Studies on the nephrotoxicity of silicon

Until recently it was generally accepted that the main source of exposure to silicon in man was the occupational inhalation of silica dust. Contrary to previously held belief silicates have been shown to be absorbed from the alimentary tract and that the kidney is the main organ of excretion of dietary absorbed silicon. In man renal functional impairment is accompanied by a fall in urinary excretion of silicon and a rise in serum silicon (Bobbie et al 1981). For the past 50 years there have been several reports on the nephrotoxicity of a variety of silicon compounds administered to experimental animals by several different routes. Moreover, there have been claims that acute or chronic exposure to siliceous dusts or prolonged intake of drinking water with a high silica content resulted in renal lesions in man. Secure in the belief that silicon compounds were nonabsorbable and non-toxic there has been an increasing use of silicates by the food and pharmaceutical industries as anticaking, antifoaming or hygroscopic agents. Thus recent evidence that silicates are absorbed and that the kidney is the main route of excretion raises a natural concern for the liberal ingestion of silicates by man in in view of the reports of nephrotoxicity in the experimented animal. Whereas, the few previous investigations of silicon nephrotoxicity have been rather limited in nature and inconclusive as to the nature of the pathogenetic mechanism, this investigation has attempted a study in depth while bringing to bear on the problem many new and different investigative techniques. This investigation has examined the renal effects of intraperitoneal injection of four silicon compounds to which man may be exposed. The intraperitoneal route was chosen since it was found to be the most convenient and reliable method, whereby the kidney could be exposed to different levels, of serum silicon. A series of acute experiments in rats determined that high serum silicon levels resulted in a tubulo-interstitial lesion, which was most pronounced in and around the distal tubule and collecting ducts. Extensive electron microscopic examination of the lesions revealed that the damage was manifest in gross swelling and oedema of the epithelial cells and their cytoplasmic contents. A marked acute inflammatory response in which eosinophils were prominent accompanied the lesions. Significant glomerular pathology did not result from acute silicon nephrotoxicity. All four silicon compounds tested produced a similar degree of renal damage. Three different, but complementary techniques were then used to demonstrate the concentration and localisation of silicon in the kidney in the acute experimental model. Atomic absorption spectroscopic (A.A.S;) measurement of silicon in ashed samples showed an early and rapid rise in renal tissue silicon concentrations in contrast to a slower accumulation in other organs. The rarely studied radioactive isotope of silicon, 31Si which was specially made in an atomic reactor for this investigation, confirmed the A.A.S. findings while additionally providing autoradiographic studies which showed silicon concentration in the distal tubule. (Abstract shortened by ProQuest.)

The effect of laser radiation on DNA damage and repair

Background: The effect of Helium Neon laser (He-Ne 632.8 nm) was reported to protect cells from damage. We studied lymphocyte cells pre irradiated with (UVC 260 nm) to induce DNA damage. Investigations were carried using gel electrophoresis and test for cell viability. It has also been reported that effect depends on incubation period after damage. The extent of damage to the cells depends on the period of irradiation with UVC also on its intensity. Objective: In this work we studied the effect of UVC on DNA damage and cell survival Also study of the effect of He-Ne laser on cell survival after all being pre irradiated with UVC light and its protective effect on DNA post UV damage. Method: This study was conducted in pathology department post graduate laboratory - College of medicine-Baghdad University. The total number of samples was (147). Blood samples were collected from healthy donors came to the blood bank, the amount of blood drown varies from 5ml to 7ml in heparin tubes .The work was carried out during the period between November 2010 to August 2011. In this experiments examination of samples was carried out to test the radiation effect on cell viability by using trypan blue dye, the experiments were preformed after 1, 24 and 72 hours post UVC irradiation to test the repair development. In other experiments Gel electrophoresis were carried out on samples to study the effect of radiation on the DNA fragmentation. Result: Results reveal a reduced DNA fragmentation appeared on gel electrophoresis experiments as the smear length is reduced significantly for both UV10 and UV20 , other results for cell viability tests revelled that He-Ne can increase survival of cells pre irradiated with UVC irradiation giving (66%, 57%, 70%( improvement in UV exposure for10 min and (59%,56%,59%) improvement for UV exposure for 20 min respectively . Conclusion: The effect of the laser in the improvement of cell survival may be attributed to the induction of endogenous radioprotectore and probably enzymes induced by laser irradiation which may be either reduce the free radical by scavenging effect or by improved cell repair, we may conclude that He-Ne laser can protect cells from radiation damag

A Review Of Cloud Manufacturing: Issues And Opportunities

Cloud Manufacturing (CM) is the latest manufacturing paradigm that enables manufacturing to be looked upon as a service industry.The aim is to offer manufacturing as a service so that an individual or organization is willing to manufacture products and utilize this service without having to make capital investment.However,industry adoption of CM paradigm is still limited.This paper compared the current adoption of CM by the industry with the ideal CM environment.The gaps between the two were identified and related research topics were reviewed. This paper also outlined research areas to be pursued to facilitate CM adoption by the manufacturing industry.This will also improve manufacturing resource utilization efficiencies not only within an organization but globally.At the end,the cost benefits will be passed down to end customer

Assessing the Effectiveness of Geography-based Online Learning During the Covid-19 Pandemic in Higher Education

The Covid-19 pandemic almost stalled the face-to-face learning method in all institutions across the globe. Consequently, for learning to continue uninterrupted, there was a need to change teaching mode to online using social media and other platforms. This research aimed to examine the effectiveness of online learning during the Covid-19 pandemic and the challenges geography students faced in implementing this type of study. The research used a descriptive qualitative approach involving questionnaires designed to determine the implementation of online learning and the challenges encountered. The questions were structured through synthesizing various components of learning. Random selection was used to select 305 participants from various higher education institutions in the Aceh Region, Indonesia. The results indicated that online learning during the Covid-19 pandemic was effectively implemented. However, some challenges were encountered, including students who could not fully participate since they could not log in to the provided learning platforms. Furthermore, students from rural areas had poor internet connectivity besides the inability to buy internet quota. There were many instances of reported power supply failures, and this hindered online learning. Overall, learning geography during the pandemic was effective, though it had a fair share of challenges. The research also identified the need to develop an online learning model, teaching material, and multimedia in supporting geography-based online learning.     Keywords: Assessing; Effectiveness; Geography-based online learning; Covid-19; Higher education Copyright (c) 2021 Geosfera Indonesia and Department of Geography Education, University of Jember     This work is licensed under a Creative Commons Attribution-Share A like 4.0 International Licens

Diazepam is not a direct allosteric modulator of alpha(1)-adrenoceptors, but modulates receptor signaling by inhibiting phosphodiesterase-4

α1A- and α1B-adrenoceptors (ARs) are G protein-coupled receptors (GPCRs) that are activated by adrenaline and noradrenaline to modulate smooth muscle contraction in the periphery, and neuronal outputs in the central nervous system (CNS). α1A- and α1B-AR are clinically targeted with antagonists for hypertension and benign prostatic hyperplasia and are emerging CNS targets for treating neurodegenerative diseases. The benzodiazepines midazolam, diazepam, and lorazepam are proposed to be positive allosteric modulators (PAMs) of α1-ARs. Here, using thermostabilized, purified, α1A- and α1B-ARs, we sought to identify the benzodiazepine binding site and modulatory mechanism to inform the design of selective PAMs. However, using a combination of biophysical approaches no evidence was found for direct binding of several benzodiazepines to purified, stabilized α1A- and α1B-ARs. Similarly, in cell-based assays expressing unmodified α1A- and α1B-ARs, benzodiazepine treatment had no effect on fluorescent ligand binding, agonist-stimulated Ca2+ release, or G protein activation. In contrast, several benzodiazepines positively modulated phenylephrine stimulation of a cAMP response element pathway by α1A- and α1B-ARs; however, this was shown to be caused by off-target inhibition of phosphodiesterases, known targets of diazepam. This study highlights how purified, stabilized GPCRs are useful for validating allosteric ligand binding and that care needs to be taken before assigning new targets to benzodiazepines

Gram scale preparation of clozapine N-oxide (CNO), a synthetic small molecule actuator for muscarinic acetylcholine DREADDs

Chemogenetics uses engineered proteins that are controlled by small molecule actuators, allowing in vivo functional studies of proteins with temporal and dose control, and include Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). One major class of DREADDs are mutated muscarinic receptors that are unresponsive to acetylcholine, and are activated by administration of clozapine N-oxide (CNO). However, CNO is available in only small amounts and large scale studies involving animals and multiple cohorts are prohibitively expensive for many investigators. The precursor, clozapine, is also expensive when purchased from specialist suppliers. Here we report: •A simple extraction method of clozapine from commercial tablets;•A simple preparation of CNO from clozapine, and for the first time its single-crystal X-ray structure; and•That the CNO prepared by this method specifically activates the DREADD receptor hM3Dq in vivo. This method provides large quantities of CNO suitable for large-scale DREADD applications that is identical to commercial material

Probing the correlation between ligand efficacy and conformational diversity at the ?(1A)-adrenoreceptor reveals allosteric coupling of its microswitches

G protein–coupled receptors (GPCRs) use a series of conserved microswitches to transmit signals across the cell membrane via an allosteric network encompassing the ligand-binding site and the G protein-binding site. Crystal structures of GPCRs provide snapshots of their inactive and active states, but poorly describe the conformational dynamics of the allosteric network that underlies GPCR activation. Here, we analyzed the correlation between ligand binding and receptor conformation of the α1A-adrenoreceptor, a GPCR that stimulates smooth muscle contraction in response to binding noradrenaline. NMR of [13CϵH3]methionine-labeled α1A-adrenoreceptor variants, each exhibiting differing signaling capacities, revealed how different classes of ligands modulate the conformational equilibria of this receptor. [13CϵH3]Methionine residues near the microswitches exhibited distinct states that correlated with ligand efficacies, supporting a conformational selection mechanism. We propose that allosteric coupling among the microswitches controls the conformation of the α1A-adrenoreceptor and underlies the mechanism of ligand modulation of GPCR signaling in cells

Thermal performance of waste materials as aggregate replacement in asphalt pavement

The high surface temperature of the conventional asphalt pavement due to high solar energy absorption could contribute to the Urban Heat Island (UHI) phenomenon. Concurrent with this phenomenon, rapid urbanization and industrial development have led to a large quantity of waste products available for disposal or recycling. Therefore, this study investigates the thermal performance of selected waste materials that could potentially be used as aggregate in asphalt pavement to combat the problem of increased pavement surface temperature. A number of waste materials were selected for the thermal performance measurement and compared to granite as conventional aggregate. The cylindrical and slab samples of AC14 dense graded asphalt were prepared for the different selected aggregate types. The samples were then measured for solar reflectance using Spectroradiometer. In addition, the surface and internal temperature profiles of the samples were monitored using infrared camera and thermocouples, respectively, in exposed environments. Based on the results, it is possible to use some of the waste materials as an aggregate replacement in order to reduce the UHI impact