacological intervention and gene knockout enhances the anti-inflammatory effects of aspirin and MK886, suggesting the possibility of modulating multiple branches to achieve better therapeutic effects.     

Effect of arthrocentesis and sodium hyaluronate injection on nitrite, nitrate, and thiobarbituric acid-reactive substance levels in the synovial fluid

OBJECTIVE: To evaluate the effect of arthrocentesis and sodium hyaluronate (SH) injections on nitrite, nitrate, and thiobarbituric acid-reactive substance (TBA-RS) levels in temporomandibular joint internal derangements. STUDY DESIGN: Arthrocentesis was performed on 10 patients, and 15 patients received a supplemental injection of SH after arthrocentesis. All these patients received an SH injection 15 days after the first intervention. The synovial fluid samples were obtained before arthrocentesis on the first appointment and before the SH injection 15 days later. Nitrite and nitrate levels were measured with a highly sensitive and specific chemiluminescence detection method, and the concentration of lipid peroxidation products was assessed by means of the thiobarbituric acid reaction. RESULTS: Symptomatic improvement was seen in both groups. Nitrite, nitrate, and TBA-RS levels only decreased significantly (P <.05) with a supplemental SH injection after arthrocentesis. CONCLUSIONS: Intra-articular injections of SH may reduce nitrite, nitrate, and TBA-RS levels that play a role in the pathogenesis of various temporomandibular disorders.     

Neuroprotective effects of recombinant human erythropoietin in the developing brain of rat after lithium-pilocarpine induced status epilepticus

Status epilepticus triggers a mixture of apoptotic and necrotic cell death within the hippocampus. This neuronal loss may result in the development of epilepsy and cognitive deficits. Erythropoietin mediates a number of biological actions within the central nervous system and has been shown to be neuroprotective. In the present study, we investigated the effects of recombinant human erythropoietin on hippocampus of rat after lithium-pilocarpine induced status epilepticus. Twenty-one dam reared Wistar male rats, 21-day-old were divided into three groups: control group, lithium-pilocarpine induced status epilepticus and lithium-pilocarpine induced status epilepticus and erythropoietin treated group. Erythropoietin treated group received recombinant human erythropoietin 10 U/g intraperitoneally 40 min after pilocarpine injection for 5 days. Rats were sacrificed and brain tissues were collected at 5th day of experiment. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that erythropoietin significantly decreased neuronal cell death in CA1, CA2, CA3 and dentate gyrus regions of hippocampus. It also diminished apoptosis in the CA1 and dentate gyrus regions of hippocampus. In conclusion, erythropoietin may preserve the number of neurons and decrease apoptosis in model of status epilepticus induced by lithium-pilocarpine. This experimental study suggests that erythropoietin administration may be neuroprotective in status epilepticus.     

Antithrombin III prevents 60 min warm intestinal ischemia reperfusion injury in rats

We investigated the effect of antithrombin III on 60 min warm intestinal ischemia-reperfusion (IR) injury in rats. Sprague-Dawley rats, weighing 220–250 g, were divided into three groups: group 1 sham-operated group (no IR injury, n=8), group 2 ischemic control group (control, Ringer’s lactate infused, n=8), group 3 Antithrombin III treated group (250 U/kg before ischemia, n=8). Intestinal ischemia was induced in rats by occluding the superior mesenteric artery for 60 min. Malondialdehyde (MDA) levels, myeloperoxi-dase activity (MPO) and mucosal damage were investigated after 120 min reperfusion. Elevated MDA levels and MPO activity and severe histopathological damage were observed in the control group compared with the sham group (P<0.05). Decreased MDA levels and MPO activity and less histopathological damage were detected in group 3 compared with the control group (P<0.05). Accumulation of lipid peroxidation products and neutrophils in mucosal tissues were significantly inhibited by antithrombin III treatment. We conclude that treatment with antithrombin III before intestinal ischemia prevents histological damage in rats.     

罗哌卡因复合不同剂量地塞米松行肌间沟臂丛神经阻滞在患儿上肢手术后的镇痛效果

目的 观察罗哌卡因复合不同剂量地塞米松行肌间沟臂丛神经阻滞(ISBPB)对患儿上肢骨折手术后镇痛效果的影响。方法 选择上肢骨折手术患儿73例,男46例,女27例,年龄3～7岁,ASAⅠ或Ⅱ级。随机分为三组：单纯罗哌卡因组(R组,n=24)、罗哌卡因复合地塞米松0.1 mg/kg组(D1组,n=24)和罗哌卡因复合地塞米松0.2 mg/kg组(D2组,n=25),三组药液容量均为0.3 ml/kg。患儿在麻醉后行超声引导下ISBPB,均保留自主呼吸。记录痛觉阻滞时间、运动阻滞时间、阻滞后24 h内镇痛药物(布洛芬混悬液、氢吗啡酮)的使用情况。记录膈神经阻滞、Horner综合征、声带麻痹、阻滞侧感觉异常等术后并发症的发生情况。结果 D2组痛觉阻滞时间明显长于R组(P<0.05)。R组和D1组痛觉阻滞时间差异无统计学意义。三组运动阻滞时间差异无统计学意义。D1组和D2组阻滞后24 h内布洛芬混悬液使用次数、氢吗啡酮使用率明显低于R组(P<0.01),D1组和D2组差异无统计学意义。三组膈神经阻滞率差异无统计学意义。三组术后未出现其余并发症。结论 与单纯罗哌卡因比较,0.25%罗哌...     

Helicobacter pylori‐associated atrophic gastritis and carotid intima‐media thickness: is there a link?

Chronic infections are associated with cardiovascular diseases. Helicobacter pylori-induced chronic active gastritis results in atrophic gastritis. In this study, we attempted to determine carotid intima-media thickness in patients with and individuals without H. pylori-induced atrophic gastritis. Oesophagogastroduodenoscopy was performed on 123 patients for various reasons. Helicobacter pylori were considered positive when histological examination and rapid urease test showed H. pylori. Helicobacter pylori-positive cases were divided into two groups, namely atrophic gastritis and non-atrophic gastritis. Of 123 patients, 92 patients had H. pylori-positive non-atrophic gastritis and 31 had H. pylori-positive atrophic gastritis. There was no significant difference in carotid intima-media thickness between the two groups. Carotid intima-media thickness is not associated with H. pylori-induced atrophic gastritis.     

Monoclonal B-cell lymphocytosis in blood donors in Turkey

Objectives: Monoclonal B-cell lymphocytosis (MBL) is a precursor state of chronic lymphocytic leukemia (CLL) with peripheral lymphocytosis below 5?×?10⁹/l. The diagnostic criteria exclude the presence of lymphadenopathy, organomegaly, infections, autoimmune diseases or any sign of a lymphoproliferative disorder. This prospective study was designed in order to evaluate the frequency of MBL in blood donors in Turkey.

Methods: The diagnosis of MBL was identified by flow cytometry method based on the International Familial CLL Consortium Report. A total of 999 volunteers [median age 34 (18–78) years; male/female: 705/294] were included in the study.

Results: Monoclonal B-cell lymphocytosis was demonstrated in 18 cases (1.8%). A total of 16 cases (1.6%) was evaluated as CLL-like MBL, while 2 (0.2%) had a non-CLL-like phenotype. The subjects were divided into three groups according to age, as <40 years, 40–60 years and >60 years. The prevalence of MBL was 1.1% below 40 years, 0.6% between 40 and 60 years and 0.1% in cases over 60 years, without statistical significance (p?>?0.05).

Discussion: The sensitivity of the flow cytometry method is essential and may be responsible for the variations in the prevalence of MBL in different populations which can also be attributed to study design, higher detection rates in the elderly and families with genetic predisposition to CLL.

Conclusion: Large population-based studies and standardized laboratory methods are needed to determine the potential risk factors of progression to CLL, including molecular markers and genetic profile.