Nickel-induced oxidative stress causes cell death in testicles: implications for male infertility.

Aligarh region is well known for its lock industry. This lock industry utilises nickel for electroplating. There have been informal reports of infertility in men and women living near the lock industry. We analysed field water samples to investigate this link, and the results showed considerable nickel contamination. To further validate our results, we exposed male rats to relevant nickel levels in drinking water. This experimental exposure resulted in abnormal sperm morphology, decline in sperm count, significant change in activities of antioxidant enzymes, pronounced oxidative stress in the rat spermatocytes and decrease in serum testosterone level, as well as damage in the hypothalamus and pituitary (in all cases, the changes were most significant at the highest concentration used i.e 2.5 mg/l). The breeding experiments showed decline in live birth rate, while pups did not survive post birth in cages where males were given 2 and 2.5 mg/l concentrations of nickel in drinking water prior to mating. Our data strongly indicate a link between industrial nickel exposure and male infertility.

The Pharmacological Properties of Red Grape Polyphenol Resveratrol: Clinical Trials and Obstacles in Drug Development.

Resveratrol is a stilbenoid from red grapes that possesses a strong antioxidant activity. Resveratrol has been shown to have anticancer activity, making it a promising drug for the treatment and prevention of numerous cancers. Several in vitro and in vivo investigations have validated resveratrol's anticancer capabilities, demonstrating its ability to block all steps of carcinogenesis (such as initiation, promotion, and progression). Additionally, resveratrol has been found to have auxiliary pharmacological effects such as anti-inflammatory, cardioprotective, and neuroprotective activity. Despite its pharmacological properties, several obstacles, such as resveratrol's poor solubility and bioavailability, as well as its adverse effects, continue to be key obstacles to drug development. This review critically evaluates the clinical trials to date and aims to develop a framework to develop resveratrol into a clinically viable drug.

Kidney Allograft Monitoring by Combining Donor-Derived Cell-Free DNA and Molecular Gene Expression: A Clinical Management Perspective.

Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx®) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx®. Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively (p = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all p = 0.01), however, no difference was found for SCr and proteinuria (p > 0.05). The AUC was 0.80 (95% CI: 0.69-0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx® was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx®, and histology has aided in early diagnosis and timely individualized intervention.

Current Understanding of Flavonoids in Cancer Therapy and Prevention.

Cancer is a major cause of death worldwide, with multiple pathophysiological manifestations. In particular, genetic abnormalities, inflammation, bad eating habits, radiation exposure, work stress, and toxin consumption have been linked to cancer disease development and progression. Recently, natural bioactive chemicals known as polyphenols found in plants were shown to have anticancer capabilities, destroying altered or malignant cells without harming normal cells. Flavonoids have demonstrated antioxidant, antiviral, anticancer, and anti-inflammatory effects. Flavonoid type, bioavailability, and possible method of action determine these biological actions. These low-cost pharmaceutical components have significant biological activities and are beneficial for several chronic disorders, including cancer. Recent research has focused primarily on isolating, synthesizing, and studying the effects of flavonoids on human health. Here we have attempted to summarize our current knowledge of flavonoids, focusing on their mode of action to better understand their effects on cancer.

Synthesis, characterization, computational studies and in vitro antiparasitic activity of novel flavanoidal-1,2,4,5-tetrazinane-6'-thione.

Keeping in view the growing resistance of conventional antiparasitic drugs, this study aimed to synthesize a series of six noble flavanoidal tetrazinane-6'-thione derivatives by employing a facile one pot reaction pathway. Structural characterizations of synthesized compounds were performed by using IR, 1HNMR, 13CNMR and LC-MS spectra. Molecular docking study showed that one of the newly synthesized compounds strongly bind with the amino residues of BSA with two hydrogen bonding interactions. Physiological properties, pharmacokinetic properties (ADME) and toxicity of all synthesized compounds was carried out using Molinspiration and pkCSM softwares. DFT calculations were performed for all synthesized compounds using B3LYP method to obtain various molecular properties. Using a previously established model for parasitic infections, Clinostomum complanatum we showed that the newly synthesized compounds have a very potent parasitic activity. To elucidate the possible mechanisms, we tested the exposed parasites and observed a perturbation in lipid peroxidation and the antioxidant enzyme superoxide dismutase. Implications of this are discussed in the light of development of these molecules as antiparasitic drugs. HIGHLIGHTSSix noble flavanoidal-1,2,4,5-tetrazinane-6'-thiones (7-12) were synthesized using flavanone derivatives and thiocarbohydrazide in acetic acid as a reagent in ethanol employing one-pot synthesis.Structural characterization of synthesized compounds was done using IR, 1HNMR, 13CNMR and LC-MS spectra.Physicochemical analysis determined that all synthesized compounds are efficiently absorbed and have good permeability.In silico ADME and Toxic properties were determined for all synthesized compounds.In vitro antiparasitic activity was performed for all synthesized compounds against Clinostomum complanatum.Molecular Docking studies demonstrated the binding interaction with BSA enzyme through hydrogen bonding.Density functional theory (DFT) have been performed to estimate the various molecular properties of the synthesized compounds.Communicated by Ramaswamy H. Sarma.

Pomegranate juice anthocyanidins induce cell death in human cancer cells by mobilizing intracellular copper ions and producing reactive oxygen species.

Anthocyanidins are the most abundant polyphenols in pomegranate juice. This class of molecules includes Delphinidin (Del), Cyanidin (Cya), and Pelargonidin (Pel). Using prostate, breast and pancreatic cancer cell lines PC3, MDA-MB-231, BxPC-3 and MiaPaCa-2, we show that anthocyanidins inhibit cell proliferation (measured by MTT assay) and induce apoptosis like cell death (measured by DNA/Histone ELISA). Copper chelator neocuproine and reactive oxygen species scavengers (thiourea for hydroxyl radical and superoxide dismutase for superoxide anion) significantly inhibit this reaction thus demonstrating that intracellular copper reacts with anthocyanidins in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitizes normal breast epithelial cells (MCF-10A) to Del-mediated growth inhibition as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters Ctr1 and ATP7A in MCF-10A cells, which is attenuated by the addition of Del in the medium. We propose that the copper mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of anthocyanidins.

Understanding the Prooxidant Action of Plant Polyphenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications.

Plant derived polyphenolic compounds are considered critical components of human nutrition and have shown chemotherapeutic effects against a number of malignancies. Several studies have confirmed the ability of polyphenols to induce apoptosis and regression of tumours in animal models. However, the mechanism through which polyphenols modulate their malignant cell selective anticancer effects has not been clearly established. While it is believed that the antioxidant properties of these molecules may contribute to lowering the risk of cancer induction by causing oxidative damage to DNA, it could not be held responsible for chemotherapeutic properties and apoptosis induction. It is a well known fact that cellular copper increases within the malignant cell and in serum of patients harboring malignancies. This phenomenon is independent of the cellular origin of malignancies. Based on our own observations and those of others; over the last 30 years our laboratory has shown that cellular copper reacts with plant derived polyphenolic compounds, by a Fenton like reaction, which generates reactive oxygen species and leads to genomic DNA damage. This damage then causes an apoptosis like cell death of malignant cells, while sparing normal cells. This communication reviews our work in this area and lays the basis for understanding how plant derived polyphenols can behave as prooxidants (and not antioxidants) within the microenvironment of a malignancy (elevated copper levels) and gives rationale for their preferential cytotoxicity towards malignant cells.

Structure of Some Green Tea Catechins and the Availability of Intracellular Copper Influence Their Ability to Cause Selective Oxidative DNA Damage in Malignant Cells.

The possible roles of elevated endogenous copper levels in malignant cells are becoming increasingly understood at a greater depth. Our laboratory has previously demonstrated that tea catechins have the ability to mobilize endogenous copper and undergo a Fenton-like reaction that can selectively damage cancer cells. In this communication, by using a diverse panel of malignant cell lines, we demonstrate that the ability of the catechin family [(-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin (EC), and (+)-catechin (C)] to induce apoptosis is dependent on their structure. We further confirm that reactive oxygen species (ROS) are the terminal effectors causing copper-mediated DNA damage. Our studies demonstrate the role of cellular copper transporters CTR1 and ATP7A in the survival dynamics of malignant cells post-EGCG exposure. The results, when considered together with our previous studies, highlight the critical role that copper dynamics and mobilization plays in cancer cells and paves the way for a better understanding of catechins as nutraceutical supplements for malignancies.

Poly (ADP-ribose) polymerase (PARP) inhibition in cancer: Potential impact in cancer stem cells and therapeutic implications.

Inhibitors of poly(ADP-ribose) polymerase (PARP) are used in mono- or combination therapies for several malignancies. They are also used as maintenance therapy for some cancers after initial treatment. While the focus of this therapeutic approach is on the effect of PARP inhibition on the bulk tumour cells, in this review, we discuss their effect on the cancer stem cells. We identify key mediators and pathways in cancer stem cells whose response to PARP inhibition is not necessarily the same as the rest of the tumour cells. Since the cancer stem cells are known drivers of growth of tumours and their resistance to therapy, the clinical outcome might be drastically different than what is expected, if the effect of PARP inhibition on the cancer stem cells is not taken into account.

Transcriptional Control of the Oxidative Stress Response and Implications of Using Plant Derived Molecules for Therapeutic Interventions in Cancer.

The oxidative stress response is critical for malignant cells. It plays a dual role by helping cancer cells survive and proliferate but also causing apoptosis and apoptosis-- like cell death. The oxidative stress response is characterized by tight regulation of gene expression by a series of transcription factors (OSRts; oxidative stress response transcription factors). In this communication, we review the role of OSRts, notably NRF2 and p53 as well as other transcription factors that modulate the response. We discuss how hierarchal the oxidative stress response is and controls 'live or die' signals. This is followed by a discussion on how plant-derived molecules, including polyphenols, which are described both as prooxidants and antioxidants within the cancer cells, have been reported to affect the activities of OSRts. Deriving an example from preliminary data from our group, we discuss how plant-derived molecules might modulate the oxidative stress response by causing structural perturbations in the proteinaceous transcription factors, notably Nrf2 and p53. We look at this information in the light of understanding how plant derived molecules may be used as lead compounds to develop modulators of the oxidative stress response.

Systematic review and meta-analysis of current rates of first pass effect by thrombectomy technique and associations with clinical outcomes.

BACKGROUND: First pass effect (FPE) in mechanical thrombectomy is thought to be associated with good clinical outcomes. OBJECTIVE: To determine FPE rates as a function of thrombectomy technique and to compare clinical outcomes between patients with and without FPE. METHODS: In July 2020, a literature search on FPE (defined as modified Thrombolysis in Cerebral Infarction (TICI) 2c-3 after a single pass) and modified FPE (mFPE, defined as TICI 2b-3 after a single pass) and mechanical thrombectomy for stroke was performed. Using a random-effects meta-analysis, we evaluated the following outcomes for both FPE and mFPE: overall rates, rates by thrombectomy technique, rates of good neurologic outcome (modified Rankin Scale score ≤2 at day 90), mortality, and symptomatic intracerebral hemorrhage (sICH) rate. RESULTS: Sixty-seven studies comprising 16 870 patients were included. Overall rates of FPE and mFPE were 28% and 45%, respectively. Thrombectomy techniques shared similar FPE (p=0.17) and mFPE (p=0.20) rates. Higher odds of good neurologic outcome were found when we compared FPE with non-FPE (56% vs 41%, OR=1.78) and mFPE with non-mFPE (57% vs 44%, OR=1.73). FPE had a lower mortality rate (17% vs 25%, OR=0.62) than non-FPE. FPE and mFPE were not associated with lower sICH rate compared with non-FPE and non-mFPE (4% vs 18%, OR=0.41 for FPE; 5% vs 7%, OR=0.98 for mFPE). CONCLUSIONS: Our findings suggest that approximately one-third of patients achieve FPE and around half of patients achieve mFPE, with equivalent results throughout thrombectomy techniques. FPE and mFPE are associated with better clinical outcomes.

Causing DNA damage and stopping DNA repair - Vitamin D supplementation with Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors may cause selective cell death of cancer cells: A novel therapeutic paradigm utilizing elevated copper levels within the tumour.

Inhibitors of PARP1 are currently being used to treat malignancies and as maintenance drugs post chemotherapy. Vitamin D has been shown to have an anticancer effect (mediated by multiple mechanisms) and is usually deficient in cancer patients. We had previously proposed and experimentally validated the selective cell death of cancer cells caused due to interaction of vitamin D with elevated copper within malignant cells, leading to ROS mediated DNA damage. In this communication we propose a Vitamin D supplementation strategy with PARP1 inhibitor treatment which would have multifaceted benefits for therapy. Besides exerting its anticancer effects by other mechanisms and addressing the deficiency, Vitamin D in principle would cause selective ROS mediated DNA breakage in malignant cells, while sparing healthy non malignant cells. Since Vitamin D is also a known inhibitor of PARP1, this therapeutic strategy would push the malignant cells to apoptosis due to DNA breakage via the vitamin D-copper mechanism, in addition to inhibiting DNA repair. Since the available levels copper within normal cells are several fold less as compared to malignant cells, the normal cells would be spared of the Vitamin D induced, ROS mediated DNA damage and would be less likely to die due to PARP1 inhibition.

Carotid plaque vulnerability on magnetic resonance imaging and risk of future ischemic events: a systematic review and meta-analysis.

INTRODUCTION: Magnetic resonance imaging (MRI) can characterize carotid plaque features, including intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and thin/ruptured fibrous cap (TRFC), that have increased tendency to cause future cerebrovascular ischemic events. We performed a systematic review and meta-analysis of studies evaluating association of MRI-identified high-risk plaque features, including IPH, LRNC, and TRFC, with risks of subsequent ischemic events of stroke, transient ischemic attack (TIA), or amaurosis fugax (AF) over follow-up duration of ≥3 months. EVIDENCE ACQUISITION: Multiple databases were searched for relevant publications between January 2000 and March 2020. Studies reporting outcomes of future ischemic events of stroke, TIA, or AF for individual MRI-identified high-risk carotid plaque features over follow-up duration of ≥3 months were included. Random effects meta-analysis was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing outcomes between MRI-positive and MRI-negative groups. EVIDENCE SYNTHESIS: Fifteen studies including 2350 patients were included. The annual rate of future ischemic events was 11.9% for MRI-positive IPH, 5.4% for LRNC, and 5.7% for TRFC. IPH, LRNC, and TRFC were associated with increased risk of future ischemic events (OR 6.37; 95% CI, 3.96 to 10.24), (OR 4.34; 95% CI, 1.65 to 11.42), and (OR 10.60, 95% CI 3.56 to 31.58), respectively. CONCLUSIONS: The current study findings strengthen the assertion that MRI-positive "high-risk" or "vulnerable" plaque features, including IPH, LRNC, and/or TRFC can predict risks of future ischemic events of stroke, TIA, or AF.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry.

BACKGROUND: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA). METHODS: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year. RESULTS: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors. CONCLUSION: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.

A Boosted Ensemble Algorithm for Determination of Plaque Stability in High-Risk Patients on Coronary CTA.

OBJECTIVES: This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics. BACKGROUND: Coronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known. METHODS: Utilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested case-control study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of this model was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion. RESULTS: CL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs. CONCLUSIONS: In a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA.

How climate change affects parasites: the case of trematode parasite Clinostomum complanatum and its fish host Trichogaster fasiatus.

This study was undertaken to understand the impact of climate change on the ecology of infection of Clinostomum complanatum, a model trematode parasite. We analysed climate change data and data from infected fish over a period of seven years (2007-2013) from the Aligarh region (India) in this retrospective study. We show that infection of the trematode parasite Clinostomum complanatum (Rudolphi, 1814) in the forage fish Trichogaster facsiatus (Bloch & Schneider, 1801) is dependent on surface air temperature amongst the (ecologically) relevant climate change variables for both the parasite and its host. This study is the first to implicate surface air temperature as an environmental variable that may contribute towards parasitism, particularly for parasites with a piscine host. The biological relevance of changing climate on the ecology of this parasite is discussed.

In vitro Remote Aspiration Embolectomy for the Treatment of Acute Ischemic Stroke.

BACKGROUND: "Remote aspiration," using suction from the proximal internal carotid artery (ICA) to open terminus occlusions, has been reported in small case series. However, it remains unclear whether remote aspiration is feasible for middle cerebral artery occlusions in the setting of potential inflow from communicating arteries. We performed an in vitro study to assess whether suction applied at various locations proximal to an occlusion could successfully aspirate the clot. METHODS: A glass model of 4 mm inner diameter (ID) with 1 mm distal narrowing and 2 mm side branch to simulate a communicating artery was constructed. A proximal side branch was placed to simulate inflow from the proximal ICA. The impact of three different-sized catheters (ID 0.088, 0.070, and 0.056 in) on histologically different (red blood cell-cell rich, fibrin-rich, and mixed) clot analogues was tested with the catheter tip placed remotely either distal or proximal to the collateral branch. Aspiration was attempted with (1) open system (flow in both the ICA and the collateral branch, (2) flow arrest with open collateral (no flow in the ICA, but flow in the collateral branch), and (3) closed system (no flow in either the ICA or the collateral branch). The outcome was success or failure of remote aspiration. RESULTS: For the 0.088-in catheter, remote aspiration was successful in all conditions. For the 0.070-in catheter, remote aspiration was unsuccessful without proximal flow arrest, but was successful in all other scenarios. For the 0.056-in catheter, remote aspiration was successful only with complete flow arrest. CONCLUSIONS: In a noncollapsible system, remote aspiration can be successfully achieved even in the setting of prominent branch arteries by using relatively large aspiration catheters. Proximal flow arrest may facilitate successful remote aspiration for some catheter sizes.

Dynamic computed tomographic assessment of the mitral annulus in patients with and without mitral prolapse.

OBJECTIVES: To obtain 3D CT measurements of mitral annulus throughout cardiac cycle using prototype mitral modeling software, assess interobserver agreement, and compare among patients with mitral prolapse (MP) and control group. BACKGROUND: Pre-procedural imaging is critical for planning of transcatheter mitral valve (MV) replacement. However, there is limited data regarding reliable CT-based measurements to accurately characterize the dynamic geometry of the mitral annulus in patients with MV disease. METHODS: Patients with MP and control subjects without any MV disease who underwent ECG-gated cardiac CT were retrospectively identified. Multiphasic CT data was loaded into a prototype mitral modeling software. Multiple anatomical parameters in 3D space were recorded throughout the cardiac cycle (0-95%): annular circumference, planar-surface-area (PSA), anterior-posterior (A-P) distance, and anterolateral-posteromedial (AL-PM) distance. Comparisons were made among the two groups, with p < 0.05 considered statistically significant. Interobserver agreement was assessed on ten patients using intraclass correlation coefficient (ICC) among 4 experienced readers. RESULTS: A total of 100 subjects were included: 50 with MP and 50 control. Annular dimensions were significantly higher in the MP group than control group, with circumference (144 ± 11 vs. 117±8 mm), PSA (1533 ± 247 vs. 1005 ± 142 mm2), A-P distance (38 ± 4 vs. 32±2 mm), and AL-PM distance (47 ± 4 vs. 39±3 mm) (all p < 0.001). Substantial size changes were observed throughout the cardiac cycle, but with maximal and minimal sizes at different cardiac phases for the two groups. The interobserver agreement was excellent (ICC≥0.75) for annular circumference, PSA, A-P- and AL-PM distance. CONCLUSION: A significant variation in the mitral annular measures between different cardiac phases and two groups was observed with excellent interobserver agreement.

Nickel toxicology with reference to male molecular reproductive physiology.

The toxicity of metals is a known phenomenon. Nickel toxicity is very common since nickel is used extensively both industrially and in items of personal use such as utensils and jewellery. Here we discuss human exposure to nickel and its toxicity in the light of the available scientific evidence to understand its underlying pathophysiology. The ability of Ni+2 to get oxidized to Ni+3 renders it's potential of generating reactive oxygen species (ROS) in the system leading to oxidative stress. Carcinogenesis, apoptosis induction, contact dermatitis, epigenetic changes, and alteration in gene regulation are a result of overexposure of nickel. Our focus is on how nickel affects the male reproductive physiology. Nickel primarily drives ROS mediated perturbations in the male reproductive system. It influences zinc metabolism, which is critical for sperm stability and affects the structure of DNA binding proteins, including protamines, thereby affecting sperm function.