Stress In Pathogenesis Research Articles

Potential role of oxidative stress in pathogenesis of benign prostatic hyperplasia in male dogs.

The pathogenesis of benign prostatic hyperplasia (BPH) in dogs is still not fully understood. Some studies suggest that oxidative stress may have a potential role in the pathogenesis of BPH in dogs. Age-related hormonal changes may activate a chronic inflammatory response in the prostate. This causes the generation of reactive oxygen species (ROS) and results in oxidative stress. Excessive production of ROS results in DNA damage and hyperplastic transformation of prostatic cells. The use of antioxidants for improvement of treatment outcomes for canine PBH has been discussed. Further research is needed on the importance of oxidative stress in the development of BPH in dogs and the usefulness of antioxidants in the supportive treatment of this condition.

Oxidative Stress and Potential Antioxidant Therapies in Vitiligo: A Narrative Review.

Vitiligo is a chronic skin disorder characterised by the loss of melanocytes and subsequent skin depigmentation. Although many theories have been proposed in the literature, none alone explains the pathogenesis of vitiligo. Oxidative stress has been identified as a potential factor in the pathogenesis of vitiligo. A growing body of evidence suggests that antioxidant therapies may offer a promising approach to managing this condition. This review summarises the potential mechanisms of oxidative stress and the types of melanocyte death in vitiligo. We also provide a brief overview of the most commonly studied antioxidants. Melanocytes in vitiligo are thought to be damaged by an accumulation of reactive oxygen species to destroy the structural and functional integrity of their DNA, lipids, and proteins. Various causes, including exogenous and endogenous stress factors, an imbalance between prooxidants and antioxidants, disruption of antioxidant pathways, and gene polymorphisms, lead to the overproduction of reactive oxygen species. Although necroptosis, pyroptosis, ferroptosis, and oxeiptosis are newer types of cell death that may contribute to the pathophysiology of vitiligo, apoptosis remains the most studied cell death mechanism in vitiligo. According to studies, vitamin E helps to treat lipid peroxidation of the skin caused by psoralen ultra-violet A treatment. In addition, Polypodium leucotomos increased the efficacy of psoralen ultra-violet A or narrow-band ultraviolet B therapy. Our review provides valuable insights into the potential role of oxidative stress in pathogenesis and antioxidant-based supporting therapies in treating vitiligo, offering a promising avenue for further research and the development of effective treatment strategies.

The Role of Endothelin-1 and Oxidative Stress In Pregnancy Induced Hypertension


 Pregnancy Induced HypertensionPIH is one of the most frequent complications of pregnancy , however little is known about its etiology. Endothelial dysfunction serves as a causative factor in the initiation of the maternal pathophysiological changes of PIH & is not just a result of this disorder. Endothelin-1 may play an important role in the pathophysiology of PIH, either by acting on vascular smooth muscle directly to induce contraction or by increasing the formation of angiotensin II. Pregnancy induced hypertension is associated with endothelial dysfunction & could be caused by oxidative stress. Recent evidence suggest the role of oxidative stress in PIH. The high level of malondiahyde MDA may reflect the excessive oxidative damage in PIH. The study sample consist of 50 normal non pregnant women, 50 normotensive pregnant women, and 50 preeclamptic pregnant women in their third trimester in Mosul city. The aim of this study was designed to evaluate the role of endothelial dysfunction and oxidative stress in pathogenesis of PIH. The results of this study showed that there was a highly significant elevation (P0.000) in the serum level of endothelin-1 in the preeclamptic pregnant women in comparison with normotensive pregnant & the control group. Also there was a highly significant elevation (P0.000) in the level of serum MDA in the preeclamptic pregnant women in comparison with normotensive pregnancy & the control group. The serum endothelin-1 has a significant negative correlation with both maternal age & gestational age, while endothelin-1 has a significant positive correlation with diastolic blood pressure. The MDA showed a significant negative correlation with maternal age, while there was a significant positive correlation between MDA & diastolic blood pressure.
 
 

Role of Oxidative Stress in Pathogenesis and Severity of COVID-19 Infection: Case-Control Study in Iraq

Coronavirus disease 2019 (COVID-19) has presented a significant threat to public health and has rapidly spread across the globe since its outbreak in Wuhan, China, in 2019. Clinical evidence suggests higher oxidative stress in COVID-19 patients, and this worsening redox status may contribute to disease progression. The present study aimed to investigate oxidative stress in patients with mild and severe COVID-19. A case-control study was conducted from September 2021 to January 2022 among eighty-eight COVID-19 patients (male: female, 35:53) and eighty-eight healthy volunteers as the control group (male: female, 53:35) with ages ranging from (18-45) years in Duhok city, Kurdistan Region-Iraq. According to the severity of infection, patients were divided into two groups (mild and severe). Serum levels of malondialdehyde (MDA) and 8-isoprostaglandin F2 alpha (8-iso-PGF2) were assessed as oxidative stress markers. In addition, serum activity of two main antioxidant enzymes, superoxide dismutase (SOD) and catalase were measured. Furthermore, their correlation with the most frequently used laboratory parameters, C-reactive protein (CRP) and D-dimer, were investigated. Serum levels of 8-iso-PGF2 and MDA were considerably higher in patients with COVID-19 compared to healthy individuals (p <0.001) and between severe and mild patients (p<0.001). The activity of CAT was greater in COVID-19 group than in controls (p=0.011), but the difference between severe and mild diseases was statistically insignificant (p>0.05). However, SOD activity showed an insignificant difference between control and case groups (p>0.05), as well as between mild and severe groups (p>0.05). Also, a significant correlation was found between oxidative stress biomarkers and laboratory parameters CRP and D-dimer (p<0.001; and p=0.020), respectively. COVID-19 patients show significantly increased oxidative stress parameters. This may play a crucial role in the disease pathophysiology and could be considered as a predictive marker for COVID19 severity.

Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia.

Peroxiredoxin 3 (PRDX3) belongs to a superfamily of peroxidases that function as protective antioxidant enzymes. Among the six isoforms (PRDX1-PRDX6), PRDX3 is the only protein exclusively localized to the mitochondria, which are the main source of reactive oxygen species. Excessive levels of reactive oxygen species are harmful to cells, inducing mitochondrial dysfunction, DNA damage, lipid and protein oxidation and ultimately apoptosis. Neuronal cell damage induced by oxidative stress has been associated with numerous neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Leveraging the large aggregation of genomic ataxia datasets from the PREPARE (Preparing for Therapies in Autosomal Recessive Ataxias) network, we identified recessive mutations in PRDX3 as the genetic cause of cerebellar ataxia in five unrelated families, providing further evidence for oxidative stress in the pathogenesis of neurodegeneration. The clinical presentation of individuals with PRDX3 mutations consists of mild-to-moderate progressive cerebellar ataxia with concomitant hyper- and hypokinetic movement disorders, severe early-onset cerebellar atrophy, and in part olivary and brainstem degeneration. Patient fibroblasts showed a lack of PRDX3 protein, resulting in decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. Moreover, PRDX3 knockdown in cerebellar medulloblastoma cells resulted in significantly decreased cell viability, increased H2O2 levels and increased susceptibility to apoptosis triggered by reactive oxygen species. Pan-neuronal and pan-glial in vivo models of Drosophila revealed aberrant locomotor phenotypes and reduced survival times upon exposure to oxidative stress. Our findings reveal a central role for mitochondria and the implication of oxidative stress in PRDX3 disease pathogenesis and cerebellar vulnerability and suggest targets for future therapeutic approaches.

Comparison of the tissue expressions of glutathione S transferase isoenzymes among patients with morphea and healthy controls: A preliminary study.

Morphea is an inflammatory connective tissue disorder, which is characterized by sclerosis in skin and subcutaneous tissues with a chronic progress. The oxidative stress in pathogenesis of sclerosing diseases was proposed in several studies with conflicting results. To explore the tissue expressions of Glutathione S transferase (GST) isoenzymes in patients with morphea and compare these expressions with healthy controls. Twenty-two morphea patients and 20 sex and age matched healthy controls were enrolled in this study. Four millimeter punch biopsies were performed from the active sclerotic plaques of morphea patients. Tissue samples of control group were obtained from nonlesional normal skin biopsy specimens. The protein expressions of GST isoenzymes were analyzed immunohistochemically. Tissue expressions of GSTP1, GSTT1, and GSTA1 isoenzymes in morphea patients were found to be significantly higher than in control tissues. There was no significant difference in GSTM1 isoenzyme expression between the two groups. The increased tissue expressions of GSTA1, GSTP1, and GSTT1 isoenzymes in morphea may represent the activated GST enzymes in response to excessive free radical formation and may also support the hypothesis of increased oxidative stress in morphea etiopathogenesis.

PBN protects NP cells from AAPH-induced degenerative changes by inhibiting the ERK1/2 pathway

ABSTRACT Aim: Intervertebral disc (IVD) degeneration (IDD) is one of the main causes for spinal degenerative diseases, such as disk herniation, spinal canal stenosis, and spinal deformities. Growing evidence has highlighted the contribution of oxidative stress in pathogenesis of IDD, and antioxidant treatment is thus considered to be a promising therapeutic strategy for IDD. The aim of this study was to investigate whether N-tert-butyl-α-phenylnitrone (PBN), a free radical scavenger, could attenuate the pathological changes of IDD by alleviating oxidative stress. Materials and Methods: Nucleus pulposus (NP) cells were isolated from rabbit lumbar disks. MTT assay, real-time PCR and western blotting were employed to evaluate the effects of PBN on oxidative damages induced by 2,2ʹ-azobis (2-amidinopropane) dihydrochloride (AAPH) in NP cells. Results: AAPH induced oxidative stress and the subsequent degenerative changes in NP cells via the ERK/MAPK pathway. On the contrary, the oxidative stress induced by AAPH was significantly ameliorated by PBN. Moreover, PBN also attenuated AAPH-induced expression of matrix degradation proteases and apoptosis. PBN suppresses AAPH-induced activation of ERK/MAPK pathway, which may be the underlying mechanism for the protective effects of PBN. Conclusions: Our study for the first time identified a novel role and mechanism for PBN in protecting the IVD against oxidative stress, matrix catabolism and apoptosis, which may have implications for its further application in combating IVD degenerative diseases. Abbreviations: AAPH: 2,2ʹ-azobis(2-methylpropanimidamidine) dihydrochloride; ADAMTS: a disintegrin and metalloproteinase with thrombospondin motifs; AF: annulus fibrosus; CEP: cartilage endplate; DCF: 2ʹ7’-dichlorofluorescein; IDD: intervertebral disc degeneration; IVD: intervertebral disc; LPS: lipopolysaccharide; MMP: matrix metalloproteinase; MTT: methyl-thiazolyl-tetrazolium; NP: nucleus pulposus; PBN: N-tert-butyl-alfa-phenylnitrone; PGs: proteoglycans; ROS: reactive oxygen species; SDS: sodium dodecyl sulfate

DECREASE IN SERUM BILIRUBIN AS AN UNFAVORABLE MARKER OF CARDIOVASCULAR DISORDERS

Serum bilirubin, the end product of heme metabolism, is a routine biochemical parameter. Bilirubin is not a liver function parameter exclusively: its concentration correlates with ischemic heart disease (IHD) risk, estimated glomerular filtration rate, retinopathy or neuropathy in diabetes mellitus, atherosclerosis etc. The aim of this paper was to estimate the clinical value of bilirubin analysis according to literature data and own clinical observations in patients with IHD and acute and chronic rheumatologic diseases. Materials and methods. We conducted a literature overview in Pubmed database and domestic sources and also analyzed the standard examinaions of 515 patients: 353 patients with coronary heart disease (acute forms, coronary bypass grafting – 98; acute myocardial infarction, pharmacotherapy – 75; unstable angina pectoris – 101; stable angina pectoris – 79) and 162 rheumatologic patients (haemorrhagic vasculitis – 71; rheumatic fever – 57; chronic rheumatic heart disease with valvular defects – 34). Control group consisted of 22 patients with gastroduodenal zone diseases without helicobacter (esophagitis, gastritis, peptic ulcer). Results and discussion. It was revealed that in case of diseases with oxidative stress in their pathogenesis (acute forms of coronary heart disease, haemorrhagic vasculitis, rheumatic fever) bilirubin level was lower than in case of non-oxidative disorders (non-infectious esophagitis, gastritis, ulcer). Increase of inflammation potency was accompanied by bilirubin decrease. Correlation analysis showed that both bilirubin increase and decrease were unfavourable. Conclusions. Bilirubin concentration correlated with parameters of cytolysis, intoxication, anemia, inflammation, carbohydrate and lipid metabolism, heart structure. Bilirubin decrease associated with the increase of stenosis of coronary arteries (left, left circumflex and anterior interventricular) in a logarithmic way. Hypobilirubinemia (< 9.6 mkmol/L) significantly more often accompanied diseases with oxidative stress in pathogenesis, acute forms and more active systemic inflammation. Keywords total bilirubin, hypobilirubinemia, coronary heart disease, haemorrhagic vasculitis, rheumatic fever, chronic rheumatic heart disease.

Effect of probiotics supplementation on glucose and oxidative stress in type 2 diabetes mellitus: a meta-analysis of randomized trials.

The role of oxidative stress in pathogenesis of diabetes is well established. In addition, an association between gut microbiota and type 2 diabetes mellitus (T2DM) is widely observed in previously published reports. This meta-analysis critically examines the association between gut microbiota, and oxidative stress in T2DM. A systematic search for clinical trials was performed in PubMed, Web of Science and Scopus web databases up to 1 Jan 2019. Primary search terms include "microbiota", "diabetes", and "oxidative stress". Study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. All clinical trials that compared the effects of probiotic supplementations with a control group using end points serum levels of fasting blood sugar (FBS), hemoglobin A1C (HbA1C) and oxidative stress biomarkers were included. Two independent researchers screened the data extracted from the relevant studies. The pooled standardized mean difference (SMD) was estimated using the random or fixed effects model. Heterogeneity among the studies was assessed using Q-test. Overall, 13 randomized clinical trials (RCTs) involving 840 subjects with T2DM were included in the meta-analysis. The analysis showed that probiotics intake resulted in significant improvement in serum levels of FBS [SMD: -0.35, 95% CI: (-0.59, -0.12)], total antioxidant status (TAS) [SMD: 0.33, 95% CI: (0.11, 0.55)], total glutathione (GSH) [SMD: 0.41, 95% CI: (0.26, 0.56)] and malondialdehyde (MDA) [SMD: -0.54, 95% CI: (-0.83, -0.26)]. No significant improvement was found in HbA1C [SMD: -0.06, 95% CI:(-0.82, 0.69)], and nitric oxide (NO) [SMD:-0.24, 95% CI:(-1.10, 0.62)] levels. It seems that gut microbiota can exert beneficial effects in diabetic patients via altering oxidative stress' biomarkers. The beneficial effect of gut microbiota however was modest on FBS and non-significant on HbA1C. These results need to be confirmed by conducting more reliable RCTs. CRD42019134905. Graphical abstract Flow diagram of the study selection process.

Diagnostics of chronic nonbacterial prostatitis

The connection between aseptic inflammation, infectious and autoimmune factors, oxidative stress in pathogenesis of chronic prostatitis, chronic pelvic pain syndrome and lower urinary tract symptoms is considered. The limitations of the currently accepted prostatitis classification and new principles to overcome them are discussed. The algorithms of prostatitis diagnosis offered by the Russian Society of Urologists and the European Association of Urology are described. Data on the current methods of detection of bacterial infection in prostatic fluid are presented.

Enhanced In Situ Availability of Aphanizomenon Flos-Aquae Constituents Entrapped in Buccal Films for the Treatment of Oxidative Stress-Related Oral Diseases: Biomechanical Characterization and In Vitro/Ex Vivo Evaluation

In recent years, the key role of oxidative stress in pathogenesis of oral diseases has been emphasized and the use of antioxidant agents has been encouraged. Aphanizomenon flos-aquae (AFA) is a unicellular blue-green alga with antioxidant and anti-inflammatory properties. The aim of this study was the formulation and characterization of mucoadhesive thin layer films loaded with AFA, finalized to the treatment of oxidative stress (OS)-related oral diseases. First, to enhance the bioavailability of AFA constituents, the raw food grade material was appropriately treated by a high frequency homogenization able to disrupt cell walls. Thus, Eudragit® E100-based buccal films were produced by the solvent casting method, containing 7% and 18% of AFA. The films, characterized by uniformity in thickness, weight, and drug content, showed low swelling degree, good muco-adhesiveness and controlled drug release. The mechanical tests showed elastic moduli of films of almost 5 MPa that is well-suitable for human buccal applications without discomfort, besides biaxial tests highlighted a marked material isotropy. Permeation studies through porcine mucosae demonstrated the ability of films to promote AFA penetration in the tissues, and when sublingually administered, they produced a drug flux up to six-fold higher than an AFA solution. The new formulations represent an interesting alternative for the development of cosmetics and nutraceuticals with a functional appeal containing plant extracts.

Oxidant-Antioxidant balance in patients with coronary slow flow.

Objective:Recent studies have focused on the probable role of oxidative stress in cardiovascular diseases. We aimed to assess the oxidant/antioxidant biomarkers in coronary slow flow (CSF).Methods:The study included 51 subjects with CSF and age and sex matched 32 controls. Detailed anamnesis of the patients in the study was taken and routine physical examinations were performed. Routine biochemical blood tests were analyzed. Total oxidative status (TOS), oxidative stress index (OSI) and lipid hydroxyperoxide (LOOH) levels as oxidant biomarkers; paraoxonase (PON1), ceruloplasmin (CP), free sulphydryl (SH) groups, and total antioxidant capacity (TAS) levels as antioxidant biomarkers were studied.Results:Baseline demographic characteristics of the study population did not differ significantly between groups.TOS, OSI and LOOH concentrations were higher in study group than in control group. However, there was no significant difference detected in levels of TAS, PON1, SH and CP. Multivariate logistic regression analysis revealed that TOS, hsCRP and smoking were indepedent risk factors of CSF.Conclusions:Although there was not any significant difference in antioxidant biomarkers (TAS, PON1, SH and CP) in CSF patients, we detected increased TOS, OSI and LOOH levels which have oxidant properties. These data supported the possible involvement of oxidative stress in pathogenesis of CSF as previous studies reported.

Oxidative stress in the pathogenesis of systemic scleroderma: An overview.

Systemic sclerosis (SSc) is a rare disorder of the connective tissue characterized by fibrosis of the skin, skeletal muscles and visceral organs. Additional manifestations include activation of the immune system and vascular injury. SSc causes disability and death as the result of end‐stage organ failure. Two clinical subsets of the SSc are accepted: limited cutaneous SSc (lc‐SSc) and diffuse cutaneous SSc (dc‐SSc). At present, the aetiology and pathogenesis of SSc remain obscure, and consequently, disease outcome is unpredictable. Numerous studies suggest that reactive oxidizing species (ROS) play an important role in the pathogenesis of scleroderma. Over the years, several reports have supported this hypothesis for both lc‐SSc and dc‐SSc, although the specific role of oxidative stress in the pathogenesis of vascular injury and fibrosis remains to be clarified. The aim of the present review was to report and comment the recent findings regarding the involvement and role of oxidative stress in SSc pathogenesis. Biomarkers proving the link between ROS and the main pathological features of SSc have been summarized.

Research progress on oxidative stress in pathogenesis of endometriosis

A large number of studies have shown that the oxidative imbalance is common in patients with endometriosis. Abnormal respiratory chain of mitochondrial, estrogen metabolism imbalance, iron overload, and ectopic foci may increase active oxygen, reduction of antioxidant enzyme and non-enzymatic substances may result in decreased antioxidant level, and the exposure to environmental hazards may further aggravate oxidative imbalance in patients with endometriosis. This article analyzes the oxidative imbalance and its role in the pathogenesis of endometriosis from the aspects of excessive oxide production and decreased antioxidant capacity.

Biomarkers of early kidney cells dysfunction in patients with membranous nephropathy

Introduction/Objective. An unfavorable prognosis of membranous nephropathy (MN) is determined by the presence of persistent proteinuria and extensive tubulointerstitial lesions at initial biopsy. Our study investigated the value of markers of renal cell dysfunction (glomerular filtration rate, urinary excretion of protein, ectoenzyme proximal tubular epithelial cells, and oxidative stress) in patients with MN, and points to the use of these markers in a possible therapeutic modification. Methods. The study included 28 patients with MN and 30 healthy individuals as control. In addition to the basic laboratory studies, enzyme [aminopeptidase N (APN), plasma cell glycoprotein-1 (PC-1), N-acetyl- ?-D-glucosaminidase (NAGA), and dipeptidyl peptidase-4] activity was determined in serum and urine, as well as parameters of oxidative damage [thiobarbituric acid concentration of substance-responders (TBARS), malondialdehyde, and the concentration of the total sulfhydryl (SH) group]. Results. In patients with MN, serum activity of PC-1 and APN and urinary excretion of NAGA were significantly higher than in the control group. Also, significant correlation between daily proteinuria and serum PC-1 activity and urinary excretion of NAGA was found in patients with MN. Serum and urine levels of TBARS as well as total SH group levels were significantly lower in patients with MN than in healthy controls. Conclusion. Kidney damage in MN is accompanied by the release of several tubular enzymes, with potential diagnostic and prognostic significance. The study suggests a possible role of oxidative stress in pathogenesis of MN and the use of antioxidants in preventing impairment as part of future therapy.

97 - Contribution of Thioredoxin1 in Modulation of Lysosomal Autophagy

The involvement of oxidative stress in pathogenesis of neurodegenerative diseases is well established. Mild oxidative conditions induce protective lysosomal autophagy, however failure of autophagy and ubiquitin systems leads to accumulation of over-oxidized proteins, followed by activation of apoptosis process. Cellular glutathione and thioredoxin systems play pivotal role in maintaining the redox balance and render protective effect by donating reducing protons to oxidized proteins. Thioredoxin 1 (Trx1) and thioredoxin reductase 1 (TrxR1), the enzyme responsible for reducing the oxidized Trx1, have protective roles against oxidative stress-mediated cytotoxicity. Moreover, in neurodegenerative conditions such as Alzheimer’s disease (AD), lower Trx1 levels have been reported in the autopsy of patients’ brains, while TrxR1 levels is increased (Lovel MA, et al. FRBM 2000). We hypothesized that dysregulated levels of Trx system may affect neuronal autophagy and apoptosis. We therefore used a model neuronal oxidative stress induction by serum deprivation in SH-SY5Y cells. Trx1 was pharmacologically inhibited using 1-methylpropyl 2-imidazolyl disulfide (PX-12), and we examined its effect of progression of autophagy and apoptosis. We found that PX-12 treated cells showed evidence of protein ubiquitination disruption and autophagy interruption, causing more apoptotic cell death. Similar to AD brain, inhibition of Trx1 was associated with increased TrxR1 protein level. Although lysosomal biosynthesis was increased after SD and in PX-12 cells, lysosomal activity was significantly decreased as assessed using lysotracker. Our data indicate that Trx1 is important for maintaining lysosomal activity and perhaps acidification. We did not observe any significant changes in mitochondrial Trx system. These data are in agreement with our previous reports that link a healthy balance of Trx-TrxR to proper protein degradation system. This project was supported by Paralyzed Veterans of America and University of Manitoba. AAS received an undergraduate summer studentship from University of Manitoba. NP received Research Manitoba/Will-to-Win studentship. JB, was supported by a MITACS Global Research Internship award.

A study of oxidative stress biomarkers in obsessive compulsive disorder

BackgroundExisting literature supports the potential role of oxidative stress in pathogenesis of psychiatric disorders like schizophrenia, depression, anxiety disorders, substance use disorders and neurodevelopmental disorders. Role of oxidative stress has also been implicated in obsessive compulsive disorder (OCD). MethodOur study was conducted in a tertiary care teaching hospital of North India. This cross-sectional observational study aimed at evaluating the markers of oxidative stress (Superoxide dismutase, Glutathione Peroxidase, Catalase, Malondialdehyde, serum cortisol) in three groups - patients with OCD, their non-affected first degree relatives, and healthy controls. Markers of oxidative stress were estimated in all 30 participants in each group. ResultsSignificantly higher levels of malondialdehyde and lower levels of plasma catalase, superoxide dismutase & glutathione peroxidase were found in patients, compared to their first degree relatives and healthy controls. Levels of plasma catalase, superoxide dismutase & glutathione peroxidase in first degree relatives were also significantly lower than healthy controls. ConclusionHigher levels of oxidative stress markers are associated with OCD and their first-degree relatives. The correlational nature of the present study, and the lack of a psychiatric control group, however, do not allow for conclusions regarding causation or the findings’ specificity to OCD.

Measuring of Plasma Melatonin Level in Patients with Preeclampsia

Background: disturbed physiological rhythm of blood pressure in preeclampsia is a common finding. The role of oxidative stress in pathogenesis of preeclampsia is well accepted. Melatonin is a powerful free radical scavenger so it's rapidly consumed by enhanced reactive oxygen species in preeclampsia causing non-dipping in blood pressure.Objective: To evaluate the change in plasma melatonin levels in patients with preeclampsia and its relationship with blood pressure.Patients and methods: In this prospective case control study a total of 40 primigravidae pregnant women were recruited during the period of 11 months between August 2015 and August 2016 in Baghdad teaching hospital, medical city, Iraq, divided into two groups:First groups: (cases group) were 20 primigravidae pregnant women with PE.Second group: (control group) were 20 normal healthy primigravidae.Blood Pressure measurement, melatonin blood samples were taken, plasma melatonin levels measurement was done by ELISA immunoassay. Urine was collected over 24 hours for protein in urine measurement.Results : Plasma Melatonin level in control , day and night was (22.72 ± 2.6 pg/mL ) , (75.26 ± 2.99 pg/mL ) compared to Plasma Melatonin level in dipper PE day and night (20.5±2.4 pg/mL ) , (75.26 ± 1.8 pg/mL) which was statistically not significant( P value 0.055 ) , (P value 1.0) respectively .Plasma Melatonin level for non-dipper ( 22.45 ± 2.48 pg/mL) were similar to dipper (20.5±2.4 pg/mL) which is not significant (P value 0.1) , while Night time Plasma Melatonin of non-dipper (36.76 ± 1.27 ) were reduced when compared to control (75.26 ± 2.99 pg/mL) and to dipper group (75.26 ± 1.8 pg/mL ) which was highly significant (p <0.0001 , p <0.0001) respectively .Conclusion: Night time Plasma Melatonin level reduced in Primigravid Women with preeclampsia that did not show nocturnal dipping in blood pressure.

Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus: How Are They Interlinked?

Oxidative stress has been considered as a major hallmark for the pathogenesis and development of type 2 diabetes mellitus (T2DM), but still it is debatable whether it is a mere aggregation of inflammatory-induced responses or clinical entity that underlies with various pathophysiological factors. In this regard, the latest studies have shown the increasing trends for the involvement of reactive oxygen species (ROS) and oxidative stress in the pathogenesis and development of T2DM. ROS are highly reactive species and almost all cellular components are chemically changed due to the influence of ROS that ultimately results in the production of lipid peroxidation. Lipid peroxidation is a major causative factor for the development of oxidative stress that leads to overt T2DM and its associated micro- and macro-vascular complications. In this article, we have briefly described the role of various causative factors, transcriptional and metabolic pathways which are responsible to increase the production of oxidative stress, a most pivotal factor for the pathogenesis and development of T2DM. Therefore, we conclude that measurement of oxidative stress biomarkers may be one of the optional tool for the diagnosis and prediction of T2DM. Moreover, the key findings described in this article also provides a new conceptual framework for forthcoming investigations on the role of oxidative stress in pathogenesis of T2DM and drug discovery. J. Cell. Biochem. 118: 3577-3585, 2017. © 2017 Wiley Periodicals, Inc.

The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma

ABSTRACTIntroduction: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. Materials and Methods: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn- superoxide dismutase (Cu,Zn-SOD) in serum. Results: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu,Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. Conclusion: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.