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Transesophageal echocardiography (TEE) has been the preferred imaging modality to help guide left atrial appendage closure. Newer technologies such as the Nuvision 4D Intracardiac echocardiography (ICE) catheter allow for real-time 3D imaging of cardiac anatomy. There are no direct comparison studies for procedural imaging between TEE and 4D ICE. To evaluate the performance and safety of left atrial appendage (LAA) closure procedures with the Watchman FLX and Amulet, guided by the Nuvision 4D ICE Catheter. This retrospective observational analysis was conducted on institutional LAAO National Cardiovascular Data Registry from January 2022 to March 2023. Patients had undergone LAA closure procedures with the Watchman FLX or Amulet device guided by TEE or a 4D ICE Catheter. The primary outcome evaluated was successful LAAO device placement. A total of 121 patients underwent LAAO device placement with 46 (38.0%) patients guided by 4D ICE during LAAO implantation. The 4D ICE group had a shorter procedural time compared with TEE guidance. Post procedural 45-day TEE post implant was also comparable for both groups with no patients in either group having incomplete closure of the left atrial appendage and peri-device leak > 5 mm. No device related complications (device related access, stroke, or pericardial effusion) occurred in either group at follow-up. There was no significant difference in device implant success or post procedural outcomes at 45 days in either the TEE or 4D ICE group. However, there was a noticeable improvement in procedural time with the 4D ICE catheter. [ABSTRACT FROM AUTHOR]

Ataxia-Telangiectasia Mutated kinase (ATM kinase) is a well-established protein, maintains genome integrity and modulates cellular responses to DNA breakage. It is acknowledged as a master regulator of Double-Strand Breaks (DSB) and redox sensor. In a variety of human malignancies, cells exhibit resistance to radiation and chemotherapeutic approach and thus, the suppression of ATM kinase is a promising strategy to promote cellular sensitivity. Several Miliusa plants are used for traditional medication and reveal appreciable cytotoxicity against tumours. The objective of this study is to achieve sensitization to resistant cells by identifying potent bioactive inhibitors which can block the activity of ATM kinase. Hence, we considered 14 phytoconstituents from genus Miliusa. In this study, we performed Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET), drug-likeliness prediction, molecular docking and Molecular Dynamics Simulation (MDS). The docking results were evaluated based on free energy binding (ΔG) and it revealed that conocarpan, epicatechin, rhamnazin and rhamnetin found to be potent inhibitors of ATM kinase. The MD simulation results showed the detailed structure and residue level changes upon binding with novel inhibitors. The present investigation proposes, rhamnazin as an efficient inhibitor owing to significant interaction with ATM kinase by exhibiting better binding energy of −29.72 kJ/mol than standard KU-55933 with −17.76 kJ/mol. [ABSTRACT FROM AUTHOR]

Background: Eclampsia is one of the riskiest acute pregnancy issues since it has a high risk of morbidity and death for both the mother and the fetus. In underdeveloped nations, there are 50 to 151 cases of eclampsia for every 10,000 deliveries. When combined with eclampsia, reversible posterior leukoencephalopathy syndrome even makes the patient's situation worse and has a negative impact on both the mother and the fetus. Objective: The present study was aimed to determine the obstetric outcomes for the mother and the newborns in PRES at a Federal Government Polyclinic (Postgraduate Medical Institute) Islamabad Study design: A cross-sectional study Place and Duration: This study was conducted in Federal Government Polyclinic (Postgraduate Medical Institute) Islamabad from December 2021 to December 2022. Methodology: Women presenting with eclampsia having neurological symptoms were included in the study. Computed Tomography (CT) of the brain was performed for the diagnosis of PRES. Women with known seizure disorders or having neurological disorder due to any cause other than eclampsia were excluded. After being diagnosed with PRES and informed consent maternal and fetal outcomes were recorded. Version 25 of SPSS (Statistical package for social sciences) was used to enter and analyse the data. For categorical variables, frequency and percentages as well as mean and standard deviation were collected. Results: Postpartum presentation of eclampsia was 18(45%), 27(67.5%) were primigravida, 65% belonged to rural type of residence, only 11(27.5%) cases were booked. Headache was the most common symptom among patients (42.5%), followed by visual disturbance (27.5%). More than half of the patients (52.5%) had 1-3 convulsions. CT scan revealed that Parieto-occipital region was involved in 19 (47.5%) of patients. The most common maternal complication was Abruptio placentae 8(20%) followed by HELLP syndrome 7(17.5%). Neonatal outcomes revealed that 37.5% of neonates were low birth weight, 7.5% were stillbirths and only 55% of neonates had APGAR scores between 7-10. Conclusion: Among patients with PRES, prompt diagnosis and therapy are crucial for survival. Clinical and radiographic features need to be carefully considered. The neonatal outcomes also were poor in the study, therefore, a multidisciplinary management strategy will aid in improving the result. [ABSTRACT FROM AUTHOR]

Pentachlorophenol (PCP) is a chlorophenolic compound that is widely used as pesticide, biocide and as a wood preservative to treat utility poles and wharf pilings. PCP is rapidly absorbed through the gastrointestinal tract and enters the blood where it generates active oxygen species in target cells. We have, therefore, examined the protective effect of plant antioxidant 3,4-dihydroxybenzaldehyde (DHB) against PCP-induced cyto-and geno-toxicity in human red blood cells (RBC) and lymphocytes, respectively. Human RBC were incubated at 37°C with 0.75 mM PCP, either alone or in presence of different concentrations of DHB (0.05–2.0 mM). Several biochemical parameters were determined in whole cells and hemolysates. Incubation of RBC with PCP alone increased the formation of reactive oxygen and nitrogen species (ROS and RNS) that resulted in oxidation of proteins, lipids, cellular thiols and plasma membrane damage. The antioxidant defense system was impaired and glucose metabolism was inhibited. However, prior treatment of RBC with DHB lowered ROS and RNS generation and attenuated PCP-induced oxidative damage of cell components. DHB alone enhanced electron transport by the plasma membrane redox system and also prevented its inhibition by PCP. DHB significantly prevented PCP-induced transformation of RBC morphology from normal biconcave shape to spherocytes, spiculated acanthocytes and echinocytes. DHB protected human lymphocytes from PCP-induced DNA damage and strand breaks, lysosomal membrane damage and collapse of the mitochondrial membrane potential. These results show that DHB mitigates PCP-induced cytotoxicity and can potentially function as a chemoprotective agent against the harmful effects of PCP and possibly other chlorophenols. [ABSTRACT FROM AUTHOR]

Chloroxylon swietenia DC. is a folklore medicinal plant that belongs to the family Rutaceae is known as 'East Indian satinwood' or 'Cylon satinwood' native to South India and Sri Lanka. Almost all parts of this plant are being used in the indigenous system of medicine for a long time. The invitro antioxidant activity screening of fruit petroleum ether, chloroform and ethanol extracts confirms that the fruit ethanol extract is stronger among the extracts tested. Therefore, this extract was considered further for invivo studies. In vivo, acute toxicity study of ethanol extract via oral administration indicated that it is non -toxic in a dose-dependent manner. This is revealed by morphological observation of no mortality and morbidity in experimental animals after completing 14 days of the experimental period. Further, the GC-MS identified phytocompounds of fruit ethanol extract from Chloroxylon swietenia DC were studied against CCl4 induced liver toxicity in Swiss albino rats. The activity was assessed by monitoring various parameters of serum marker enzyme activity such as Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), and liver tissue architecture. In silico ADMET studies and docking techniques were carried out to authenticate the drug likeliness. The results from the invivo and insilico studies have revealed that the fruit ethanol extract of Chloroxylon swietenia DC could be useful in preventing CCl4 induced liver toxicity. [ABSTRACT FROM AUTHOR]

Chloroxylon swietenia is a medicinal plant used in folklore remedies to treat wounds, cuts, burns, and skin diseases for quick relief and also used for wounds infected with animal worms, fungal skin infections, and rheumatism, etc. The present aim is to appraise the anti-inflammatory and wound healing efficacy of Chloroxylon swietenia fruit phytocompounds and to authenticate its traditional claims. This study was designed using protein denaturation methods and rat wound models. Among selected fruit extracts, the fruit ethanol extract offered significant inhibition of BSA (Bovine serum album) denaturation with IC50=201.05µg/ml and HRBC (Human red blood cell) membrane lysis with IC50 132.94µg/ml. The fruit ethanol extract exhibited prominent results i.e. healing the lesion within day 14 in the excision wound model. Also showed better wound breaking strength(WBS) of 766.88 ± 3.95g which is comparatively closer to the standard povidoneiodine (813.24±2.51g) treatment in the incision wound model. Conclusively, the increased fruit ethanol extract concentration exhibited early epithelisation, enhanced wound contraction, increased WBS, and superior skin collagen tissue development. The wound healing potential was further indicated by downregulation of free radicals and inflammatory markers associated with enhanced antioxidants of wet granulation tissue and biochemical markers of dry granulation tissue shown to be up-regulated in a dead space wound model. The current study might establish Chloroxylon swietenia as a good source of therapeutic wound healing drugs with anti-inflammatory and antioxidant potentials. [ABSTRACT FROM AUTHOR]

Gardenia gummifera L.f is a medicinal plant that belongs to the Rubiaceae family. The plant is well known for its traditional practice. The current investigation was to evaluate the wound healing and anti-inflammatory capabilities of Gardenia gummifera fruit methanol extract (GFME) and Gardenia gummifera stem bark ethanol extract (GSEE). The acute dermal toxicity, wound healing activity of excision, and incision in rat models were evaluated. Wound contraction and epithelialization periods were measured by the excision model and tensile strength was evaluated from the incision model. Similarly, denaturation of protein, human red blood cell (HRBC) membrane stabilization, proteinase inhibitory action was evaluated for the inflammatory action. In vivo, acute dermal toxicity of extracts did not show any toxicity. GFME and GSEE treated wounds showed effective healing capability as proven by increased wound contraction and less epithelialization period and higher tensile strength. The anti-inflammatory studies revealed that GFME and GSEE had significant antiinflammatory capacity. The outcome of this present study displayed remarkable wound healing and antiinflammatory action. [ABSTRACT FROM AUTHOR]

Hexavalent chromium [(Cr(VI)] is widely used in several industries, but human exposure results in multiple organ toxicity. Enhanced generation of free radicals and reactive species is thought to play a key role in Cr(VI)-induced toxicity. We have examined the effect of taurine, a simple sulphur-containing amino acid and an antioxidant, on potassium dichromate [K2Cr2O7, a Cr(VI) compound]-induced cytotoxicity and genotoxicity in human blood cells. Erythrocytes were treated with K2Cr2O7, either alone or after incubation with different concentrations of taurine. Treatment of erythrocytes with K2Cr2O7 alone led to marked increase in generation of reactive oxygen and nitrogen species, lipid and protein oxidation. This was accompanied by decrease in total sulfhydryl and glutathione content and lowered antioxidant power of the cells. This suggests that Cr(VI) induces oxidative stress in the cells. Incubation of erythrocytes with taurine prior to addition of K2Cr2O7, resulted in a concentration-dependent decrease in the generation of reactive oxygen and nitrogen species, mitigation of oxidative stress and amelioration of antioxidant power of these cells. It also restored the activities of several metabolic, antioxidant and membrane-bound enzymes. Cr(VI)-induced damage to erythrocyte membrane and lymphocyte DNA was also significantly attenuated by prior administration of taurine. These results suggest that taurine can function as a chemoprotectant against Cr(VI)-induced oxidative injury and can be potentially used to mitigate the toxic effects of this transition metal ion. [ABSTRACT FROM AUTHOR]

Studies were initiated in two sets of experiments, to know the impact of augmentation of parasitoid AcerophaguspapayaeNoyes &Schauffon mealy bug ParacoccusmarginatusWilliam Granara de Willinkpopulations. In one set of experimentinoculative (one time)release was made in March in papaya orchard of about one acre area at the rate of 1000 mummies (parasitized mealy bugs)per 5; 10 and 20 plants; each in three replicates. In the other set of experiment 10,000 mummies of the parasitoid were released every month per acre from March onwards in three replicates. Impact of augmentation was found not very effective in controlling mealy bug as compared with orchards existing nearer to where natural enemies field reservoir (NEFR)was maintained. Howeverinocoultive release of the parasitoid @ 1000 mummies per five plants seemed better for biological management of the pest. More observations are needed to standardize the required doze of the parasitoid quantum for one time release atbeginning of spring season when the mealy bug started breeding at faster rate. This could be recommended to cover a wide area for biological control of the papaya mealy bug. Pest densities measured in biologically managed orchards indicated significant decrease in mealy bug densities compared with pesticides managed orchards. [ABSTRACT FROM AUTHOR]

Objective: The plant Cassia fistula L. (Caesalpiniaceae) is traditionally used to treat heart diseases, abdominal pain and fever. The present study was aimed to investigate the toxic effects acute and sub-acute administration of ethanol extract of C. fistula fruit (CFE) in male Wistar rats. Materials and Methods: In acute toxicity, the effects of a single oral dose (1000, 3000 and 5000 mg/kg) of CFE have been determined. Animal behaviour and mortality were determined for up to 14 days. In sub-acute study, the effects of CFE in daily single oral administration at the doses of 250, 500 and 1000 mg/kg during 28 days were determined. The blood haematological and biochemical parameters, as well as the histopathological examination of the liver, heart and kidneys were studied. Results: In acute study, a single administration of the CFE up to a dose of 5000 mg/kg did not induce mortality. Thus, the LD50 of the CFE has been estimated higher than 5000 mg/kg. In sub-acute toxicity study, administration of CFE at the doses of 250, 500 and 1000 mg/kg to rats did not induce mortality. No significant differences were found in relative organ weight, and haematological and biochemical analyses in treated groups compared to control group. No noticeable histological changes were observed in organs of CFE-treated rats compared to controls. Conclusion: These results have shown that oral administration of C. fistula fruit did not produce any significant toxic effect in male rats. Hence, C. fistula fruit could be regarded as a safe natural product for therapeutic use. [ABSTRACT FROM AUTHOR]

Hexavalent chromium [Cr(VI)] is the most toxic and potent form of chromium and induces multiple organ damage in humans and experimental animals. Oxidative stress has been implicated in the toxicity of Cr(VI). We have examined the potential role of 3,4-dihydroxybenzaldehyde (DHB), a plant polyphenolic antioxidant, in protecting human erythrocytes and lymphocytes from Cr(VI)-induced cytotoxicity and genotoxicity. Erythrocytes were treated with potassium dichromate, a Cr(VI) compound, in presence and absence of DHB. Incubation of erythrocytes with Cr(VI) enhanced the generation of reactive oxygen and nitrogen species, increased lipid and protein oxidation, methemoglobin levels, and lowered antioxidant power of cells. However, prior treatment of erythrocytes with DHB, resulted in a significant DHB dose-dependent decrease in reactive oxygen and nitrogen species levels and restoration of oxidative stress parameters. DHB also improved the antioxidant power of erythrocytes and restored the activities of major antioxidant, metabolic and membrane bound enzymes. Electron microscopic studies images DHB prevented Cr(VI)-induced morphological changes in erythrocytes. The single cell gel electrophoresis assay showed that DHB mitigated Cr(VI)-induced DNA damage in lymphocytes. These results clearly show that DHB protects human blood cells from Cr(VI)-induced oxidative damage and can be potentially used in reducing the toxic effects of this metal ion. [ABSTRACT FROM AUTHOR]

Abstract: Sodium nitrite (NaNO2) is widely used in the food industry as a preservative and colorant in meat and fish products. Industrialization and improper agricultural practices have greatly increased human exposure to high nitrite levels, mainly through contaminated drinking water, causing various health disorders. We have investigated the protective effect of carnosine (CAR) and N‐acetyl cysteine (NAC) on NaNO2‐induced toxicity in rat blood. CAR is a bioactive dipeptide found in mammalian muscle while NAC is a synthetic sulfhydryl amino acid and an important precursor of glutathione. Animals were given a single acute oral dose of NaNO2 at 60 mg/kg body weight with or without prior administration of either CAR or NAC. Rats were sacrificed after 24 h, blood was withdrawn and plasma and erythrocytes were isolated. Administration of NaNO2 alone increased methemoglobin levels and methemoglobin reductase activity, decreased the activities of antioxidant defense and metabolic enzymes and significantly weakened the total antioxidant capacity of rat erythrocytes. Similar effects were seen in plasma of NaNO2‐treated rats. In contrast, administration of CAR or NAC, prior to NaNO2 treatment, markedly attenuated the NaNO2‐elicited deleterious effects. Thus, CAR and NAC can mitigate nitrite‐induced metabolic alterations and oxidative damage probably due to their intrinsic biochemical antioxidant properties. This study suggests that CAR and NAC can be potentially used as therapeutic/protective agents against NaNO2 toxicity. [ABSTRACT FROM AUTHOR]

The toxicity of hexavalent chromium [Cr(VI)] in biological systems is thought to be closely associated with the generation of free radicals and reactive oxygen species. These species are produced when Cr(VI) is reduced to its trivalent form in the cell. This process results in oxidative stress due to an imbalance between the detoxifying ability of the cell and the production of free radicals. We have studied the effect of potassium dichromate (K2Cr2O7), a [Cr(VI)] compound, on the antioxidant power of human erythrocytes and lymphocytes under in vitro conditions. Incubation of erythrocytes and lymphocytes with different concentrations of K2Cr2O7 resulted in a marked dose-dependent decrease in reduced glutathione and an increase in oxidized glutathione and reactive oxygen species levels. The antioxidant power of the cells was decreased, as determined by metal reducing and free radical quenching assays. These results show that [Cr(VI)] upregulates the generation of reactive oxygen species and, as a consequence, the cellular antioxidant defences are compromised. The resulting oxidative stress may contribute to Cr(VI)-induced cellular damage. [ABSTRACT FROM AUTHOR]

Purpose: Standardised MedDRA Queries (SMQs) have been developed since the early 2000’s and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). Methods: We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. Results: A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with “narrow terms” to enhance specificity over strategies using “broad terms” to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. Conclusions: SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions. [ABSTRACT FROM AUTHOR]

B Conclusions: b Elderly patients, including octo/nonagenarians, who survive IHCA have a 3-year survival rate of 70%. The study aims to evaluate the 3-year mortality and analyze the 3-year hospital readmission in elderly patients of age 65-79 versus elderly patients aged 80 and above after in-hospital cardiac arrest (IHCA). Elderly patients aged 65-79 have a higher readmission rate than aged >= 80 years. [Extracted from the article]

Context:The plantCassia fistulaL. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant. Objective:To investigate the hypolipidemic and antioxidant effects of ethanol extract ofC. fistulafruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice. Materials and methods:Oral administration of CFE at 100, 300 and 500 mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20 mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined. Results:Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500 mg/kg showed remarkable (p < 0.001) hypolipidemic and antioxidant effects in HFD fed mice. Conclusion:C. fistulafruit demonstrated hypolipidemic and antioxidant propertiesin vivoand the results corroborate the use of this plant in traditional medicine for cardiac ailments. [ABSTRACT FROM AUTHOR]

Nitrite/nitrate salts are used in fertilizers and as food preservatives. Human exposure to high levels of nitrite results in its uptake and subsequent entry into blood where it can interact with erythrocytes. We show that treatment of human erythrocytes with sodium nitrite (NaNO2) results in a dose-dependent increase in the production of reactive oxygen species. This was accompanied by a decrease in the antioxidant power which lowered the free radical quenching and metal-reducing ability. NaNO2 treatment also inhibited plasma membrane redox system (PMRS) of erythrocytes. These changes increase the susceptibility of erythrocytes to oxidative damage, decrease the antioxidant power of whole blood, and can be a major cause of nitrite-induced cellular toxicity. [ABSTRACT FROM AUTHOR]

S10 Management of Hyperlipidemia Induced by Primary Biliary Cholangitis We suggest initiating moderate-intensity statins in the presence of diabetes or pre-existing CVD and close monitoring PBC in patients with pre-existing CVD, diabetes, or primary hypercholesterolemia. Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic autoimmune liver disease characterized by the destruction of intrahepatic bile ducts with portal inflammation and scarring. [Extracted from the article]

Creatine (Cr) is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Recent reports have shown that Cr displays antioxidant activity which could explain its beneficial cellular effects. We have evaluated the ability of Cr to protect human erythrocytes and lymphocytes against oxidative damage. Erythrocytes were challenged with model oxidants, 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and hydrogen peroxide (H2O2) in the presence and absence of Cr. Incubation of erythrocytes with oxidant alone increased hemolysis, methemoglobin levels, lipid peroxidation and protein carbonyl content. This was accompanied by decrease in glutathione levels. Antioxidant enzymes and antioxidant power of the cell were compromised while the activity of membrane bound enzyme was lowered. This suggests induction of oxidative stress in erythrocytes by AAPH and H2O2. However, Cr protected the erythrocytes by ameliorating the AAPH and H2O2 induced changes in these parameters. This protective effect was confirmed by electron microscopic analysis which showed that oxidant-induced cell damage was attenuated by Cr. No cellular alterations were induced by Cr alone even at 20 mM, the highest concentration used. Creatinine, a by-product of Cr metabolism, was also shown to exert protective effects, although it was slightly less effective than Cr. Human lymphocytes were similarly treated with H2O2 in absence and presence of different concentrations of Cr. Lymphocytes incubated with oxidant alone had alterations in various biochemical and antioxidant parameters including decrease in cell viability and induction of DNA damage. The presence of Cr attenuated all these H2O2-induced changes in lymphocytes. Thus, Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase their lifespan. [ABSTRACT FROM AUTHOR]

Citrus is attacked by a number of inect pests in Pakistan. The list includes citrus psylla Diaphorina citri; leaf miner Phyllocnistis citrella; white flies Aleurocanthus woglumi Aleurocanthus husaini, Aleurotuberculatus citrifolii, A. jasmine, Amurrayae, Aleurolobus niloticus, Aleurotrachelus sp, Dialeurodes citri and D. elongata; scale insects Aonidiella aurantii, A. citrina, and A. orientalis; mealy bugs Nipaecoccus vastator, Ferrisia virgata, Planococcus citri, Pseudococcus filamenetosus, Spilococcus sp, and Rastrococcus spinosus; coccids Coccus hesperidum and Pulvinaria psidii; margarodids Drosicha stebbingi and Iceryia egyptiaca; fruit flies Bactrocera zonata and B. dorsalis and butter fly Papiliode moleus. At present farmers rely on pesticide sprayings in orchards to control pests and diseases. These practices have not only worsened the pest status overtime but also have created the risks of pesticide residues in produce. If present plant protection practices continue, Pakistani growers may have a setback in exporting their produce. Consumers, especially in the developed world, being health conscious force their governments to protect them from ill effects of pesticides. The need of the time therefore is to shift from the present pesticide based plant protection to integrated pest management based on bio-ecological principles to reduce the use of pesticides in crops particularly in horticulture. In the paper, status of key pests of citrus in Pakistan is reviewed and possibilities of their management by non-chemical measures have been discussed. [ABSTRACT FROM AUTHOR]

Aim and Objectives: To evaluate anxiolytic effect of stem bark ethanol and chloroform extracts of Erythrina mysorensis in mice. Materials and Methods: The anxiolytic activity was examined by using the elevated plus maze (EPM) and open field test (OFT), and motor coordination by rotarod test (RRT). Twenty four Swiss albino male mice were divided into four groups of six mice each. Group 1 received vehicle (normal saline); group 2 received diazepam (1 mg/kg); groups 3 and 4 received ethanolic and chloroform extract of Erythrina mysorensis, 200 and 400 mg/kg p.o., respectively. Results: Mice treated with diazepam (1 mg/kg, p.o.) showed significant (P < 0.001) increase ini the percentage of open arms entries and time spent whereas, in closed arm the number of entries and time spent were significantly (P < 0.05) decreased. Oral administration of chloroform and ethanol extract of E. mysorensis exhibited significant (P < 0.05) increase in the number of open arm entries and time spent with significant (P < 0.05) reduction in number of entries and time spent in the closed arm as compared to group 1. Chloroform and ethanol extracts treated mice also produced significant increase in the number of rearings (P < 0.05), assisted rearings and number of squares crossed (P < 0.01). Rotarod test showed significant (P < 0.01) reduction in motor activity at 45 min with diazepam and E. mysorensis extracts (400 mg/kg) as compared to groups 3 and 1. Conclusion: Erythrina mysorensis possess significant anxiolytic activity in the mice. It can be a promising anxiolytic agent. [ABSTRACT FROM AUTHOR]

Hyperglycemia is a state in which excess glucose circulates in blood. Erythrocytes are in direct contact with this high glucose concentration and are greatly affected by it. We have examined the effect of hyperglycemic condition on isolated human erythrocytes under in vitro conditions. Erythrocytes were incubated with different concentrations of glucose (5, 15, 30, 45 mmol/L) for 24 h, and several biochemical parameters were determined. Treatment with high glucose concentrations increased heme degradation and methemoglobin level, while methemoglobin reductase activity was decreased. A significant increase in protein oxidation and lipid hydroperoxides with a decrease in total sulfhydryl content was seen. This suggested the generation of oxidative stress, which was confirmed by an enhanced production of reactive oxygen and nitrogen species. Hyperglycemia led to a significant decline in the antioxidant power of erythrocytes, lowering their ability to quench free radicals and reduce metal ions to lower oxidation states. The plasma membrane redox system was upregulated, while ascorbate free radical reductase activity was lowered. Glucose exposure inhibited the enzymes of glycolysis and hexose monophosphate shunt. Electron microscopy showed morphological changes resulting in the formation of echinocytes. Thus, the hyperglycemic condition generates reactive species that oxidize proteins, hemoglobin, and lipids; impair the total antioxidant capacity; and alter morphology in human erythrocytes. [ABSTRACT FROM AUTHOR]

Cadmium chloride (CdCl2) is a widely used industrial compound that exhibits multiple organ toxicity. Cadmium is transported through blood where erythrocytes are exposed to its action. Here the effect of CdCl2 on human erythrocytes was examined under in vitro conditions. Human erythrocytes were treated with 0.01–0.5 mM CdCl2 for 24 h at 37 °C. Lysates were made from CdCl2 treated and untreated (control) cells and used for further analysis. CdCl2 treatment resulted in marked hemolysis of erythrocytes and oxidation of hemoglobin to methemoglobin. This will result in anemia and also reduce the oxygen carrying ability of erythrocytes. Hemoglobin oxidation was accompanied by degradation of heme and release of free ferrous iron moiety. Further analysis showed elevated lipid hydroperoxides and formation of advanced oxidation protein products along with reduction in total sulfhydryl content, indicating the generation of oxidative stress condition in the cell. Incubation of erythrocytes with CdCl2 enhanced generation of reactive oxygen and nitrogen species, decreased the antioxidant power and inhibited pathways of glucose metabolism. Plasma membrane was damaged as indicated by enhanced osmotic fragility and inhibition of membrane bound enzymes. This was confirmed by electron microscopy which showed formation of echinocytes. These results show that CdCl2 generates reactive species which impair the antioxidant system resulting in oxidative damage to erythrocytes. [ABSTRACT FROM AUTHOR]

Abstract: Potassium bromate (KBrO3) is a widely used food additive, a water disinfection by-product and a known nephrotoxic agent. The effect of KBrO3 on rat blood, especially on the anti-oxidant defense system, was studied in this work. Animals were given a single oral dose of KBrO3 (100mg/kg body weight) and sacrificed 12, 24, 48, 96 and 168h after this treatment. Blood was collected from the animals and separated into plasma and erythrocytes. KBrO3 administration resulted in increased lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased the reduced glutathione content indicating the induction of oxidative stress in blood. Methemoglobin levels and methemoglobin reductase activity were significantly increased while the total anti-oxidant power was greatly reduced upon KBrO3 treatment. Nitric oxide levels were enhanced while vitamin C concentration decreased in KBrO3 treated animals. The activities of major anti-oxidant enzymes were also altered upon KBrO3 treatment. The maximum changes in all these parameters were 48h after the administration of KBrO3 and then recovery took place. These results show for the first time that KBrO3 induces oxidative stress in blood and impairs the anti-oxidant defense system. Thus impairment in the anti-oxidant power and alterations in the activities of major anti-oxidant enzymes may play an important role in mediating the toxic effects of KBrO3 in the rat blood. The study of such biochemical events in blood will help elucidate the molecular mechanism of action of KBrO3 and also for devising methods to overcome its toxic effects. [Copyright &y& Elsevier]

Abstract: Background: Exposure to chromium compounds can result in nephrotoxicity. The administration of potassium dichromate (K2Cr2O7), a hexavalent chromium compound, results in impairment in functions of renal brush border membrane (BBM). Methods: The effect of vitamin C (ascorbic acid) on K2Cr2O7-induced nephrotoxicity, changes in BBM enzymes, Pi transport and the anti-oxidant status of rat kidney were studied. Animals were divided into 4 groups and were intraperitoneally given saline (control), vitamin C alone, K2Cr2O7 alone and vitamin C plus K2Cr2O7. Nephrotoxicity was evaluated by urea and creatinine levels in the serum. Anti-oxidant status was evaluated in kidney homogenates. Results: A single dose of K2Cr2O7 (15 mg/kg body weight) resulted in an increase of serum urea nitrogen and creatinine levels, increase in lipid peroxidation and decrease in total sulfhydryl groups. However, prior treatment with a single dose of vitamin C (250 mg/kg body weight) protected the kidney from the damaging effects of K2Cr2O7. It greatly ameliorated the K2Cr2O7-induced nephrotoxicity and reduction in Pi transport, activities of catalase, Cu–Zn superoxide dismutase and BBM enzymes. This was accompanied by decrease in lipid peroxidation and recovery of sulfhydryl content of renal cortex. Conclusions: Vitamin C is an effective chemoprotectant against K2Cr2O7-induced acute renal failure and dysfunction of the renal BBM in rats. [Copyright &y& Elsevier]

Introduction. Hypereosinophilic syndrome (HES) is a rare disease characterized by unexplained peripheral eosinophilia along with evidence of end-organ damage. Cardiac involvement is the most life-threatening consequence and is frequently underreported with a prevalence of around 5%. The gold standard for diagnosis is myocardial biopsy, but less-invasive imaging such as cardiac MR (CMR) has been frequently used to help with the diagnosis. We are presenting a unique case of a patient diagnosed with Eosinophilic myocarditis (EM) supported by CMR with rapid improvement after starting steroid treatment. Case Presentation. A 67-year-old African American female with extensive cardiovascular disease history presenting with chest pain was diagnosed with EM secondary to hypereosinophilic syndrome (HES). Lab workup revealed absolute eosinophils of 4.70 × 10 3 / μ L (normal 0 – 0.75 × 10 3 / μ L). Transthoracic echocardiography showed mild reduction in left ventricular function and a large obliterating thrombus in the right ventricular apex. CMR showed increased signal intensity at the left ventricular and right ventricular apex, consistent with myocardial edema. Subsequently, the patient was placed on dexamethasone 10 mg daily with significant symptomatic improvement. Discussion. EM is a rare complication of hypereosinophilic syndrome and can mimic common cardiovascular diseases such as acute exacerbation of heart failure or myocardial infarction. A high index of suspicion is essential especially in the setting of suggestive lab workup. CMR is a promising noninvasive and cost-effective alternative for myocardial biopsy in diagnosis. [ABSTRACT FROM AUTHOR]

Copper (Cu) is an essential micronutrient but human exposure to high level of this metal results in adverse health effects. Oxidative stress is assumed to play a major role in the mechanism of Cu-induced toxicity. The protective role of carnosine, an antioxidant and antiglycating agent, was examined against Cu-induced toxicity in isolated human blood cells. Red blood cells (RBC) were treated with 0.5 mM copper chloride (CuCl 2), a Cu(II) compound, either alone or after treatment with carnosine. Incubation of RBC with CuCl 2 increased protein oxidation, lipid peroxidation, methemoglobin formation and lowered glutathione content. The antioxidant defense system was impaired and production of reactive oxygen (ROS) and reactive nitrogen species (RNS) was enhanced. Pre-incubation of RBC with carnosine protected the cells against CuCl 2 -induced oxidative damage. It restored the activities of several antioxidant, membrane-bound and metabolic enzymes, decreased the generation of ROS and RNS, enhanced the antioxidant power of cells and prevented inactivation of plasma membrane redox system. Carnosine also protected human lymphocytes from CuCl 2 -induced DNA damage. The protective effects of carnosine were concentration-dependent while carnosine itself did not exhibit any adverse effect. Carnosine can, therefore, be used as a possible chemoprotectant against the harmful effects of this extremely redox active metal. • Cu(II) induces oxidative and nitrosative stress in human blood cells. • Carnosine pre-treatment lowers ROS and RNS generation. • Carnosine protects blood cells from Cu(II)-induced cytotoxicity and genotoxicity. [ABSTRACT FROM AUTHOR]

• IARC classified occupational exposure to asphalt as possibly carcinogenic to humans. • In India, asphalt workers do not use a adequate personal protective measures to reduce exposure. • Increased biomarkers of genetic damage were seen in asphalt workers compared with controls. • The observed genetic damage in asphalt workers is associated with possibility of increased malignancy risk. • Asphalt workers should be provided PPE to reduce risk for severe adverse health effects. There are contradictory reports about bitumen exposure and malignancy risk worldwide. Also, the evidence for genotoxicity risk among workers occupationally exposed to asphalt is insufficient. The study intended to evaluate particulate matter 10 (PM 10) at the workplace and biomarkers of genotoxicity effects among a group of asphalt workers in and around Bangalore, India. This study involved a total of 107 participants (54 exposed group and 53 unexposed control group). To evaluate the genotoxicity, the urinary 8-OHdG and relative telomere length as oxidative damage while micronucleus (MN) assay for cytogenetic damage was carried out during the study. The majority of workers have reported health complaints and 57.4% of them were not using any personal protective equipments (PPE's). The level of PM 10 detected was 104 ± 9.5 μg/m3 and 619 ± 22.7 μg/m3 in the road paving and asphalt mixing sites respectively. The biomonitoring study observed a highly significant (p = <0.001) increase in the level of 8-hydroxy-2-deoxyguanosine (8-OHdG) in the exposed group (23.17 ± 8.65 ng/mg creatinine) compared to the control (13.6 ± 7.12 ng/mg creatinine), revealed age significant associated and non-smoking borderline significant associated for oxidative stress. The relative telomere length (TL) analysis revealed its highly significant (p = 0.004) reduction in the exposed group, adjusted mean 0.95 (95% CI 0.83–1.07) compared to the control 1.06 (95% CI 0.91–1.26). The job category (p = 0.028), non-smoking (p = 0.026), and tobacco chewing (p = 0.013) were associated with reduced relative TL in the asphalt exposed group. In cytogenotoxicity analysis, the mean micronucleus (MN) frequency per 100 cells in the exposed group (26.46 ± 19.8) was significantly (p = <0.001) increased over the control group (8.56 ± 7.18). Neither smoking habit nor age appeared to influence the MN frequencies in either group. In the present study, we have demonstrated genetic damage in workers occupationally exposed to asphalt and particulate matter, raising concern for an increased risk of malignancy in these workers. [ABSTRACT FROM AUTHOR]

• Caffeic acid interacts with human hemoglobin (HHb) through ground state complex formation. • Caffeic acid quenches fluorescence intensity of HHb by static mechanism. • Caffeic acid alters the microenvironment around tryptophan residues of HHb. • Caffeic acid binds spontaneously to HHb at single site and increases its α-helical content. • Binding of caffeic acid to HHb is stabilized by multiple non-covalent interactions. Caffeic acid (CA) is a hydroxycinnamic acid derivative that possess a wide variety of biological properties and is non-toxic to humans. The binding mechanism of CA with human hemoglobin (HHb) was studied for the first time using multispectroscopic and molecular docking methods. The UV–visible absorption spectra showed that CA interacts with HHb through the formation of ground state complex. The fluorescence studies revealed that CA quenches HHb fluorescence by the static mechanism and confirmed the presence of a single CA binding site on the HHb molecule. The negative values of thermodynamics parameters (Δ H , Δ S and Δ G) showed that the binding of CA to HHb is a spontaneous and exothermic process. Hydrogen bonds and van der Waal interactions are the major intermolecular forces that stabilize the HHb-CA complex. Synchronous fluorescence experiments showed that binding of CA altered the microenvironment around tryptophan residues of HHb. Fluorescence resonance energy transfer studies indicated a high propensity of energy transfer from tryptophan residues of HHb to CA. Circular dichroism spectra and catalytic esterase activity confirmed that only minor changes occur in the secondary structure of HHb in the presence of CA. Molecular docking study identified the HHb amino acid residues involved in binding to CA. Analysis of the binding mode of CA with HHb represents an important step in elucidating the molecular mechanism of the protection of HHb from oxidative damage. This will help in understanding the potential role of CA and related antioxidants as therapeutic agents in various blood-related diseases. Interaction of caffeic acid with human hemoglobin [Display omitted] [ABSTRACT FROM AUTHOR]

Bioallethrin is a synthetic pesticide that is widely used to control insect pests. The wide use of bioallethrin has resulted in inevitable human exposure. In this study we report the effect of different concentrations of bioallethrin (10 to 200 µM, 2 h at 37 °C) on human lymphocytes under in vitro conditions. Bioallethrin treatment resulted in loss of cell viability (> 30% at 200 µM bioallethrin). Oxidative stress markers like lipid peroxidation and protein oxidation were significantly increased accompanied by lower ratio of reduced to oxidized glutathione. Enhanced ROS generation was observed through fluorescence spectroscopy and microscopy. Bioallethrin-induced oxidative stress also compromised the antioxidant defence as it reduced antioxidant capacity of cells and inhibited major antioxidant enzymes. Biomolecular modifications and systemic toxicity by bioallethrin resulted in plasma membrane damage with mitochondrial depolarization. Comet assay showed nuclear DNA fragmentation and strand scission with significant increase in tail length and olive tail moment. Apoptosis and necrosis of cells was confirmed through acridine orange/ethidium bromide dual staining and visualization under fluorescence microscope. Thus, bioallethrin causes oxidative damage and compromises the antioxidant system leading to DNA damage, cellular and organelle toxicity, resulting in apoptosis and necrosis of human lymphocytes. [ABSTRACT FROM AUTHOR]

According to International Diabetes Federation data, in 2015 there were 415 million people suffering from diabetes worldwide and this number is expected to increase to 642 million in 2040. Studies have shown a strong relationship between hyperglycemia and oxidative stress (OS) that seems to play a crucial role in progression of diabetes mellitus (DM). In hyperglycemia associated oxidative stress conditions, reactive oxygen species (ROS) induced injury of erythrocytes results in abnormalities in their function, morphology and metabolism. Moreover, the ROS present in erythrocytes can be transferred to other cells, thus inducing and spreading tissue damage and inflammation. Hyperglycemia mediated erythrocyte redox state alterations might be a potential risk factor for the development of non-proliferative diabetic retinopathy in poorly controlled diabetic subjects. Antioxidants (AO) are now being looked upon as persuasive therapeutics to combat free radicals. AO are expected to prevent oxidative stress and diabetes-related complications by inhibiting the formation of and/or scavenging free radicals or by enhancing the capability of the endogenous antioxidant system. Creatine (Cr) is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Our previous work suggests that Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase erythrocyte lifespan. In this study, glucose cytoxicity is induced in erythrocytes and various biochemical parameters for assessing OS, ROS and nitrogen species were assayed in packed erythrocytes and cell lysates. Protection from oxidative damage to erythrocytes was analyzed using Cr and carnosine. [ABSTRACT FROM AUTHOR]

Tetramethylthiuram disulfide, commonly known as thiram, is an organosulfur compound which is used as a bactericide, fungicide and ectoparasiticide to prevent disease in seeds and crops. Being a fungicide there is a high probability of human occupational exposure to thiram and also via consumption of contaminated food. In this work, the cytotoxicity of thiram was studied under in vitro conditions using human erythrocytes as the cellular model. Erythrocytes were incubated with different concentrations of thiram (25–500 μM) for 4 h at 37 °C. Control cells (thiram untreated) were similarly incubated at 37 °C. Whole cells and hemolysates were analyzed for various biochemical parameters. Treatment of erythrocytes with thiram increased protein and lipid oxidation and hydrogen peroxide level in hemolysates but decreased glutathione and total sulfhydryl group content. This was accompanied by hemoglobin oxidation, heme degradation and release of free iron. Activities of all major antioxidant enzymes were inhibited. The antioxidant power of thiram treated erythrocytes was lowered resulting in decreased metal reducing and free radical quenching ability. These results suggest that thiram enhances the generation of reactive species that cause oxidative modification of cell components. This was confirmed by experiments that showed enhanced generation of reactive oxygen and nitrogen species in thiram treated erythrocytes. Activities of marker enzymes of glucose metabolism and erythrocyte membrane were also inhibited. All effects were seen in a thiram concentration-dependent manner. Electron microscopy further supported the damaging effect of thiram on erythrocytes. Thus thiram induces oxidative stress condition in human erythrocytes and causes oxidative modification of cell components. Unlabelled Image • Pesticide thiram causes hemoglobin oxidation, heme degradation and free iron release in human erythrocytes. • Protein and lipid oxidation was increased while antioxidant power was compromised. • Membrane bound and antioxidant enzymes were inhibited. • Thiram induced gross alterations in erythrocyte morphology. • Thiram increased generation of reactive oxygen and nitrogen species in erythrocytes. [ABSTRACT FROM AUTHOR]

Cadmium is a toxic heavy metal with no physiological role in the human body. Cadmium has high mobility due to its widespread industrial use, with no safe and effective therapeutic management. Cadmium toxicity manifests by increasing oxidative stress in target cells. We have explored the potential role of vanillin, a plant phenolic aldehyde and antioxidant, in mitigating cadmium chloride (CdCl 2) induced hemotoxicity using isolated human erythrocytes. CdCl 2 was added to erythrocytes, in the absence and presence of vanillin. Incubation of erythrocytes with CdCl 2 alone inhibited methemoglobin reductase and enhanced methemoglobin level. Heme degradation and release of free iron (Fe2+), along with protein and membrane lipid oxidation, were also increased. A CdCl 2 -induced enhancement in reactive oxygen and nitrogen species was also seen, lowering the overall antioxidant power of cells. However, pre-incubation of erythrocytes with vanillin resulted in significant decreased generation of reactive species and prevented heme degradation and heme oxidation. Vanillin augmented the erythrocyte antioxidant capacity and reinstated the activities of major antioxidant, plasma membrane-bound and glucose metabolism enzymes. Scanning electron microscopy showed that CdCl 2 treatment led to the formation of echinocytes which was prevented by vanillin. In all cases, no harmful effects of vanillin alone were seen. Thus, vanillin alleviates the toxicity of cadmium and can be potentially employed as a chemoprotectant against the damaging effects of this heavy metal. [Display omitted] • CdCl 2 induces oxidative damage in human erythrocytes. • Vanillin pre-treatment significantly attenuates CdCl 2 induced methemoglobin formation. • Enzymatic and non-enzymatic defense systems were improved. • Membrane damage and morphological changes induced by CdCl 2 were restored by vanillin pre-treatment. [ABSTRACT FROM AUTHOR]

Copper (Cu) is widely present in environment, mainly in +1 and +2 oxidation states. Exposure to excess Cu has adverse effects on human health. Cu toxicity is thought to be mediated through oxidative stress. The protective effect of carnosine, a dipeptide with antioxidant and antiglycating properties, against Cu(II) induced cytotoxicity was examined. Human erythrocytes and lymphocytes were incubated with 0.5 mM CuCl 2 for 1 h in presence and absence of carnosine. Cell lysates were prepared and analyzed for several parameters. Treatment of cells with CuCl 2 elevated carbonyl content, lipid peroxidation and methemoglobin levels and decreased glutathione. Impaired antioxidant power and increased formation of reactive oxygen species were observed. The activities of major antioxidant enzymes were prominently altered. The plasma membrane redox system (PMRS) of erythrocytes was inhibited and there was substantial change in membrane morphology. Preincubation of cells with carnosine attenuated the oxidative damage induced by CuCl 2 , restored the enzyme activities and antioxidant power and also prevented inactivation of erythrocyte PMRS. Carnosine protected human erythrocytes and lymphocytes from CuCl 2 -induced oxidative damage. It fortified the enzymatic and non-enzymatic antioxidant systems of these cells. The protection by carnosine can be attributed to its antioxidant nature. [ABSTRACT FROM AUTHOR]

Pentachlorophenol (PCP) is used as pesticide and wood preservative. We have previously shown that PCP causes oxidative damage in rat intestine. This study aimed to delineate the possible therapeutic potential of curcumin (CUR) and gallic acid (GA) against PCP-induced damage in rat intestine. PCP alone group received 125 mg PCP/kg body weight/day orally for 4 days. Animals in combination groups received CUR or GA (100 mg/kg bw) for 18 days and PCP (125 mg/kg bw) for the last four days. Rats were sacrificed and intestinal preparations were analyzed for various parameters. Administration of PCP alone altered the activities of metabolic, antioxidant and brush border membrane enzymes. It also increased DNA-protein crosslinking and DNA-strand scission. Animals in combinations groups showed significant amelioration against PCP-induced oxidative damage. Histological abrasions were seen in PCP alone group which were reduced in the intestines of combination groups. CUR was more effective protectant than GA. CUR and GA protected rat intestine from PCP-mediated changes in the activities of metabolic, antioxidant and brush border membrane enzymes. They also prevented DNA damage and histological abrasions. The antioxidant character of CUR and GA may be responsible for the diminution of PCP-mediated oxidative damage. • Pentachlorophenol (PCP) induces oxidative stress in rat intestine. • Curcumin (CUR) and gallic acid (GA) significantly mitigated PCP-induced damage. • Both antioxidants protected the lowering of antioxidant defense systems. • The antioxidant capacity of cells was restored. • PCP-induced DNA damage and histological abrasions were prevented by CUR and GA. [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HOCl) is a major oxidant produced by activated neutrophils via the myeloperoxidase catalyzed reaction. The production of HOCl eliminates a wide range of pathogens. However, HOCl can also cause significant oxidative damage in cells and tissues where it is generated. The protective effect of curcumin was studied on HOCl-induced oxidative damage to human red blood cells (RBC). Isolated RBC were incubated with HOCl at 37 °C in absence or presence of different concentrations of curcumin. Hemolysates were prepared and assayed for various biochemical parameters. Treatment of RBC with HOCl alone increased hemolysis, protein carbonyls, heme degradation and chloramines as compared to untreated control cells. This was accompanied by reduction in glutathione level, total sulfhydryls and free amino groups. HOCl also lowered the activities of major antioxidant enzymes and diminished the antioxidant power of RBC. Pre-treatment of RBC with different concentrations of curcumin resulted in concentration-dependent attenuation in all these parameters while curcumin alone had no significant effect. Scanning electron microscopy showed that curcumin prevented HOCl-induced morphological changes in RBC and restored their normal biconcave shape. Thus curcumin can be used as a chemoprotective agent to mitigate HOCl-induced oxidative damage to cells. These results also explain the beneficial effects of curcumin against Helicobacter pylori induced stomach ulcers, caused by excessive production of HOCl at the site of bacterial infection. [Display omitted] • HOCl causes significant oxidative damage to adjacent cell and tissues where it is generated. • Curcumin being an agricultural food product protects the damage induced by HOCl. • Curcumin acts as antioxidant and scavenger of HOCl. • Curcumin can be beneficial against peptic ulcer for which one of the causes is excess HOCl generation. [ABSTRACT FROM AUTHOR]

Pentachlorophenol (PCP) is a synthetic organochlorine compound that is widely used in biocide and pesticide industries, and in preservation of wood, fence posts, cross arms and power line poles. Humans are usually exposed to PCP through air, contaminated water and food. PCP enters the body and adversely affects liver, gastrointestinal tract, kidney and lungs. PCP is a highly toxic class 2B or probable human carcinogen that produces large amount of reactive oxygen species (ROS) within cells. This work aimed to determine PCP-induced oxidative damage in rat kidney. Adult rats were given PCP (25, 50, 100, 150 mg/kg body weight), in corn oil, once a day for 5 days while control rats were given similar amount of corn oil by oral gavage. PCP increased hydrogen peroxide level and oxidation of thiols, proteins and lipids. The antioxidant status of kidney cells was compromised in PCP treated rats while enzymes of brush border membrane (BBM) and carbohydrate metabolism were inhibited. Plasma level of creatinine and urea was also increased. Administration of PCP increased DNA fragmentation, cross-linking of DNA to proteins and DNA strand scission in kidney. Histological studies supported biochemical findings and showed significant damage in the kidneys of PCP-treated rats. These changes could be due to redox imbalance or direct chemical modification by PCP or its metabolites. These results signify that PCP-induced oxidative stress causes nephrotoxicity, dysfunction of BBM enzymes and DNA damage. [Display omitted] • Pentachlorophenol (PCP) enhances oxidation of thiols, proteins and lipids in rat kidney. • PCP impairs the antioxidant status of renal cells. • Enzymes of brush border membrane and glycolytic pathway were inhibited. • PCP increases DNA strand scission and DNA-protein cross-linking. • PCP also alters the renal histology.s [ABSTRACT FROM AUTHOR]

Arsenic (As) is an air and water toxicant that causes cancer in multiple organs. Humans are exposed to As through contaminated water. We have examined the cytotoxicity of sodium meta-arsenite (SA), an As(III) compound, in human red blood cells (RBC) underin vitroconditions. Haemolysates were prepared from human RBC treated with different concentrations of SA (0.1–5.0 mM) for 5 h at 37 °C. SA treatment of RBC caused significant increase in methaemoglobin formation, protein and lipid oxidation, and nitric oxide levels. It also resulted in decrease in glutathione levels, methaemoglobin reductase activity and plasma membrane redox system. SA exposure also inhibited the pathways of glucose metabolism while increasing AMP deaminase and glyoxalase-I. It impaired the enzymatic and non-enzymatic antioxidant defence systems which resulted in decreased antioxidant power and a compromised ability to quench free radicals. SA exposure also damaged the membrane since it decreased the activity of membrane bound enzymes, increased the osmotic fragility of treated cells and induced gross morphological changes. This cytotoxicity was the result of oxidative damage since the production of reactive oxygen species (ROS) was increased in SA treated erythrocytes. Thus As(III) causes extensive damage to RBC which impairs their antioxidant system and alters the major cellular metabolic pathways. All this has the potential to lower the oxygen carrying capacity of RBC and reduce their lifespan in blood. [ABSTRACT FROM PUBLISHER]

Sodium nitrite (NaNO2) is a common contaminant of drinking water and food and feed chain. Nitrite induces oxidative damage in humans and animals. In this work, we studied the protective effect of crocin, the active constituent of Crocus sativus (saffron), on NaNO2-induced oxidative damage in human erythrocytes. Changes in oxidative stress parameters following NaNO2 incubation of erythrocytes in presence and absence of crocin were determined. It was found that crocin pre-treatment significantly attenuated NaNO2-induced oxidative damage of proteins, lipids, and plasma membrane. Crocin reduced the level of methemoglobin, the primary acute effect of nitrite intoxication. It also improved the antioxidant capacity of cells and NaNO2-induced morphological changes in erythrocytes. Crocin is thus a potent protective agent against nitrite-induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Nitrite salts are present as contaminants in drinking water and in the food and feed chain. In this work, the effect of sodium nitrite (NaNO 2 ) on human erythrocytes was studied under in vitro conditions. Incubation of erythrocytes with 0.1–10.0 mM NaNO 2 at 37 °C for 30 min resulted in dose dependent decrease in the levels of reduced glutathione, total sulfhydryl and amino groups. It was accompanied by increase in hemoglobin oxidation and aggregation, lipid peroxidation, protein oxidation and hydrogen peroxide levels suggesting the induction of oxidative stress. Activities of all major erythrocyte antioxidant defense enzymes were decreased in NaNO 2 -treated erythrocytes. The activities of enzymes of glycolytic and pentose phosphate pathways were also compromised. However, there was a significant increase in acid phosphatase and also AMP deaminase, a marker of erythrocyte oxidative stress. Thus, the major metabolic pathways of cell were altered. Erythrocyte membrane damage was suggested by lowered activities of membrane bound enzymes and confirmed by electron microscopic images. These results show that NaNO 2 -induced oxidative stress causes hemoglobin denaturation and aggregation, weakens the cellular antioxidant defense mechanism, damages the cell membrane and also perturbs normal energy metabolism in erythrocytes. This nitrite-induced damage can reduce erythrocyte life span in the blood. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein (LDL) transports cholesterol to various tissues via the blood. Glycation of LDL occurs during hyperglycemic condition which is characterised by persistently high blood glucose level. Circulating erythrocytes can come in direct contact with glycated LDL (G-LDL). The objective of this study was to investigate the effect of G-LDL on human erythrocytes, specifically on hemoglobin, intracellular generation of reactive species and the antioxidant defence system. Isolated erythrocytes were incubated with G-LDL (3 and 6 mg/ml) and native LDL (6 mg/ml) at 37 °C for 24 h. Native LDL and G-LDL untreated erythrocytes were similarly incubated at 37 °C and served as control. G-LDL treatment increased hemolysis compared to control and native LDL-treated erythrocytes. Incubation of erythrocytes with G-LDL led to an increase in protein oxidation and lipid peroxidation while greatly decreasing the total sulfhydryl content. It also significantly enhanced hemoglobin oxidation, heme degradation, and the release of free iron moiety. Treatment with G-LDL led to an appreciable increase in the production of reactive oxygen and nitrogen species. The antioxidant power and activities of major antioxidant enzymes were drastically reduced, while critical membrane-bound enzymes were inhibited. The surface morphology of G-LDL-treated erythrocytes was altered leading to the formation of echinocytes. Importantly, treatment of erythrocytes with native LDL did not significantly affect the above-mentioned parameters and values were similar to the corresponding controls. Thus, G-LDL is cytotoxic to human erythrocytes and causes oxidative damage to cell components. This can reduce the oxygen-transporting ability of blood and also result in red cell senescence and anemia. [Display omitted] • G-LDL forms reactive species in human erythrocytes that oxidized proteins, lipids and thiols. • Hemoglobin oxidation, heme degradation and free iron release are seen in G-LDL exposed erythrocytes. • G-LDL impairs the antioxidant defence and damages erythrocyte plasma membrane. • The surface morphology is altered in G-LDL-treated erythrocytes. [ABSTRACT FROM AUTHOR]

The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae) is a serious pest of crucifers, worldwide, and has developed high levels of resistance to insecticides including Bacillus thuringiensis (Bt). This serious situation requires the identification of non-chemical, alternate, futuristic pest management strategies, which might involve gene silencing. This would first require the identification of small RNAs and their targets, and later their suitable deployment. Micro RNAs (miRNAs) are a class of small RNAs directly involved in various biological functions by regulating gene expression at the post transcriptional level. Finding new miRNAs and predicting their targets from Insect genome would lead to better understanding of their diverse functions. In the present study we have identified 8 new mature miRNAs of P. xylostella and predicting their mRNA targets by computational methods. The following 4 miRNAs are reported for the first time in arthropods, viz., miR-244, miR-3529, miR-4704, and miR-7267. We have also analyzed the precursor sequences of the newly identified miRNAs, and we have predicted their secondary structure with minimum free energy index, MFEI, which ranges 0.85 to 1.24. The mRNA target predictions for novel miRNAs were carried out using the Miranda program employing the available putative gene set sequences of P. xylostella. [ABSTRACT FROM AUTHOR]

Highlights: [•] Crotonaldehyde-modified DNA exhibited altered structure. [•] Structurally perturbed DNA exhibits neo-epitopes, not ordinarily present on the native molecule. [•] The modified DNA may have different physiological and biochemical properties. [•] The possible role of modified DNA in cancer has been suggested. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) models for the 79.2 kDa activated Cry1Ib9 and 77.4 kDa activated Cry3A δ-endotoxins from Bacillus thuringiensis ( Bt) native isolates that are specifically toxic to Coleopteran insect pests were constructed by utilizing homology modeling online tool. Evidences presented here, based on the identification of structural equivalent residues of Cry1Ib9 and Cry3A toxin through homology modelling indicate that, they share a common Bt toxin tridimensional structure. The main differences observed in Cry1I9 domain I at positions α2b (S56-I60), α4 (F78-l93) and additionally β0 (Q10-L12), α8a (T280-V282) were observed, in domain II at positions α9b (P333-L339), β6(T390-Q393), β7(V398-W404), β8 (V418-W425), β9 (E453-N454), β10 (S470-I479) where as in domain III the changes were observed at positions β19 (R601-F607), β20 (609-L613), β21 (S618-F627) and α11a (K655-F664), α13, α14 components present at downstream sites, where as in Cry3A main differences observed in domain I is at the position of α4 (P105-I152), α5 (Q163-A185), β1A(E190-L192), α6 (F193-Y217), Domain II is not consevered and main variations were observed at β2 (E292-L295), β3(V299-L308), β4(I340-F347), β5(D356-P368), β6(I375-T377), β7(V389-F394), β8(K398-N405), β9(Y416-Y427), β10 (T436-Y439), β12(G476-H495), β12A (M503-I504) where as in domain III main variations observed at positions of β18 (P583-I593), β19(F604-S610), β20(P611-L615), β21(N619-G626). Cry1Ib9 and Cry3A contain the most variable regions in the loops of domain II, which determine the specificity of these toxins. These are the first models of Coleopteran-active protein from native isolates of Bt and its importance can be perceived since members of this group of toxins are potentially important candidates for coleoptera insect pest control programs. [ABSTRACT FROM AUTHOR]

Potassium bromate (KBrO) is widely used as a food additive and is a major water disinfection by-product. Several studies have shown that it causes nephrotoxicity in humans and experimental animals. We have investigated the potential role of the sulfonic amino acid taurine in protecting the kidney from KBrO-induced damage in rats. Animals were randomly divided into four groups: control, KBrO alone, taurine alone and taurine + KBrO. Administration of single oral dose of KBrO alone caused nephrotoxicity as evident by elevated serum creatinine and urea levels. Renal lipid peroxidation and protein carbonyls were increased while total sulfhydryl groups and reduced glutathione levels were decreased suggesting the induction of oxidative stress. The enzymes of renal brush border membrane were inhibited and those of carbohydrate metabolism were altered. There was an increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive renal damage in KBrO-treated animals and greatly reduced tissue injury in the taurine + KBrO group. These results show that taurine is an effective chemoprotectant against bromate-induced renal damage and this amino acid could prove to be useful in attenuating the toxicity of this compound. [ABSTRACT FROM AUTHOR]