Molecular Basis for the Involvement of Mammalian Serum Albumin in the AGE/RAGE Axis: A Comprehensive Computational Study.

In mammals, glycated serum albumin (gSA) contributes to the pathogenesis of many metabolic diseases by activating the receptors (RAGE) for advanced glycation end products (AGEs). Many aspects of the gSA-RAGE interaction remain unknown. The purpose of the present paper was to study the interaction of glycated human albumin (gHSA) with RAGE using molecular modeling methods. Ten models of gHSA modified with different lysine residues to carboxymethyl-lysines were prepared. Complexes of gHSA-RAGE were obtained by the macromolecular docking method with subsequent molecular dynamics simulation (MD). According to the MD, the RAGE complexes with gHSA glycated at Lys233, Lys64, Lys525, Lys262 and Lys378 are the strongest. Three-dimensional models of the RAGE dimers with gHSA were proposed. Additional computational experiments showed that the binding of fatty acids (FAs) to HSA does not affect the ability of Lys525 (the most reactive lysine) to be glycated. In contrast, modification of Lys525 reduces the affinity of albumin for FA. The interspecies differences in the molecular structure of albumin that may affect the mechanism of the gSA-RAGE interaction were discussed. The obtained results will help us to learn more about the molecular basis for the involvement of serum albumin in the AGE/RAGE axis and improve the methodology for studying cellular signaling pathways involving RAGE.

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

Serum Albumin in Health and Disease: From Comparative Biochemistry to Translational Medicine.

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions, electrically neutral molecules and in maintaining the colloid osmotic pressure of the blood [...].

Anticholinesterase and Serotoninergic Evaluation of Benzimidazole-Carboxamides as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease.

The etiology and pathogenesis of Alzheimer's disease are multifactorial, so one of the treatment strategies is the development of the drugs that affect several targets associated with the pathogenesis of the disease. Within this roadmap, we investigated the interaction of several substituted 1,3-dihydro-2-oxo-1H-benzimidazol-2-ones with their potential molecular targets: cholinesterases (ChE) and three types of the Gs-protein-coupled serotonin receptors (5-HTR) 5-HT6, 5-HT4 and 5-HT7 (5-HT4R, 5-HT6R and 5-HT7R, respectively). A microplate modification of the Ellman method was used for the biochemical analysis of the inhibitory ability of the drugs towards ChE. Molecular modeling methods, such as molecular docking and molecular dynamics (MD) simulation in water and the lipid bilayer, were used to study the interaction of the compounds with ChE and 5-HTR. In vitro experiments showed that the tested compounds had moderate anticholinesterase activity. With the help of molecular modeling methods, the mechanism of interaction of the tested compounds with ChE was investigated, the binding sites were described and the structural features of the drugs that determine the strength of their anticholinesterase activity were revealed. Primary in silico evaluation showed that benzimidazole-carboxamides effectively bind to 5-HT4R and 5-HT7R. The pool of the obtained data allows us to choose N-[2-(diethylamino)ethyl]-2-oxo-3-(tert-butyl)-2,3-dihydro-1H-benzimidazole-1-carboxamide hydrochloride (compound 13) as the most promising for further experimental development.

Albumin Is a Component of the Esterase Status of Human Blood Plasma.

The esterase status of blood plasma can claim to be one of the universal markers of various diseases; therefore, it deserves attention when searching for markers of the severity of COVID-19 and other infectious and non-infectious pathologies. When analyzing the esterase status of blood plasma, the esterase activity of serum albumin, which is the major protein in the blood of mammals, should not be ignored. The purpose of this study is to expand understanding of the esterase status of blood plasma and to evaluate the relationship of the esterase status, which includes information on the amount and enzymatic activity of human serum albumin (HSA), with other biochemical parameters of human blood, using the example of surviving and deceased patients with confirmed COVID-19. In experiments in vitro and in silico, the activity of human plasma and pure HSA towards various substrates was studied, and the effect of various inhibitors on this activity was tested. Then, a comparative analysis of the esterase status and a number of basic biochemical parameters of the blood plasma of healthy subjects and patients with confirmed COVID-19 was performed. Statistically significant differences have been found in esterase status and biochemical indices (including albumin levels) between healthy subjects and patients with COVID-19, as well as between surviving and deceased patients. Additional evidence has been obtained for the importance of albumin as a diagnostic marker. Of particular interest is a new index, [Urea] × [MDA] × 1000/(BChEb × [ALB]), which in the group of deceased patients was 10 times higher than in the group of survivors and 26 times higher than the value in the group of apparently healthy elderly subjects.

Molecular Mechanisms of Acute Organophosphate Nephrotoxicity.

Organophosphates (OPs) are toxic chemicals produced by an esterification process and some other routes. They are the main components of herbicides, pesticides, and insecticides and are also widely used in the production of plastics and solvents. Acute or chronic exposure to OPs can manifest in various levels of toxicity to humans, animals, plants, and insects. OPs containing insecticides were widely used in many countries during the 20th century, and some of them continue to be used today. In particular, 36 OPs have been registered in the USA, and all of them have the potential to cause acute and sub-acute toxicity. Renal damage and impairment of kidney function after exposure to OPs, accompanied by the development of clinical manifestations of poisoning back in the early 1990s of the last century, was considered a rare manifestation of their toxicity. However, since the beginning of the 21st century, nephrotoxicity of OPs as a manifestation of delayed toxicity is the subject of greater attention of researchers. In this article, we present a modern view on the molecular pathophysiological mechanisms of acute nephrotoxicity of organophosphate compounds.

Nephrotoxic Effects of Paraoxon in Three Rat Models of Acute Intoxication.

The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specific effects. The present study was designed to investigate the nephrotoxic effects of paraoxon (O,O-diethyl O-(4-nitrophenyl) phosphate, POX) using three models of acute poisoning in outbred Wistar rats. In the first model (M1, POX2x group), POX was administered twice at doses 110 µg/kg and 130 µg/kg subcutaneously, with an interval of 1 h. In the second model (M2, CBPOX group), 1 h prior to POX poisoning at a dose of 130 µg/kg subcutaneously, carboxylesterase activity was pre-inhibited by administration of specific inhibitor cresylbenzodioxaphosphorin oxide (CBDP, 3.3 mg/kg intraperitoneally). In the third model (M3), POX was administered subcutaneously just once at doses of LD16 (241 µg/kg), LD50 (250 µg/kg), and LD84 (259 µg/kg). Animal observation and sampling were performed 1, 3, and 7 days after the exposure. Endogenous creatinine clearance (ECC) decreased in 24 h in the POX2x group (p = 0.011). Glucosuria was observed in rats 24 h after exposure to POX in both M1 and M2 models. After 3 days, an increase in urinary excretion of chondroitin sulfate (CS, p = 0.024) and calbindin (p = 0.006) was observed in rats of the CBPOX group. Morphometric analysis revealed a number of differences most significant for rats in the CBPOX group. Furthermore, there was an increase in the area of the renal corpuscles (p = 0.0006), an increase in the diameter of the lumen of the proximal convoluted tubules (PCT, p = 0.0006), and narrowing of the diameter of the distal tubules (p = 0.001). After 7 days, the diameter of the PCT lumen was still increased in the nephrons of the CBPOX group (p = 0.0009). In the M3 model, histopathological and ultrastructural changes in the kidneys were revealed after the exposure to POX at doses of LD50 and LD84. Over a period from 24 h to 3 days, a significant (p = 0.018) expansion of Bowman's capsule was observed in the kidneys of rats of both the LD50 and LD84 groups. In the epithelium of the proximal tubules, stretching of the basal labyrinth, pycnotic nuclei, and desquamation of microvilli on the apical surface were revealed. In the epithelium of the distal tubules, partial swelling and destruction of mitochondria and pycnotic nuclei was observed, and nuclei were displaced towards the apical surface of cells. After 7 days of the exposure to POX, an increase in the thickness of the glomerular basement membrane (GBM) was observed in the LD50 and LD84 groups (p = 0.019 and 0.026, respectively). Moreover, signs of damage to tubular epithelial cells persisted with blockage of the tubule lumen by cellular detritus and local destruction of the surface of apical cells. Comparison of results from the three models demonstrates that the nephrotoxic effects of POX, evaluated at 1 and 3 days, appear regardless of prior inhibition of carboxylesterase activity.

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties.

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions-electrically neutral and charged molecules-and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

Esterase Activity of Serum Albumin Studied by 1H NMR Spectroscopy and Molecular Modelling.

Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (1H NMR) has been applied to the study of true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA). The site of BSA esterase activity was then determined using molecular modelling methods. According to the data obtained, the accumulation of acetate in the presence of BSA in the reaction mixture is much more intense as compared with the spontaneous hydrolysis of NPA, which indicates true esterase activity of albumin towards NPA. Similar results were obtained for p-nitophenyl propionate (NPP) as substrate. The rate of acetate and propionate release confirms the assumption that there is a site of true esterase activity in the albumin molecule, which is different from the site of the pseudo-esterase activity Sudlow II. The results of molecular modelling of BSA and NPA interaction make it possible to postulate that Sudlow site I is the site of true esterase activity of albumin.

Higher ambient temperature is associated with worsening of HbA1c levels in a Saudi population.

BACKGROUND: Ambient temperature is predicted to rise in Saudi Arabia, and how this will impact the health of its population has not been investigated. Saudi Arabia is one of the top ten countries with the highest prevalence of diabetes. The current study investigates the correlation between ambient temperature and HbA1c levels in a group of Saudis in Riyadh. METHODS: Age, gender, and HbA1c data for six years were obtained from patients' records. The maximum daily temperature of Riyadh city for the same period was obtained. RESULTS: A total of 168,614 patient records were obtained. There was a statistically significant positive correlation between ambient temperature and HbA1c levels, where for each 1°C increase in average weekly temperature HbA1c increased by 0.007%. Patients were at higher risk of having HbA1c ≥ 7% in high and moderate temperature than in low temperature (P < 0.001, odds ratio (OR): 1.134, and P < 0.001, odds ratio (OR): 1.034; respectively). The mean of HbA1c in females (7.27±1.96) was significantly lower than in males (7.40±1.86), and the probability of males having HbA1c ≥ 7% was about 17.4% higher than females. However, the HbA1c levels in females were significantly more affected by rising temperature compared to males (B = 0.003, P = 0.008). CONCLUSION: Overall, rise in ambient temperature is associated with worsening HbA1c, which could be harmful to the health of Saudis suffering from diabetes. Possible reasons for the increase in HbA1c could include reduced physical activity, reduced sunlight exposure, and dehydration during hot weather. More research on the relationship between climate change and public health in Saudi Arabia is needed.

The Influence of Gender and Menopausal Status on Hba1c Variation in a Big Data Study of a Saudi Population.

BACKGROUND: Glycated haemoglobin (HbA1c) is the gold standard measurement in the screening, diagnosis and monitoring of diabetes mellitus. Saudi Arabia has a high prevalence of diabetes mellitus that is expected to rise, and the HbA1c test is commonly used in the screening, diagnosis and monitoring of diabetes. OBJECTIVE: This study aims to assess the impact of age and gender on HbA1c levels, and the influence of menopausal status on HbA1c variation in a large group of Saudis. METHODS: Age, gender, and HbA1c results of 168,614 Saudi adult individuals were obtained from their medical records. Patients' records were extracted irrespective of their status regarding the presence of diabetes and the status of glycaemic control. Linear regression models were used for predicting HbA1c from age and gender, and their interaction term. HbA1c levels were compared between genders in different age groups and different HbA1c categories. RESULTS: There was a statistically significant positive correlation between age and HbA1c levels, where for each ten years increase in age, HbA1c increased by 0.35%. Although the overall mean HbA1c in women was significantly lower than in men (P < 0.001), women showed a significant increase in HbA1c with older age compared to men (B = 0.014, P < 0.001). Furthermore, the mean HbA1c levels in the age group > 50 years was significantly higher than before that age (P < 0.001). Thus, HbA1c increased by 1.118% in age > 50 years group compared to age ≤ 50 years, and this increase in HbA1c was significantly higher in women compared to men (B = 0.495, P < 0.001). CONCLUSION: HbA1c levels are lower in women before the estimated menopausal age, which should be taken into consideration when using HbA1c for screening, diagnosis, and monitoring of diabetes in Saudi adult women. The short lifespan of red blood cells, due to loss of blood through menstruation, in women before menopause age, is a possible reason for these variations.

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin.

As a carrier of many biologically active compounds, blood is exposed to oxidants to a greater extent than the intracellular environment. Serum albumin plays a key role in antioxidant defence under both normal and oxidative stress conditions. This review evaluates data published in the literature and from our own research on the mechanisms of the enzymatic and non-enzymatic activities of albumin that determine its participation in redox modulation of plasma and intercellular fluid. For the first time, the results of numerous clinical, biochemical, spectroscopic and computational experiments devoted to the study of allosteric modulation of the functional properties of the protein associated with its participation in antioxidant defence are analysed. It has been concluded that it is fundamentally possible to regulate the antioxidant properties of albumin with various ligands, and the binding and/or enzymatic features of the protein by changing its redox status. The perspectives for using the antioxidant properties of albumin in practice are discussed.

Impact of Ramadan on Physical Activity and Sleeping Patterns in Individuals with Type 2 Diabetes: The First Study Using Fitbit Device.

INTRODUCTION: The impact of Ramadan fasting, a type of intermittent fasting, on the management of diabetes has not been well investigated. Physical activity, sleep duration, and time of sleep are susceptible to alterations during Ramadan due to the changes in the times and numbers of meals. This study compared physical activity and sleep patterns of individuals with type 2 diabetes mellitus (T2DM) during and after Ramadan using the international physical activity questionnaire (IPAQ) and a Fitbit Flex 2 accelerometer. METHODS: Saudi individuals (n = 36) with T2DM completed a self-reported questionnaire and wore a Fitbit device for seven consecutive days during and after Ramadan. Fitbit generated weekly step counts, activity intensities, sedentary time, and sleep durations and times. IPAQ was used to estimate the physical activity and sitting time of participants in each period. Sleep patterns were assessed in each period by a self-reported questionnaire. RESULTS: Both Fitbit and IPAQ indicated a high prevalence of low physical activity among the participants with non-significant variances between the during and after Ramadan periods. Also, a significant short daily total sleeping hours and daily night-time sleeping hours was seen during the Ramadan period. The duration of night-time sleep was observed to be low in each period. CONCLUSIONS: This is the first study to use a Fitbit device to monitor individuals with T2DM who chose to fast during Ramadan. The study shows a high prevalence of low physical activity among Saudi individuals with T2DM in each period, and short sleep durations in the during Ramadan period compared to after Ramadan period. A high prevalence of short night-time sleep duration and excessive daytime sleeping was observed in both periods and significantly in the during Ramadan period. A larger study is needed in the future covering before, during, and after Ramadan to evaluate the impact of lifestyle changes related to Ramadan fasting on type 2 diabetes.

The Role of Two-Pore Channels in Norepinephrine-Induced [Ca2+]i Rise in Rat Aortic Smooth Muscle Cells and Aorta Contraction.

Second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) triggers Ca2+ release via two-pore channels (TPCs) localized in endolysosomal vesicles. The aim of the present work is to evaluate the role of TPCs in the action of norepinephrine (NE), angiotensin II (AngII), vasopressin (AVP), and 5-hydroxytriptamine (5-HT) on free cytoplasmic calcium concentration ([Ca2+]i) in smooth muscle cells (SMCs) isolated from rat aorta and on aorta contraction. To address this issue, the NAADP structural analogue and inhibitor of TPCs, NED 19, was applied. We have demonstrated a high degree of colocalization of the fluorescent signals of cis-NED 19 and endolysosmal probe LysoTracker in SMCs. Both cis- or trans-NED 19 inhibited the rise of [Ca2+]i in SMCs induced by 100 µM NE by 50-60%. IC50 for cis- and trans-NED 19 were 2.7 and 8.9 µM, respectively. The inhibition by NED 19 stereoisomers of the effects of AngII, AVP, and 5-HT was much weaker. Both forms of NED 19 caused relaxation of aortic rings preconstricted by NE, with relative potency of cis-NED 19 several times higher than that of trans-NED 19. Inhibition by cis-NED 19 of NE-induced contraction was maintained after intensive washing and slowly reversed within an hour of incubation. Cis- and trans-NED 19 did not cause decrease in the force of aorta contraction in response to Ang II and AVP, and only slightly relaxed aorta preconstricted by 5-HT and by KCl. Suppression of TPC1 in SMCs with siRNA caused a 40% decrease in [Ca2+]i in response to NE, whereas siRNA against TPC2 did not change NE calcium signaling. These data suggest that TPC1 is involved in the NE-stimulated [Ca2+]i rise in SMCs. Inhibition of TPC1 activity by NED 19 could be the reason for partial inhibition of aortic rings contraction in response to NE.

Rational in silico design of aptamers for organophosphates based on the example of paraoxon.

Poisoning by organophosphates (OPs) takes one of the leading places in the total number of exotoxicoses. Detoxication of OPs at the first stage of the poison entering the body could be achieved with the help of DNA- or RNA-aptamers, which are able to bind poisons in the bloodstream. The aim of the research was to develop an approach to rational in silico design of aptamers for OPs based on the example of paraoxon. From the published sequence of an aptamer binding organophosphorus pesticides, its three-dimensional model has been constructed. The most probable binding site for paraoxon was determined by molecular docking and molecular dynamics (MD) methods. Then the nucleotides of the binding site were mutated consequently and the values of free binding energy have been calculated using MD trajectories and MM-PBSA approach. On the basis of the energy values, two sequences that bind paraoxon most efficiently have been selected. The value of free binding energy of paraoxon with peripheral anionic site of acetylcholinesterase (AChE) has been calculated as well. It has been revealed that the aptamers found bind paraoxon more effectively than AChE. The peculiarities of paraoxon interaction with the aptamers nucleotides have been analyzed. The possibility of improving in silico approach for aptamer selection is discussed.

From ward to washer: The survival of Clostridium difficile spores on hospital bed sheets through a commercial UK NHS healthcare laundry process.

OBJECTIVE: To quantify the survival of Clostridium difficile spores on hospital bed sheets through the United Kingdom National Health System (UK NHS) healthcare laundry process (Health Technical Memorandum (HTM) 01-04) in vitro and on bed sheets from patients with C. difficile through the commercial laundry. METHODS: Clostridium difficile spores were inoculated onto cotton sheets and laundered through a simulated washer extractor cycle using an industrial bleach detergent with sodium hypochlorite 15% and peracetic acid sour 14% (acetic acid and hydrogen peroxide; pH, 2-4). Spore survival on hospital sheets naturally contaminated with C. difficile was also assessed using a washer extractor plus drying and finishing cycles at a commercial laundry.PatientsNaturally contaminated C. difficile bed sheets were taken from beds of patients that had previously been diagnosed with C. difficile infection (CDI) and had received care on an isolated C. difficile ward. RESULTS: The simulated washer extractor cycle, with an industrial detergent, demonstrated survival of 2 strains of C. difficile NCTC 11209 (0-4 colony-forming units [cfu] per 25 cm2) and ribotype 001/072 (0-9 cfu per 25 cm2). Before laundering, naturally contaminated bed sheets had an average spore load of 51 cfu per 25 cm2, and after washing, drying, and finishing, the spore load was 33 cfu per 25 cm2. Before and after washing, the C. difficile strain was identified as ribotype 001/072. Both the simulated and in-situ laundering processes failed the microbiological standards of no pathogenic bacteria remaining. CONCLUSIONS: Clostridium difficile spores are able to survive laundering through a commercial washer extractor and may be contributing to sporadic outbreaks of CDI. Further research to establish exposure of laundry workers, patients, and the hospital environment to C. difficile spores from bed sheets is needed.

Extending the geographic reach of the water hyacinth plant in removal of heavy metals from a temperate Northern Hemisphere river.

Water hyacinth (Eichhornia crassipes) has been used for environmentally sustainable phytoremediation of water, though its use has been geographically restricted. For the first time we extend its geographical reach by investigating its potential for clean-up of water from a highly polluted British river (Nant-Y-Fendrod, a tributary of the River Tawe). Investigations using the plant were conducted at three levels: a bench-scale study using polluted river water and synthetic solutions; an in-situ trial using water hyacinth within the Nant-Y-Fendrod; and a bankside trial to pump and treat river water. The removal of the largest number of heavy metals (21) from water in a single study using ICP-MS is reported, including Sb, for the first time. Results are promising, with bench-scale tests demonstrating up to 63% removal of Al, 62% Zn, 47% Cd, 22% Mn and 23% As, during just seven hours exposure to the plant. When extended to three weeks exposure, removal is evident in the order Al > Cd > Zn > Mn > Ni > As > V. Furthermore, in-situ mean removal of 6%, 11% and 15% of Mn, Zn and Cd respectively is demonstrated. As the world learns to adapt to climate change, studies of the type reported here are needed to exploit the remarkable phytoremediation potential of water hyacinth.

Serum Albumin Binding and Esterase Activity: Mechanistic Interactions with Organophosphates.

The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes.

Sulfated glycosaminoglycans in bladder tissue and urine of rats after acute exposure to paraoxon and cyclophosphamide.

Glycosaminoglycans (GAGs) in the urine of Wistar rats, and on the surface of the epithelium and lamina propria of the bladder, were quantitatively assessed before and after acute intoxication with paraoxon or cyclophosphamide. Paraoxon was administered subcutaneously (s.c.) twice with an interval of 1h to a final dose of 275mg/kg; cyclophosphamide was administered intraperitoneally (i.p.) with a single dose of 100mg/kg or to a final dose of 240mg/kg (three times per 80mg/kg every 12h). GAGs on the surface of the epithelium and lamina propria of the urinary bladder of rats were quantitatively determined by Alcian blue dye staining. GAGs in the urine were determined spectrophotometrically with 1-9-dimethyl methylene blue. By 48-96h after intoxication with either paraoxon or cyclophosphamide, statistically significant increases in the concentration of GAGs were obtained both for the tissues of the bladder and the urine of rats. Cyclophosphamide, in contrast to paraoxon, caused the development of hemorrhagic cystitis in the animals. The synthesis of GAGs is considered to be compensatory response to the toxic xenobiotics.

Markers and Biomarkers of Endothelium: When Something Is Rotten in the State.

Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneously the cause and effect of many diseases, and this is coupled with modifications of endothelial phenotype represented by markers and with biochemical profile of blood represented by biomarkers. In this paper, we briefly review data on the functional role of endothelium, give definitions of endothelial markers and biomarkers, touch on the methodological approaches for revealing biomarkers, present an implicit role of endothelium in some toxicological mechanistic studies, and survey the role of reactive oxygen species (ROS) in modulation of endothelial status.