Do PON1-Q192R and PON1-L55M polymorphisms modify the effects of hypoxic training on paraoxonase and arylesterase activity?

Background:Low levels of antioxidant paraoxonase 1(PON 1)enzyme activity,PON1-Q192R polymorphism(a glutamine(Q)to arginine(R)substitution at position 192),PON1-L55M polymorphism(a leucine(L)to methionine(M)substitution at position 55),and oxidized low-density lipoprotein(oxLDL)are risk factors for coronary heart disease.Aerobic exercise improves PON1 activity,but the effects of hypoxic exercise are yet unclear.The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms.Methods:Serum PON1 and arylesterase activities(ARE),PON1,PON3,and oxLDL protein levels(by using the enzyme-linked immunosorbent assays)were determined in an athletic group(42 trained male underwater rugby players;age=21.7±4.2 years,mean±SD)and a control group(43 sedentary men;age=23.9±3.2 years).The polymorphisms were determined from genomic DNA samples.Results:PON1 activity(25.1%,p=0.052),PON3(p<0.001),and oxLDL(p<0.001)of the athletic group,including most genotype groups,were higher than those of the control group.In comparison to the controls,PON1 activity levels(p=0.005)of the PON1-Q192R homozygote QQ genotype group and PON1 activity levels(30%,p=0.116)of the PON1-L55M homozygote LL genotype group were higher,whereas ARE activity values of athletic R allele carrier(Rc=QR+RR)(p=0.005)and LL group(p=0.002)were lower than the control genotype groups related to their polymorphisms.Conclusion:Hypoxic training can cause(1)significant oxidative stress,including oxLDL,and an antioxidant response(increase in PON1 activity and PON3),(2)differences in the activity of PON1 and ARE,which are modified by PON1-Q192R and PON1-L55M polymorphisms,respectively,and(3)improvements in PON1 activity of QQ and LL groups.However,hypoxic training can cause a disadvantage of LL and Rc groups for ARE.

High density lipoprotein as a therapeutic target:Focus on its functionality

Cardiovascular diseases(CVDs)are the leading cause of death globally.CVDs are a group of disorders of the heart and blood vessels and include coronary heart disease,cerebrovascular disease and rheumatic heart disease among other conditions.There are multiple independent risk factors for CVD,including hypertension,age,smoking,insulin resistance,elevated low-density lipoprotein cholesterol(LDL-C)levels,and triglyceride levels.LDL-C levels have traditionally been the target for therapies aimed at reducing CVD risk.High density lipoprotein(HDL)constitutes the only lipoprotein fraction with atheroprotective functions.Early HDL-targeted therapies have focused on increasing HDL-C levels.However,clinical trials have shown that raising HDL-C with niacin failed to achieve CVD reduction.A possible explanation for these findings is that these drugs could interfere with lipid metabolism and cause alterations in HDL structure and composition,leading to loss of functionality.As a result,targeting HDL-C levels would be insufficient to achieve CVD risk reduction,making HDL functionality a more desirable focus for HDL-directed therapies.There are several drugs which show the potential to improve HDL functionality.These drugs include molecules already approved for human use,such as statins and niacin,and particularly,compounds currently undergoing development such as apolipoprotein A-I mimetics and reconstituted HDL preparations.These therapies show promising potential to improve HDL functionality specifically.Future therapeutic strategies should incorporate HDL functionality as a main target of interest.

高同型半胱氨酸血症患者氧化应激指标的研究

目的观察高同型半胱氨酸血症(HHcy)患者氧化应激指标的水平,并对其临床价值做初步评价。方法检测108例HHcy患者、106名健康体检者(正常对照组)循环谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、对氧磷酯酶1(PON1)、一氧化氮合酶(NOS)活性及同型半胱氨酸(Hcy)、一氧化氮(NO)和丙二醛(MDA)水平。分析Hcy与GSH-Px、SOD、PON1、NOS、NO、MDA之间的相关性。结果 HHcy患者血浆MDA水平[(6.23±1.55)μmol/L]明显高于正常对照组[(4.14±1.13)μmol/L](P<0.01),而GSH-Px[(189.3±25.1)U/L]、SOD[(77.3±20.5)NU/mL]、PON1[(133.6±23.9)kU/L]、NOS活性[(25.3±2.9)U/mL]及NO[(68.3±10.1)μmol/L]水平低于正常对照组[(240.3±78.1)U/L、(89.2±24.8)NU/mL、(168.2±26.0)kU/L、(30.0±3.3)U/mL、(92.1±12.1)μmol/L](P均<0.01)。HHcy患者血浆Hcy与MDA呈正相关(r=0.72,P<0.01),与GSH-Px、SOD、PON1、NOS、NO呈明显负相关(r值分别为-0.60、-0.49、-0.51、-0.43、-0.50,P均<0.01)。结论 HHcy患者氧化应激增强可能与Hcy氧化过程中产生过多的过氧化物及活性氧、Hcy损伤NO/L-精氨酸系统及直接抵制抗氧化酶活性有关。Hcy可能通过增加氧化应激和降低抗氧化能力在动脉粥样硬化发生、发展中起重要的作用。

对氧磷酶(Paraoxonase)的测定方法与临床意义

对氧磷酶 (Paraoxonase)是结合在高密度脂蛋白 (HDL)上的一种有机磷三酯化合物水解酶。最近研究表明 ,对氧磷酶可以保护低密度脂蛋白 (LDL)的氧化 ,其活性与基因多态性被认为是动脉粥样硬化、冠心病的独立危险因素。本文综述Paraoxonase的生化特征、基因的多态性。

黄芪多糖抑制对氧磷所致血管功能障碍的作用研究(英文)

[ Objective] The paper was to explore the effect of astragalin on paraoxon-indueed vascular endothelium dysfunction and analyze the potential mecha- nism. [Method]The isolated rat thoracic aorta rings were exposed to medium contained paraoxon （3.63 μmol/L）, and astragalin （10 μmol/L） was used to inhib- it the damage effect. Rat thoracic aorta rings were suspended in organ chambers to assess vas orelaxation activity in vitro by acetyleholine （ACh）-induced endotheli- um dependent relaxation reaction （EDRR） and sodium nitroprusside （SNP）-induced endothdium-independent relaxation reaction. [Result]The exposure to parao- xon （3.63 μmol/L） resulted in an inhibition of the EDRR, markedly reduced the level of nitric oxide （NO）, the activity of paraoxonasel （PON1） and superoxide dismutase （SOD）, and significantly increased the level of malondialdehyde （MDA） in isolated rat thoracic aorta. However, the presence of astragalin （10 μmol/L） markedly attenuated the vascular endothelium dysfunction induced by paraoxon via increasing level of NO, activity of PON1 and SOD, as well as reducing level of MDA. In addition, treatment of astragalin （ 10 μmol/L） showed a similar effect to hydrogen peroxide （ 1.0 μmol/L）, a kind of antioxidant, on paraoxon- induced vascular endothelium dysfunction. [ Conclusion] Astragalin could protect the vascular endothelium against the paraoxon-induced dysfunction in isolated rat thoracic aorta, and＇the beneficial effects of astragalin might be concerned with the antioxidation of astragalin due to inhibiting the decreased activity of PONI.

Anti-ulcer Activity of Curcumin on Experimental Gastric Ulcer in Rats and Its Effect on Oxidative Stress/Antioxidant,IL-6 and Enzyme Activities

Objective To investigate the possible mechanism by which curcumio protects stomach during the acute chronic phase of gastric ulcer disease. Methods The rats were divided into four groups and fasted for 2 days with flee access to water. On the third day, the animals were fasted for a further 24 h with no access to water followed by surgery. Rats received different doses of curcumin （20, 40, and 80 mg/kg） or vehicle by oral gavage. Nineteen hours after ulcer induction, the rats were killed by decapitation. Stomach was opened along the greater curvature and ulcerative lesions were counted. Total juice acidity, neutrophils activity, mitochondrial activity, total antioxidants, paraoxonase （PON 1）/arylesterase and total peroxides were evaluated. DNA fragmentation （%） and pro-inflammatory cytokine IL-6 level were measured. The level of different gastro-cytoprotective effectors including total antioxidants and paraoxonase （PON 1）/arylesterase activities was measured. Results The anti-ulcer activity of curcumin was displayed by attenuating the different ulcerative effectors including gastric acid hyper-secretion, total peroxides, myeloperoxiase （MPO） activity, IL-6 and apoptotic incidence. Conclusion Cureumin appears to have a propitious protective effect against gastric ulcer development.

Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

To investigate the malondialdehyde（MDA） levels,paraoxonase1（PON1） activity and 8-hydroxy 2-deoxyguanosine（8-OHd G） levels in the primary open angle glaucoma（POAG） patient.Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHd G by high-performance liquid chromatography（HPLC） and PON1 by spectrophotometry.The data obtained were analyzed statistically.MDA levels were 10.46±8.4 and 4.70±1.79 μmol; PON1 levels were 121 ±39.55 and 161.62 ±60.22 U/m L; and 8-OHd G values were1.32 ±0.53/10~6 d G and 0.47 ±0.27/10~6 d G in the POAG patients and the control group,respectively.The difference was significant in MDA levels,8-OHd G levels and PON1 activity in POAG patients in comparison with controls（P 〈0.001）.We concluded that the observed increase in MDA and 8-OHd G levels may be correlated with decreased PON1 activity.Oxidative stress plays an important role in glaucoma development.

Monitoring the level of serum paraoxonase 1 activity in liver transplantation patients

BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of mo- nitoring the level of serum PON1 activity in liver transplan- tation patients. METHODS: A series of biochemical indexes were moni- tored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of se- rum PON1 level and its relations with other biochemical in- dexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level be- gan to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after open- ing of the portal vein ( P <0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.

Novel neuroprotective and hepatoprorective effects of citric acid in acute malathion intoxication

Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods: Rats were received intraperitoneal(i.p.) injection of malathion 150 mg/kg along with citric acid(200 or 400 mg/kg, orally), atropine(1 mg/kg, i.p.) or citric acid 200 mg/kg+atropine 1 mg/kg and euthanized 4 h later. Results: Malathion resulted in increased lipid peroxidation(malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase(GPx) activity, total antioxidant capacity(TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase(ACh E) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The Comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase(i NOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain ACh E increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and i NOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, ACh E and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and i NOS expression in brain and liver. Conclusions: The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.

Total oxidative stress, paraoxonase and arylesterase levels at patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma

AIMTo investigate the oxidative stress status of the aqueous humor and serum of patients with pseudoexfoliation (PEX) syndrome and pseudoexfoliative glaucoma (PEG) and to measure paraoxonase (PON) and arylesterase (ARE) levels.METHODSA total of 78 patients were enrolled in the study, with 26 patients in each separate group. The patients were divided into three groups: the first group entailed PEX syndrome patients, while the second group consisted of patients with PEG and the third group involved patients with no additional systemic diseases, other than the diagnosis of cataract as control. Total oxidative stress (TOS), total antioxidant capacity (TAC), PON, and ARE levels in aqueous humor and serum were measured.RESULTSTAC, PON and arylesterase levels in aqueous humor and serum of the PEX syndrome and PEG patients were significantly decreased compared with control group (P&#x0003c;0.05). TOS values were higher in patients with PEX syndrome and PEG than controls (P&#x0003c;0.05). TAC, PON and ARE levels of aqueous humor did not differ significantly between the PEX syndrome and PEG groupsCONCLUSIONThese findings are potentially of significance and add to the growing body of evidence for oxidative stress in PEX syndrome and PEG. Decreased antioxidant defense and increased oxidative stress system may play an important role in the pathogenesis of PEX syndrome and PEG.

Paraoxonase 1 gene (Gln¹⁹²-Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported. Objectives: To investigate the relationship between PON1 gene (Gln192-Arg) poly-morphism and the presence, extent and severity of CAD in type 2 DM. Methods: The study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into 4 groups;Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) non diabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1 (Gln192-Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion. Results: The frequency of Gln allele (Type A) was significantly higher in group I and group II compared to group III and group IV (62.5%, 60% vs 38.3%, 31.25% respectively, p 100 mg/dL [OR 4.31, CI (1.25 - 12.5), P < 0.001], high density lipoprotein (HDL) cholesterol <40 mg/dL [OR 5.11, CI (1.79 - 16.33), P < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67 - 13.57), P < 0.001] were significantly independent predictors of CAD. Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.

Association of Race and Change in Ankle-Brachial Index: The Atherosclerosis Risk in Communities (ARIC) Cohort

Objective: This study evaluates the association of self-reported race with change in ankle-brachial index (ABI) over time and modification of this association by paraoxonase gene (PON1, PON2 and PON3) single nucleotide polymorphisms (SNPs). Methods: This longitudinal study included 11,992 (N = 2952 Black, N = 9040 White) participants from the Atherosclerosis Risk in Communities (ARIC) cohort with PON genotyping. Mixed-effects models examined whether race was associated with change in ABI over time after adjustment for known peripheral artery disease (PAD) risk factors. Results: Change in ABI over time differed between Whites and Blacks (race-time interaction, p < 0.0001). Stratified analyses showed that ABI values were better in both Blacks and Whites who completed high school or more education compared to those who completed less education. None of the PON SNPs met the significance level (p < 0.001) after Bonferroni correction for multiple comparisons. Conclusions: ABI differences by race were small and although statistically significant, may not be clinically significant. Change in ABI over time varies by race and may be modified by education. Results suggest that higher education may influence the lifestyle and behavioral choices contributing to better ABI in both Blacks and Whites. Further studies are needed to confirm this observation.

Neuroprotection by misoprostol against rotenone-induced neurotoxicity in rat brain

Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods:Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1 st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of10, 100 or 1 000 μg/kg. Rats were evaluated for brain lipid peroxidation(malondialdehyde:MDA), reduced glutathione(GSH), nitric oxide(NO) levels, and paraoxonase-1(PON-1) activity.The concentrations of the anti-apoptotic protein B cell/lymphoma-2(Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase(iNOS) in the cerebral cortex and striatum were also performed. Results: Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation(MDA)by 61%(P<0.05) accompanied by an increase in NO by 73.1%(P<0.05) and a decrease in GSH concentration by 29.4%(P<0.05). In addition, brain PON-1 activity significantly decreased by63.0%(P<0.05) and striatal Bcl-2 significantly decreased by 27.9%(P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation.Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum.Treatment with misoprostol at doses of 100 and 1 000 μg/kg resulted in decreased brain MDA(by 16.5%-23.0%)(P<0.05) and NO levels(by 37.1%-40.7%)(P<0.05) and increased GSH concentrations(by 18.8%-30.1%)(P<0.05). PON-1 activity was significantly increased by80.0%-114.8%(P<0.05) by misoprostol at 100 and 1 000 μg/kg, respectively. In addition,misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats. Conclusions: These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress.

An assessment of antioxidant status in patients with carbon monoxide poisoning

BACKGROUND: Carbon monoxide poisoning(COP) is an important cause of mortality and morbidity worldwide. This study was to investigate the levels of serum paraoxonase(PON), arylesterase(ARYL), ceruloplasmin(Cp), and sulfhydryl(-SH) in the treatment of COP, and to further understand the pathophysiology of COP.METHODS: This prospective study comprised 107 individuals with COP(group 1) and 50 healthy volunteers(group 2). Serum, plasma, and erythrocyte samples were taken on admission from all participants with COP. This process was repeated in the 90 th and 180 th minutes of treatment. Samples were taken from the control group only once. The levels of plasma PON, ARYL, Cp activity and-SH were measured in both groups.RESULTS: Age, gender, and carboxyhemoglobin level were not correlated with PON, ARYL, Cp, and-SH levels. PON, ARYL, and-SH levels were signifi cantly decreased in group 1 compared with group 2. Conversely, Cp was signifi cantly elevated in group 1 in contrast to group 2. Although ARYL was lower on admission in patients with COP than that was observed in the 90 th and 180 th minutes(P<0.001), Cp was higher on admission than at the other time points(P<0.001).CONCLUSIONS: Participants with COP had decreased levels of antioxidants(PON, ARLY, and-SH). COP represses the antioxidant system.

Analysis of Single Nucleotide Polymorphism in Human Paraoxonase 1 Gene(Q192R) with Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry

Introduction Single nucleotide polymorphisms （SNPs） are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the analysis of single nucleotide polymorphisms, including restriction fragment length polymorphism （RFLP）, direct sequencing by using laser-induced fluorescence detectionTM, fluorescence energy transfer, MALDI-TOF MS combined with primer extension or invasive cleavage, and fluorescence polarization. During the past two decades, mass spectrometry has become a very popular tool in the analysis of biomolecules and is perfectly suited to the analysis of single nucleotide polymorphisms （SNPs） due to its speed, low cost, and accuracy. In this work, we used MALDI TOF mass spectrometry to detect the fragments of restriction endonuclease hydrolysis of PCR products flanking a SNP located at paraoxonase 1（Q192R）. Compared with electrophoresis, this method requires less time of analysis and possess a higher accuracy.

Increased Oxidant Stress and Inflammation in Patients with Chronic Schizophrenia

Background: Several lines of evidence, including postmortem studies, suggest increased oxidative stress and inflammation in patients with schizophrenia. Alteration of oxidative stress markers has been reported in schizoprenia studies, but with inconsistent results. Oxidized low-density lipoproteins (oxLDL) have been reported to be capable of eliciting neurocytotoxicity. On the other hand, paraoxonase (PON1), an arylesterase(ARE), plays a role in protection against oxidative modifications of LDL and is considered to be one of the antioxidant enzymes. There are no studies showing the changes in oxidative stress and inflammation together, nor the activities of PON1 and ARE in schizophrenic patients. In this study, we examined PON1, ARE activities and oxidative/anti-oxidative markers in patients with chronic schizophrenia and healthy controls. Methods: We recruited 30 male chronic schizophrenic patients and 30 male healthy control subjects and examined C-reactive protein(CRP), fibrinogen, PON1, ARE and plasma total antioxidant status (TAS) and total oxidant status (TOS), oxidative stress index(OSI) in both groups. Schizophrenia symptoms were assessed using the positive and negative syndrome scale (PANSS). The related routine lipid profile parameters including HDL were also examined. Results: Patients had significantly higher CRP, fibrinogen, TOS and OSI levels;but the patients and control subjects did not differ on activities of the antioxidant enzymes PON1 and ARE. Interestingly, there were not any group differences in the lipid profile parameters except the triglyceride levels, that increased significantly in the patient group. Conclusions: In the present study, reporting the ARE activities besides the PON1 activities in schizophrenic patients for the first time, we showed that PON1 and ARE enzyme activities were not statistically different in patients with chronic schizophrenia. This study provides additional evidence of increased oxidative stress and inflammation in chronic schizophrenia, but no alterations in the antioxidant status were observed. Our results suggest that other mechanisms than the high density lipoprotein(HDL)-disfunctionality, namely decreases in PON1 or ARE enzyme activities, are more important in oxidative or antioxidative pathophysiological processes in schizophrenia.

Paraoxonase-1 gene in patients with chronic obstructive pulmonary disease investigation Q192R and L55M polymorphisms

BACKGROUND: The effect of increased oxidative stress on the development of chronic obstructive pulmonary disease(COPD) is well known. One of the antioxidative systems against oxidative stress in human body is paraoxonase(PON) enzyme that protects low density lipoproteins(LDL) against oxidation. This study aimed to explore the polymorphisms on PON1, Q192 R, L55 M genes of patients with COPD.METHODS: DNAs extraction was obtained from blood samples of 50 patients diagnosed with COPD and 50 patients as a control group who were presented to emergency clinic. Genotypes were obtained with polymerase chain reaction(PCR) and AIw I and Hsp92 II restriction enzymes were used for Q192 R and L55 M polymorphisms, respectively. Analysis of data was done with the Chi-square test and Fisher's exact test.RESULTS: A statistically significant difference in Q192 R polymorphism was found between the COPD patients and the control group(P=0.05). There was no statistically significant difference in L55 M polymorphisms between the patient and control groups(P>0.05). Q192 R polymorphism was significantly correlated with the PON1 gene and cigarette smoking; however other risk factors did not show any significant correlation with this polymorphism. Though L55 M polymorphism was significantly correlated with family history and tuberculosis, there was no significant correlation with other risk factors.CONCLUSION: We believe that more studies are needed to study the correlation of L55 M polymorphism with other factors.

Connecting inorganic mercury and lead measurements in blood to dietary sources of exposure that may impact child development

Pre-natal and post-natal chemical exposures and co-exposures from a variety of sources including contaminated air,water,soil,and food are common and associated with poorer birth and child health outcomes.Poor diet is a contributing factor in the development of child behavioral disorders.Child behavior and learning can be adversely impacted when gene expression is altered by dietary transcription factors such as zinc insufficiency or deficiency or by exposure to toxic substances permitted in our food supply such as mercury,lead,or organophosphate pesticide residue.Children with autism spectrum disorder and attention deficit hyperactivity disorders exhibit decreased or impaired PON1 gene activity which is needed by the body to metabolize and excrete neurotoxic organophosphate pesticides.In this current review we present an updated macroepigenetic model that explains how dietary inorganic mercury and lead exposures from unhealthy diet may lead to elevated blood mercury and/or lead levels and the development of symptoms associated with the autism and attention deficithyperactivity disorders.PON1 gene activity may be suppressed by inadequate dietary calcium,selenium,and fatty acid intake or exposures to lead or mercury.The model may assist clinicians in diagnosing and treating the symptoms associated with these childhood neurodevelopmental disorders.Recommendations for future research are provided based on the updated model and review of recently published literature.

Inhibitory effect of the paraoxonase gene on the formation of rabbit coronary atherosclerosis

Objective:To observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene(PON-1) which transfected to the rabbit epicardial adipose tissue.Methods: Rabbit coronary atherosclerosis model was established by high-fat feeding,liposome-encapsulated recombinant plasmid pEGFP-PON-1 50μL was injected to the rabbit pericardial cavity,and was harvested 4 weeks after transfection.Results:The epicardial fat transfected PON-1 gene had effect on the high lipid level.It significantly increased expression of PON-1 in peripheral arterial vascular tissue(P【0.05);and significantly reduced total cholesterol and low-density lipoprotein cholesterol levels(P【0.05).and the thickness ratio of coronary artery intima/ media(P【0.05).Conclusions:The injection of the PON-1 gene in the pericardial cavity can effectively suppress the formation of coronary atherosclerosis.

Impact of antibacterial drugs on human serum paraoxonase-1(hPON1)activity:an in vitro study

Objective:To investigate the in vitro effects of the antihacterial drugs,mcropenem trihydrate.piperacillin sodium,and cefoperazone sodium,on the activity of human serum paraoxonase mPOND.Methods:hPQN1 was purified from human serum using simple chromatographic methods.including DEAE-Sephadex anion exchange and Sephadex G-200 gel filtration chromatography.Results:The three antihacterial drugs decreased in vitro hPON1 activity.Inhibition mechanisms meropcnem trihydrate was noncompetitive while piperacillin sodium and cefoperazone sodium were competitive.Conclusions:Our results showed that antihacterial drugs significantly inhibit hPON1 activity,both in vitro,with rank order meropenem trihydrate piperacillin sodium cefoperazone sodium in vitro.