Electrolytes Play a Role in Detecting Cisplatin-Induced Kidney Complications and May Even Prevent Them-Retrospective Analysis.

Background and Objective: Cisplatin is a chemotherapy drug used to treat several types of malignancies. It is a platinum-based compound that interferes with cell division and DNA replication. Cisplatin has been associated with renal damage. This study evaluates the early detection of nephrotoxicity through routine laboratory tests. Materials and Methods: This is a retrospective chart review based on the Saudi Ministry of National Guard Hospital (MNGHA). We evaluated deferential laboratory tests for cancer patients treated with cisplatin between April 2015 and July 2019. The evaluation included age, sex, WBC, platelets, electrolytes, co-morbidities and interaction with radiology. Results: The review qualified 254 patients for evaluation. Around 29 patients (11.5%) had developed kidney function abnormality. These patients presented with abnormally low magnesium 9 (31%), potassium 6 (20.7%), sodium 19 (65.5%) and calcium 20 (69%). Interestingly, the whole sample size had abnormal electrolytes presenting magnesium 78 (30.8%), potassium 30 (11.9%), sodium 147 (58.1%) and calcium 106 (41.9%). Some pathological features were detected, such as hypomagnesemia, hypocalcemia and hypokalemia. In addition, infections that needed antibiotics were dominant in patients treated with cisplatin alone, representing 50% of this group. Conclusions: We report that an average of 15% of patients with electrolyte abnormalities develop renal toxicity and reduced function. Moreover, electrolytes may serve as an early indicator for renal damage as part of chemotherapy complication. This indication represents 15% of renal toxicity cases. Changes in electrolyte levels have been reported with cisplatin. Specifically, it has been linked to hypomagnesemia, hypocalcemia and hypokalemia. This study will help reduce the risk of dialysis or the need for kidney transplant. It is also important to manage any underlying conditions and control patients' intake of electrolytes.

A unique investigation of thallium, tellurium, osmium, and other heavy metals in recurrent pregnancy loss: A novel approach.

OBJECTIVE: To study the impact of heavy metals especially tellurium, thallium, and osmium, in recurrent pregnancy loss (RPL) and to study their association with antioxidant status and DNA damage. METHODS: This case-control study included women with RPL (n = 30) and healthy pregnant women as control (n = 30). Following blood collection, serum levels of thallium, tellurium, osmium, lead, mercury, and cadmium were estimated by inductively coupled plasma mass spectrophotometer. RESULTS: Women with RPL exhibited significantly higher levels of heavy metals (P < 0.001) when compared with control women. Intriguingly, increased levels of serum thallium, tellurium, osmium, and lead were negatively correlated with total antioxidant status (P < 0.05). Further, the RPL group demonstrated strong positive correlation between heavy metals (thallium, tellurium, osmium, lead) and DNA damage (P < 0.05). No significant correlation between other heavy metals and markers of cellular damage was noted. CONCLUSION: Enhanced levels of heavy metals in women with RPL and correlation of thallium, tellurium, osmium, and lead with markers of cellular damage reflect the role of heavy metal poisoning, especially thallium, tellurium, and osmium, as potential risk factor in the etiology underlying recurrent miscarriage.

Comprehensive investigations of key mitochondrial metabolic changes in senescent human fibroblasts.

There is a paucity of detailed data related to the effect of senescence on the mitochondrial antioxidant capacity and redox state of senescent human cells. Activities of TCA cycle enzymes, respiratory chain complexes, hydrogen peroxide (H2O2), superoxide anions (SA), lipid peroxides (LPO), protein carbonyl content (PCC), thioredoxin reductase 2 (TrxR2), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPx1), glutathione reductase (GR), reduced glutathione (GSH), and oxidized glutathione (GSSG), along with levels of nicotinamide cofactors and ATP content were measured in young and senescent human foreskin fibroblasts. Primary and senescent cultures were biochemically identified by monitoring the augmented cellular activities of key glycolytic enzymes including phosphofructokinase, lactate dehydrogenase, and glycogen phosphorylase, and accumulation of H2O2, SA, LPO, PCC, and GSSG. Citrate synthase, aconitase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, and complex I-III, IIIII, and IV activities were significantly diminished in P25 and P35 cells compared to P5 cells. This was accompanied by significant accumulation of mitochondrial H2O2, SA, LPO, and PCC, along with increased transcriptional and enzymatic activities of TrxR2, SOD2, GPx1, and GR. Notably, the GSH/GSSG ratio was significantly reduced whereas NAD+/NADH and NADP+/NADPH ratios were significantly elevated. Metabolic exhaustion was also evident in senescent cells underscored by the severely diminished ATP/ADP ratio. Profound oxidative stress may contribute, at least in part, to senescence pointing at a potential protective role of antioxidants in aging-associated disease.

Antioxidant status in relation to heavy metals induced oxidative stress in patients with polycystic ovarian syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is a global health concern for women of reproductive age, as 6.5% of women worldwide are affected by this syndrome. PCOS is marked by hyperandrogenism, anovulation, menstrual abnormalities, and polycystic ovaries. Metals such as arsenic, cadmium, lead and mercury are considered to be systemic toxicants/human carcinogens and seem to have devastating effects on humans, even at minimal exposures. One of the probable aetiological factors for PCOS has been identified as oxidative stress. In view of the probable associations among oxidative stress, metal toxicity and PCOS, the present study examined the role of heavy metals in the generation of oxidative stress among females. This prospective study included 106 women (56 women diagnosed with PCOS and 50 women who were not diagnosed with PCOS as control women). There were no significant differences in the sociodemographic characteristics between the two groups except for the irregularity of menses and the presence of acne. The serum As, Cd, Pb, and Hg levels increased and the serum glutathione (GSH) and superoxide dismutase (SOD) levels diminished significantly in the PCOS group compared to the control group at P < 0.001. The SOD levels were negatively correlated with the As and Pb levels at P < 0.05. Additionally, the PCOS group exhibited a strong negative correlation between the GSH and As levels (P < 0.01), GSH and Pb levels (P < 0.05) and GSH and Hg levels (P < 0.01). Furthermore, the As levels were positively correlated with increased levels of Cd, Pb and Hg among PCOS women. Significant positive correlations were observed between Pb and Cd and between Cd and Hg at P < 0.001. The outcome of the study provides clear insight into the role of metal-induced oxidative stress, which plays a vital role in the pathophysiology underlying PCOS and suggests the use of these markers as prognostic tools to reduce the consequences of high-risk exposure to these metals among females.

Bioymifi, a novel mimetic of TNF-related apoptosis-induced ligand (TRAIL), stimulates eryptosis.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a cytokine that initiates apoptosis upon binding to death receptor 5 (DR5) on cancer cells. Small molecule TRAIL mimetics have therefore been investigated as promising chemotherapeutic agents. Since anemia of chemotherapy is common, our goal is to investigate the hemolytic and eryptotic properties of novel DR5 agonist bioymifi (BMF) and identify the underlying molecular mechanisms. Whole blood (WB) was stimulated with 100 µM of BMF, whereas red blood cells (RBCs) were treated with 10-100 µM of BMF for 24 h at 37 °C. WB was analyzed for RBC, leukocyte, and platelet indices, while RBCs were examined for hemolysis by light absorbance of free hemoglobin, membrane scrambling by Annexin V-FITC, calcium by Fluo4/AM, cellular morphology by light scatter, and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) using flow cytometry. Caspase inhibitor Z-VAD-FMK, p38 inhibitor SB203580, casein kinase 1α inhibitor D4476, receptor-interacting protein 1 inhibitor necrostatin-2, reduced glutathione, or cyclooxygenase (COX) inhibitor aspirin were added accordingly. BMF exerted dose-responsive, calcium-independent hemolysis, reduced RBC hemoglobin, significantly increased Annexin V-, Fluo4-, and DCF-positive cells, along with a dual effect on forward and side light scatter. Notably, the cytotoxic potential of BMF was significantly mitigated upon pharmacological inhibition of p38. Furthermore, BMF exhibited selective toxicity to eosinophils and significantly diminished reticulocyte hemoglobin content. Altogether, these novel findings highlight the adverse outcomes of BMF exposure on RBC physiology and provide the first toxicological assessment of BMF as an antitumor agent.

Effect of trace elements on the seminal oxidative status and correlation to sperm motility in infertile Saudi males.

The impact of trace elements, especially zinc, selenium, copper, and magnesium, on male fertility has gained great interest and significance. Increased oxidative stress and altered trace element levels are probable etiological factors underlying male reproductive dysfunction and infertility. The present study focused on the evaluation of seminal oxidative markers, such as reactive oxygen species (ROS), malondialdehyde (MDA), and total antioxidant capacity (TAC), and trace element levels in the normozoospermic fertile control group (n = 40) and asthenozoospermic infertile group (n = 30). Semen from infertile men exhibited significantly higher ROS and MDA levels accompanied with significant decline in TAC and trace element (zinc and magnesium) levels. Furthermore, a significant correlation was observed between trace elements and oxidative markers with sperm motility. The current study revealed increased lipid peroxidation and oxidant-reductant imbalance that leads to deterioration of semen quality and male infertility. Thus, oxidative stress and trace elements can be considered important biomarkers of male infertility. Measurement of seminal oxidative stress with conventional seminological parameters must be integrated in fertility assessment from early stages to ensure healthy semen characteristics and fertility in men.

Identification of Novel Mutations in Colorectal Cancer Patients Using AmpliSeq Comprehensive Cancer Panel.

Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. Discovery of novel variants in local population provides confident targets for developing biomarkers for personalized medicine. We identified the need to generate high-quality sequencing data from local colorectal cancer patients and understand the pattern of occurrence of variants. In this report, we used archived samples from Saudi Arabia and used the AmpliSeq comprehensive cancer panel to identify novel somatic variants. We report a comprehensive analysis of next-generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity, and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in the large intestine. APC, RET, and EGFR genes were most frequently mutated. A higher number of variants were identified in the left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.

Glutathione and oxidized nicotinamide adenine dinucleotide (NAD+) redox status in plasma and placental tissue of Saudi patients with intrauterine growth restriction.

OBJECTIVES: To assess the oxidation state and gene expression profiles of relevant enzymes in intrauterine growth restriction (IUGR) patients in Saudi Arabia. METHODS: Current case-control study involved plasma and placental tissue samples from 25 IUGR patients and 25 healthy pregnant (HP) women attending the Obstetrics and Gynecology Clinic, King Khalid University Hospital, Riyadh, Saudi Arabia, between April and November 2017. We compared hydrogen peroxide, superoxide anions, malondialdehyde, and oxidative stress markers levels and the activities of glutathione-related enzymes (glutathione peroxidase [GPx], glutathione reductase [GR], glutathione S-transferase [GST], glutamate cysteine ligase [GCL], glutathione synthetase [GS], reduced glutathione [GSH], oxidized glutathione [GSSG], and oxidized nicotinamide adenine dinucleotide [NAD+], and reduced NAD [NADH]) between the 2 groups. We also compared differential expression levels of glutathione-related enzyme genes using reverse transcription-quantitative polymerase chain reaction. RESULTS: Oxidative stress markers significantly differed in IUGR samples, while GSH levels and GPx, GR, GST, GCL, and GS activities and their placental mRNA transcriptional levels were significantly lower. Plasma and placental NAD+ levels were also significantly lower, while NADH levels were significantly higher, causing lowered NAD+-NADH ratios in the IUGR group compared to control. CONCLUSIONS: Intrauterine growth restriction patients show a metabolic shift in favor of oxidation compared to HP women.

Role of Oxidative Stress and Severity of Diabetic Retinopathy in Type 1 and Type 2 Diabetes.

BACKGROUND: Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus (DM). Oxidative stress generated on account of hyperglycemic state may lead to retinal abnormalities including DR. OBJECTIVES: The aim of the study was to evaluate the status of antioxidant enzymes; superoxide dismutase (SOD), and catalase (CAT), in different stages of DR severity in subjects with type 1 DM (T1DM) and type 2 DM (T2DM). METHODS: The cross-sectional study enrolled 148 subjects with T1DM (n = 17), T2DM (n = 96), and nondiabetic controls (n = 35). Subjects with DM were divided into 2 subgroups based on DR severity (mild-to-severe nonproliferative DR [NPDR] and proliferative DR [PDR]), and serum glycated hemoglobin (HbA1c), lipid profile, SOD, and CAT were estimated. RESULTS: Both SOD and CAT levels were lower in diabetic subjects than nondiabetic controls. A significant positive correlation was found between HbA1C level and severity of DR (p < 0.0001). Levels of SOD and CAT varied significantly with DR severity in both diabetic groups at p < 0.05. Furthermore, levels of SOD and CAT were found to decrease significantly (p < 0.001) in DR (+) compared to DR (-) patients. Also, increased levels of HbA1c were significantly associated (p < 0.001) with decreased SOD in both subgroups (NPDR and PDR). DR severity was significantly associated with SOD and CAT in the NPDR and PDR subgroups (p < 0.05). CONCLUSION: Oxidative stress and decreased antioxidant defenses are associated with DR progression to its PDR stage.

Epigallocatechin gallate and coenzyme Q10 attenuate cisplatin-induced hepatotoxicity in rats via targeting mitochondrial stress and apoptosis.

Despite the extensive use of cisplatin (CP) as a chemotherapeutic agent, its clinical use is often restricted by undesirable side effects, such as toxicity to normal tissues. The aim of this study was to probe the effect of a combinatorial treatment of low multiple doses of antioxidants on CP-induced toxicity and the mitochondrial apoptotic pathway in hepatocytes. Animals received a single toxic dose of CP (7.5 mg/kg body weight) with or without combined multiple doses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight, respectively). CP-treated animals showed altered biochemical parameters, denoting hepatotoxicity, which was markedly improved by the multidose treatment with EGCG + CoQ10. The increased levels of oxidants found in the cytosolic and mitochondrial fractions isolated from the liver of CP-administered rats were significantly attenuated by the combinatorial doses of antioxidants. EGCG + CoQ10 ameliorated the CP-induced compromised antioxidant defenses, oxidative modification of macromolecules, decreased activities of respiratory chain enzymes, altered membrane depolarization, and swelling of liver mitochondria. Furthermore, EGCG + CoQ10 treatment inhibited CP-induced apoptosis by suppressing the activation and mitochondrial accumulation of proapoptotic proteins and preventing the inhibition of antiapoptotic protein expression, cytochrome c efflux, caspase-3 activation, and DNA fragmentation. Histological findings further confirmed the protective effects of EGCG + CoQ10 against CP-induced cellular injury. Our findings revealed that the combination of EGCG and CoQ10, owing to their individual antioxidant properties, can be an effective remedy, which by maintaining redox hemostasis attenuate the mitochondrial stress-mediated molecular and cellular processes involved in CP-induced liver toxicity and cell death.

Association of Vitamin D deficiency with primary glaucoma among Saudi population - A pilot study.

PURPOSE: Glaucoma is a complex multifactorial disorder that is influenced by various systemic conditions. Several studies investigated the association between systemic factors such as Vitamin D deficiency for glaucoma development and reported contradicted findings. The aim of this study was to assess Vitamin D levels in glaucomatous Saudi subjects and its association with cup/disc ratio in primary open- and closed-angle glaucoma. METHODS: This was a pilot study that included subjects aged 41-78 years from both genders recruited from a tertiary hospital, Riyadh city, Kingdom of Saudi Arabia. Subjects were divided into three groups: Group 1: subjects with primary open-angle glaucoma (POAG), Group 2: subjects with primary angle-closure glaucoma (PACG), and Group 3: control subjects. All participants underwent detailed ophthalmic examinations including visual acuity, intraocular pressure measurement (IOP), gonioscopy, and fundus examinations. In addition, blood samples were collected from glaucoma patients and controls to measure the serum 25-hydroxyvitamin D levels. RESULTS: A total of 75 subjects were included in this study. Measurement of IOP was within the range of 9-27 for all subjects. Mean serum 25-hydroxyvitamin D levels were 72.58 ± 31.79, 69.20 ± 24.24, and 67.14 ± 29.02 in Groups 1, 2, and 3, respectively. There were insignificant differences in Vitamin D levels among the three groups (P > 0.05). Moreover, no significant correlation was noted between Vitamin D levels and cup/disc ratio in Groups 1 and 2. CONCLUSION: No association was found between Vitamin D deficiency and both POAG and PACG among Saudi population despite low serum level of Vitamin D in glaucomatous and control subjects. This study suggested that Vitamin D level may not contribute in augmenting the severity and progression of glaucoma.

Possible Prophylactic Approach for SARS-CoV-2 Infection by Combination of Melatonin, Vitamin C and Zinc in Animals.

SARS-CoV-2, an epidemic, causes severe stress in both human and animals and may induce oxidative stress (OS) and increases susceptibility to infection. Domestic animals are found infected by their COVID-2 suffering owners. Chronic immobilization stress (CIS), a model of psychological and physical stress of confinement, can trigger depression and anxiety in animals. We evaluated the ameliorative effect of the proposed SARS-CoV-2 prophylactic drugs melatonin, vitamin C, and zinc on CIS-induced OS, inflammation, and DNA damage in rats. Forty male Swiss albino rats (200-250 g, 7-9 weeks old) were divided into five groups as controls, CIS, treated with melatonin (20 mg/kg), and vitamin C plus zinc [VitC+Zn (250 + 2.5 mg/kg)] alone or in combination (melatonin+VitC+zinc) subjected to CIS for 3 weeks. CIS was induced by immobilizing the whole body of the rats in wire mesh cages of their size with free movement of head. Exposure to CIS significantly compromised the circulatory activities of superoxide dismutase, catalase, and glutathione with enhanced malondialdehyde, inflammatory markers (IL-6, IL10, and TNFα), and lymphocyte DNA damage in comparison to controls. Treatment with melatonin and VitC+Zn alone or in combination significantly restored the altered biochemical parameters and DNA damage of stressed rats to their respective control values. However, the cumulative action of melatonin with VitC+Zn was more effective in alleviating the CIS-induced OS, inflammation, and DNA damage. The present study indicates that the antioxidant combination can be an effective preventive measure to combat severe psychological and confinement stress-induced biochemical changes in animals due to abnormal conditions such as SARS-CoV-2.

Preservation of fertility in female: Indications, available options, and current status in Saudi Arabia.

Refinement of therapies continues to improve the prognosis and survival of cancer patients. However, women of reproductive age face a risk of premature ovarian failure due to the gonadotoxicity of aggressive oncological treatment, which may also be used to treat other nonmalignant disorders. Development of cryobiology and assisted reproduction has allowed fertility preservation, which is increasingly requested, and can also aid fertility in iatrogenic and noniatrogenic conditions. Established protocols including embryo and oocyte freezing are only performed for adult women; however, ovarian tissue cryopreservation is an approach that can also assist prepubertal girls. Medical fertility cryopreservation for females has been recently legalized in Saudi Arabia. However, prior to implementing the service in clinical practice in Saudi Arabia, guidelines on patient selection criteria and adequate staff training are essential. Moreover, worldwide registry data and the findings of long-term studies involving many patients on the safety of ovarian tissue freezing are required to conclusively establish medical fertility cryopreservation as a safe procedure. Progress can be achieved in oncofertility by improving and optimizing techniques that include immature oocyte growth and maturation and artificial ovary development.

Restraint stress abates the antioxidant potential of melatonin on dimethyl benz (a) anthracene (DMBA) induced carcinogenesis.

Free radical involvement in initiation, promotion and progression of carcinogenesis, implicates that scavengers of free radicals may act as inhibitors in the carcinogenic process. Melatonin, an antioxidant was used in the present study to evaluate its effectiveness on skin carcinogenesis induced by DMBA both with and without chronic restraint stress (CRS). Fifty Swiss albino young male rats were divided into five groups of 10 rats each as controls, topical DMB alone, Pre CRS-DMBA, melatonin DMBA and Pre-CRS-DMBA-melatonin treated groups. After 18 weeks blood was collected along with liver and skin samples. These were used for antioxidant enzyme assay, DNA damage and fluorescent spectra analysis. Melatonin showed antioxidant potential in combatting DMBA induced skin carcinogenesis measured by free radical scavenging enzymes and in vivo antioxidant status, DNA damage. Sensitive detection of the DMBA induced micro biochemical changes was possible by fluorescent spectroscopy from the transformed ratio of fluorescent intensity (F1 530 nm/630 nm) otherwise found constant for normal tissues. By melatonin treatment this ratio was similar to control values. The decreased antioxidant biochemical parameters depicting oxidative stress were comparable to comet assay and fluorescent studies, endorsing the chemo-preventive efficacy of melatonin against skin carcinogenesis caused by DMBA. CRS pre-exposure diminished the chemo-preventive/antioxidant ability of melatonin and the results were same as DMBA alone treatment, showing stress affected both cancer development and chemoprevention. CRS decreased the antioxidant potential of melatonin. Hence, managing stress could be perceived in cancer chemoprevention. Further studies focusing on stress reduction are needed.

Association between the Inflammatory Potential of Diet and Stress among Female College Students.

A pro-inflammatory diet may have an adverse influence on stress and inflammatory biomarker levels among college students. The dietary inflammatory index (DII®) is a tool used to assess the inflammatory potential of a diet. However, evidence for the association between DII and stress is limited. We examined the association between energy-adjusted DII (E-DIITM), high sensitivity-C-reactive protein [hs-CRP], and stress among female college students. This cross-sectional study included 401 randomly selected female students, aged 19-35 years. Data collection included blood, anthropometric measurements, a healthy-history questionnaire, the perceived stress scale (PSS-10), the Saudi food frequency questionnaire (FFQ), and E-DII. Multiple linear regression analyses were used to examine the association between FFQ-derived E-DII score, hs-CRP, and PSS. A higher E-DII score per 1SD (1.8) was associated with a 2.4-times higher PSS score (95% CI: 1.8, 3.1). Higher hs-CRP per 1SD (3.3 mg/L) was associated with a 0.9 (95% CI: 0.7-1.1) times higher PSS score, independent of lifestyle and dietary factors. Our findings indicate that pro-inflammatory diets were highly prevalent among Saudi college students and were associated with higher stress levels. Consideration of the role of stress and focusing on anti-inflammatory foods may be key for healthier dietary habits.

Association between antinuclear antibodies (ANA) patterns and extractable nuclear antigens (ENA) in HEp-2 cells in patients with autoimmune diseases in Riyadh, Saudi Arabia.

Antinuclear antibodies (ANA) and extractable nuclear antigens (ENA) are instrumental biomarkers crucial in the detection of autoimmune disorders (AID) such as systemic lupus erythematosus (SLE), Sjogren syndrome, etc.. In the present study, an assessment of the most frequent ANA patterns associated with most detectable ENA that could be used as efficient prognostic markers in the diagnosis of autoimmune diseases was conducted. Data was retrospectively analyzed from AID patients, retrieved from the medical records of King Fahad Medical City, Riyadh, KSA, from January 2016 to October 2018 who underwent ANA immunofluorescence of HEp-2 cells and their ENA detection was studied. Of the 453 total patients, 39/55 AID males (71%) and 332/398 AID females (83.4%) exhibited ANA positivity. The most common pattern was speckled S-ANA (32.4%) in females and homogenous H-ANA pattern (25.4%) in males. The histones were found at higher frequency in different ANA patterns. anti-Sjogren syndrome related antigen A (SSA), anti-ribonucleoprotein antibody (RNP-Sm), and histones were observed to be associated with homogenous and speckled nuclear patterns. Frequencies of ENA in all ANA patterns were found significant at p < 0.05 in males and p < 0.001 in females. Spearman's rank correlation of ENA within and among the ANA patterns was non-significant. SSA was significantly correlated with RNP-Sm and Sm at p < 0.05 and p < 0.01, respectively. The extractable nuclear antigens SSA, RNP-Sm, and histones were found associated with the S-ANA and H-ANA patterns. These correlations are of relevance for the accurate diagnosis of autoimmune diseases.

Effect of seminal redox status on lipid peroxidation, apoptosis and DNA fragmentation in spermatozoa of infertile Saudi males.

OBJECTIVES: To assess the effect of seminal redox status on lipid peroxidation (LPO), apoptosis and integrity of sperm DNA in infertile males. Methods: In this case-control study, the total antioxidant status (TAS) and reactive oxygen species (ROS) levels were analyzed within the seminal plasma of fertile normozoospermic, n=40 and infertile (asthenozoospermic, n=30; oligoasthenoteratozoospermic, n=30) males. Additionally, the level of 4-hydroxynonenal (4-HNE), DNA fragmentation, and caspase-3 activity were estimated in the spermatozoa. RESULTS: Significantly (p less than 0.001) increased seminal ROS level with decreased TAS scores was observed in the infertile groups compared to normozoospermics. The infertile males showed marked elevated (p less than 0.001) levels of 4-HNE, DNA fragmentation and caspase-3 activity compared to normozoospermics, which was positively correlated to increased seminal ROS levels and negatively to the TAS score in the studied groups. Seminal ROS level was significantly inverse correlated to the semen parameters. Additionally, a strong negative correlation between DNA fragmentation, LPO, caspase-3activity and seminal parameters were observed. Conclusion: Seminal oxidative stress is a potential risk factor for LPO, DNA damage, and apoptosis in spermatozoa, which can affect semen quality and male fertility. Thus, in addition to conventional seminological parameters, measurement of seminal oxidative stress and sperm DNA integrity may also be employed to investigate the functional integrity of spermatozoa at the molecular level.

Molecular and biochemical investigations of key antioxidant/oxidant molecules in Saudi patients with recurrent miscarriage.

The present study was undertaken to: i) Determine the levels of oxidative stress (OS) markers, malondialdehyde (MDA), superoxide anions (SOA) and hydrogen peroxide (H2O2), in both plasma and placental tissues of recurrent miscarriage (RM) patients in comparison with those of healthy pregnant (HP) and non-pregnant (NP) women; ii) determine the levels of enzymatic antioxidants [glutathione peroxidase (GPx), glutathione reductase (GSR), superoxide dismutase (SOD) and catalase (CAT)], and non-enzymatic antioxidant micronutrients [selenium (Se), zinc (Zn), copper (Cu) and manganese (Mn)] in both plasma and placental tissues of RM patients, in comparison with those of HP and NP women; iii) profile differential expression levels of selected antioxidant and apoptosis-related genes in the placental tissues of RM cases, in relation to those of HP women of matched gestational age, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results revealed highly significant increases of all investigated OS markers in plasma and placental tissues of RM patients compared with those of HP women. Moderate, but significant, increases of OS markers were observed in the plasma of HP patients in relation to those of NP women. The activities of antioxidant enzymes exhibited statistically significant decreases in both plasma and placental tissues of RM patients compared with those of HP women. The significantly reduced level of antioxidant enzymes was also evident in the plasma of HP women as compared with those of NP women. Results of RT-qPCR assays clearly indicated that the expression level of apoptosis-related genes [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and S100A8], and pro-inflammatory cytokine genes [tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8] were significantly upregulated in placental tissue of RM cases in relation to those of HP subjects. By contrast, mRNA transcriptional levels of key antioxidant genes (GPx, SOD, GSR and CAT) were found to be significantly reduced in placental tissue of RM patients in comparison to those of HP women. In conclusion, our data highlight a plausible cause-effect association between the observed increase in placental OS level and depletion of the activity of antioxidant enzymes. This suggests that OS is a contributing factor in the pathogenesis of idiopathic RM.

Correlation between glycemic control and peripapillary retinal nerve fiber layer thickness in Saudi type II diabetics.

OBJECTIVE: To evaluate the effect of diabetes mellitus (DM), diabetic retinopathy, and degree of glycemic control (glycosylated hemoglobin [HbA1c]) on peripapillary retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography. METHODS: The study included 126 eyes of healthy controls (n=32) and diabetics patients (n=31), whose ages ranged from 40 to 70 years. The diabetic group was divided into: Subgroup 1: with HbA1c <7% and Subgroup 2: with HbA1c ≥7%. All patients underwent full ophthalmic examination. HbA1c level was obtained with the A1cNow+ system and the peripapillary RNFLT was measured using 3D-OCT 2000 Topcon (360-degree circular scan with 3.4 mm diameter centered on optic disc). RESULTS: The obtained data demonstrates significant decrease in peripapillary RNFLT in superior and inferior quadrants of the right eye (p=0.000 and p=0.039, respectively), and in superior quadrant of the left eye (p=0.002) with impairment of glycemic control. Pearson's correlation test showed significant negative correlation of RNFLT with HbA1c in the superior quadrant in both eyes. CONCLUSION: Impairment of glycemic control affects the peripapillary RNFLT mainly in the superior quadrant. This thickness also tends to decrease with long-standing DM, use of DM medications, and development of diabetic retinopathy. The measurement of peripapillary RNFLT may become a useful method to monitor early retinal changes in diabetic patients.

Ascorbate ameliorates Echis coloratus venom-induced oxidative stress in human fibroblasts.

Reports related to the effects of Echis coloratus venom (EcV) on the antioxidant capacity of human tissues is very scarce. The present study was undertaken to investigate the activities and gene expression levels of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), as well as the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the generation rates of superoxide anions (SOA), hydrogen peroxide (H2O2) and lipid peroxides (LPO) in cultured human fibroblasts incubated with EcV, ascorbate (Asc) and EcV plus Asc at concentrations and incubation periods that maintained cell viability. Results indicated that the activities of all antioxidant enzymes and their corresponding transcripts underwent highly significant decreases and downregulation in EcV-treated cultures (0.5 µg/ml medium for 4 h) compared to venom-free controls (P<0.001). Additionally, there were concurrent equally significant increases in SOA, H2O2 and LPO generation rates in the venom-incubated cultures compared to controls (P<0.001). Results also indicated very significant decreases and parallel equally significant increases in GSH and GSSG levels respectively in the envenomed cultures compared to controls (P<0.001) leading to a drastically lower GSH/GSSG ratio. However, further incubation of the EcV-treated cultures with Asc (400 µM for 12 h) restored the activities and levels of all investigated parameters including the expression levels of the antioxidant genes to control venom-free values. It is concluded that Asc acted to neutralize the increased reactive oxygen species generation, thus ameliorating the EcV-induced oxidative stress and alleviating the downregulation of antioxidant genes.