The effects of hormone replacement therapy on lipid peroxidation and antioxidant status

OBJECTIVE: A number of studies have consistently shown a lower cardiovascular risk in women who received postmenopausal hormone replacement therapy (HRT). The aim of our study was to examine the effects of HRT on lipid peroxidation and antioxidant status, which were likely to be involved in the pathophysiology of atherosclerosis. METHODS: We measured erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels as expression of lipid peroxidation-end product malondialdehyde, and also erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity as indicators of the antioxidant status of the 35 postmenopausal women with HRT (mean age: 51.81 +/- 4.57 yr; body mass index (BMI): 26.56 +/- 3.78 kg/m(2)) and 35 postmenopausal women without HRT (mean age: 47.50 +/- 3.64; BMI: 27.42 +/-3.43 kg/m2). RESULTS: In the group with HRT, erythrocyte and plasma TBARS levels were significantly lower than in the group without HRT (P < 0.003 and P < 0.001, respectively). Erythrocyte GSH level and GSH-Px activity was found to be increased significantly in the group with HRT in comparison with the group without HRT (P < 0.001 and P < 0.001, respectively). There was not any correlation between the erythrocyte and plasma TBARS and erythrocyte GSH levels and GSH-Px activity with duration of HRT (mean 3.5+/-1.3 yr). CONCLUSION: Our results show that HRT is beneficial in the protection against oxidative damage and can prevent atherosclerotic complications.     

肺炎支原体诱导的皮疹和黏膜炎8例临床特征及预后分析

【摘要】 目的 分析肺炎支原体诱导的皮疹和黏膜炎（MIRM）的临床特征及预后。方法 调阅中山大学附属第一医院2004年11月至2021年5月出院诊断为多形红斑/重症多形红斑或Stevens-Johnson综合征患者的资料,以MIRM诊断标准筛选出其中的MIRM患者,且排除了其他病因,分析其临床表现、实验室和辅助检查、治疗和预后。结果 8例符合MIRM诊断,其中男4例,女4例,发病年龄4 ~ 30（15.63 ± 9.16）岁。8例均有发热,其中5例有咳嗽、咽痛等上呼吸道前驱症状。所有患者均有口腔黏膜损害,其中5例有口唇血痂;7例有眼损害,表现为结膜充血及分泌物增多。所有患者均有皮损,表现为靶形损害5例、水疱4例。所有患者血清学肺炎支原体IgM均阳性。1例反复出现干咳等上呼吸道感染,每次发作与肺炎支原体感染密切相关,取外周血行全外显子测序显示,NLRC4和IRGM杂合突变。3例患者行皮损组织病理检查,符合多形红斑。7例系统使用糖皮质激素治疗,6例静脉注射免疫球蛋白,5例阿奇霉素,5例使用阿昔洛韦或伐昔洛韦或利巴韦林。平均随访2.9年,3例痊愈,1例失明,1例反复出现干咳和口腔溃疡及四肢皮疹,余3例分别出现眼睑板腺功能障碍、泪点狭窄及角膜上皮损害等眼部损害。结论 MIRM好发于儿童及年轻成人,多有发热、咽痛、咳嗽等前驱症状,黏膜损害明显,部分有皮肤靶形损害。多数患者单次发病后痊愈,个别反复发作者可能与自身炎症相关基因和感染相关基因突变有关。     

Glioma‐associated microglial MMP9 expression is upregulated by TLR2 signaling and sensitive to minocycline

The invasiveness of malignant gliomas is one of the major obstacles in glioma therapy and the reason for the poor survival of patients. Glioma cells infiltrate into the brain parenchyma and thereby escape surgical resection. Glioma associated microglia/macrophages support glioma infiltration into the brain parenchyma by increased expression and activation of extracellular matrix degrading proteases such as matrix metalloprotease (MMP) 2, MMP9 and membrane‐type 1 MMP. In this work we demonstrate that, MMP9 is predominantly expressed by glioma associated microglia/macrophages in mouse and human glioma tissue but not by the glioma cells. Supernatant from glioma cells induced the expression of MMP9 in cultured microglial cells. Using mice deficient for different Toll‐like receptors we identified Toll‐like receptor 2/6 as the signaling pathway for the glioma induced upregulation of microglial MMP9. Also in an experimental mouse glioma model, Toll‐like receptor 2 deficiency attenuated the upregulation of microglial MMP9. Moreover, glioma supernatant triggered an upregulation of Toll‐like receptor 2 expression in microglia. Both, the upregulation of MMP9 and Toll‐like receptor 2 were attenuated by the antibiotic minocycline and a p38 mitogen‐activated protein kinase antagonist in vitro. Minocycline also extended the survival rate of glioma bearing mice when given to the drinking water. Thus glioma cells change the phenotype of glioma associated microglia/macrophages in a complex fashion using Toll‐like receptor 2 as an important signaling pathway and minocycline further proved to be a potential candidate for adjuvant glioma therapy.     

Abdominal aortic aneurysm or aortic occlusive disease: role of trace element imbalance

The nature of the relationship between atheromatous disease and degenerative aneurysm is yet to be defined. The purpose of this study was to compare tissue Fe, Cu, Zn, and thiobarbituric acid reactive substances (TBARS) levels (as a marker of lipid peroxidation) in the abdominal aorta in relation to the development of aneurysmal and occlusive disease in the infrarenal aorta. This was a prospective clinical study in an institutional referral center, in hospitalized patients. Eighty male patients who underwent surgery for abdominal aortic aneurysm (AAA) or aortic occlusive disease (AOD) were included in the study. Age, risk factors and comorbid conditions were recorded, including diabetes mellitus, hypertension, coronary artery disease, smoking, and chronic obstructive pulmonary disease. Aortic wall biopsies were collected at operation from the anterolateral section of the infrarenal aorta. Tissue Fe, Cu, Zn, and TBARS levels were determined. The mean age of the AAA group was 66.2 (56-75) years and of the AOD group 57.8 (47-72) years (p <0.001). There was a higher prevalence of hypertension in AAA patients compared to AOD patients (62.5%, 35% respectively; p <0.05). The comparison of tissue Zn levels showed no significant difference. Tissue levels of Fe, Cu, and TBARS were found to be higher in the AAA group, compared with the AOD group (p<0.001 for each). These results suggest that higher oxidative stress as a result of higher Fe and Cu levels in the AAA, compared with AOD, may be one of the contributing factors in aneurysmal formation as a result of promoted wall erosion.     

Aprotinin ameliorates ischemia/reperfusion injury in a rat hind limb model

The aim of the study was to investigate the protective effect of aprotinin in a rat hind limb ischemia/reperfusion (I/R) model. A well-known antioxidant, alpha-tocopherol, was also tested for comparison. Ischemia was induced for 4 h by vascular clamping of the iliac arteries of 24 Sprague-Dawley rats, followed by 1 h of reperfusion. Muscle injury was evaluated in three groups: a saline group, an alpha-tocopherol group and an aprotinin group. Blood pH, pO2, pCO2, HCO3, creatine kinase (CPK), lactate dehyrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) as well as muscle TBARS were measured at the end of the reperfusion. Muscle tissue samples were taken for histological examination. alpha-Tocopherol and aprotinin groups showed a significant amelioration of plasma CPK (p=0.002, p=0.002), LDH (p=0.004, p=0.004) and muscle tissue TBARS (p=0.001, p=0.001) compared with the control. Plasma TBARS were significantly lower in the aprotinin group compared with the control (p=0.017). Also, tissue TBARS was significantly lower in the aprotinin group than the alpha-tocopherol group (p<0.001). Neutrophil infiltration was less prominent in the alpha-tocopherol and aprotinin groups compared to the control (p=0.006, p=0.001). These results suggest that aprotinin, a potent anti-inflammatory drug, is more useful than alpha-tocopherol, a powerful antioxidant, for attenuating muscle injury after I/R.     

Advantages of the intrabreath technique as a measure of lung function before and after heart transplantation

BACKGROUND: Pulmonary function testing is an integral part of evaluating patients who are being considered for cardiac transplantation. The accurate measurement of diffusing capacity (DLCO) and alveolar volume (VA) is dependent on a 10-s breath-holding maneuver that may be difficult for patients with congestive heart failure to perform. The intrabreath (IB) technique is not dependent on a breath-holding maneuver and may provide more accurate pulmonary function testing results in chronically debilitated patients. METHODS: Seventy-five patients performed maneuvers with IB and single-breath (SB) techniques during evaluation for heart transplantation and at 3 and 12 months following transplantation. The DLCO, VA, and total lung capacity (TLC) were compared using Pearson correlation coefficients, a Student t test, and intercorrelation coefficients. RESULTS: The DLCO and VA, when determined with the IB technique, had excellent correlations to the SB technique over all ranges of DLCO values. VA values that were determined by the IB technique were greater than those determined by the SB technique and more closely approximated the TLC values. The satisfactory correlation between the two techniques was maintained when DLCO was corrected for VA. However, due to the lower values for VA as determined by the SB method, the corrected measurements were consistently higher for the SB technique. CONCLUSION: Pulmonary function can be measured accurately in a population of patients with long-standing congestive heart failure, both before and after cardiac transplantation, using the IB technique. Furthermore, the IB technique may provide a more accurate measurement of VA.     

The effects of cholesterol levels on hemorheological parameters in diabetic patients

Red blood cell (RBC) deformability is an important hemorheological parameter to determine the passage of RBC through narrow capillaries and the reduction of blood viscosity under high shear rates. Although it has been substantial evidence that diabetes mellitus (DM) and hypercholesterolemia increase the risk of coronary heart disease, the mechanism is unclear. In this study the relationship between hemorheological parameters and plasma cholesterol in type 2 diabetic patients (n=55, mean age 43.4+/-9.2 years) was examined. Type 2 diabetic patients were classified as normocholesterolemic (n=25; cholesterol < or = 200 mg/dl) and hypercholesteroloemic (n=30; cholesterol > 200 mg/dl) subgroups. Hypercholesterolemic type 2 diabetic patients had the highest blood and plasma viscosity and the lowest RBC deformability. The results were significantly different from normocholesterolemic type 2 diabetic patients (p<0.001). Our data suggest that elevated plasma cholesterol may impair RBC deformability and increase in blood and plasma viscosity by an additional effect to hyperglycemia in type 2 diabetic patients.     

False positivity of FDG-PET/CT in a child with Hodgkin disease

Role of Positron Emission Tomography (PET) with F-18-2-fluoro-2-deoxy-D-glucose (FDG) in staging of Hodgkin disease is well established despite several controversies. We report a Stage III Hodgkin lymphoma patient with false positive FDG-PET/CT results. Seven-year-old male with Hodgkin lymphoma was in remission at end of chemotherapy. At third and fourth month of postchemotherapy follow-up, increased Gallium uptake and positive FDG-PET/CT in right lower quadrant of abdomen was observed. Open biopsy revealed lymphoid hyperplasia. He has been followed for 21 months without any evidence of disease. Despite its documented benefit, we believe that results of FDG-PET/CT should be interpreted with great caution in order to avoid unnecessary interventions.     

Glioma-derived versican promotes tumor expansion via glioma-associated microglial/macrophages Toll-like receptor 2 signaling

BackgroundAccumulation and infiltration of microglia/brain macrophages around and into glioma tissue promote tumor invasion and expansion. One tumor-promoting mechanism of microglia/brain macrophages is upregulation of membrane type 1 matrix metalloprotease (MT1-MMP), which promotes the degradation of extracellular matrix. MT1-MMP upregulation is induced by soluble factors released by glioma cells activating microglial Toll-like receptor 2 (TLR2).MethodsVersican identified by proteomics was silenced in glioma cells by short interference RNA and short hairpin RNA approaches and studied in vitro and after injection into mouse brains or organotypic brain slices.ResultsThe splice variants V0/V1 of the endogenous TLR2 ligand versican are highly expressed in mouse and human glioma tissue. Versican-silenced gliomas induced less MT1-MMP expression in microglia both in vitro and in vivo, which resulted in smaller tumors and longer survival rates as compared with controls. Recombinant versican V1 induced significantly higher levels of MT1-MMP in wild-type microglia compared with untreated and treated TLR2 knockout microglial cells. Using glioma-injected organotypic brain slices, we found that the impact of versican signaling on glioma growth depended on the presence of microglia. Moreover, we found that TLR2 expression is upregulated in glioma-associated microglia but not in astrocytes. Additionally, an established TLR2 neutralizing antibody reduced glioma-induced microglial MT1-MMP expression as well as glioma growth ex vivo.ConclusionsOur results show that versican released from glioma promotes tumor expansion through glioma-associated microglial/macrophage TLR2 signaling and subsequent expression of MT1-MMP. This signaling cascade might be a novel target for glioma therapies.