Crevicular fluid levels of plasma glutathione peroxidase (eGPx) in periodontal health and disease

Background & objectives

Reactive oxygen species (ROS) have been implicated in numerous human diseases, including periodontal diseases. Plasma glutathione peroxidase (eGPx) as an important antioxidant, has a protective role against ROS and is an established marker of oxidative stress. The present study evaluated the levels of eGPx in GCF to further probe into the role of oxidants and antioxidants in periodontal disease.

Methods

60 subjects were divided into three groups consisting of 20 subjects in each group based on gingival index, pocket probing depth, clinical attachment loss and radiological parameters (bone loss): healthy (group 1), gingivitis (group 2) and periodontitis (group 3), whilst, group 3 patients after the treatment constituted group 4. GCF samples were collected from all groups to estimate the levels of eGPx using ELISA.

Results

The mean eGPx concentration in GCF were observed to be the highest in group 3 i.e., 30.89 ± 4.93 ng/μl and lowest in group 1 i.e., 15.32 ± 3.06 ng/μl. The mean eGPx concentration in group 2 (23.77 ± 2.91 ng/μl) and group 4 (18.92 ± 3.53 ng/μl) fell between the highest and the lowest values.

Conclusion

This suggests that eGPx levels in GCF increase proportionally with the severity of periodontal diseases. eGPx can be considered as a marker of oxidative stress in periodontal diseases. However, controlled, longitudinal studies with larger samples have to be carried out to confirm this possibility.     

Potential function of TGF-β isoforms in maturation-stage ameloblasts

Objectives

To investigate potential functions of transforming growth factor-beta (TGF-β) isoforms in maturation-stage ameloblasts during amelogenesis.

口腔鳞癌P-gp、GST-π表达与化疗药物耐受性

目的 探讨P－糖蛋白（P－glycoprotein,P-gp)和谷胱甘肽S转移酶π（glutathione transferase-π，GST-π）表达与化疗药物耐受性的关系。方法 采用免疫组化过氧化物酶标记法检测口腔颌面部鳞癌和正常口腔粘膜组织样本中P－gp和GST-π的表达，结合MTT药敏检测结果分析。结果 P－gp和GST-π在恶性肿瘤中阳性表达率分别为57．1％和53．6％，在正常组织中未见表达；P－gp的表达与化疗药物总体耐受性有关；GST-π的表达与患者顺铂耐受性有关。结论 P－gp和GST-π的阳性表达提示患者有化疗药物耐受倾向。P－pg和GST-π检测对判断口腔颌面部恶性肿瘤化疗耐药性有指导意义。     

Differential expression of salivary S100A7 in oral submucous fibrosis

Aim

To investigate the expression of salivary S100A7 levels among patients with oral submucous fibrosis (OSF) and healthy controls.

牙周病变组织谷胱甘肽过氧化物酶的测定

目的：探讨谷胱甘肽过氧化物酶与牙周组织病的关系。方法：选择了１２例慢性龈炎，１３例单纯性牙周炎，９例健康对照，采用ＤＴＮＢ显色法测定酶的活性，对其病变龈组织做ＧＳＨ－ＰＸ测定，并分析了临床指标与实验室指标的相关关系。结果：１．龈炎组，ＧＳＨ－ＰＸ含量为２９３．７４±１２１．７０，牙周炎组为２４２．９７±１１０．５９，对照组７８１．２５±１１３．３９，龈炎组、牙周炎组的ＧＳＨ－ＰＸ活性显著低于对照组（Ｐ＜０．０１），龈炎组与牙周炎组ＧＳＨ－ＰＸ活性无显著差异（Ｐ＞０．０５）。２．龈炎组牙龈指数与ＧＳＨ－ＰＸ活性成负相关（ｒ＝－０．７２２５，Ｐ＜０．００５），牙周炎组牙周袋深度，附着丧失量与ＧＳＨ－ＰＸ活性成负相关（ｒ＝－０．７６５３，ｒ＝－０．８５７８，Ｐ＜０．００２５）。结论：牙周病变组织ＧＳＨ－ＰＸ活性降低可能有两方面的原因，其一是牙周病是细菌引起的非特异性炎症，由于细菌的存在，局部自由基生成增多对ＧＳＨ－ＰＸ消耗增大；其二是由于全身因素的影响局部ＧＨＳ－ＰＸ合成减少。     

Inhibition of Candida albicans by the peroxidase/SCN−/H2O2 system

Effects of the salivary peroxidase (SPO) system on the growth, glucose uptake and metabolic activities of oral bacteria are well documented but the effects on oral fungi are virtually unknown. Therefore, the viability of Candida albicans (ATCC 28366) exposed to the peroxidase/SCN^?/H₂O₂: system was studied in sterilized saliva, in phosphate-buffered saline (PBS) and in potassium chloride. The growth of C. albicans in glucose-supplemented saliva was faster at pH 5.5 than at pH 7. The addition of the complete SPO (or lactoperoxidase) system to either sterilized saliva, KC1 (50 μM) or PBS at pH 5.5 inhibited dose-dependently the viability of C. albicans in KC1, but no inhibition was found in PBS or saliva. Maximal inhibition was achieved in 2 h and with > 320 μM of peroxidase-generated HOSCN/OSCN^?. However, physiological salivary concentrations of phosphate (> 1.0 μM) and PBS blocked the antifungal effect of HOSCN/OSCN^?. The relative proportions of SCN^? and H₂O₂: were critical to the antifungal effects. With 0.2 mM KSCN, a complete loss of viability was achieved, though the HOSCN/OSCN^? concentrations did not exceed 100 μM. It is concluded that C. albicans is sensitive to HOSCN/OSCN^? but salivary concentrations of phosphate block the antifungal effect of the peroxidase systems.     

Low plasma antioxidant status in patients with epilepsy and the role of antiepileptic drugs on oxidative stress

Background:

Oxidative stress has been implicated in various disorders including epilepsy. We studied the antioxidant status in patients with epilepsy and aimed at determining whether there was any difference in the antioxidant levels between patients and controls, patients who are not on antiepileptic drugs (AEDs), and on treatment, between individual AEDs and patients on monotherapy and polytherapy.

Materials and Methods:

Antioxidant levels like catalase, glutathione peroxidase (GPx), vitamin E, glutathione (GSH), thiol group (SH), uric acid, and total antioxidant capacity (TAC) were compared between 100 patients with epilepsy and equal number of controls. Twenty-five patients who were not on AEDs were compared with patients on AEDs and the control group. Patients were divided into monotherapy and polytherapy group and antioxidant status was compared between the two groups and between individual drugs.

Results:

Catalase, SH, vitamin E, and TAC were significantly low in patients with epilepsy than those in the control group (P < 0.001). GSH and uric acid did not show any difference; GPx in patients was significantly higher than those in the control group There were no differences in the antioxidant levels between the treated and the untreated groups; however, it was lower in untreated patients than controls (P < 0.001), suggesting that AEDs do not modify the oxidative stress. Patients on Valproate (VPA) showed higher catalase and GPx levels. Catalase was higher in the monotherapy than polytherapy group (P < 0.04).

Conclusion:

Our study found significantly low levels of antioxidant in patients as compared to controls. AED did not influence the antioxidant status suggesting that seizures induce oxidative stress.     

Target-mediated clearance and bio-distribution of a monoclonal antibody against the Kunitz–type protease inhibitor 2 domain of Tissue Factor Pathway Inhibitor

Introduction

A humanised monoclonal antibody, concizumab, that binds with high affinity to the Kunitz-type protease inhibitor (KPI) 2 domain of human tissue factor pathway inhibitor (TFPI) is in clinical development. It promotes coagulation by neutralising the inhibitory function of TFPI and may provide a subcutaneous prophylaxis option for patients with haemophilia. We aimed to study biodistribution and pharmacokinetics (PK) of concizumab.

Materials and Methods

Blockage of cellular TFPI by concizumab was measured by tissue factor/Factor VIIa-mediated Factor X activation on human EA.hy926 cells. Biodistribution of concizumab was analysed in rabbits by immunohistology, and the PK was measured in rabbits and rats.

Results and Conclusions

Concizumab bound to cell surface TFPI on EA.hy926 cells and neutralised TFPI inhibition of Factor X activation. The antibody cross-reacted with rabbit TFPI, but not with rat TFPI, allowing for comparative PK studies. PK data in rats described a log-linear profile typical for a non-binding antibody, whereas PK data in rabbits revealed a non-linear, dose-dependent profile, consistent with a target-mediated clearance mechanism. Immunohistology in rabbits during target-saturation showed localisation of the antibody on the endothelium of the microvasculature in several organs. We observed a marked co-localisation with endogenous rabbit TFPI, but a negligible sub-endothelial build-up. Concizumab binds and neutralises the inhibitory effect of cell surface-bound TFPI. The PK profile observed in rabbits is consistent with a TFPI-mediated drug disposition. Double immunofluorescence shows co-localisation of the antibody with TFPI on the endothelium of the microvasculature and points to this TFPI as a putative target involved in the clearance mechanism.     

The ontogeny of drug metabolism enzymes and implications for adverse drug events

Profound changes in drug metabolizing enzyme (DME) expression occurs during development that impacts the risk of adverse drug events in the fetus and child. A review of our current knowledge suggests individual hepatic DME ontogeny can be categorized into one of three groups. Some enzymes, e.g., CYP3A7, are expressed at their highest level during the first trimester and either remain at high concentrations or decrease during gestation, but are silenced or expressed at low levels within one to two years after birth. SULT1A1 is an example of the second group of DME. These enzymes are expressed at relatively constant levels throughout gestation and minimal changes are observed postnatally. ADH1C is typical of the third DME group that are not expressed or are expressed at low levels in the fetus, usually during the second or third trimester. Substantial increases in enzyme levels are observed within the first one to two years after birth. Combined with our knowledge of other physiological factors during early life stages, knowledge regarding DME ontogeny has permitted the development of robust physiological based pharmacokinetic models and an improved capability to predict drug disposition in pediatric patients. This review will provide an overview of DME developmental expression patterns and discuss some implications of the data with regards to drug therapy. Common themes emerging from our current knowledge also will be discussed. Finally, the review will highlight gaps in knowledge that will be important to advance this field.     

过氧化物酶-抗过氧化物酶复合物(PAP)检测血清抗核抗体

目的 探讨过氧化物酶－抗过氧化物酶复合物（PAP）检测血清抗核抗体（ANA）的实用性。方法 以小鼠肝细胞为基质,对PAP方法测定血清ANA的滴度、核型进行了方法学检测,并同时与间接免疫荧光法相比较,测定了203例正常人及46例风湿病患者的血清ANA。结果 PAP法敏感性高于IIF法,滴度是IIF法的10－640倍。PAP可提高血清ANA的阳性检出率,还可提高核型的清晰度。结论 PAP法适用于缺乏荧光显微镜的基层医院开展ANA的检测。